CA2293824A1 - (amidino)6-membered aromatics as factor xa inhibitors - Google Patents

Abstract

The present application describes 6-membered aromatics of formula (I) or pharmaceutically acceptable salt forms thereof, wherein D may be CH2NH2 or C(=NH)NH2, which are useful as inhibitors of factor Xa.

Description

TITLE
(AMIDINO)6-MEMBERED AROMATICS AS FACTOR Xa INHIBITORS
FIELD OF THE INVENTION
This invention relates generally to novel 6-membered aromatics which are inhibitors of trypsin-like serine protease enzymes, especially factor Xa, pharmaceutical compositions containing the same, and methods of using the same as anticoagulant agents for treatment and prevention of thromboembolic disorders.
BACKGROUND OF THE INVENTION
WO 96/28427 describes benzamidine anticoagulants of the formula:
R5 Rs R ~/ I ~ R~
'Z A Z2 R~ ~ Rs wherein Z1 and Z2 are O, N(R), S or OCH2 and the central ring may be phenyl or a variety of heterocycles. The presently claimed compounds do not contain the Z1 linker or the substitution pattern of the above compounds.
WO 95/18111 addresses fibrinogen receptor antagonists, containing basic and acidic termini, of the formula:
/NRs'C c ~~Rs Rt-U-V ~ ~R~o wherein R1 represents the basic termini, U is an alkylene or heteroatom linker, V may be a heterocycle, and the right hand portion of the molecule represents the acidic termini. The presently claimed compounds do not contain the acidic termini of WO 95/18111.

Activated factor Xa, whose major practical role is the generation of thrombin by the limited proteolysis of prothrombin, holds a central position that links the intrinsic and extrinsic activation mechanisms in the final common pathway of blood coagulation. The generation of thrombin, the final serine protease in the pathway to generate a fibrin clot, from its precursor is amplified by formation of prothrombinase complex (factor Xa, factor V, Ca2+ and phospholipid). Since it is calculated that one molecule of factor Xa can generate 138 molecules of thrombin (Elodi, S., Varadi, K.: Optimization of conditions for the catalytic effect of the factor IXa-factor VIII Complex: Probable role of the complex in the amplification of blood coagulation.
Thromb. Res. 1979, 15, 617-629), inhibition of factor Xa may be more efficient than inactivation of thrombin in interrupting the blood coagulation system.
Therefore, efficacious and specific inhibitors of factor Xa are needed as potentially «al»able therapeutic agents for the treatment of thromboembolic disorders. It is thus desirable to discover new factor Xa inhibitors.
SUMMARY OF THE INVENTION
Accordingly, one object of the present invention is to provide novel 6-membered aromatics which are useful as factor Xa inhibitors or pharmaceutically acceptable salts or prodrugs thereof.
It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
It is another object of the present invention to provide a method for treating thromboembolic disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of tie compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.

These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that compounds of formula (I):
Rta Rtb 'M' D~E Z'A~B
I
or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, D, E, M, Rla, Rlb, and Z are defined below, are effective factor Xa inhibitors.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[1] Thus, in a first embodiment, the present invention provides novel compounds of formula I:
f ' M ' D~E Z~A~B
I
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein;
ring M contains from 0-4 N atoms;
D is selected fram CN, C(=NR~)NRaR9, NHC(=NR~)NR8R9, NRBCH(=NR~), C(O)NR8R9, and (CR8R9)tNRBR9;
E is selected from phenyl, 2-pyridyl, 4-pyridyl, pyrimidyl, and piperidinyl substituted with 1 R;
R is selected from H, F, C1, Br, I, OR3, SR3, C02R3, N02, and CH20R3, and (CR8R9)tNR8R9;
alternatively, E and R combine to form methylenedioxy or ethylenedioxy;

Z is selected from a bond, Cl_4 alkylene, (CH2)r0(CH2)r, ( CH2 ) r~3 ( CH2 ) r , ( CH2 ) rC ( O ) ( CH2 ) r , ( CH2 ) rC ( 0 ) O ( CHZ
) r , (CH2)rOC(0)(CH2)r, (CH2)rC(0)NR3(CHZ)r, (CH2)rNR3C(O)(CH2)r, (CH2)rOC(O)O(CH2)r, (CH2)rOC(O)NR~(CH2)r. (CH2)rNR3C(O)O(CH2)r, (CH2)rNR'C(0)NR3(CH2)r, (CH2)rS(O)p(CH2)r, (CH?)rS0?NR3(CHZ)r, (CH2)rNR3S02(CH2)r, arid (CH2)rNR3S02NR3(CH2)r, provided that Z does not form a N-N, N-O, N-S, NCH~N, NCH20, or NCH2S bond with ring M or group A;
Rla and Rlb are independently absent or selected from -(CH2)r-R1,, -CH=CH-Rl,, NCH2R1", OCH2R1" SCH2R1", NH(CHZ)2(CH?)tRl,, O(CH2)2(CH?)tRl,, and S(CH2)2(CH2)tRl,;
alternatively, Rya and Rlb, when attached to adjacent carbon atoms, together with the atoms to which they are attached fcrm a 5-8 membpred saturated, partially saturated or unsaturated ring substituted with 0-2 R4 and which contains from 0-2 heteroatoms selected from the group consisting of N, O, and S;
alternatively, when Z is C(O)NH and Rla is attached to a ring carbon adjacent to Z, then Rla is a C(O) which replaces the amide hydrogen of Z to form a cyclic imide;
R1, is selected from H, C1_3 alkyl, F, C1, Br, I, -CN, -CHO, (CF2)rCF3, (CH2)rOR2, NR2R2a, C(O)R2c, OC(0)R2, (CFZ)rC02R2c, S(O)pR2b NR2(CHz)rOR2. CH(=NR2c)NR2R2a, NR2C (O) R2b, NR2C (O)NHR2b, NR2C (O) 2R2a, OC (O)NR2aR2b C(O)NR2R2a, C(0)NR2(CH2)rOR2, S02NR2R2a, NR2SOZR2b, C3-6 carbocyclic residue substituted with 0-2 R4, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4;
R1" is selected from H, CH(CH20R2)2, C(O)R2c, C(0)NR2R2a, S(O)R2b S(O)2R2b and S02NR2R2a;

R2, at each occurrence, is selected from H, CF3, Ci_6 alkyl, benzyl, C3_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with U-2 R4b;
RZa, at each occurrence, is selected from H, CF3, Ci_6 alkyl, benzyl, phenethyl, C3_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, 0, and S substituted with 0-2 R4b;
Rzb, at each occurrence, is selected from CF3, C1_4 alkoxy, C1_6 alkyl, benzyl, C3_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, 0, and S substituted with 0-2 R4b;
R2~, at each occurrence, is selected from CF3, OH, C1_4 alkoxy, C1_6 alkyl, benzyl, C3_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
alternatively, RZ and R2a, together with the atom to which they are attached, combine to form a 5 or 6 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4b and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;
R3, at each occurrence, is selected from H, C1_4 alkyl, and phenyl;
R3a, at each occurrence, is selected from H, C1_4 alkyl, and phenyl;

R3b, at each occurrence, is selected from H, C1_4 alkyl, and phenyl;
R3~, at each occurrence, is selected from C1_4 alkyl, and phenyl;
A is selected from:
C3-1o carbocyclic residue substituted with 0-2 R4, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R4;
B is selected from: H, Y, and X-Y;
X is selected from C~_4 alkylene, -CRZ(CRZR~b)(CHZ)t-, -C(0) -C (=NR1" ) _ _CR2 (NR1"R2 ) - _CR2 (OR' ) -, -CRZ (SR2 ) -, -C(O)CR2R2a_ _CR2R2aC(O), -S(O)p-, -S(O)pCR2R2a_ -CR2R2aS(0)p-, -S(O)zNR2-, -NRZS(O)2-, -~TR2S(O)2CR2R~a_ -CR2R2aS (O) 2NR2-, -NR2S (O) 2NR2-, -C (O)NR2-, -NR2C (p) -, -C (O)NR2CR2R2a_ _~2C (O) CR2R2a_ _CR2R2aC (O)NR2-, -CR2R2aNR2C (O) -, -NR2C (O) O-, -OC (O) NR2-, -NR2C (O)NR2-, _~2_ _~2CR2R2a_ _CR2R2aNR2_ O _CR2R2a0_ and -OCR2R2a_.
Y is selected from:
(CH2)rNR2R2a, provided that X-Y do not form a N-N, O-N, or S-N bond, C3-1o carbocyclic residue substituted with 0-2 R4a, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R4a;
R4, at each occurrence, is selected from H, =O, (CH2)rOR2, F, C1, Br, I, C1_4 alkyl, -CN, N02, (CH2)rNR2R2a (CH2) rC (O) R2c NR2C (O) R2b, C (O) NR2R2a,, NR2C (O)NR2R2a, CH(=NR2)NR2R2a, CH(=NS(O)2R5)NR2RZa, NHC(=NRZ)NR2R2a, C(O)NHC(=NR2)NR2R2a, S02NR2R2a, NR2S02NR2R2a, NR2S02-C1_4 alkyl , NR2S02R~ , S ( O ) pR5 , ( CF2 ) rCF3 , NCH2R1,~ , OCH2R1 ° , WO 98/57934 PCT/US98/12b82 SCH2R1", N(CH2)2(CH2)tRl,. O(CHZ)2(CH2)tRl,, and S ( CH2 ) 2 ( CH2 ) tRl ~ ;
alternatively, one R4 is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;
R4a, at each occurrence, is selected from H, =O, (CHz)rOR2, (CH2)r-F, (CHZ)r-Br, (CH2)r-Cl, I, C1_4 alkyl, -CN. N02, (CH2)rNR2R2a~ (CH2)rNR2R2b, (CH2)rC(O)R2c NR2C(0)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a, NR~C(O)NR2R2a CH(=NR2)NR2R2a, NHC(=NR2)NR2R2a, S02NR2R2a, NR2S02NR2R2a, NR2S02-Cl_4 alkyl, C(O)NHS02-C1_4 alkyl, NRZS02R', S(O)pRS, and (CF2)rCF3;
alternatively, one R4a is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-1 R5;
R4b, at each occurrence, is selected from H, =O, (CH~)rOR3, F, C1, Br, I , C1_4 alkyl , -CN, N02 , ( CH2 ) rNR3R3a (CH2)rC(O)R3, (CH2)rC(0)OR3~, NR3C(O)R3a, C(0)NR3R3a NR3C(O)NR3R3a, CH(=NR3)NR3R3a, NH3C(=NR3)NR3R3a, S02NR3R3a NR3S02NR3R3a, NR3S02-C1_4 alkyl, NR3S02CF3, NR3S02-phenyl, S(0)pCF3, S(O)p-Cl_4 alkyl, S(O)p-phenyl, and (CF2)rCF3;
R5, at each occurrence, is selected from CF3, C1_6 alkyl, phenyl substituted with 0-2 R6, and benzyl substituted with 0-2 R6;
R6, at each occurrence, is selected from H, OH, (CH2)rOR2, F, C1, Br, I, C1_4 alkyl, CN, N02, (CH2)rNR2R2a, (CH2) rC (O) R2b, NR2C (O) R2b, NR2C (0)NR2R2a. CH (=NH)NH2.
NHC(=NH)NH2, S02NR2R2a, NR2S02NR2RZa, and NR2S02C1_4 alkyl;
R~, at each occurrence, is selected from H, OH, C1_6 alkyl, C1_6 alkylcarbonyl, C1_6 alkoxy, C1_4 alkoxycarbonyl, (CH2)n-phenyl, Cg-1p aryloxy, C6_lo aryloxycarbonyl, C6_lo arylmethylcarbonyl, C1_4 alkylcarbonyloxy C1_4 alkoxycarbonyl, C6_1o arylcarbonyloxy Cl_4 alkoxycarbonyl, Cl_6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl-C1_q alkoxycarbonyl;
R8, at each occurrence, is selected from H, Cl_6 alkyl and (CH2)n-phenyl;
alternatively, R~ and R8 combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, 0, and S;
R9, at each occurrence, is selected from H, C1_6 alkyl and IS (CH2)n-phenyl;
n is selected from 0, 1, 2, and 3;
m is selected from 0, 1, and 2;
p is selected from 0, 1, and 2;
r is selected from 0, 1, 2, and 3;
s is selected from 0, 1, and 2; and, t is selected from 0 and 1.
[2] In a preferred embodiment, the present invention provides novel compounds of formulae Ia-Io:

R1a R7a Rya ~/R~a ~~~ Rya N~ Rya _N R1a ~,~ Ria N\
'~,,. ~''' ''~,. .,~' ~''z. o ,~'' a b Ria Rya Rya ~ ~ Rya N~,pt; ~~/Ria N ~ ~ ~N N\ ~ ~ ~N N\//N
f ~ g h ~ 1 Rva Rya i a N~ N~! ~=N N
~~ R N\ / Ria R1 ~ /N \ /N and N\ /N
I m n o wherein:
Z is selected from a bond, CH20, OCH2, CH2NH, NHCH2, CHZC(O), C (O) CH2, C (O) NH, C (O) DIH, CHZS (O) 2, S (O) 2 (CH2 ) , S02NH, and SOZNH;
B is selected from: Y, X-Y, and NR2R2a;
Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran, benzothiofuran, indole, benzimidazole, benzoxazole, benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;
Y may also be selected from the following bicyclic heteroaryl ring systems:

R '}
R'~
R4 ~ N~ ~~\ N.~ ~ i R4'\~
N~ N R , \K~ R3 \K ~ 'R~ N
, , ~ R~
R'~
K N/'~~ ~ ~ ~'~N ~~ ri R4 ~, ~~ ~~ 9 N I I II ~, SRS ~ ~ N R \~ ~ N arid N ~ ~R4 , K is selected from 0, S, NH, and N.
[3] In a more preferred embodiment, the present invention provides novel compounds of formulae:
Ria R1a Rib N~ Rib Rib ~~ Rib N\~~ N ~ N~~ N~ ~N
\ ~ \
b f Rib Rib N~V
N Rib ,=N
\ ~ \ %N and N\ /N
I

n wherein:
D is selected from C(=NR~)NR8R9 and (CR8R9)tNR8R9;
R is selected from H, F, C1, OR3, CH20R3, CH2NH2;
A is selected from:
piperidinyl, piperazinyl, C5_6 carbocyclic residue substituted with 0-2 R4, and 5-6 membered heteroaryl containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4;

Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxa.zolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, benzimidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, and 1,3,4-triazole.
[4] In an even more preferred embodiment, the present invention provides novel compounds wherein:
E is phenyl;
D is selected from C(=NH)NH2 and CH2NH2;
R is selected from H, F, C1, and Br;
A is selected from:
C5_6 carbocyclic residue substituted with 0-2 R~, and 5-6 membered heteroaryl containing from 1-3 heteroatoms selected from the group consisting of N, 0, and S substituted with 0-2 R4;
Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, benzimidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, and 1,3,4-triazole;
R2, at each occurrence, is selected from H, CF3, C,_6 alkyl, benzyl, C5_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic sysLem.containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2a, at each occurrence, is selected from H, CF3, C1_6 alkyl, benzyl, phenethyl, C5_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2b, at each occurrence, is selected from CF3, C1_4 alkoxy, C1_6 alkyl, benzyl, C5_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membere~. heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, 0, and S substituted with 0-2 R4b;
R2~, at each occurrence, is selected from CF3, OH, C1_4 alkoxy, C1_6 alkyl, benzyl, C5_6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
alternatively, R2 and R2a, together with the atom to which they are attached, combine to form a ring selected from imidazolyl, mozpholino, piperazinyl, pyridyl, and pyrrolidinyl, substituted with 0-2 R4b R4, at each occurrence, is selected from H, =O, OR2, CH20R2, F, Cl, C1_4 alkyl, NR2R2a, CH2NR2R2a, C(O)R2~, CH2C(O)R2c C(0)NR2R2a, CH(=NR2)NR2R2a, CH(=NS(0)2R5)NR2R2a, S02NR?R2a, NR2S02-C1_4 alkyl, S(O)ZRS, and CF3 provided that if B is H, then R4 is other than tetrazole, C(0)-alkoxy, and C(O)NR2R2a;
R4a, at each occurrence, is selected from H, =O, (CH2)rOR2, F, Cl, C1_g alkyl, NR2R2a, CH2NR2R2a, NR2R2b, CH2NR2RZb, (CH2)rC(O)R2c NRZC(O)R2b C(0)NR2R2a, C(O)NH(CH?)2NR2R°a, - NR2C (O)NR2R2a, S02NR2R'a, S (O) 2R5, and CF3; and, R4b, at each occurrence, is selected from H, =0, (CH2)rOR3, F, C1, C1_4 alkyl, NR3R3a, CHzNR3R3a, C(O)R3, CHZC(0)R3, C(O)OR3c, C(O)NR3R3a, CH(=NR3)NR3R3a, S02NR3R3a NR3S02-C1_4 alkyl, NR3S02CF3, NR3S02-phenyl, S(O)2CF3, S(0)2-C~_4 alkyl, S(O)2-phenyl, and CF3.
[5) In a further preferred embodiment, the present invention provides novel compounds selected from:
N-(2'-Aminosulfonyl-[1,1']biphen-4-yl)-2-(3'-amidinophenyl)nicotinamide;
N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide;
N-[5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide; and, N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-carboxamidophenyl)nicotinamide;
or a pharmaceutically acceptable salt thereof.
In a second embodiment, the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof.

In a third embodiment, the present invention provides a novel method for treating or preventing a thromboemboiic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt form thereof.
DEFINITIONS
The compounds herein described may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.
The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substitent is keto (i.e., =O), then 2 hydrogens on the atom are replaced.
Keto substituents are not present on aromatic moieties.
The present invention is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium. Isotopes of carbon include C-13 and C-14.

When any variable (e.g., R6) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R6, then said group may optionally be substituted with up to two R6 groups and R6 at each occurrence is selected independently from the definition of R6. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. "Haloalkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example -C~Fw where v = 1 to 3 and w =
1 to (2v+1)). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl. "Alkoxy" represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. "Cycloalkyl" is intended to include saturated ring groups, such as cyclopropyl, cyclobutyl, or cyclopentyl.
Alkenyl" is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl and the like. "Alkynyl"
is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like.
"Halo" or "halogen" as used herein refers to fluoro, chloro, bromo, and iodo; and "counterion" is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate, and the like.
As used herein, "carbocycle" or "carbocyclic residue" is intended to mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic.
Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0)bicyclodecane, [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl.
As used herein, the term "heterocycle" or "heterocyclic system" is intended to mean a stable 5-to 7-membered monocyclic or bicyclic or 7-to 10-membered bicyclic heterocyclic ring which is saturated partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S
and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term "aromatic heterocyclic system" is intended to mean a stable 5-to 7-membered monocyclic or bicyclic or 7-to 10-membered bicyclic - 5 heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heterotams independently selected from the group consisting of N, O and S. It is preferred that the total number of S and 0 atoms in the aromatic heterocycle is not more than 1.
Examples of heterocycles include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnoiinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl.; imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, pyrrolidinyl, imidazolyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.
The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
As used herein, "pharmaceutically acceptable salts" refer to derivatives of the disclosed compounds wherein the parent compound is modified by maksng acid or base salts thereof.
Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, malefic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.
The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two;
generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, PA, 1985, p. 1418, the disclosure of which is hereby incorporated by reference.
"Prodrugs" are intended to include any covalently bonded carriers which release the active parent drug according to formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of formula (I) are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of formula (I) wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug or compound of formula (I) is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively.
Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I), and the like. Preferred prodrugs are amidine prodrugs wherein D is C(=NR~)NH2, and R~ is selected from OH, C1_4 alkoxy, C6_1o aryloxy, C1_4 alkoxycarbonyl, C6_1o aryloxycarbonyl, C6_lp arylmethylcarbonyl, C1_4 alkylcarbonyloxy Cl_4 alkoxycarbonyl, and C6_1o arylcarbonyloxy C1_4 alkoxycarbonyl. More preferred prodrugs are where R~ is OH, methoxy, ethoxy, benzyloxycarbonyl, methoxycarbonyl, and methylcarbonyloxyrnethoxycarbonyl.
"Stable compound" and "stable structure" are meant to indic~ae a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.

"Substituted" is intended to indicate that one or more hydrogens on the atom indicated in the expression using "substituted" is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., =O) group, then 2 hydrogens on the atom are replaced.
"Therapeutically effective amount" is intended to include an amount of a compound of the present invention or an amount of the combination of compounds claimed effective to inhibit HIV infection or treat the symptoms of HIV infection in a host. The combination of compounds is preferably a synergistic combination. Synergy, as described for example by Chou and Talalay, Adv. Enzyme Regul. 22:27-55 (1984), occurs when the effect (in this case, inhibition of HIV replication) of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at suboptimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, increased antiviral effect, or some other beneficial effect of the combination compared with the individual components.
SYNTHESIS
The compounds of the present invention can be prepared in a number of ways known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will sometimes require a judgment to modify the order of synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. It will also be recognized that another major consideration in the planning of any synthetic route in this field is the judicious choice of the protecting group used for the protection of the reactive functional groups present in the compounds described in this invention. An authoritative account describing the many alternatives to the trained practitioner is Greene and Wuts (Protective Groups in Organic Chemistry, Wiley and Sons, 1991). All references cited herein are hereby incorporated in their entirety herein by reference.
Compounds of this invention where B is either a carbocyclic or heterocyclic residue as defined in Formula 1 are coupled to A
as shown generically and by specific example in Schemes 1 and 2, respectively. Either or both of A and B may be substituted with 0-2 R4. W is defined as a suitable protected nitrogen, such as NO~ or NHBOC; a protected sulfur, such as S-tBu or SMOM; or a methyl ester. Halogen-metal exchange of the bromine in bromo-B with n-butyl lithium, quenching with triisopropyl borate and acidic hydrolysis gives the required boronic acid, B-B(OH)~. The W-A-Br subunit may be already linked to ring M before the Suzuki coupling reaction.
Deprotection provides the complete subunit.
Scheme 1 B-Br 1) n-BuLi 2) (iPrO)3B
3) HC1 B-B(OH)z W
I
A ~ W-A-B
Br Pd(0) Scheme 2 describes a typical example of how the A-B
subunit is prepared for attachment to ring M. 4-Bromoaniline is protected as Boc-derivative and the coupled to 2-(t-butylamino)sulfonylphenylboronic acid under Suzuki conditions.
2-(t-Butylamino)sulfonylphenylboronic acid is prepared by the method described by Rivero (Bioorg. Med. Chem. Lett. 1994, 189). Deprotection with TFA can provide the aminobiphenyl compound. The aminobiphenyl is then coupled to the core ring structures as described below.
Scheme 2 B (OH) ~ NHBOC ~JH~
NHS NHBOC
/ SO~NH-t-Bu / /
NaH
( BO~ \ ~ \ ~ \ ~ TFA
SO~NH-t-Bu Pd(0) / ~ / SO~NH-t-Bu Br Br \ \
When B is defined as X-Y, the following description applies. Groups A and B are available either through commercial sources, known in the literature or readily synthesized by the adaptation of standard procedures known to practitioners skilled in the art of organic synthesis. the required reactive functional groups appended to analogs of A
and B are also available either- through commercial sources, known in the literature or readily synthesized by the adaptation of standard procedures known to practitioners skilled in the art of synthesis. In the tables that follow the chemistry required to effect the coupling of A to B is outlined.
Table A: Preparation of Amide Ester, Urea, Sulfonamide and Sulfamide Linkages Between A and B.
If A contains: then the reactive to give the following substituent of Y is: product A-X-Y:
A-NHRz as a C1C(O)-Y A-NRz-C{0)-Y
substituent a secondary NH C1C(O)-Y A-C(O)-Y
as part of a ring or chain A-OH as a C1C(O)-Y A-O-C(O)-Y
substituent A-NHRz as a C1C (O) -CRZR2a-Y A-NRZ-C (O) -CRzR2a-Y
substituent a secondary C1C (O) -CRZR~a-Y A-C (O) -CR2R2a-Y
NH

as part of a ring or chain A-OH aS a C1C (0) -CR~R~a-Y A-O-C (0) -CR~Rza-Y

substituent .

A-NHRZ as a C1C(O)-CNR'-Y A-NR-C(O)-CNR2-Y

substituent a secondary CIC(O)-CNR'-Y A-C(O)-CNR'-Y
NH

as part of a ring or chain A-OH as a C1C(0)-CNRZ-Y A-O-C(O)-CNRz-Y

substituent A-NHR2 as a C1S02-Y A-NR'-S02-Y

substituent a secondary C1S02-Y A-SO~-Y
NH

as part of a ring or chain A-NHRZ as a C1S02-CR2R2a-Y A-NRZ-SO~-CR2Rza-Y

substituent a secondary C1S02-CRzR2a-Y A-S02-CRzR2a-Y
NH

as part of a ring or chain A-NHRz as a C1S02-NR~-Y A-NR2-SOZ-NRz-Y

substituent a secondary C1S02-NR'-Y A-SOz-NRZ-Y
NH

as part of a ring or chain A-C(O)C1 HO-Y as a substituent A-C(O)-O-Y

A-C(O)Cl NHRz-Y as a A-C(O)-NR2-Y

substituent A-C(O)C1 a secondary NH as A-C(O)-Y

part of a ring or chain A-CRZR2aC (O) HO-Y as a substituent A-CRZRzaC (O) -O-Y

A-CRzR2aC (O) NHRZ-Y aS a A-CR2RZaC (O) -NRZ-Y

substituent A-CRZR'aC (O) a secondary NH as A-CR2RzaC (O) -Y

part of a ring or chain A-SO~Cl NHRZ-Y as a A-S0~-NR'-Y

substituent A-SO~C1 a secondary NH as A-S02-Y

part of a ring or chain A-CR2R~aSOZCl NHR~-Y aS a A-CR2RzaS0~-NRZ-Y

substituent A-CRZRZaSO2C1 a secondary NH as A-CRZRzaSOz-Y

part of a ring or chain The chemistry of Table A can be carried out in aprotic solvents such as a chlorocarbon, pyridine, benzene or toluene, at temperatures ranging from -20°C to the reflux point of the solvent and with or without a trialkylamine base.
Table H: Preparation of Ketone Linkages between A and B.
If A contains: then the reactive to give the following substituent of Y is: product A-X-Y:
A-C(O)C1 BrMg-Y A-C(O)-Y
A-CRzRZaC ( O ) C1 BrMg-Y A-CRzR2aC ( O ) -Y
A-C (O) C1 Br'MgCR2R2a-Y A-C (O) CR2R'a-Y
A-CR'R2aC (O) C1 BrMgCR2R2a-Y A-CRZRZaC (O) CRzR2a-Y
The coupling chemistry of table B can be carried out by a variety of methods. The Grignard reagent required for Y is prepared from a halogen analog of Y in dry ether, dimethoxyethane or tetrahydrofuran at 0°C to the reflux point of the solvent. This Grignard reagent can reacted directly under very controlled conditions, that is low temperature (-20°C or lower) and with a large excess of acid chloride or with catalytic or stoichiometric copper bromide~diinethyl sulfide complex in dimethyl sulfide as a solvent or with a variant thereof. Other methods available include transforming the Grignard reagent to the cadmium reagent and coupling according to the procedure of Carson and Prout (Org. Syn. Col.
Vol. 3 (1955) 601) or a coupling mediated by Fe(acac)3 according to Fiandanese et al.(Tetr. Lett. 1984, 4805), or a coupling mediated by manganese (II) catalysis (Cahiez and Laboue, Tetr. Lett. 1992, 33(31), 4437).
Table C: Preparation of Ether and Thioether linkages between A and B.
If A contains: then the reactive to give the following substituent of Y is: product A-X-Y:
A-OH Br-Y A-O-Y
A-CRzR2a-OH Br-Y A-CRzR'a0-Y
A-OH Br-CR2Rza-Y A-OCR'R'a-Y
A-SH Br-Y A-S-Y
A-CRzR'a-SH Br-Y A-CR'RzaS-Y
A-SH Br-CR2Rza-Y A-SCR'Rza-Y
The ether and thioether linkages of Table C can be prepared by reacting the two components in a polar aprotic solvent such as acetone, dimethylformamide or dimethylsulfoxide in the presence of a base such as potassium carbonate, sodium hydride or potassium t-butoxide at a temperature ranging from ambient to the reflux point of the solvent used.
Table D: Preparation of -SO- and -SOa- linkages from thioether of Table C.
If the starting then it is oxidized then it is oxidized material is: with wet with m-Alumina/Oxone to chloroperbenzoic acid give: to give:
A-S-Y A-S{O)-Y A-SOZ-Y
A-CRZR2aS-Y A-CRZR2aS (O) -Y A-CR2R2aSO2-Y
A-SCRZRza-Y A-S (O) CR2R2a-Y A-SOzCRZR2a-Y
The thioethers of Table C serve as a convenient starting material for the preparation of the sulfoxide and sulfone analogs of Table D. A combination of wet alumina and Oxone can provide a reliable reagents for the oxidation of the thioether to the sulfoxide as shown by Greenhalgh (Syn. Lett.
1992, 235). The sulfone can be prepared according to the method of Satoh CChem. Lett. 1992, 381) using m-chloroperbenzoic acid.
Scheme 3 describes the synthesis of compounds wherein M
is a benzene ring and Q is a protected precursor of group D of Formula I and V is a nitro, protected sulfonamide or ester group and precursor of group Z of Formula I. The V group is placed on an appropriately substituted phenol either via nitration as shown by Poirier et al. (Tetrahedron 1989, 45(5), 1415), sulfonylation as shown by Kuznetsov (Akad. Nauk SSSR
Ser. Khim 1990, 8, 1888) or carboxylation by Sartori et al.
(Synthesis 1988, 10, 763). Bromination with triphenylphosphine and bromine (J. Am. Chem. Soc. 1954, 86, 964) gives the desired bromide. Suzuki coupling with the appropriate boronic acid provides the desired substitute~3 pyridine.
Scheme 3 lb R 1 ) V / v Rlb Q-E-B ( OH ) 2 v Rlb -~ ~ v 2) Ph3P, (Ph3P)qPd HO gr2 Br V NazC03 Q~ E V
Schemes 4, 5, 6, and 7 describe the synthesis of compounds wherein M is pyridine and Q is a protected precursor of group D of Formula I. Each scheme represents a different substitution pattern for the pyridine ring. In Scheme 4, a suitably protected aldehyde is subjected to base-catalyzed condensation with an activated ester to give after deprotection the desired aldehyde. Refluxing with ammonium chloride as shown by Dornow and Ische CChem. Ber. 1956, 89, 876) provides the pyridinol which is brominated with POBr3 (Tjeenk et al. Rec. Trav. Chim. 1948, 67, 380) to give the desired 2-bromopyridine. Suzuki coupling with the appropriate boronic acid provides the desired substituted pyridine.

Scheme 4 CORlb OY 'CHO 1) NaOEt OHC-~ R1b ~ R1b O Er_CaC~ V ~ 1 ) NH4C1 N/ i or 2 ) H OT EtO2C'--~V ? ) POBr3 Br~V

~~ CORlb O
Q-E-B (OH) 2 ~,Rlb (Ph3P)qPd /\ ~~
Na CO ~ E V

Treatment of an appropriately substituted 5-ethoxyoxazole with an alkene as shown by Kondrat'eva et al. Dokl. Akad. Nauk SSSR 1955, 164, 816) provides a pyridine with the V
substituent at the para position. Bromination at the 3-position as shown by van der Does and Hertog (Roc. Trav. Khim.
Pays-eas 1955, 84, 951) followed b~~ palladium-catalyzed boronic acid coupling provides the desired substituted pyridine.
Scheme 5 Rlb OEt ~~ -- r O

lb V N-~
R O OEt 1b .-.' /
v -Rlb or OEt .. N~
V

p OEt V V

Rib Br . N ~ Rlb Q-E-B(OH)2 2 / N ~
/ Rib ' /

H O - ( Ph3 2 4 P ) q Pd Br V Na2C03 Q E
V

_ Scheme 6 describes a synthesis of a third substitution pattern on a pyridine ring. The appropriate tricarbonyl compound which can be prepared by methods described in Scheme 4 is treated with ammonium chloride to form the pyridinol which is subsequently brominated. Palladium-catalyzed coupling provides the desired substituted pyridine.
Scheme 6 CHO
R1b-r CHO
V 1) NHqCl N R1b Q-E-B(OH)2 I~ Rlb Rlb O 2) Br2, (Ph3P)qPd CHO Ph3P Br V Na~COs Q~ E V
o~ w Scheme 7 takes a suitably substituted dicarbonyl compound and by chemistry illustrated in Schemes 4 and 6, reacts it with ammonium chloride. Bromination gives the 3-bromopyridine which upon palladium-catalyzed coupling provides the desired substituted pyridine.
Scheme 7 R1 ~~-CHO
~O
V 1 ) NHqCl ~ Rlb Q-E-B (OH ) 2 ~ Rib or ~ N ~ N
Rlb 2) Br2, (Ph3P)qPd HZSOq gr V Na~C03 Q~ E V
w O
O
V
Schemes 8, 9, and 10 describe the synthesis of compounds wherein M is pyridazine and Q is a protected precursor of group D of Formula I. Each scheme represents a different substitution pattern for the pyridine ring. In Scheme 8 an activated ester is reacted with an appropriately substituted a-keto aldehyde and hydrazine as shown by Schmidt and Druey (Helv. Chim. Acta 1954, 3 7, 134 and 1467). Conversion of the pyridazinone to the bromide using POBr3 and palladium-catalyzed coupling provides the desired substituted pyridazine.
Scheme 8 1) NHzNH~
EtOzC~-~ ~Rlb NaOEt NN~ Rlb Q-E-B (OH) 2 CHO ~) POBr3 ~ (Ph3P)qPd Br V Na2C03 Q ~E V
In Scheme 9, glyoxal can react under basic conditions with an activated ketone and subsequently brominated/dehydro-brominated to give the desired ketoaldehyde. Alternatively, a protected ketone can react with an activated aldehyde, undergo bromination/dehydrobromination, be deprotected and oxidized to give the regioisomeric ketoaldehyde. Cyclization as shown by Sprio and Madonia (Ann. Chim. 1958, 48, 1316) with hydrazine followed by palladium-catalyzed coupling provides the desired substituted pyridazine.
Scheme 9 O O
OH ~R~b 1 ) NaOEt OH Rib CHO + 2 ) V Br V
~2~2 or -OTBS 1) NaoEt O
O + ~HO 2 )~ R1 HO
3) TBAF
R1b 41 PDC Bf V
N-N, Q-E-B ( off > 2 N-N, ~Rlb (Ph3P)qPd Q' ~-=CR~b B V Na2C03 E V
By analogy to Scheme 9, in Scheme 10 a aldehyde can be reacted with an activated ketone, brominated, dehydro-brominated and deprotected to give the desired diketone.
Alternatively, a regioisomeric ketone can be placed through the same reaction sequence to produce an isomeric keto aldehyde. Reaction with hydrazine followed by palladium-catalyzed coupling provides the desired substituted pyridazine.
Scheme 10 Rib R~bO/'~ O ? ) NaOEt O
O + -~ -- ~ O
CHO V ? ) Br2 3) TsOH Br V NH~NH~
o r --O O O i ) NaOEt HO
+ ---~ R ~ ~ O
R~~O V ? ) Br2 3) TSOH Br V
R1~~N,N Q-E-B (oH> z R~~~~'N
Br~ (Ph3P)qPd V NazCOz E V
Schemes 11, and 12 describe the synthesis of compounds wherein M is pyrimidine and Q is a protected precursor of group D of Formula I. Each scheme represents a different substitution pattern for the pyrimidine ring. In Scheme 11, a condensation with an appropriately substituted acid chloride and an activated ester followed by conjugate reduction by tin hydride (Moriya et al. ~T. Org. Chem. 1986, 51, 4?08) gives the desired 1,4 dicarbonyl compound. Cyclization with forrnamidine or a substituted amidine followed by bromination gives the desired regioisomeric pyrimidine. Palladium-catalyzed coupling provides the desired substituted pyrimidine.

Scheme 11 1) NaOEt ~ 1) formamidine Et02C~V
CIOC-Rib Et02''~.''~~~/ 2 ) POBr3 2) nBu3SnH
AIBN V N~N R1b Rtb NH B~~V
HO 1 ) H
Et02G--V 2) POBr3 Q-E-B (oH) z NON R1b (Ph3P)qPd NazC03 Q~E~V
Using similar chemistry, Scheme 12 shows how an amidine can be condensed with a 1,3-dicarbonyl compound and subsequently brominated in the 5-position (J. Het. Chem. 1973, 10, 153) to give a specific regioisomeric bromopyrimidine.
Palladium-catalyzed coupling provides the desired substituted pyrimidine.
Scheme 12 O 1) formamidine Rlb--~~0 2) Br2 V N~/R1° Q-E-B(OH)2 N-~/Rlb or ~ N ~ N
Rlb ~ (Ph3P)qPd -NH2 Br V Na2C03 Q~ E V
OHC_ ,_O 1 ) FAN
\~//V 2 ) Br2 Using the same ketoaldehyde from Scheme 12, cyclization with an appropriately substituted 1,2-diamine (Chimia 1967, 21, 510) followed by aromatization (Helv. Chim. Acta 1967, 50, 1754) provides a regioisomeric mixture of pyrazines as illustrated in Scheme 13. Bromination of the hydrobromide salt (U.S. Patent No. 2,403,710) yields the intermediate for the palladium-catalyzed coupling step which occurs as shown above.
Scheme 13 Rlb OHC O 1) H~ ~ H~ ~/R1D Q_E_g(OH)2 ~/R1b N N
~V 2) Cu0~Cr203 ~ (Ph3P)qPd 3) HBr/Br2 Br V Na2C03 Q' E V
Schemes 14 and 15 describe the synthesis of compounds wherein M is a 1,2,3-triazine and Q is a protected precursor of group D of Formula I. In Scheme 14, a vinyl bromide is palladium coupled to a molecule containing the substituent Rlb. Allylic bromination followed by azide displacement provide the cyclization precursor. Triphenylphosphine-mediated cyclization (J. Org. Chem. 1990, 55, 4724) give the 1-aminopyrazele which is subsequently brominated with N-bromosuccimide. Lead tetraacetate mediated rearrangement as shown by Neunhoeffer et al. (Ann. 1985, 1732) provides the desired regioisomeric 1,2,3-triazine. Palladium-catalyzed coupling provides the substituted triazine.
Scheme 14 1 ) RlbCH2Br r Pd ( 0 ) N3 Rlb Ph3 P Hz~ ~ ~ R1b V 2) NBS
V V
3) NaN3 1 ) NBS ,N- Q-E-B (OH) 2 N-I~~Rib ''-~ Rlb 2) Pb(OAc)q /\~~/ (Ph3P)4Pd Br V Na2C03 Q~ E V
In Scheme 15, an alkene is allylically brominated and the bromide is displaced to give a regioisomer of the azide in Scheme 14. Following the same reaction sequence as shown above, cyclization provides the 1-aminopyrazole. Bromination followed by lead tetraacetate mediated rearrangement give the 1,2,3-triazine. Palladium-catalyzed coupling provides the other desired triazine.
Scheme 15 ~V 1) NBS N3 V Ph3P H'~N'Nw V
2 ) NaN 3 Rlb Rlb Rlb 1 ) NBS N-I~ Q-E-B (OH) ~ N-N
Rlb / ~N Rlb /-\N
2) Pb(OAc)q ~. _~ (Ph3P)qPd Br V NazC03 Q~ E V
Schemes 16 and 17 describe the synthesis of compounds wherein M is a 1,2,4-triazine and Q is a protected precursor of group D of Formula I. In Scheme 16, a nitrile is converted using hydrazine to give the amidrazone which is condensed with a a-ketoester to give the triazinone as shown by Paudler and Lee (J. Org. Chem. 1971, 36, 3921). Bromination as shown by Rykowski and van der Plas (J. Org. Chem. 1987, 52, 71) followed by palladium-catalyzed coupling provides the desired 1,2,4-triazine.
Scheme 16 0 R1b lb EtO2C~
R 1 ) --N
NH ~
NH

V /
Z IQ ,N
z R CN I~

3 ~
HZN NHZ 2) POBr Br V

Rlb Q-E-B (OH) z ~-I

IQ N

(Ph3P)qPd Na2C03 Q~ E V

In Scheme 16, to achieve the oppositeregioisomer the reaction scheme shown above is modify by the substituting a protect a-ketoester. 'This allows the nucleophilic most nitrogen to attack the ester functionalitysetting up the opposite regiochemistry. Deprotection and thermal cyclization gives th e triazinone which is brominated as shown above.

Palladium-catalyzed coupling provides the other desired 1,2,4-triazine.
Scheme 17 Rib 1b EtO~C-~-RlbCN NH~NH~ R N 1) V
HEN NHS 2) Aq. HC1 3) O Br V
4) POBr3 Rlb Q-E-B(OH)~ N
~N
(Ph3P)qPd NaZC03 Q~ E V
Scheme 18 describes the synthesis of compounds wherein M
is a 1,2,3,4-tetrazine and Q is a protected precursor of group D of Formula I. Lithiation of a vinyl bromide, transmetallation with tin, palladium catalyzed carbonylation and hydrazone formation provides a diene for a subsequent Diels-Alder reaction as shown by Carboni and Lindsey (J. Am.
Chem. Soc. 1959, 8.2, 4342). Reaction with dibenzyl azodicarboxylate followed by catalytic hydrogenation to debenzylate and decarboxylate should give after bromination the desired 1,2,3,4-tetrazine. Palladium-catalyzed coupling provides the desired substitution.
Sch~ne 18 COZBn 1) nBuLi 1) N
~Br 2 ) (nBu) 3SnCl B
Bn0-, ~ N
V 3) Pd(0), CO 2) H2, Pd 4) BnNHNH2 V 3) NBS
~N-I~ Q-E-B (OH) z ~N (PhgP) qPd -\ iN
Br V Na2C03 Q~ E V
Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration fo the invention and are not intended to be limiting thereof.
EXAMPLES
Example 1 N-(2'-Aminosulfonyl-[1,1']biphen-4-yij-~-(3~
amidinophenyl)nicotinamide, trif luoroacetic acid salt Part A. Preparation of 2-bromonicotinic acid.
Potassium permanganate (18.4 g, 116 mmol) was dissolved in water (400 mL) and added to 2-bromo-3-methylpyridine (10.0 g, 58 mmol) and refluxed for 16 hours. After cooling to room temperature, the slurry was filtered through a celite plug and rinsed with water and chloroform. The entire filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted again with CHC13 and acidified with 6N HC1 to pH 1. A white solid was obtained on standing (2.08 g of product). The pH of the remaining aqueous was adjusted to pH 4 with 2M NaOH and 2M HC1, then concentrated to <100mL. A white precipitate was filtered.
The pH was adjusted to 4 and the mixture filtered again, combining the isolated solids for a total of 3.88 g of product. The filtrate was concentrated again to <100mL and adjusted to pH 1.5 and an additional quanitity of white solid was obtained (1.80 g), for a combined yield of 3 crops, (8.76 g, 66~). 1H NMR (DMSO-d6): 8 13.76 (bs, 1H), 8.46 (m, 1H), 8.09 (dd, 1H, J = 7.7, J' - 2.2), 7.51 (m, 1H).
Part B. Preparation of methyl 2-bromonicotinate.
2-Bromonicotinic acid (7.33 g, 36 mmol) was suspended in dry Et20 (40 mL), and MeOH (2.3 mL) and diethyl azodicarboxylate (5.8 mL, 37 mmol) were added.
Triphenylphosphine (9.61 g in 40mL Et20, 37 mmol) was added dropwise over 2.5 hours. After stirring an additional two hours, the reaction was filtered and evaporated. The resulting clear liquid was chromatographed on silica gel (10-40% EtOAc/hexanes) to yield a clear oil (8.63 g, 100%). 1H
NMR (CDC13): ~ 8.49 (dd, 1H, J = 4.8, J' - 2.2), 8.09 (dd, 1H, J = 7.7, J' - 1.8), 7.36 (m, 1H), 3.97 (s, 3H).
Part C. Preparation of 3-cyanophenylboronic acid.
3-Bromobenzonitrile (10.0 g, 55 mmol) was dissolved in dry THF (100 mL) and cooled to -100°C (Et~O/Nz) . n-Butyllithium (24.2 mL, 2.5 M in hexane) was added over 30 minutes, maintaining the internal temp under -90°. After 20 minutes, triisopropylborate (18.0 mL) was added over 15 minutes, again maintaining the internal temperature. After the addition was complete, the reaction was allowed to warn slowly to room temperature over 1.5 hours. The reaction was stirred at room temp for 16 hours, then cooled to 15°C, after which 6 M HC1 (25 mL) was added. After stirring vigorously for 3.5 hours, the reaction was partitioned between water and EtOAc. After extracting a second time with EtOAc, the combined organics were washed with 2 M NaOH. The aqueous extract was neutralized with 6 M HCl. The white precipitate was filtered, yielding the desired product (4.80 g, 60%). 1H
NMR (DMSO-d6): 8 8.37 (s, 2H), 8.10 (s, 1H), 8.03 (dt, 1H, J
- 7.3, J' - 1.1), 7.83 (dt, 1H, J = 7.6, J' - 1.4), 7.53 (t, 1H, J = 7.7).
Part D. Preparation of methyl 2-(3'-cyanophenyl)nicotinate.
Methyl 2-bromonicotinate (2.0 g, 9.3 mmol) and 3 cyanophenylboronic acid (2.7 g, 18.4 mmol) were combined in 190 mL benzene. Sodium carbonate (19 mL of a 2 M aqueous solution), tetrabutylammonium bromide (152 mg, 0.5 mmol), and bis(triphenylphosphine)palladium(II) chloride (325 mg, 0.5 mmol) were added. The entire mixture was evacuated to remove dissolved gasses, then placed under argon. The reaction was refluxed for 14 hours, diluted with water and EtOAc, separated, dried over Na2S04, filtered, and evaporated. The resulting yellow solid was chromatographed on silica gel (30%
EtOAc/hexanes) to yield a light yellow solid (1.70 g, 77~).

~H NMR (CDC13): ~ 8.81 (dd, 1H, J = 4.8, J' - 1.8), 8.23 (dd, 1H, J = 8.0, J' =1.9), 7.85 (s, 1H), 7.73 (m, 2H), 7.55 (t, 1H, J = 7.7), 7.43 (m, 1H), 3.76 (s, 3H).
Part E. Preparation ri ?,-(t-butylaminosulfonyl)phenylboronic acid.
To a solution of 206.5 g (0.968 mol) of benzene-(N-t-butyl)sulfonamide in 2500 mL of THF under NZ was added 790 mL
(1.98 mol) of 2.5M n-butyllithium in hexane over 35 minutes, keeping the temperature between 0-5°C. The reaction mixture was allowed to warm to 10°C, at which time a thick precipitate formed. Triisopropylborate (305 mL, 1.32 mol) was added keeping the temperature below 35°C. After 1 hour, the reaction mixture was cooled, 1N HCl (1570 mL) was added, and the mixture was stirred overnight. The mixture was extracted with 400 mL of ether three times, and the combined organic extracts were extracted with 50G mL of 1N NaOH three times.
The aqueous extracts were acidified to pH 1 with 6N HCl, and then extracted with 500 mL ether three times. The combined ether extracts were dried over MgSOQ, and the solvents evaporated in vacuo until the volume was 700 mL. Hexane (150 mL) was added and overnight, a white precipitate formed. The solid was collected and washed with 10o ether/hexane (250 mL), then dried in vacuo to give 216.3 g (870) of the desired compound as white crystals. m.p. 118-119°C; 1H NMR (CDC13): $
8.00 (d, 1H); 7.82 (d, 1H); 7.53 (m, 2H); 6.29 (br s, 2H);
5.13 (s, 1H); 1.18 (s, 9H).
Part F. Preparation of 4-amino-2'-t-butylaminosulfonyl-[1,1']biphenyl.
A mixture of 3.44 g (20 mmol) of 4-bromoaniline and 5.14 g (20 mmol) of 2-(t-butylaminosulfonyl)phenylboronic acid, 1.16 g of tetrakis(triphenylphosphine) palladium(0) (1 mmol), 0.32 g of tetrabutylammonium bromide (1 mmol) and 20 mL of 2M
aqueous sodium carbonate were refluxed with 180 mL of benzene under NZ for 5.5 hours. After cooling, the mixture was diluted with methylene chloride and water. The two phases were separated and the organic phase was washed with water, dried with MgS04 and concentrated in vacuo. The resulting thick oil was chromatographed on silica with 30% EtOAc/hexane to afford 2.52 g (410) of the aniline. 1H NMR (CDC13): $ g.14 (d, 1H) ; 7.53 (t, 1H) ; 7.43 (t, 1H) ; 7.33 (d, 2H) ; 7.27 (d, 1H); 6.76 (d, 2H); 3.7 (br s, 1H); 0.99 (s, 9H).
Part G. Preparation of N-(2'-t-butylaminosulfonyl-[1,1']biphen-4-yl)-2-(3'-cyanophenyl)nicotinamide.
Methyl 2-(3'-cyanophenyl)nicotinate (300 mg, 1.3 mmol) was combined with of 4-amino-2'-t-butylaminosulfonyl-[1,1']biphenyl (383 mg, 1.3 mmol) in 12 mL dry CHZClz. A
solution of trimethylaluminum (3.8 mL, 2.0 M in heptane) was added, and an exothermic reaction immediately occurred and the mixture darkened. The resulting solution was stirred at room temperature under argon for 3 days and then quenched carefully with a few drops of 1 M HC1. An emulsion was obtained on dilution with EtOAc and water. The layers were separated, and the organic was extracted again with water and brine, dried over Na2S04, filtered, and evaporated. A small amount of additional material was obtained from the aqueous extract by adjusting the pH to 8 with sat. NaHC03 and extracting with EtOAc. This material was dried over Na2S04, filtered, evaporated, and combined with the previous extract for chromatography on silica gel (50-60o EtOAc/hexanes) to yield the desired product (190 mg, 30~). 1H NMR (CDC13): 8 8.86 (dd, 1H, J = 4.7, J' - 1.9), 8.14 (m, 3H), 8.00 (d, 1H, J =
7.7), 7.73 (d, 1H, J = 8.1), 7.50 (m, 9H), 7.29 (dd, 1H, J =
7.4, J' - 1.1), 3.60 (s, 1H), 1.02 (s, 9H).
Part H. Preparation of N-(2'-aminosulfonyl-[1,1']biphen-4-yl)-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt.
N-(2'-t-butylaminosulfonyl-[1,1']biphen-4-yl)-2-(3' cyanophenyl)nicotinamide (190 mg, 0.37 mmol) was dissolved in dry MeOH (10 mL) and cooled to 0°C. HC1(g) was generated by the addition of cancentrated H~SO~ (60 mL) to NaCl (240 g) over 40 minutes and was bubbled into the reaction mixture.
The gas was permitted to continue bubbling through the - 5 reaction for 3 hours after the H~S04 addition was complete.
At this point, the HCl generator and ice bath were removed, and the reaction stirred under argon for 19 hours. This solution was then evaporated, placed under high vacuum, and redissolved in dry MeOH (10 mL). Ammonium carbonate (200 mg) was added, stirred for 24 hours under argon, and evaporated.
The product was purified by preparative HPLC on a C-18 reverse phase column (10-70o MeCN/Hz0/0.05o TFA), yielding a white powder (140 mg, 54~). 1H NMR (DMSO-d~): b 10.65 (s, 1H), 9.38 (s, 2H), 8.92 (s, 2H), 8.81 (dd, 1H, J = 4.4, J' - 1.4), 8.10 (m, 2H), 7.97 (m, 2H), 7.76 (m, 1H), 7.67 (t, 1H, J = 8.0), 7.57 (m, 5H), 7.29 (m, 5H). HRMS calc. for CZSHzaN503S: m/z 472.1443; found, 472.1457.
Examples 2, 3 and 4 N-[5-(2-aminosulfonyl)phenyipyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 2), N-I5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 3), and N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3' carboxamidophenyl)nicotinamide, trifluoroacetic acid salt (Example 4) Part A. Preparation of 2-(3'-cyanophenyl)nicotinic acid.
Methyl 2-(3'-cyanophenyl)nicotinate (1.21 g, 5.1 mmol) was partially dissolved in MeOH (40 mL), and lithium hydroxide monohydrate (234 mg dissolved in 6 mL H20, 5.6 mmol) was added. After 20 hours, the resulting solution was diluted with water and extracted with CHC13. The aqueous was acidified to pF~i 4 with 1 M HC1 and extracted several times with CHC13. Solid sodium chloride was added to the aqueous solution and the solution was extracted with 5-10~ MeOH/CHC13.
The organic extracts were combined, dried over NaZS04, filtered, and evaporated to yield a white solid (1.06 g, 93%).
1H NMR (CDC13): 8 8.85 (dd, 1H, J = 5.1, J' - 1.5), 8.35 (dd, 1H, J = 7.6, J' - 1.4), 7.84 (s, 1H), 7.75 (m, 2H), 7.55 (t, 1H, J = 7.7), 7.47 (m, 1H).
Part B. Preparation of 2-amino-5-(2-t-butylamino-sulfonyl)phenylpyridine.
A mixture of 1.55 g (9.0 mmol) of 2-amino-5-bromopyridine and 2.3 g (9.0 mmol) of 2-(t-butylaminosulfonyl)phenylboronic acid, 0.52 g of tetrakis(triphenylphosphine) palladium(0) (0.45 mmol), 0.15 g of tetrabutylammonium bromide (0.45 mmol) and 9 mL of 2M aqueous sodium carbonate were refluxed with 80 mL of benzene under Ar for 5 hours. After cooling, the mixture was diluted with 25 mL of methylene chloride and 25 mL
of water. The two phases were separated and the organic phase was washed with water, dried with MgS04 and concentrated in vacuo. The resulting thick oil was chromatographed on silica with 50~ EtOAc/hexane to afford 1.34 g (49~) of the aniline.
1H NMR (CDC13): 8 8.18 (d, 1H); 8.07 (m, 1H); 7.70 (dd, 1H);
7.58 (dt, 1H); 7.48 (dt, 1H); 7.28 (d, 1H); 6.56 (d, 1H); 4.62 (br s, 2H); 3.88 (br s, 1H); 1.06 (s, 9H).
Part C. Preparation of N-[5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-cyanophenyl)nicotinamide.
2-(3'-cyanophenyl)nicotinic acid (300 mg, 1.3 mmol) was suspended in 5 mL dry CHZCIz, and oxalyl chloride (175 ~,1, 2.0 mmol) was added, followed by 2 drops of dry DMF. The reaction stirred at room temperature under argon for 2 hours and then evaporated. This solid was redissolved in 8 mL dry CHZClz, and dimethylaminopyridine (490 mg, 4.0 mmol) was added, followed by 2-amino-5-(2-t-butylaminosulfonyl)phenylpyridine (410 mg, 1.3 mmol). The reaction was stirred 3 days at room temperature, diluted with CH2C12, extracted with saturated NaHC03, dried over Na2S04, filtered, and evaporated. The resulting material was chromatographed on silica gel (50-75~

EtOAc / hexanes) to yield the desired product (423 mg, 620).

~H NM R (CDCl~):d 8.83 (dd, 1H, = 4.8, - 1.5), 8.40 (bs, J J' 1H), 8.29 (bd,1H, J = 8.4), 8.17 (dd, J = 8.0, J' -1H), 1.1), 8.09 (m, 3H), 7.97 (d, 1H, = 7.7), 7.79 (d, 1H, J
J =

8.4), 7.69 (d, 1H, J = 7.7), 7.54 (m. 4H),7.25 (m, 1H), 4.19 (bs, 1H), 1.08(s, 9H).

Part D. Preparation of N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 2), N-[5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 3), and N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-carboxamidophenyl)nicotinamide, trifluoroacetic acid salt (Example 4).
N-[5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-cyanophenyl)nicotinamide (410 mg, 1.03) was dissolved in a mixture of dry MeOH (5mL) and dry CHC1~ (l5mL) and cooled to 0°C. HC1(g) was generated by the addition of concentrated HzS04 (45 mL) to NaCl (220 g) over 55 min and was bubbled into the reaction mixture. The HC1 generator and ice bath were removed, and the reaction was stirred under argon for 16 hours and evaporated. The resulting solid was redissolved in dry MeOH (15 mL), and ammonium carbonate (385 mg) was added. The reaction was stirred 19 hours at room temperature under argon and evaporated. The resulting solid was purified by preparative HPLC on a C-18 reverse phase column (5-70~ MeCN /
H20 / 0.05 TFA) to yield N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 2), (250 mg, 45~). 1H NMR (DMSO-d6): 8 11.27 (s, 1H), 9.43 (s, 2H), 8.98 (s, 2H), 8.83 (dd, 1H, J = 4.8, J' - 1.9), 8.32 (s, 1H), 8.13 (m, 2H), 8.05 (m, 2H), 7.96 (d, 1H, J = 7.3), 7.81 (d, 2H, J = 8.4), 7.65 (m, 4H), 7.47 (s, 2H), 7.37 (m, 1H). HRMS calc. for CZ4HaiN60sS: m/z 473.1396; found, 473.1397. A second product, N-[5-(2-t-butylaminosulfonyl)-phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide, trifluoroacetic acid salt (Example 3), was also obtained (58 rng, 10~). 1H NMR (DMSO-d6): 8 9.7 (s, 1H), 9.41 (s, 2H), 8.95 (s, 2H), 8.82 (m, 1H), 8.28 (s, 1H), 8.09 (m, 4H), 7.95 (d, 1H, J = 7.7), 7.79 (m, 2H), 7.63 (m, 4H), 7.34 (d, 1H, J =
7.7) , 7.18 (s, 1H) , 1.04 (s, 9H) . HRMS calc. for CzeHz9N6O,S:
529.2022; found, 529.2050. A third product, N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-carboxamidophenyl)nicotinamide, trifluoroacetic acid salt (Example 4) was isolated and chromatographed on silica gel (10-20% MeOH/CHC13) to yield a white solid (77 mg, 20%). 1H
NMR (DMSO-d5): 8 11.13 (s, 1H), 8.75 (dd, 1H, J = 4.8, J' -1.9), 8.26 (m, 2H), 8.02 (m, 4H), 7.84 (d, 1H, J = 7.7), 7.74 (m, 2H), 7.59 (m, 2H), 7.47 (m, 2H), 7.36 (m, 4H).

Table 1 N~
H
\ N A~ R

/ O ~/ \
D
MS
Ex D R2 A~ (M+H)+

1 C(=NH)NH2 S02NH2 CH 472.1 2 C(=NH)NH2 S02NH2 N 473.1 3 C(=NH)NH2 S02NHtBu N 529.2 4 C(O)NH2 S02NH2 N 474.1 The following table contains representative examples of the present invention. Each entry in the table is intended to be paired with each formulae at the start of the table. For example, example 2 in Table 2 is intended to be paired with S each of formulae al-ss4.
Table 2 '~R~b M
H
D,E N~A~B
O
1b I /R ~/R~b ~R~b ~ ~ / I
E
I E I E
R ~ .""". R I / ."",.,.
D a p b R p c a~ R=F, D=NH2 b~ R=F, D=NH2 ci R=F, D=NH2 a2 R=H, D=NH2 b2 R=H, D=NH2 c2 R=H, D=NH2 a3 R=F, D=CH2NH2 b3 R=F. D=CH2NH2 c3 R=F, D=CH2NH2 a4 R=H, D=CH2NH2 b4 R=H, D=CH2NH2 c4 R=H, D=CH2NH2 a5 R=F, D=C(=NH)NH2 b5 R=F, D=C(=NH)NH2 c5 R=F, D=C(=NH)NH2 as R=H, D=C(=NH)NH2 bs R=H, D=C(=NH)NH2 cs R=H, D=C(=NH)NH2 a~ R=F, D=C(O)NH2 b~ R=F, D=C(O)NH2 c~ R=F, D=C(O)NH2 a8 R=H, D=C(O)NH2 ba R=H, D=C(O)NH2 ce R=H, D=C(O)NH2 1b ~b R1b N' Ij R
D f d~ R=F, D=NH2 ei R=F, D=NH2 f~ R=F, D=NH2 d2 R=H, D=NH2 e2 R=H, D=NH2 f2 R=H, D=NH2 d3 R=F, D=CH2NH2 e3 R=F, D=CH2NH2 f3 R=F, D=CH2NH2 d4 R=H, D=CH2NH2 e4 R=H, D=CH2NH2 f4 R=H, D=CH2NH2 d5 R=F, D=C(=NH)NH2 e5 R=F, D=C(=NH)NH2 f5 R=F, D=C(=NH)NH2 ds R=H, D=C(=NH)NH2 es R=H, D=C(=NH)NH2 fs R=H, D=C(=NH)NH2 d~ R=F, D=C(O)NN2 e~ R=F, D=C(O)NH2 f~ R=F, D=C(O)NH2 de R=H, D=C(O)NH2 e8 R=H, D=C(O)NH2 f8 R=H, D=C(O)NH2 Rib Rtb 1b N~~N N~
\ I iN
I, ~ i, R ~ R
D 9 D h g1 R=F, D=NH2 h1 R=F, D=NH2 i1 R=F, D=NH2 g2 R=H, D=NHZ h2 R=H, D=NH2 i2 R=H, D=NH2 g3 R=F, D=CH2NH2 h3 R=F, D=CH2NH2 i3 R=F, D=CH2NH2 g4 R=H, D=CH2NHa h4 R=H, D=CH2NH2 i4 R=H, D=CH2NH2 g5 R=F, D=C(=NH)NH2 h5 R=F, D=C(=NH)NH2 i5 R=F, D=C(=NH)NH2 gs R=H, D=C(=NH)NHZ hs R=H, D=C(=NH)NH2 i6 R=H, D=C(=NH)NH2 g~ R=F, D=C(O)NH2 h~ R=F, D=C(O)NH2 i~ R=F, D=C(O)NH2 g8 R=H, D=C(O)NH2 ha R=H, D=C(O)NH2 i$ R=H, D=C(O)NH2 1b R1b I ~N i.N~~N
I ~ ~N I E ~ Rib R ~ '~ R
D k D I
ji R=F, D=NH2 k~ R=F, D=NH2 I~ R=F, D=NH2 j2 R=H, D=NHz k2 R=H, D=NH2 12 R=H, D=NH2 j3 R=F, D=CH2NH2 k3 R=F, D=CH2NH2 13 R=F, D=CH2NH2 j4 R=H, D=CH2NH2 k4 R=H, D=CH2NH2 14 R=H, D=CH2NH2 j5 R=F, D=C(=NH)NH2 k5 R=F, D=C(=NH)NH2 15 R=F, D=C(=NH)NH2 js R=H, D=C(=NH)NH2 ks R=H, D=C(=NH)NH2 I6 R=H, D=C(=NH)NH2 j~ R=F, D=C(O)NH2 k~ R=F, D=C(O)NH2 h R=F, D=C(O)NH2 je R=H, D=C(O)NH2 k8 R=H, D=C(O)NHp I8 R=H, D=C(O)NHZ
Rib N R1b ~ 1b N' \ IV R N~~ N
iN \ I iN \ I iN
R I % I R I j I R
D m D n D o m1 R=F, D=NH2 n~ R=F, D=NH2 01 R=F, D=NH2 m2 R=H, D=NH2 n2 R=H, D=NH2 02 R=H, D=NH2 m3 R=F, D=CH2NH2 n3 R=F, D=CH2NH2 03 R=F, D=CH2NH2 m4 R=H, D=CH2NH2 n4 R=H, D=CH2NH2 04 R=H, D=CH2NH2 m5 R=F, D=C(=NH)NH2 ns R=F, D=C(=NH)NH2 05 R=F, D=C(=NH)NH2 ms R=H, D=C(=NH)NH2 ns R=H, D=C(=NH)NH2 os R=H, D=C(=NH)NH2 m~ R=F, D=C(O)NH2 n~ R=F, D=C(O)NH2 0~ R=F, D=C(O)NH2 m8 R=H, D=C(O)NH2 na R=H, D=C(O)NH2 08 R=H, D=C(O)NH2 1b ~b Rtb R R
j r pi R=F, D=NH2 qi R=F D=NH2 r1 R=F, D=NH2 p2 R=CI D=NH2 p3 R=OMe, D=NH2 q2 R=CI, D=NH2 r2 R=CI, D=NH2 pa R=F, D=CH2NH2 qa R=OMe, D=NH2 r3 R=OMe, D=NH2 R=CI D=CH NH qa R=F, D=CH2NH2 ra R=F, D=CH2NH2 ps 2 2 q5 R=CI, D=CH2NH2 rs R=CI, D=CH2NH2 ps R=OMe, D=CH2NH2 qs R=OMe, D=CH2NH2 rs R=OMe, D=CH2NH2 p~ R=F, D=C(=NH)NH2 q~ R=F, D=C(=NH)NH2 r~ R=F, D=C(=NH)NH2 pe R=CI, D=C(=NH)NH2 qe R=CI, D=C(=NH)NH2 r8 R=Cl, D=C(=NH)NH2 p9 R=OMe, D=C(=NH)NH2 q9 R=OMe, D=C(=NH)NH2 r9 R=OMe, D=C(=NH)NH2 p1o R=F, D=C(O)NH2 quo R=F, D=C(O)NH2 r~o R=F, D=C(O)NH2 pig R=CI D=C(O)NH2 q1~ R=CI, D=C(O)NH2 r~i R=CI, D=C(O)NH2 p~2 R=OMe, D=C(O)NH2 q~2 R=OMe, D=C(O)NH2 ri2 R=OMe, D=C(O)NH2 Rib Rib Rib ~/N ~/1 y%
R ~ / R ~ ,N R ~
j ~ ~ j D s D t D a s~ R=F, D=NH2 ti R=F, D=NH2 u~ R=F, D=NH2 s2 R=CI, D=NH2 t2 R=CI, D=NH2 u2 R=CI, D=NH2 s3 R=OMe, D=NH2 t3 R=OMe, D=NH2 u3 R=OMe, D=NH2 sa R=F, D=CH2NH2 to R=F, D=CH2NH2 u4 R=F, D=CH2NH2 ss R=Ci, D=CH2NH2 t5 R=CI, D=CH2NH2 us R=CI, D=CH2NH2 s6 R=OMe, D=CH2NH2 is R=OMe, D=CH2NH2 us R=OMe, D=CH2NH2 s~ R=F, D=C(=NH)NH2 t~ R=F, D=C(=NH)NH2 u~ R=F, D=C(=NH)NH2 s8 R=CI, D=C(=NH)NH2 to R=CI, D=C(=NH)NH2 u8 R=CI, D=C(=NH)NH2 s9 R=OMe, D=C(=NH)NH2 t9 R=OMe, D=C(=NH)NH2 u9 R=OMe, D=C(=NH)NH2 s~o R=F, D=C(O)NH2 t1o R=F, D=C(O)NH2 uio R=F, D=C(O)NH2 s1~ R=CI, D=C(O)NH2 tip R=Ci, D=C(O)NH2 u~i R=CI, D=C(O)NH2 s12 R=OMe, D=C(O)NH2 tt2 R=OMe, D=C(O)NH2 u~2 R=OMe, D=C(O)NH2 1b R1b 1b N''/1 R ~ ~ ,N
j w n v~ R=F, D=NH2 w~ f-i=F, O=NH2 x1 R=F, D=NH2 v2 R=CI, D=NH2 w2 R=CI, D=NH2 x2 R=CI, D=NH2 v3 R=OMe, D=NH2 w3 R=OMe, D=NH2 x3 R=OMe, D=NH2 v4 R=F, D=CH2NH2 w4 R=F, D=CH2NH2 x4 R=F, D=CH2NH2 v5 R=CI, D=CH2NH2 w5 R=CI, D=CH2NH2 x5 R=CI, D=CH2NH2 vs R=OMe, D=CH2NH2 ws R=OMe, D=CH2NH2 xs R=OMe, D=CH2NH2 v~ R=F D=C(=NH)NH2 w~ R=F, D=C(=NH)NH2 x~ R=F, D=C(=NH)NH2 vg R=CI, D=C(=NH)NHg wa R=CI, D=C(=NH)NHp x8 R=CI, D=C(=NH)NH2 v9 R=OMe, D=C(=NH)NH2 w9 R=OMe, D=C(=NH)NH2 x9 R=OMe, D=C(=NH)NH2 vio R=F, D=C(O)NH2 wio R=F, D=C(O)NH2 xio R=F, D=C(O)NH2 v~ i R=CI, D=C(O)NH2 ",~» R=CI, D=C(O)NH2 x~ 1 R=CI, D=C(O)NH2 v~2 R=OMe, D=C(O)NH2 "v~2 R=OMe, D=C(O)NH2 x~2 R=OMe, D=C(O)NH2 N. R1b 1b N' N' ' N
~N R R ~ E ~ ib R
D y D as y~ R=F D=NH2 zi R=F, D=NH2 aa1 R=F, D=NH2 y2 R=C~I D=NH2 z2 R=CI, D=NHZ aa2 R=CI, D=NH2 y3 R=OMe, D=NH2 z3 R=OMe, D=NH2 aa3 R=OMe, D=NH2 y4 R=F, D=CH2NH2 z4 R=F, D=CH2NH2 aa4 R=F, D=CH2NH2 y5 R=CI, D=CH2NH2 z5 R=CI, D=CH2NH2 aa5 R=Ci, D=CH2NH2 ys R=OMe, D=CH2NH2 Z6 R=OMe, D=CH2NH2 aas R=OMe, D=CH2NH2 y~ R=F, D=C(=NH)NH2 z~ R=F, D=C(=NH)NHz aa~ R=F, D=C(=NH)NH2 y8 R=CI, D=C(=NH)NH2 z8 R=CI, D=C(=NH)NH2 aae R=CI, D=C(=NH)NH2 y9 R=OMe, D=C(=NH)NH2 z9 R=OMe, D=C(=NH)NH2 aa9 R=OMe, D=C(=NH)NH2 y~o R=F, D=C(O)NH2 zoo R=F, D=C(O)NH2 aayo R=F, D=C(O)NH2 y1 ~ R=CI, D=C(O)NH2 z~ 1 R=Ci, D=C(O)NH2 aa~ ~ R=CI, D=C(O)NH2 y~2 R=OMe, D=C(O)NH2 z~2 R=OMe, D=C(O)NH2 aa~2 R=OMe, D=C(O)NH2 Rib .N~Rib ~ Rib N.
R ~ ~ i R ~ ~ i R ~ I i i~ I I
D bb D cc ~ dd bbi R=F, D=NH2 cci R=F, D=NH2 ddi R=F, D=NH2 bb2 R=CI, D=NH2 cc2 R=CI, D=NH2 dd2 R=CI, D=NH2 bb3 R=OMe, D=NH2 cc3 R=OMe, D=NH2 dd3 R=OMe, D=NH2 bb4 R=F, D=CH2NH2 cc4 R=F, D=CH2NH2 dd4 R=F, D=CH2NH2 bbs R=CI, D=CH2NH2 cc5 R=CI, D=CH2NH2 dds R=CI, D=CH2NH2 bbs R=OMe, D=CH2NH2 ccs R.OMe, D=CH2NH2 dds R=OMe, D=CH2NH2 bb~ R=F, D=C{=NH)NH2 cc~ R=F, D=C(=NH)NH2 dd~ R=F, D=C(=NH)NH2 bb8 R=CI, D=C(=NH)NH2 cca R=CI, D=C(=NH)NH2 ddb R=CI, D=C(=NH)NH2 bb9 R=OMe, D=C(=NH)NH2 cc9 R=OMe, D=C(=NH)NH2 dd9 R=OMe, D=C(=NH)NH2 bb~p R=F, D=C(O)NH2 ccip R.F, D=C(O)NH2 ddip R=F, D=C(O)NH2 bb~ i R=CI, D=C(O)NH2 cci ~ R=CI, D=C(O)NH2 ddi i R=CI, D=C(O)NH2 bbi2 R=OMe, D=C(O)NH2 cci2 R=OMe, D=C(O)NH2 ddi2 R=OMe, D=C(O)NH2 Rib Rtb 1b R I j R i~~ R I ~R
I' I% / Ij D ee ff eei R=F, D=CH2NH2 ffi R=F, D=CH2NH2 ggi R=F, D=CH2NH2 ee2 R=CI, D=CH2NH2 ff2 R=CI, D=CH2NH2 gg2 R=CI, D=CH2NH2 ee3 R=OMe, D=CH2NH2 ff3 R=OMe, D=CH2NH2 gg3 R=OMe, D=CH2NH2 ee4 R=CH2NH2, ff4 R=CH2NH2, gg4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib R1b R1b R ~ /-N R I ~1 R N
~ ,N ~
I~ I I~ ~ I
D hh D ii D jj hh1 R=F, D=CH2NH2 iii R=F, D=CH2NH2 jji R=F, D=CH2NH2 hh2 R=CI, D=CH2NH2 ii2 R=CI, D=CH2NH2 jj2 R=CI, D=CH2NH2 hh3 R=OMe, D=CH2NH2 iii R=OMe, D=CH2NH2 jj3 R=OMe, D=CH2NH2 hh4 R=CH2NH2, ii4 R=CH2NH2, jj4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 WO 98/57934 PCTlUS98/12682 R NI~'~N ~b Rib Rib R I~~N R I /' N
I '.. ~ ~ ~ ~ /
I
p kk p II p mm Kk~ R=F, D=CH2NH2 Ili R=F, D=CH2NH2 mm~ R=F, D=CH2NH2 kkp R=CI, D=CH2NH2 112 R=CI, D=CH2NH2 mm2 R=CI, D=CH2NH2 kk3 R=OMe, D=CH2NH2 113 R=OMe. D=CH2NH2 mm3 R=OMe, D=CH2NHz kk4 R=CH2NH2, 114 R=CH2NH2, mm4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 R I ~1 ib R ~ /N ~b R N,N''N
~N ~ ~N ~ ( ~ in I ~ j ~ I j ~ R
p nn p oo p PP
nni R=F, D=CH2NH2 00~ R=F, D=CH2NH2 pp1 R=F, D=CH2NH2 nn2 R=CI, D=CH2NH2 002 R=CI, D=CH2NH2 pp2 R=CI, D=CH2NH2 nn3 R=OMe, D=CH2NH2 003 R=OMe, D=CH2NH2 pp3 R=OMe, D=CH2NH2 nn4 R=CH2NH2, 004 R=CH2NH2, pp4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib R 'N~RIb R ' \N Rib N''N
R I
,N ~ ,N ~ ,N
j D qq D rr p ss qq~ R=F, D=CH2NH2 rr~ R=F, D=CH2NH2 ss~ R=F, D=CH2NH2 qq2 R=CI D=CH2NH2 rr2 R=CI, D=CH2NH2 ss2 R=CI, D=CH2NH2 qq3 R=OMe, D=CH2NH2 rr3 R=OMe, D=CH2NH2 ss3 R=OMe, D=CH2NH2 qq4 R=CH2NH2, rr4 R=CH2NH2, ss4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 ~ # Rlb A B
1 H phenyl 2-(aminosulfonyl)phenyl 2 H phenyl 2-(methylaminosulfonyl)phenyl 3 H phenyl 1-pyrrolidinocarbonyl 4 H phenyl 2-(methylsulfonyl)phenyl 5 H phenyl 4-morpholino 6 H phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 7 H phenyl 4-morpholinocarbonyl 8 H 2-pyridyl 2-(aminosulfonyl)phenyl 9 H 2-pyridyl 2-(methylaminosulfonyl)phenyl 10 H 2-pyridyl 1-pyrrolidinocarbonyl 11 H 2-pyridyl 2-(methylsulfonyl)phenyl 12 H 2-pyridyl 4-morpholino 13 H 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 14 H 2-pyridyl 4-morpholinocarbonyl 15 H 3-pyridyl 2-(aminosulfonyl)phenyl 16 H 3-pyridyl 2-(methylaminosulfonyl)phenyl 17 H 3-pyridyl 1-pyrrolidinocarbonyl 18 H 3-pyridyl 2-(methylsulfonyl)phenyl 19 H 3-pyridyl 4-morpholino 20 H 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 21 H 3-pyrvd~1 4-morpholinocarbonyl 22 H 2-pyrimidyl 2-(aminosulfonyl)phenyl 23 H 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 24 H 2-pyrimidyl 1-pyrrolidinocarbonyl 25 H 2-pyrimidyl 2-(methylsulfonyl)phenyl 26 H 2-pyrimidyl 4-morpholino 27 H 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 28 H 2-pyrimidyl 4-morpholinocarbonyl 29 H 5-pyrimidyl 2-(aminosulfonyl)phenyl 30 H 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 31 H 5-pyrimidyl 1-pyrrolidinocarbonyl 32 H 5-pyrimidyl 2-(methylsulfonyl)phenyl 33 H 5-pyrimidyl 4-morpholino 34 H 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 35 H 5-pyrimidyl 4-morpholinocarbonyl 36 H 2-C1-phenyl 2-(aminosulfonyl)phenyl 37 H 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 38 H 2-Cl-phenyl 1-pyrrolidinocarbonyl 39 H 2-Cl-phenyl 2-(methylsulfonyl)phenyl 40 H 2-C1-phenyl 4-morpholino 41 H 2-Cl-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 42 H 2-C1-phenyl 4-morpholinocarbonyl 43 H 2-F-phenyl 2-(aminosulfonyl)phenyl 44 H 2-F-phenyl 2-(methylaminosulfonyl)phenyl 45 H 2-F-phenyl 1-pyrrolidinocarbonyl 46 H 2-F-phenyl 2-(methylsulfonyl)phenyl 47 H 2-F-phenyl 4-morpholino 48 H 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 49 H 2-F-phenyl 4-morpholinocarbonyl 50 H 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 51 H 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 52 H 2,5-diF-phenyl 1-pyrrolidinocarbonyl 53 H 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 54 H 2,5-diF-phenyl 4-morpholino 55 H 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 56 H 2,5-diF-phenyl 4-mozpholinocarbonyl 57 H phenyl 2-(N-pyrrolidinyl-methyl)phenyl 58 H phenyl 2-(N-piperidinyl-methyl)phenyl 59 H phenyl 2-(N-morpholino-methyl)phenyl 60 H phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 61 H phenyl 2-(N-pyridinium-methyl)phenyl 62 H phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 63 H phenyl 2-(N-azatanyl-methyl)phenyl 64 H phenyl 2-(N-azetidinyl-methyl)phenyl 65 H phenyl 2-(N-piperazinyl-methyl)phenyl 66 H phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 67 H phenyl 2-(N-imidazolyl-methyl)phenyl 68 H phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 69 H phenyl 2-(N-pyridonyl-methyl)phenyl 70 H phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 71 H phenyl 2-(amidiny7.)phenyl 72 H phenyl 2-(N-guan=din~rl)phenyl 73 H phenyl 2-(imidazolyl)phenyl 74 H phenyl 2-(imidazolidinyl)phenyl 75 H phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 76 H phenyl 2-(2-pyrrolidinyl)phenyl 77 H phenyl 2-(2-piperidinyl)phenyl 78 H phenyl 2-(amidinyl-methyl)phenyl 79 H phenyl 2-(2-imidazolidinyl-methyl)phenyl 80 H phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 81 H phenyl 2-dimethylaminoimidazol-1-yl 82 H phenyl 2-(3-aminophenyl) 83 H phenyl 2-(3-pyrrolidinylcarbonyl) 84 H phenyl 2-glycinoyl 85 H phenyl 2-(imidazol-1-ylacetyl) 86 H 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 87 H 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 88 H 2-pyridyl 2-(N-morpholino-methyl)phenyl 89 H 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 90 H 2-pyridyl 2-(N-pyridinium-methyl)phenyl 91 H 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 92 H 2-pyridyl 2-(N-azatanyl-methyl)phenyl 93 H 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 94 H 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 95 H 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 96 H 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 97 H 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 98 H 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 99 H 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 100 H 2-pyridyl 2-(amidinyl)phenyl 101 H 2-pyridyl 2-(N-guanidinyl)phenyl 102 H 2-pyridyl 2-(imidazolyl)phenyl 103 H 2-pyridyl 2-(imidazolidinyl)phenyl 104 H 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 105 H 2-pyridyl 2-(2-pyrrolidinyl)phenyl 106 H 2-pyridyl 2-(2-piperidinyl)phenyl 107 H 2-pyridyl 2-(amidinyl-methyl)phenyl 108 H 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 109 H 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 110 H 2-pyridyl 2-dimethylaminoimidazol-1-yl 111 H 2-pyridyl 2-(3-aminophenyl) 112 H 2-pyridyl 2-(3-pyrrolidinyicarbonyl) 113 H 2-pyridyl 2-glycinoyl 114 H 2-pyridyl 2-(imidazol-1-ylacetyl) 115 H 3-pyridyl 2-(N-pyrrolidinyi-methyl)phenyl 116 H 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 1i7 H 3-pyridyl 2-(N-morpho~ino-methyl)pheny?

118 H 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 119 H 3-pyridyl 2-(N-pyridinium-methyl)phenyl 120 H 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 121 H 3-pyridyl 2-(N-azatanyl-methyl)phenyl 25 122 H 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 123 H 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 124 H 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 125 H 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 126 H 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 127 H 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 128 H 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 129 H 3-pyridyl 2-(amidinyl)phenyl 130 H 3-pyridyl 2-(N-guanidinyl)phenyl 131 H 3-pyridyl 2-(imidazolyl)phenyl 132 H 3-pyridyl 2-(imidazolidinyl)phenyl 133 H 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 134 H 3-pyridyl 2-(2-pyrrolidinyl)phenyl 135 H 3-pyridyl 2-(2-piperidinyl)phenyl 136 H 3-pyridyl 2-(amidinyl-methyl)phenyl 137 H 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 138 H 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 139 H 3-pyridyl 2-dimethylaminoimidazol-1-yl la0 H 3-pyridyl 2-(3-aminophenyl) 141 H 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 142 H 3-pyridyl 2-glycinoyl 143 H 3-pyridyl 2-(imidazol-1-ylacetyl) 144 H 2-pyrimidyl 2-(N-pyrrolidinyl-methyl)phenyl 145 H 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 146 H 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 147 H 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 148 H 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 149 H 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 150 H 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 151 H ~-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 152 H 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 153 H 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 154 H 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 155 H 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 156 H 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 157 H 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 158 H 2-pyrimidyl 2-(amidinyl)phenyl 159 H 2-pyrimidyl 2-(N-guanidinyl)phenyl 160 H ?-pyrimidyl 2-(imidazolyl)phenyl 161 H 2-pyrimidyl 2-(imidazolidinyl)phenyl 162 H 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 163 H 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 164 H 2-pyrimidyl 2-(2-piperidinyl)phenyl 165 H 2-pyrimidyl 2-(amidinyl-methyl)phenyl 166 H 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 167 H 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 168 H 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 169 H 2-pyrimidyl 2-(3-aminophenyl) 170 H 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 171 H 2-pyrimidyl 2-glycinoyl 172 H 2-pyrimidyl 2-(imidazol-1-ylacetyl) 173 H 2-Cl-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 174 H 2-C1-phenyl 2-(N-piperidinyl-methyl)phenyl 175 H 2-C1-phenyl 2-(N-morpholino-methyl)phenyl 176 H 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 177 H 2-Cl-phenyl 2-(N-pyridinium-methyl)phenyl 178 H 2-Cl-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 179 H 2-Cl-phenyl 2-(N-azatanyl-methyl)phenyl 180 H 2-C1-phenyl 2-(N-azetidinyl-methyl)phenyl 181 H 2-C1-phenyl 2-(N-piperazinyl-methyl)phenyl 182 H 2-Cl-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 183 H 2-C1-phenyl 2-(N-imidazolyl-methyl)phenyl 184 H 2-C1-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 185 H 2-Cl-phenyl 2-(N-pyridonyl-methyl)phenyl 186 H 2-Cl-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 187 H 2-C1-phenyl 2-(amidinyl)phenyl 188 H 2-C1-phenyl 2-(N-guanidinyl)phenyl 189 H 2-C1-phenyl 2-(imidazolyl)phenyl 190 H 2-C1-phenyl 2-(imidazolidinyl)phenyl 191 H 2-C1-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 192 H 2-Cl-phenyl 2-(2-pyrrolidinyl)phenyl 193 H 2-C1-phenyl 2-(2-piperidinyl)phenyl 194 H 2-C1-phenyl 2-(amidinyl-methyl)phenyl 195 H 2-Cl-phenyl 2-(2-~imidazolidinyl-methyl)phenyl 196 H 2-Cl-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 297 H 2-C1-phenyl 2-dimethylaminoimidazol-1-yl 198 H 2-Cl-phenyl 2-(3-aminophenyl) 199 H 2-Cl-phenyl 2-(3-pyrrolidinylcarbonyl) 200 H 2-Cl-phenyl 2-glycinoyl 201 H 2-C1-phenyl 2-(imidazol-1-ylacetyl) 202 H 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 203 H 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 204 H 2-F-phenyl 2-(N-morpholino-methyl)phenyl 205 H 2-F-phenyl 2-(N, N'-m~thylmorpholinium-methyl)phenyl 206 H 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 207 H 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 208 H 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 209 H 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 210 H 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 211 H 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 212 H 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 213 H 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 214 H 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 215 H 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 216 H 2-F-phenyl 2-(amidinyl)phenyl 217 H 2-F-phenyl 2-(N-guanidinyl)phenyl 218 H 2-F-phenyl 2-(imidazolyl)phenyl 219 H 2-F-phenyl 2-(imidazolidinyl)phenyl 220 H 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 221 H 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 222 H 2-F-phenyl 2-(2-piperidinyl)phenyl 223 H 2-F-phenyl 2-(amidinyl-methyl)phenyl 224 H 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 225 H 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 226 H 2-F-phenyl 2-dimethylaminoimidazol-1-yl 227 H 2-F-phenyl 2-(3-aminophenyl) 228 H 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 229 H 2-F-phenyl 2-glycinoyl 230 H 2-F-phenyl 2-(imidazol-1-ylacetyl) 231 H 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 232 H 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 233 H 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 234 H 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 235 H 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 236 H 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 237 H 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 238 H 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 239 H 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 240 H 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 241 H 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 242 H 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 243 H 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 244 H 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 245 H 2,5-diF-phenyl 2-(amidinyl)phenyl 246 H 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 247 H 2,5-diF-phenyl 2-(imidazolyl)phenyl 248 H 2,5-diF-phenyl 2-(imic?azolidinyl)phenyl_ 249 H 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 250 H 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 251 H 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 252 H 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 253 H 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 254 H 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 255 H 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 256 H 2,5-diF-phenyl 2-(3-aminophenyl) 257 H 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 258 H 2,5-diF-phenyl 2-glycinoyl 259 H 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 260 -CN phenyl 2-(aminosulfonyl)phenyl 261 -CN phenyl 2-(methylaminosulfonyl)phenyl 262 -CN phenyl 1-pyrrolidinocarbonyl 263 -CN phenyl 2-(methylsulfonyl)phenyl 264 -CN phenyl 4-morpholino 265 -CN phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 266 -CN phenyl 4-morpholinocarbonyl 267 -CN 2-pyridyl 2-(aminosulfonyl)phenyl 268 -CN 2-pyridyl 2-(methylaminosulfonyl)phenyl 269 -CN 2-pyridyl 1-pyrrolidinocarbonyl 270 -CN 2-pyridyl 2-(methylsulfonyl)phenyl 271 -CN 2-pyridyl 4-morpholino 272 -CN 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 273 -CN 2-pyridyl 4-morpholinocarbonyl 274 -CN 3-pyridyl 2-(aminosulfonyl)phenyl 275 -CN 3-pyridyl 2-(methylaminosulfonyl)phenyl 276 -CN 3-pyridyl 1-pyrrolidinocarbonyl 2?7 -CN 3-pyridyl 2-(methylsulfonyl)phenyl 278 -CN 3-pyridyl 4-morpholino 279 -CN 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 280 -CN 3-pyridyl 4-morpholinocarbonyl 281 -CN 2-pyrimidyl 2-(aminosulfonyl)phenyl 282 -CN 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 283 -CN 2-pyrimidyl 1-pyrrolidinocarbonyl 284 -CN 2-pyrimidyl 2-(methylsulfonyl)phenyl 285 -CN 2-pyrimidyl 4-morpholino 286 -CN 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 287 -CN 2-pyrimidyl 4-morpholinocarbonyl 288 -CN 5-pyrimidyl 2-(aminosulfonyl)phenyl 289 -CN 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 290 -CN 5-pyrimidyl 1-pyrrolidinocarbonyl 291 -CN 5-pyrimidyl 2-(methylsulfonyl)phenyl 292 -CN 5-pyrimidyl 4-morpholino 293 -CN 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 294 -CN 5-pyrimidyl 4-morpholinocarbonyl 295 -CN 2-Cl-phenyl 2-(aminosulfonyl)phenyl 296 -CN 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 297 -CN 2-Cl-phenyl 1-pyrrolidinocarbonyl 298 -CN 2-Cl-phenyl 2-(methylsulfonyl)phenyl 299 -CN 2-C1-phenyl 4-morpholino 300 -CN 2-Cl-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 301 -CN 2-Cl-phenyl 4-morpholinocarbonyl 302 -CN 2-F-phenyl 2-(aminosulfonyl)phenyl 303 -CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 304 -CN 2-F-phenyl 1-pyrrolidinocarbonyl 305 -CN 2-F-phenyl 2-(methylsulfonyl)phenyl 306 -CN 2-F-phenyl 4-rnorpholino 307 -CN 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 308 -CN 2-F-phenyl 4-morpholinocarbonyl 309 -CN 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 310 -CN 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 311 -CN 2,5-diF-phenyl 1-pyrrolidinocarbonyl 312 -CN 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 313 -CN 2,5-diF-phenyl 4-morpholino 314 -CN 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 315 -CN 2,5-diF-phenyl 4-morpholinocarbonyl 316 -CN phenyl 2-(N-pyrrolidinyl-methyl)phenyl 317 -CN phenyl 2-(N-piperidinyl-methyl)phenyl 318 -CN phenyl 2-(N-morpholino-methyl)phenyl 319 -CN phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 320 -CN phenyl 2-(N-pyridinium-methyl)phenyl 321 -CN phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 322 -CN phenyl 2-(N-azatanyl-methyl)phenyl 323 -CN phenyl 2-(N-azetidinyl-methyl)phenyl 324 -CN phenyl 2-(N-piperazinyl-methyl)phenyl 325 -CN phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 326 -CN phenyl 2-(N-imidazolyl-methyl)phenyl 327 -CN phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 328 -CN Fhenyl 2-(N-pyridonyl-methyl)phenyl 329 -CN phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 330 -CN phenyl 2-(amidinyl)phenyl 331 -CN phenyl 2-(N-guanidinyl)phenyl 332 -CN phenyl 2-(imidazolyl)phenyl 333 -CN phenyl 2-(imidazolidinyl)phenyl 334 -CN phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 335 -CN phenyl 2-(2-pyrrolidinyl)phenyl 336 -CN phenyl 2-(2-piperidinyl)phenyl 337 -CN phenyl 2-(amidinyl-methyl)phenyl 338 -CN phenyl 2-{2-imidazolidinyl-methyl)phenyl 339 -CN phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 340 -CN phenyl 2-dimethylaminoimidazol-1-yl 341 -CN phenyl 2-(3-aminophenyl) 342 -CN phenyl 2-(3-pyrrolidinylcarbonyl) 343 -CN phenyl 2-glycinoyl 344 -CN phenyl 2-(imidazol-1-ylacetyl) 345 -CN 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 346 -CN 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 347 -CN 2-pyridyl 2-(N-morpholino-methyl)phenyl 348 -CN 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 349 -CN 2-pyridyl 2-(N-pyridinium-methyl)phenyl 350 -CN 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 351 -CN 2-pyridyl 2-(N-azatanyl-methyl)phenyl 352 -CN 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 353 -CN 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 354 -CN 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 355 -CN 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 356 -CN 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 357 -CN 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 358 -CN 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 359 -CN 2-pyridyl 2-(amidinyl)phenyl 360 -CN 2-pyridyl 2-(N-guanidinyl)phenyl 361 -CN 2-pyridyl 2-(imidazolyl)phenyl 362 -CN 2-pyridyl 2-(imidazolidinyl)phenyl 363 -CN 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 364 -CN 2-pyridyl 2-(2-pyrrolidinyl)phenyl 365 -CN 2-pyridyl 2-(2-piperidinyl)phenyl 366 -CN 2-pyridyl 2-(amidinyl-methyl)phenyl 367 -CN 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 368 -CN 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyi)phenyl 369 -CN 2-pyridyl 2-dimethylaminoimidazol-1-yl 370 -CN 2-pyridyl 2-(3-aminophenyl) 371 -CN 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 372 -CN 2-pyridyl 2-glvcinoyl 373 -CN 2-pyridyl 2-(imidazol-1-ylacetyl) 374 -CN 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 375 -CN 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 376 -CN 3-pyridyl 2-(N-morpholino-methyl)phenyl 377 -CN 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 378 -CN 3-pyridyl 2-(N-pyridinium-methyl)phenyl 379 -CN 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 380 -CN 3-pyridyl 2-(N-azatanyl-methyl)phenyl 381 -CN 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 382 -CN 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 383 -CN 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 384 -CN 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 385 -CN 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 386 -CN 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 387 -CN 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 388 -CN 3-pyridyl 2-(amidinyl)phenyl 389 -CN 3-pyridyl 2-(N-guanidinyl)phenyl 390 -CN 3-pyridyl 2-(imidazolyl)phenyl 391 -CN 3-pyridyl 2-(imidazolidinyl}phenyl 392 -CN 3-pyridyl 2 (2-imidazolidin~1-sulfonyl)phenyl 393 -CN 3-pyridyl 2-(2-pyrrolidinyl)phenyl 394 -CN 3-pyridyl 2-(2-piperidinyl)phenyl 395 -CN 3-pyridyl 2-(amidinyl-methyl)phenyl 396 -CN 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 397 -CN 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 398 -CN 3-pyridyl 2-dimethylaminoimidazol-1-yl 399 -CN 3-pyridyl 2-(3-aminophenyl) 400 -CN 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 401 -CN 3-pyridyl 2-glycinoyl 402 -CN 3-pyridyl 2-(imidazol-1-ylacetyl) 403 -CN 2-pyrimidyl 2-(N-pyrrolidinyl-methyl}phenyl 404 -CN 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 405 -CN 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 406 -CN 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 407 -CN 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 408 -CN 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 409 -CN 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 410 -CN 2-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 411 -CN 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 412 -CN 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 413 -CN 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 414 -CN 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 415 -CN 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 416 -CN 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 417 -CN 2-pyrimidyl 2-(amidinyl)phenyl 418 -CN 2-pyrimidyl 2-(N-guanidinyl)phenyl 419 -CN 2-pyrimidyl 2-(imidazolyl)phenyl 420 -CN 2-pyrimidyl 2-(imidazolidinyl)phenyl 421 -CN 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 422 -CN 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 423 -CN 2-pyrimidyl 2-(2-piperidinyl)phenyl 424 -CN 2-pyrimidyl 2-(amidinyl-methyl)phenyl 425 -CN 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 426 --CN 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 427 -CN 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 428 -CN 2-pyrimidyl 2-(3-aminophenyl) 429 -CN 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 430 -CN 2-pyrimidyl 2-glycinoyl 431 -CN 2-pyrimidyl 2-(imidazol-1-ylacetyl) 432 -CN 2-C1-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 433 -CN 2-Cl-phenyl 2-(N-piperidinyl-methyl)phenyl 434 -CN 2-C1-phenyl 2-(N-morpholino-methyl)phenyl 435 -CN 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 436 -CN 2-C1-phenyl 2-(N-pyridinium=methjTl)phenyl 437 -CN 2-Cl-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 438 -CN 2-C1-phenyl 2-(N-azatanyl-methyl)phenyl 439 -CN 2-Cl-phenyl 2-(N-azetidinyl-methyl)phenyl 440 -CN 2-Cl-phenyl 2-(N-piperazinyl-methyl)phenyl 441 -CN 2-C1-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 442 -CN 2-C1-phenyl 2-(N-imidazolyl-methyl)phenyl 443 -CN 2-C1-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 444 -CN 2-Cl-phenyl 2-(N-pyridonyl-methyl)phenyl 445 -CN 2-C1-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 446 -CN 2-C1-phenyl 2-(amidinyl)phenyl 447 -CN 2-C1-phenyl 2-(N-guanidinyl)phenyl 448 -CN 2-Cl-phenyl 2-(imidazolyl)phenyl 449 -CN 2-C1-phenyl 2-(imidazolidinyl)phenyl 450 -CN 2-C1-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 451 -CN 2-C1-phenyl 2-(2-pyrrolidinyl)phenyl 452 -CN 2-C1-phenyl 2-(2-piperidinyl)phenyl 453 -CN 2-Cl-phenyl 2-(amidinyl-methyl)phenyl 454 -CN 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 455 -CN 2-C1-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 456 -CN 2-C1-phenyl 2-dimethylaminoimidazol-1-yl 457 -CN 2-C1-phenyl 2-(3-aminophenyl) 458 -CN 2-C1-phenyl 2-(3-pyrrolidinylcarbonyl) 459 -CN 2-C1-phenyl 2-glycinoyl 460 -CN 2-C1-phenyl 2-(imidazol-1-ylacetyl) 461 -CN 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 462 -CN 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 463 -CN 2-F-phenyl 2-(N-morpholino-methyl)phenyl 464 -CN 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 465 -CN 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 466 -CN 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 467 -CN 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 468 -CN 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 469 -CN 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 470 -CN 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 471 -CN 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 472 -CN 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 473 -CN 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 474 -CN 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 475 -CN 2-F-phenyl 2-(amidinyl)phenyl 476 -CN 2-F-phenyl 2-(N-guanidinyl)phenyl 477 -CN 2-F-phenyl 2-(imidazolyl)phenyl 478 -CN 2-F-phenyl 2-(imidazolidinyl)phenyl 479 -CN 2-F-phenyl 2-(2-imidazolidinyi-sulfonyl)phenyl 480 -CN 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 481 -CN 2-F-phenyl 2-(2-piperidinyl)phenyl 482 -CN 2-F-phenyl 2-(amidinyl-methyl)phenyl 483 -CN 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 484 -CN 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 485 -CN 2-F-phenyl 2-dimethylaminoimidazol-1-yl 486 -CN 2-F-phenyl 2-(3-aminophenyl) 487 -CN 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 488 -CN 2-F-phenyl 2-glycinoyl 489 -CN 2-F-phenyl 2-(imidazol-1-ylacetyl) 490 -CN 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 491 -CN 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 492 -CN 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 493 -CN 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 494 -CN 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 495 -CN 2,5-diF-phenyl 2-(N-4-(N, N'-dimethyiamino)-pyridinium-methyl)phenyl 496 -CN 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 497 -CN 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 498 -CN 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 499 -CN 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 500 -CN 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 501 -CN 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 502 -CN 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 503 -CN 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 504 -CN 2,5-diF-phenyl 2-(amidinyl)phenyl 505 -CN 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 506 -CN 2,5-diF-phenyl 2-(imidazolyl)phenyl 507 -CN 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 508 -CN 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 509 -CN 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 510 -CN 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 511 -CN 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 512 -CN 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 513 -CN 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)ph'nyl 514 -CN 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 515 -CN 2,5-diF-phenyl 2-(3-aminophenyl) 516 -CN 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 517 -CN 2,5-diF-phenyl 2-glycinoyl 518 -CN 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 519 CF3 phenyl 2-(aminosulfonyl)phenyl 520 CF3 phenyl 2-(methylaminosulfonyl)phenyl 521 CF3 phenyl 1-pyrrolidinocarbonyl 522 CF3 phenyl 2-(methylsulfonyl)phenyl 523 CF3 phenyl 4-morpholino 524 CF3 phenyl 2-(1'-CF3-tetra~ol-2-yl)pher=yl 525 CF3 phenyl 4-morpholinocarbonyl 526 CF3 2-pyridyl 2-(aminosulfonyl)phenyl 527 CF3 2-pyridyl 2-(methylaminosulfonyl)phenyl 528 CF3 2-pyridyl 1-pyrrolidinocarbonyl 529 CF3 2-pyridyl 2-(methylsulfonyl)phenyl 530 CF3 2-pyridyl 4-morpholino 531 CF3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 532 CF3 2-pyridyl 4-morpholinocarbonyl 533 CF3 3-pyridyl 2-(aminosulfonyl)phenyl 534 CF3 3-pyridyl 2-(methylaminosulfonyl)phenyl 535 CF3 3-pyridyl 1-pyrrolidinocarbonyl 536 CF3 3-pyridyl 2-(methylsulfonyl)phenyl 537 CF3 3-pyridyl 4-morpholino 538 CF3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 539 CF3 3-pyridyl 4-morpholinocarbonyl 540 CF3 2-pyrimidyl 2-(aminosulfonyl)phenyl 541 CF3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 542 CF3 2-pyrimidyl 1-pyrrolidinocarbonyl 543 CF3 2-pyrimidyl 2-(methylsulfonyl)phenyl 544 CF3 2-pyrimidyl 4-morpholino 545 CF3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 546 CF3 2-pyrimidyl 4-morpholinocarbonyl 547 CF3 5-pyrimidyl 2-(aminosulfonyl)phenyl 548 CF3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 549 CF3 5-pyrimidyl 1-pyrrolidinocarbonyl 550 CF3 5-pyrimidyl 2-(methylsulfonyl)phenyl 551 CF3 5-pyrimidyl 4-morpholino 552 CF3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 553 CF3 5-pyrimidyl 4-morpholinocarbonyl 554 CF3 2-C1-phenyl 2-(aminosulfonyl)phenyl 555 CF3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 556 CF3 2-C1-phenyl 1-pyrrolidinocarbonyl 557 CF3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 558 CF3 2-C1-phenyl 4-morpholino 559 CF3 2-Cl-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 560 CF3 2-C1-phenyl 4-morpholinocarbonyl 561 CF3 2-F-phenyl 2-(aminosulfonyl)phenyl 562 CF3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 563 CF3 2-F-phenyl 1-pyrrolidinocarbonyl 564 CF3 2-F-phenyl 2-(methylsulfonyl)phenyl 565 CF3 2-F-phenyl 4-morpholino 566 CF3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 567 CF3 2-F-phenyl 4-morpholinocarbonyl 568 CF3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 569 CF3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 570 CF3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 571 CF3 2,5-diF-phenyl 2-{methylsulfonyl)phenyl 572 CF3 2,5-diF-phenyl 4-morpholino 573 CF3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 574 CF3 2,5-diF-phenyl 4-morpholinocarbonyl 575 CF3 phenyl 2-(N-pyrrolidinyl-methyl)phenyl 576 CF3 phenyl 2-(N-piperidinyl~-methyl)phenyl 577 CF3 phenyl 2-(N-morpholino-methyl)phenyl 578 CF3 phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 579 CF3 phenyl 2-(N-pyridinium-methyl)phenyl 580 CF3 phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 581 CF3 phenyl 2-(N-azatanyl-methyl)phenyl 582 CF3 phenyl 2-(N-azetidinyl-methyl)phenyl 583 CF3 phenyl 2-(N-piperazinyl-methyl)phenyl 584 CF3 phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 585 CF3 phenyl 2-(N-imidazolyl-methyl)phenyl 586 CF3 phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 587 CF3 phenyl 2-(N-pyridonyl-methyl)phenyl 588 CF3 phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 589 CF; phenyl 2-(amidinyl)phenyl 590 CF3 phenyl 2-(N-guanidinyl)phenyl 591 CF3 phenyl 2-(imidazolyl)phenyl 592 CF3 phenyl 2-(imidazolidinyl)phenyl 593 CF3 phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 594 CF3 phenyl 2-(2-pyrrolidinyl)phenyl 595 CF3 phenyl 2-(2-piperidinyl)phenyl 596 CF3 phenyl 2-(amidinyl-methyl)phenyl 597 CF3 phenyl 2-t2-imidazolidinyl-methyl)phenyl 598 CF3 phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 599 CF3 phenyl 2-dimethylaminoimidazol-1-yl 600 CF3 phenyl 2-(3-aminophenyl) 601 CF3 phenyl 2-(3-pyrrolidinylcarbonyl) 602 CF3 phenyl 2-glycinoyl 603 CF3 phenyl 2-(imidazol-1-ylacetyl) 604 CF3 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 605 CF3 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 606 CF3 2-pyridyl 2-(N-morpholino-methyl)phenyl 607 CF3 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 608 CF3 2-pyridyl 2-(N-pyridinium-methyl)phenyl 609 CF3 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 610 CF3 2-pyridyl 2-(N-azatanyl-methyl)phenyl 611 CF3 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 612 CF3 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 613 CF3 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 614 CF3 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 615 CF3 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 616 CF3 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 617 CF3 2-pyridyl 2-(IJ-(N',N'-dimethylhydrazinyl-methyl)phenyl 618 CF3 2-pyridyl 2-(amidinyl)phenyl 619 CF3 2-pyridyl 2-(N-guanidinyl)phenyl 620 CF3 2-pyridyl 2-(imidazolyl)phenyl 621 CF3 2-pyridyl 2-(imidazolidinyl)phenyl 622 CF3 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 623 CF3 2-pyridyl 2-(2-pyrrolidinyl)phenyl 624 CF3 2-pyridyl 2-(2-piperidinyl)phenyl 625 CF3 2-pyridyl 2-(amidinyl-methyl)phenyl 626 CF3 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 627 CF3 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 628 CF3 2-pyridyl 2-dimethylaminoimidazol-1-yl 629 CF3 2-pyridyl 2-(3-aminophenyl) 630 CF3 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 631 CF3 2-pyridyl 2-glycinoyl 632 CF3 2-pyridyl 2-(imidazol-1-ylacetyl) 633 CF3 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 634 CF3 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 635 CF3 3-pyridyl 2-(N-morpholino-methyl)phenyl 636 CF3 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 637 CF3 3-pyridyl 2-(N-pyridinium-methyl)phenyl 638 CF3 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 639 CF3 3-pyridyl 2-(N-azatanyl-methyl)phenyl 640 CF3 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 641 CF3 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 642 CF3 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 643 CF3 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 644 CF3 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 645 CF3 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 646 CF3 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 647 CF3 3-pyridyl 2-(amidinyl)phenyl 648 CF3 3-pyridyl 2-(N-guanidinyl)phenyl 649 CF3 3-pyridyl 2-(imidazolyl)phenyl 650 CF3 3-pyridyl 2-(imidazolidinyl)phenyl 651 CF3 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 652 CF3 3-pyridyl 2-(2-pyrrolidinyl)phenyl 653 CF3 3-pyridyl 2-(2-piperidinyl)phenyl 654 CF3 3-pyridyl 2-(amidinyl-methyl)phenyl 655 CF3 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 656 CF3 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 657 CF3 3-pyridyl 2-dimethylaminoimidazol-1-yl 658 CF3 3-pyridyl 2-(3-aminop.zenyl) 659 CF3 3-pyridyl 2-(3-pyrruiidinylcarbonyl) 660 CF3 3-pyridyl 2-glycinoyl 661 CF3 3-pyridyl 2-(imidazol-1-ylacetyl) 662 CF3 2-pyrimidyl 2-(N-pyrrolidinyl-methyl)phenyl 663 CF3 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 664 CF3 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 665 CF3 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 666 CF3 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 667 CF3 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 668 CF3 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 669 CF3 2-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 670 CF3 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 671 CF3 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 672 CF3 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 673 CF3 2-pyrimidyl 2-(D1-methoxy-N-methylamino-methyl)phenyl 674 CF3 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 675 CF3 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 676 CF3 2-pyrimidyl 2-(amidinyl)phenyl 677 CF3 2-pyrimidyl 2-(N-guanidinyl)phenyl 678 CF3 2-pyrimidyl 2-(imidazolyl)phenyl 679 CF3 2-pyrimidyl 2-(imidazolidinyl)phenyl 680 CF3 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 681 CF3 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 682 CF3 2-pyrimidyl 2-(2-piperidinyl)phenyl 683 CF3 2-pyrimidyl 2-(amidinyl-methyl)phenyl 684 CF3 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 685 CF3 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 686 CF3 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 687 CF3 2-pyrimidyl 2-(3-aminophenyl) 688 CF3 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 689 CF3 2-pyrimidyl 2-glycinoyl 690 CF3 2-pyrimidyl 2-(imidazol-1-ylacetyl) 691 CF3 2-C1-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 692 CF3 2-C1-phenyl 2-(N-piperidinyl-methyl)phenyl 693 CF3 2-Cl-phenyl 2-(N-morpholino-methyl)phenyl 694 CF3 2-Cl-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 695 CF3 2-Cl-phenyl 2-(N-pyridinium-methyl)phenyl 696 CF3 2-C1-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 697 CF3 2-C1-phenyl 2-(N-azatanyl-methyl)phenyl 698 CF3 2-C1-phenyl 2-(N-azetidinyl-methyl)phenyl 699 CF3 2-C1-phenyl 2-(N-piperazinyl-methyl)phenyl 700 CF3 2-C1-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 701 CF3 2-Cl-phenyl 2-(N-imidazolyl-methyl)phenyi 702 CF3 2-C1-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 703 CF3 2-C1-phenyl 2-(N-pyridonyl-methyl)phenyl 704 CF3 2-C1-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 705 CF3 2-C1-phenyl 2-(amidinyl)phenyl 706 CF3 2-C1-phenyl 2-(N-guanidinyl)phenyl 707 CF3 2-C1-phenyl 2-(imidazolyl)phenyl 708 CF3 2-Cl-phenyl 2-(imidazolidinyl)phenyl 709 CF3 2-Cl-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 710 CF3 2-C1-phenyl 2-(2-pyrrolidinyl)phenyl 711 CF3 2-Cl-phenyl 2-(2-piperidinyl)phenyl 712 CF3 2-Cl-phenyl 2-(amidinyl-methyl)phenyl 713 CF3 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 714 CF3 2-C1-phenyl 2-(N-(2-aminoimidazolyll-methyl)phenyl 715 CF3 2-C1-phenyl 2-dimethylaminoimidazol-1-yl 716 CF3 2-C1-phenyl 2-(3-aminophenyl) 717 CF3 2-C1-phenyl 2-(3-pyrrolidinylcarbonyl) 718 CF3 2-Cl-phenyl 2-glycinoyl 719 CF3 2-C1-phenyl 2-(imidazol-1-ylacetyl) 720 CF3 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 721 CF3 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 722 CF3 2-F-phenyl 2-(N-morpholino-methyl)phenyl 723 CF3 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 724 CF3 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 725 CF3 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 726 CF3 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 727 CF3 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 728 CF3 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 729 CF3 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 730 CF3 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 731 CF3 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 732 CF3 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 733 CF3 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 734 CF3 2-F-phenyl 2-(amidinyl)phenyl 735 CF3 2-F-phenyl 2-(N-guanidinyl)phenyl 736 CF3 2-F-phenyl 2-(imidazolyl)phenyl 737 CF3 2-F-phenyl 2-(imidazolidinyl)phenyl 738 CF3 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 739 CF3 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 740 CF3 2-F-phenyl 2-(2-piperidinyl)phenyl 741 CF3 2-F-phenyl 2-(amidinyl-methyl)phenyl 742 CF3 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 743 CF3 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 744 CF3 2-F-phenyl 2-dimethylaminoimidazol-1-yl 745 CF3 2-F-phenyl 2-(3-aminophenyl) 746 CF3 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 747 CF3 2-F-phenyl 2-glycinoyl 748 CF3 2-F-phenyl 2-(imidazol-1-ylacetyl) 749 CF3 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 750 CF3 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 751 CF3 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 752 CF3 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 753 CF3 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 754 CF3 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 755 CF3 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 756 CF3 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 757 CF3 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 758 CF3 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 759 CF3 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 760 CF3 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 761 CF3 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 762 CF3 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 763 CF3 2,5-diF-phenyl 2-(amidinyl)phenyl 764 CF3 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 765 CF3 2,5-diF-phenyl 2-(imidazolyl)phenyl 766 CF3 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 767 CF3 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 768 CF3 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 769 CF3 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 770 CF3 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 771 CF3 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 772 CF3 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 773 CF3 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 774 CF3 2,5-diF-phenyl 2-(3-aminophenyl) 775 CF3 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 776 CF3 2,5-diF-phenyl 2-glycinoyl 777 CF3 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 778 CONH2 phenyl 2-(aminosulfonyl)phenyl 779 CONH2 phenyl 2-(methylaminosulfonyl)phenyl 780 CONH2 phenyl 1-pyrrolidinocarbonyl 781 CONH2 phenyl 2-(methylsulfonyl)phenyl 782 CONH2 phenyl 4-morpholino 783 CONH2 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 784 CONH2 phenyl 4-morpholinocarbonyl 785 CONH2 2-pyridyl 2-(aminosulfonyl)phenyl 786 CONH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 787 CONH2 2-pyridyl 1-pyrrolidinocarbonyl 788 CONH2 2-pyridyl 2-(methylsulfonyl)phenyl 789 CONH2 2-pyridyl 4-morpholino 790 CONH2 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 791 CONH2 2-pyridyl 4-morpholinocarbonyl 792 CONHZ 3-pyridyl 2-(aminosulfonyl)phenyl 793 CONH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 794 CONH2 3-pyridyl 1-pyrrolidinocarbonyl 795 CONH2 3-pyridyl 2-(methylsulfonyl)phenyl 796 CONHZ 3-pyridyl 4-morpholino 797 CONH2 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 798 CONH2 3-pyridyl 4-morpholinocarbonyl 799 CONH2 2-pyrimidyl 2-(aminosulfonyl)phenyl 800 CONH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 801 CONH2 2-pyrimidyl 1-pyrrolidinocarbonyl 802 CONH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 803 CONH2 2-pyrimidyl 4-morphoiino 804 CONH2 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 805 CONH2 2-pyrimidyl 4-morpholinocarbonyl 806 CONH2 5-pyrimidyl 2-(aminosulfonyl)phenyl 807 CONH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 808 CONH2 5-pyrimidyl 1-pyrrolidinocarbonyl 809 CONH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 810 CONH2 5-pyrimidyl 4-morpholino 811 CONH2 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 812 CONH2 5-pyrimidyl 4-morpholinocarbonyl 813 CONHZ 2-Cl-phenyl 2-(aminosulfonyl)phenyl 814 CONHZ 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 815 CONH2 2-C1-phenyl 1-pyrrolidinocarbonyl 816 CONH2 2-Cl-phenyl 2-(methylsulfonyl)phenyl 817 CONH2 2-C1-phenyl 4-morpholino 818 CONH2 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 819 CONH2 2-C1-phenyl 4-morpholinocarbonyl 820 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 821 CONF32 2-F-phenyl 2-(methylaminosulfonyl)phenyl 822 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 823 CONHZ 2-F-phenyl 2-(methylsulfonyl)phenyl 824 CONH2 2-F-phenyl 4-morpholino 825 CONH2 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 826 CONH2 2-F-phenyl 4-morpholinocarbonyl 827 CONH2 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 828 CONH2 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 829 CONH2 2,5-diF-phenyl 1-pyrrolidinocarbonyl 830 CONH2 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 831 CONHZ 2,5-diF-phenyl 4-morpholino 832 CONH2 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 833 CONHZ 2,5-diF-phenyl 4-morpholinocarbonyl 834 CONH2 phenyl 2-(N-pyrrolidinyl-methyl)phenyl 835 CONHZ phenyl 2-(N-piperidinyl-methyl)phenyl 836 CONH~ phenyl 2-(N-morpholino-methyl)phenyl 837 CONH2 phenyl 2-(N, N'-methylmorpholiniurr,-methyl)phenyl 838 CONH2 phenyl 2-(N-pyridinium-methyl)phenyl 839 CONH2 phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 840 CONH2 phenyl 2-(N-azatanyl-methyl)phenyl 841 CONH2 phenyl 2-(N-azetidinyl-methyl)phenyl 842 CONH2 phenyl 2-(N-piperazinyl-methyl)phenyl 843 CONH2 phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 844 CONHZ phenyl 2-(N-imidazolyl-methyl)phenyl 845 CONH2 phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 846 CONH2 phenyl 2-(N-pyridonyl-methyl)phenyl 847 CONH2 phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 848 CONH2 phenyl 2-(amidinyl)phenyl 849 CONH2 phenyl 2-(N-guanidinyl)phenyl 850 CONH2 phenyl 2-(imidazolyl)phenyl 851 CONH2 phenyl 2-(imidazolidinyl)phenyl 852 CONH2 phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 853 CONH2 phenyl 2-(2-pyrrolidinyl}phenyl 854 CONI~i2 phenyl 2-(2-piperidinyl)phenyl 855 CONH2 phenyl 2-(amidinyl-methyl)phenyl 856 CONHZ phenyl 2-(2-imidazolidinyl-methyl)phenyl 857 CONH2 phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 858 CONH2 phenyl 2-dimethylaminoimidazol-1-yl 859 CONH2 phenyl 2-(3-aminophenyl) 860 CONH2 phenyl 2-(3-pyrrolidinylcarbonyl) 861 CONH2 phenyl 2-glycinoyl 862 CONH2 phenyl 2-(imidazol-1-ylacetyl) 863 CONH2 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 864 CONH2 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 865 CONH2 2-pyridyl 2-(N-morpholino-methyl)phenyl 866 CONH2 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 867 CONH2 2-pyridyl 2-(N-pyridinium-methyl)phenyl 868 CONH2 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 869 CONH2 2-pyridyl 2-(N-azatanyl-methyl)phenyl 870 CONH2 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 871 CONH2 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 872 CONH2 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 873 CONH2 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 874 CONH2 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 875 CONH2 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 876 CONH2 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 877 CONH2 2-pyridyl 2-(amidinyl)phenyl 878 CONH2 2-pyridyl 2-(N-guanidinyl)phenyl 879 CONH2 2-pyridyl 2-(imidazolyl)phenyl 880 CONH2 2-pyridyl 2-(imidazolidinyl)phenyl 881 CONH2 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 882 CONH2 2-pyridyl 2-(2-pyrrolidinyl)phenyl 883 CONH2 2-pyridyl 2-(2-piperidinyl)phenyl 884 CONH2 2-pyridyl 2-(amidinyl-methyl)phenyl 885 CONHZ 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 886 CONH2 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 887 CONH2 2-pyridyl 2-dimethylaminoimidazol-1-yl 888 CONH2 2-pyridyl 2-(3-aminophenyl) 889 CONH2 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 890 CONH2 2-pyridyl 2-glycinoyl 891 CONHZ 2-pyridyl 2-(imidazol-1-ylacetyl) 892 CONH2 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 893 CONH2 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 894 CONH2 3-pyridyl 2-(N-morpholino-methyl)phenyl 895 CONH2 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 896 CONFi2 3-pyridyl 2-(N-pyridinium-methyl)phenyl 897 CONH2 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 898 CONH2 3-pyridyl 2-(N-azatanyl-methyl)phenyl 899 CONH2 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 900 CONH2 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 901 CONHZ 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 902 CONH2 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 903 CONH2 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 904 CONH2 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 905 CONH2 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 906 CONH2 3-pyridyl 2-(amidinyl)phenyl 907 CONH2 3-pyridyl 2-(N-guanidinyl)phenyl 908 CONHZ 3-pyridyl 2-(imidazolyl)phenyl 909 CONH2 3-pyridyl 2-(imidazolidinyl)phenyl 910 CONH2 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 911 CONH2 3-pyridyl 2-(2-pyrrolidinyl)phenyl 912 CONH2 3-pyridyl 2-(2-piperidinyl)phenyl 913 CONH2 3-pyridyl 2-(amidinyl-methyl)phenyl 914 CONH2 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 915 CONH~ 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 916 CONH2 3-pyridyl 2-dimethylaminoimidazol-1-yl 917 CONH2 3-pyridyl 2-(3-aminophenyl) 918 CONH2 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 919 CONH~ 3-pyridyl 2-glycinoyl 920 CONH~ 3-pyridyl z-~imidazol-1-ylacetyl) 921 CONH2 2-pyrimidyl 2-(N-pyrrolidinyl-methyl)phenyl 922 CONH~ 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 923 CONH2 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 924 CONH2 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 925 CONH2 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 926 CONH2 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 927 CONH2 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 928 CONH2 2-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 929 CONH2 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 930 CONHZ 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 931 CONHZ 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 932 CONH2 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 933 CONH2 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 934 CONH2 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 935 CONH2 2-pyrimidyl 2-(amidinyl)phenyl 936 CONH2 2-pyrimidyl 2-(N-guanidinyl)phenyl 937 CONHZ 2-pyrimidyl 2-(imidazolyl)phenyl 938 CONH2 2-pyrimidyl 2-(imidazolidinyl)phenyl 939 CONH2 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 940 CONH2 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 941 CONH2 2-pyrimidyl 2-(2-piperidinyl)phenyl 942 CONH2 2-pyrimidyl 2-(amidinyl-methyl)phenyl 943 CONH2 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 944 CONH2 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 945 CONH2 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 946 CONH2 2-pyrimidyl 2-(3-aminophenyl) 947 CONHZ 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 948 CONH2 2-pyrimidyl 2-glycinoyl 949 CONH2 2-pyrimidyl 2-(imidazol-1-ylacetyl) 950 CONH2 2-C1-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 951 CONH2 2-C1-phenyl 2-(N-piperidinyl-methyi)phenyl 952 CONH2 2-C1-phenyl 2-(N-morpholino-methyl)phenyl 953 CONH2 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 954 CONH2 2-C1-phenyl 2-(N-pyridinium-methyl)phenyl 955 CONH2 2-C1-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 956 CONH2 2-C1-phenyl 2-(N-azatanyl-methyl)phenyl 957 CONH2 2-Cl-phenyl 2-(N-azetidinyl-methyl)phenyl 958 CONH2 2-C1-phenyl 2-(N-piperazinyl-methyl)phenyl 959 CONHZ 2-C1-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 960 CONH2 2-C1-phenyl 2-(N-imidazolyl-methyl)phenyl 961 CONH2 2-C1-phenyl 2-(N-methoxy-N-methljla,mino-methyl)phenyl 962 CONH2 2-C1-phenyl 2-(N-pyridonyl-methyl)phenyl 20 963 CONH2 2-C1-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 964 CONH2 2-C1-phenyl 2-(amidinyl)phenyl 965 CONH2 2-Cl-phenyl 2-(N-guanidinyl)phenyl 966 CONH2 2-Cl-phenyl 2-(imidazolyl)phenyl 967 CONH2 2-C1-phenyl 2-(imidazolidinyl)phenyl 968 CONH2 2-Cl-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 969 CONH2 2-C1-phenyl 2-(2-pyrrolidinyl)phenyl 970 CONH2 2-C1-phenyl 2-(2-piperidinyl)phenyl 971 CONHZ 2-C1-phenyl 2-(amidinyl-methyl)phenyl 972 CONH2 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 973 CONH2 2-C1-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 974 CONH2 2-C1-phenyl 2-dimethylaminoimidazol.-1-yl 975 CONH2 2-C1-phenyl 2-(3-aminophenyl) 976 CONH2 2-C1-phenyl 2-(3-pyrrolidinylcarbonyl) 977 CONH2 2-C1-phenyl 2-glycinoyl 978 CONHz 2-C1-phenyl 2-(imidazol-1-ylacetyl) 979 CONH2 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 980 CONH2 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 981 CONH2 2-F-phenyl 2-(N-morpholino-methyl)phenyl 982 CONH2 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 983 CONH2 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 984 CONH2 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 985 CONH2 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 986 CONH2 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 987 CONH2 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 988 CONH2 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 989 CONH2 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 990 CONH2 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 991 CONH2 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 992 CONH2 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 993 CONH2 2-F-phenyl 2-(amidinyl)phenyl 994 CONH2 2-F-phenyl 2-(N-guanidinyl)phenyl 995 CONH2 2-F-phenyl 2-(imidazolyl)phenyl 996 CONH2 2-F-phenyl 2-(imidazolidinyl)phenyl 997 CONH2 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 998 CONHZ 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 999 CONH2 2-F-phenyl 2-(2-piperidinyl)phenyl 1000 CONH2 2-F-phenyl 2-(amidinyl-methyl)phenyl 1001 CONH2 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1002 CGNH2 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1003 CONH2 2-F-phenyl 2-dimethylaminoimidazol-1-yl 1004 CONH2 2-F-phenyl 2-(3-aminophenyl) 1005 CONH2 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 1006 CONH2 2-F-phenyl 2-glycinoyl 1007 CONH2 2-F-phenyl 2-(imidazol-1-ylacetyl) 1008 CONH2 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1009 CONH2 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 1010 CONH2 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 1011 CONH2 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1012 CONH2 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 1013 CONH2 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1014 CONH2 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 1015 CONH2 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 1016 CONHZ 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 1017 CONHZ 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1018 CONH2 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 1019 CONH2 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1020 CONH2 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 1021 CONH2 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1022 CONH2 2,5-diF-phenyl 2-(amidinyl)phenyl 1023 CONH2 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 1024 CONH2 2,5-diF-phenyl 2-(imidazolyl)phenyl 1025 CONH2 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 1026 CONH2 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1027 CONH2 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 1028 CONH2 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 1029 CONH2 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 1030 CONH2 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1031 CONH2 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1032 CONH2 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 1033 CONH2 2,5-diF-phenyl 2-(3-aminophenyl) 1034 CONH2 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 1035 CONH2 2,5-diF-phenyl 2-glycinoyl 1036 CONH2 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 1037 SCH3 phenyl 2-(aminosulfonyl)phenyl 1038 SCH3 phenyl 2-(methylaminosulfonyl)phenyl 1039 SCH3 phenyl 1-pyrrolidinocarbonyl 1040 SCH3 phenyl 2-(methylsulfonyl)phenyl 1041 SCH3 phenyl 4-morpholino 1042 SCH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1043 SCH3 phenyl 4-morpholinocarbonyl 1044 SCH3 2-pyridyl 2-(aminosulfonyl)phenyl 1045 SCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 1046 SCH3 2-pyridyl 1-pyrrolidinocarbonyl 1047 SCH3 2-pyridyl 2-(methylsulfonyl)phenyl 1048 SCH3 2-pyridyl 4-morpholino 1049 SCH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1050 SCH3 2-pyridyl 4-morpholinocarbonyl 1051 SCH3 3-pyridyl 2-(aminosulfonyl)phenyl 1052 SCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 1053 SCH3 3-pyridyl 1-pyrrolidinocarbonyl 1054 SCH3 3-pyridyl 2-(methylsulfonyl)phenyl 1055 SCH3 3-pyridyl 4-morpholino 1056 SCH3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1057 SCH3 3-pyridyl 4-morpholinocarbonyl 1058 SCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 1059 SCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1060 SCH3 2-pyrimidyl 1-pyrrolidinocarbonyl 1061 SCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 1062 SCH3 2-pyrimidyl 4-morpholino 1063 SCH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1064 SCH3 2-pyrimidyl 4-morpholinocarbonyl 1065 SCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 1066 SCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1067 SCH3 5-pyrimidyl 1-pyrrolidinocarbonyl 1068 SCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 1069 SCH3 5-pyrimidyl 4-morpholino 1070 SCH3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1071 SCH3 5-pyrimidyl 4-morpholinocarbonyl 1072 SCH3 2-C1-phenyl 2-(aminosulfonyl)phenyl 1073 SCH3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 1074 SCH3 2-C1-phenyl 1-pyrrolidinocarbonyl 1075 SCH3 2-C1-phenyl 2-(methylsulfonyl)phenyl 1076 SCH3 2-Cl-phenyl 4-morpholino 1077 SCH3 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1078 SCH3 2-C1-phenyl 4-morpholinocarbonyl 1079 SCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1080 SCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1081 SCH3 2-F-phenyl 1-pyrrolidinocarbonyl 1082 SCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1083 SCH3 2-F-phenyl 4-morpholino 1084 SCH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1085 SCH3 2-F-phenyl 4-morpholinocarbonyl 1086 SCH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 1087 SCH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 1088 SCH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 1089 SCH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 1090 SCH3 2,5-diF-phenyl 4-morpholino 1091 SCH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1092 SCH3 2,5-diF-phenyl 4-morpholinocarbonyl 1093 SCH3 phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1094 SCH3 phenyl 2-(N-piperidinyl-methyl)phenyl 1095 SCH3 phenyl 2-(N-morpholino-methyl)phenyl 1096 SCH3 phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1097 SCH3 phenyl 2-(N-pyridiniurn-methyl)phenyl 1098 SCH3 phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1099 SCH3 phenyl 2-(N-azatanyl-methyl)phenyl 1100 SCH3 phenyl 2-(N-azetidinyl-methyl)phenyl 1101 SCH3 phenyl 2-(N-piperazinyl-methyl)phenyl 1102 SCH3 phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1103 SCH3 phenyl 2-(N-imidazolyl-methyl)phenyl 1104 SCH3 phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1105 SCH3 phenyl 2-(N-pyridonyl-methyl)phenyl 1106 SCH3 phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1107 SCH3 phenyl 2-(amidinyl)phenyl 1108 SCH3 phenyl 2-(N-guanidinyl)phenyl 1109 SCH3 phenyl 2-(imidazolyl)phenyl 1110 SCH3 phenyl 2-(imidazolidinyl)phenyl 1111 SCH3 phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1112 SCH3 phenyl 2-(2-pyrrolidinyl)phenyl 1113 SCH3 phenyl 2-(2-piperidinyl)phenyl 1114 SCH3 phenyl 2-(amidinyl-methyl)phenyl 1115 SCH3 phenyl 2-(2-imidazolidinyl-methyl)phenyl 1116 SCH3 phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1117 SCH3 phenyl 2-dimethylaminoimidazol-1-yl 1118 SCH3 phenyl 2-(3-aminophenyl) 1119 SCH3 phenyl 2-(3-pyrrolidinylcarbonyl) 1120 SCH3 phenyl 2-glycinoyl 1121 SCH3 phenyl 2-(imidazol-1-ylacetyl) 1122 SCH3 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1123 SCH3 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 1124 SCH3 2-pyridyl 2-(N-morpholino-methyl)phenyl 1125 SCH3 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1126 SCH3 2-pyridyl 2-(N-pyridinium-methyl)phenyl 1127 SCH3 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1128 SCH3 2-pyridyl 2-(N-azatanyl-methyl)phenyl 1129 SCH3 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 1130 SCH3 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 1131 SCH3 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1132 SCH3 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 1133 SCH3 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1134 SCH3 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 1135 SCH3 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1136 SCH3 2-pyridyl 2-(amidinyl)phenyl 1137 SCH3 2-pyridyl 2-(N-guanidinyl)phenyl 1138 SCH3 2-pyridyl 2-(imidaz~lyl)phenyl 1139 SCH3 2-pyridyl 2-(imidazolidinyl)phenyl 1140 SCH3 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1141 SCH3 2-pyridyl 2-(2-pyrrolidinyl)phenyl 1142 SCH3 2-pyridyl 2-(2-piperidinyl)phenyl 1143 SCH3 2-pyridyl 2-(amidinyl-methyl)phenyl 2144 SCH3 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1145 SCH3 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1146 SCH3 2-pyridyl 2-dimethylaminoimidazol-1-yl 1147 SCH3 2-pyridyl 2-(3-aminophenyl) 1148 SCH3 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 1149 SCH3 2-pyridyl 2-glycinoyl 1150 SCH3 2-pyridyl 2-(imidazol-1-ylacetyl) 1151 SCH3 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1152 SCH3 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 1153 SCH3 3-pyridy 1 2- (r3-m:,~pholino-methyl ) phenyl 1154 SCH3 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1155 SCH3 3-pyridyl 2-(N-pyridinium-methyl)phenyl 1156 SCH3 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1157 SCH3 3-pyridyl 2-(N-azatanyl-methyl)phenyl 1158 SCH3 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 1159 SCH3 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 1160 SCH3 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1161 SCH3 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 1162 SCH3 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1163 SCH3 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 1164 SCH3 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1165 SCH3 3-pyridyl 2-(amidinyl)phenyl 1166 SCH3 3-pyridyl 2-(N-guanidinyl)phenyl 1167 SCH3 3-pyridyl 2-(imidazolyl)phenyl 1168 SCH3 3-pyridyl 2-(imidazolidinyl)phenyl 1169 SCH3 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1170 SCH3 3-pyridyl 2-(2-pyrrolidinyl)phenyl 1171 SCH3 3-pyridyl 2-(2-piperidinyl)phenyl 1172 SCH3 3-pyridyl 2-(amidinyl-methyl)phenyl 1173 SCH3 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1174 SCH3 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1175 SCH3 3-pyridyl 2-dimethylaminoimidazol-1-yl 1176 SCH3 3-pyridyl 2-(3-aminophenyl) 1177 SCH3 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 1178 SCH3 3-pyridyl 2-glycinoyl 1179 SCH3 3-pyridyl 2-(imidazol-1-ylacetyl) 1180 SCH3 2-pyrimidyl 2-(N-pyrrolidinyl-n~~thyl)phenyl 1181 SCH3 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 1182 SCH3 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 1183 SCH3 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1184 SCH3 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 1185 SCH3 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1186 SCH3 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 1187 SCH3 2-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 1188 SCH3 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 1189 SCH3 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1190 SCH3 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 1191 SCH3 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1192 SCH3 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 1193 SCH3 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1194 SCH3 2-pyrimidyl 2-(amidinyl)phenyl 1195 SCH3 2-pyrimidyl 2-(N-guanidinyl)phenyl 1196 SCH3 2-pyrimidyl 2-(imidazolyl)phenyl 1197 SCH3 2-pyrimidyl 2-(imidazolidinyl)phenyl 1198 SCH3 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1199 SCH3 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 1200 SCH3 2-pyrimidyl 2-(2-piperidinyl)phenyl 1201 SCH3 2-pyrimidyl 2-(amidinyl-methyl)phenyl 1202 SCH3 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 1203 SCH3 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1204 SCH3 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 1205 SCH3 2-pyrimidyl 2-(3-aminophenyl) 1206 SCH3 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 1207 SCH3 2-pyrimidyl 2-glycinoyl 1208 SCH3 2-pyrimidyl 2-(imidazol-1-ylacetyl) 1209 SCH3 2-Cl-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1210 SCH3 2-Cl-phenyl 2-(N-piperidinyl-methyl)phenyl 1211 SCH3 2-C1-phenyl 2-(N-morpholino-methyl)phenyl 1212 SCH3 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 12i~ SCH3 2-C1-phenyl 2-(N-pyridinium-methyl)phenyl 1214 SCH3 2-C1-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 2215 SCH3 2-Cl-phenyl 2-(N-azatanyl-methyl)phenyl 1216 SCH3 2-C1-phenyl 2-(N-azetidinyl-methyl)phenyl 1217 SCH3 2-Cl-phenyl 2-(N-piperazinyl-methyl)phenyl 1218 SCH3 2-Cl-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1219 SCH3 2-Cl-phenyl 2-(N-imidazolyl-methyl)phenyl 1220 SCH3 2-Cl-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1221 SCH3 2~-C1-phenyl 2-(N-pyridonyl-methyl)phenyl 1222 SCH3 2-Cl-phenyl 2-(N-(N',N'-dimethyihydrazinyl-methyl)phenyl 1223 SCH3 2-C1-phenyl 2-(amidinyl)phenyl 1224 SCH3 2-Cl-phenyl 2-(N-guanidinyl)phenyl 1225 SCH3 2-Cl-phenyl 2-(imidazolyl)phenyl 1226 SCH3 2-C1-phenyl 2-(imidazolidinyl)phenyl 1227 SCH3 2-C1-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1228 SCH3 2-Cl-phenyl 2-(2-pyrrolidinyl)phenyl 1229 SCH3 2-CI-phenyl 2-(2-piperidinyl)phenyl 1230 SCH3 2-Cl-phenyl 2-(amidinyl-methyl)phenyl 1231 SCH3 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1232 SCH3 2-C1-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1233 SCH3 2-C1-phenyl 2-dimethylaminoimidazol-1-yl 1234 SCH3 2-C1-phenyl 2-(3-aminophenyl) 1235 SCH3 2-C1-phenyl 2-(3-pyrrolidinylcarbonyl) 1236 SCH3 2-C1-phenyl 2-glycinoyl 1237 SCH3 2-C1-phenyl 2-(imidazol-1-ylacetyl) 1238 SCH3 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1239 SCH3 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 1240 SCH3 2-F-phenyl 2-(N-morpholino-methyl)phenyl 1241 SCH3 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1242 SCH3 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 1243 SCH3 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1244 SCH3 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 1245 SCH3 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 1246 SCH3 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 1247 SCH3 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1248 SCH3 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 1249 SCH3 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1250 SCH3 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 1251 SCH3 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1252 SCH3 2-F-phenyl 2-(amidinyl)phenyl 1253 SCH3 2-F-phenyl 2-(N-guanidinyl)phenyl 1254 SCH3 2-F-phenyl 2-(imidazolyl)phenyl 1255 SCH3 2-F-phenyl 2-(imidazolidinyl)phenyl 1256 SCH3 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1257 SCH3 2-F-phenyl 2-(2-pyrrolidinyl)phenyl WO 98/57934 PCT/US98/i2682 1258 SCH3 2-F-phenyl 2-(2-piperidinyl)phenyl 1259 SCH3 2-F-phenyl 2-(amidinyl-methyl)phenyl 1260 SCH3 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1261 SCH3 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1262 SCH3 2-F-phenyl 2-din!ethylaminoimidazol-1-yl 1263 SCH3 2-F-phenyl 2-(3-aminophenyl) 1264 SCH3 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 1265 SCH3 2-F-phenyl 2-glycinoyl 1266 SCH3 2-F-phenyl 2-(imidazol-1-ylacetyl) 1267 SCH3 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1268 SCH3 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 1269 SCH3 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 1270 SCH3 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1271 SCH3 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 1272 SCH3 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1273 SCH3 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 1274 SCH3 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 1275 SCH3 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 1276 SCH3 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1277 SCH3 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 1278 SCH3 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1279 SCH3 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 1280 SCH3 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1281 SCH3 2,5-diF-phenyl 2-(amidinyl)phenyl 1282 SCH3 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 1283 SCH3 2,5-diF-phenyl 2-(imidazolyl)phenyl 1284 SCH3 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 1285 SCH3 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1286 SCH3 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 1287 SCH3 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 1288 SCH3 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 1289 SCH3 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1290 SCH3 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1291 SCH3 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 1292 SCH3 2,5-diF-phenyl 2-(3-aminophenyl) 1293 SCH3 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 1294 SCH3 2,5-diF-phenyl 2-glycinoyl 1295 SCH3 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 1296 S02CH3 phenyl 2-(aminosulfonyl)phenyl 1297 S02CH3 phenyl 2-(methylaminosulfonyl)phenyl 1298 S02CH3 phenyl 1-pyrrolidinocarbonyl 1299 S02CH3 phenyl 2-(methylsulfonyl)phenyl 1300 S02CH3 phenyl 4-morpholino 1301 S02CH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1302 S02CH3 phenyl 4-morpholinocarbonyl 1303 S02CH3 2-pyridyl 2-(aminosulfonyl)phenyl 1304 S02CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 1305 S02CH3 2-pyridyl 1-pyrrolidinocarbonyl 1306 S02CH3 2-pyridyl 2-(methylsulfonyl)phenyl 1307 S02CH3 2-pyridyl 4-morpholino 1308 S02CH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1309 S02CH3 2-pyridyl 4-morpholinocarbonyl 1310 S02CH3 3-pyridyl 2-(aminosulfonyl)phenyl 1311 S02CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 1312 S02CH3 3-pyridyl 1-pyrrolidinocarbonyl 1313 S02CH3 3-pyridyl 2-(methylsulfonyl)phenyl 1314 S02CH3 3-pyridyl 4-morpholino 1315 S02CH3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1316 S02CH3 3-pyridyl 4-morpholinocarbonyl 1317 SOZCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 1318 S02CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1319 S02CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 1320 S02CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 1321 S02CH3 2-pyrimidyl 4-morpholino 1322 S02CH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1323 S02CH3 2-pyrimidyl 4-morpholinocarbonyl 1324 S02CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 1325 S02CH3 5-pyrimidyl 2-(mechyiaminosulfonyl)phenyl 1326 S02CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 1327 S02CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 1328 S02CH3 5-pyrimidyl 4-morpholino 1329 S02CH3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1330 S02CH3 5-pyrimidyl 4-morpholinocarbonyl 1331 S02CH3 2-C1-phenyl 2-(aminosulfonyl)phenyl 1332 S02CH3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 1333 SOzCH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 1334 S02CH3 2-C1-phenyl 2-(methylsulfonyl)phenyl 1335 S02CH3 2-Cl-phenyl 4-morpholino 1336 S02CH3 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1337 S02CH3 2-C1-phenyl 4-morpholinocarbonyl 1338 S02CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1339 S02CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1340 S02CH3 2-F-phenyl 1-pyrrolidinocarbonyl 1341 S02CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1342 S02CH3 2-F-phenyl 4-morpholino 1343 S02CH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1344 S02CH3 2-F-phenyl 4-morpholinocarbonyl 1345 S02CH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 1346 S02CH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 1347 S02CH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 1348 S02CH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 1349 S02CH3 2,5-diF-phenyl 4-morpholino 1350 S02CH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1351 S02CH3 2,5-diF-phenyl 4-morpholinocarbonyl 1352 S02CH3 phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1353 S02CH3 phenyl 2-(N-piperidinyl-methyl)phenyl 1354 S02CH3 phenyl 2-(N-morpholino-methyl)phenyl 1355 S02CH3 phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1356 SOZCH3 phenyl 2-(N-pyridinium-methyl)phenyl 1357 SOZCH3 phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl s358 S02CH3 phenyl 2-(N-azatanyl-methyl)phenyl 1359 S02CH3 phenyl 2-(N-azetidinyl-methyl)phenyl 1360 S02CH3 phenyl 2-(N-piperazinyl-methyl)phenyl 1361 S02CH3 phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1362 S02CH3 phenyl 2-(N-imidazolyl-methyl)phenyl 1363 S02CH3 phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1364 S02CH3 phenyl 2-(N-pyridonyl-methyl)phenyl 1365 SOZCH3 phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1366 S02CH3 phenyl 2-(amidinyl)phenyl 1367 S02CH3 phenyl 2-(N-guanidinyl)phenyl 1368 S02CH3 phenyl 2-(imidazolyl)phenyl 1369 S02CH3 phenyl 2-(imidazolidinyl)phenyl 1370 S02CH3 phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1371 S02CH3 phenyl 2-(2-pyrrolidinyl)phenyl 1372 SOZCH3 phenyl 2-(2-piperidinyl)phenyl 1373 S02CH3 phenyl 2-(amidinyl-methyl)phenyl 1374 S02CH3 phenyl 2-(2-imidazolidinyl-methyl)phenyl 1375 S02CH3 phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1376 S02CH3 phenyl 2-dimethylaminoimidazol-1-yl 1377 S02CH3 phenyl 2-(3-aminophenyl) 1378 S02CH3 phenyl 2-(3-pyrrolidinylcarbonyl) 1379 SOZCH3 phenyl 2-glycinoyl 1380 S02CH3 phenyl 2-(imidazol-1-ylacetyl) 1381 S02CH3 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1382 S02CH3 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 1383 S02CH3 2-pyridyl 2-(N-morpholino-methyl)phenyl 1384 S02CH3 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1385 S02CH3 2-pyridyl 2-(N-pyridinium-methyl)phenyl 1386 S02CH3 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1387 S02CH3 2-pyridyl 2-(N-azatanyl-methyl)phenyl 1388 S02CH3 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 1389 S02CH3 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 1390 S02CH3 2-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1391 S02CH3 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 1392 S02CH3 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1393 S02CH3 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 1394 SOZCH3 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 2395 S02CH3 2-pyridyl 2-(amidinyl)phenyl 1396 SOZCH3 2-pyridyl 2-(N-guanidinyl)phenyl 1397 S02CH3 2-pyridyl 2-(imidazolyl)phenyl 1398 S02CH3 2-pyridyl 2-(imidazolidinyl)phenyl 1399 S02CH3 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1400 S02CH3 2-pyridyl 2-(2-pyrrolidinyl)phenyl 1401 S02CH3 2-pyridyl 2-(2-piperidinyl)phenyl 1402 S02CH3 2-pyridyl 2-(amidinyl-methyl)phenyl 1403 S02CH3 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1404 S02CH3 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1405 S02CH3 2-pyridyl 2-dimethylaminoimidazol-1-yl 1406 S02CH3 2-pyridyl 2-(3-aminophenyl) 1407 S02CH3 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 1408 S02CH3 2-pyridyl 2-glycinoyl 1409 SOZCH3 2-pyridyl 2-(imidazol-1-ylacetyl) 1410 S02CH3 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1411 S02CH3 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 1412 S02CH3 3-pyridyl 2-(N-morpholino-methyl)phenyl 1413 SOzCH3 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1414 S02CH3 3-pyridyl 2-(N-pyridinium-methyl)phenyl 1415 S02CH3 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1416 S02CH3 3-pyridyl 2-(N-azatanyl-methyl)phenyl 1417 S02CH3 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 1418 S02CH3 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 1419 S02CH3 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1420 S02CH3 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 1421 S02CH3 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1422 S02CH3 3-pyrid;~l 2-(N-pyridonyl-methyl)phenyl 1423 S02CH3 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1424 S02CH3 3-pyridyl 2-(amidinyl)phenyl 1425 S02CH3 3-pyridyl 2-(N-guanidinyl)phenyl 1426 S02CH3 3-pyridyl 2-(imidazolyl)phenyl 1427 S02CH3 3-pyridyl 2-(imidazolidinyl)phenyl 1428 S02CH3 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1429 S02CH3 3-pyridyl 2-(2-pyrrolidinyl)phenyl 1430 S02CH3 3-pyridyl 2-(2-piperidinyl)phenyl 1431 S02CH3 3-pyridyl 2-(amidinyl-methyl)phenyl 1432 S02CH3 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1433 SOZCH3 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1434 S02CH3 3-pyridyl 2-dimethylaminoimidazol-1-yl 1435 S02CH3 3-pyridyl 2-(3-aminophenyl) 1436 S02CH3 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 1437 S02CH3 3-pyridyl 2-glycinoyl 1438 S02CH3 3-pyridyl 2-(imidazol-1-ylacetyl) S 1439 S02CH3 2-pyrimidyl 2-(N-pyrrolidinyl-methyl)phenyl 1440 S02CH3 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 1441 SOZCH3 2-pyrimidyl 2-(N-mcrprolino-methyl)phenyl 1442 S02CH3 2-pyrimidyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1443 S02CH3 2-pyrimidyl 2-(N-pyridinium-methyl)phenyl 1444 S02CH3 2-pyrimidyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1445 S02CH3 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 1446 S02CH3 2-pyrimidyl 2-(N-azetidinyl-methyl)phenyl 1447 S02CH3 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 1448 S02CH3 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1449 S02CH3 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 1450 S02CH3 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1451 S02CH3 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 1452 S02CH3 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1453 S02CH3 2-pyrimidyl 2-(amidinyl)phenyl 1454 S02CH3 2-pyrimidyl 2- (n?-guanidi nlT1 ) phenyl 1455 S02CH3 2-pyrimidyl 2-(imidazolyl)phenyl 1456 SOZCH3 2-pyrimidyl 2-(imidazolidinyl)phenyl 1457 S02CH3 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1458 S02CH3 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 1459 S02CH3 2-pyrimidyl 2-(2-piperidinyl)phenyl 1460 SOZCH3 2-pyrimidyl 2-(amidinyl-methyl)phenyl 1461 S02CH3 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 1462 S02CH3 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1463 S02CH3 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 1464 SOZCH3 2-pyrimidyl 2-(3-aminophenyl) 1465 S02CH3 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 1466 S02CH3 2-pyrimidyl 2-glycinoyl 1467 S02CH3 2-pyrimidyl 2-(imidazol-1-ylacetyl) 1468 S02CH3 2-C1-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1469 S02CH3 2-Cl-phenyl 2-(N-piperidinyl-methyl)phenyl 1470 S02CH3 2-Cl-phenyl 2-(N-morpholino-methyl)phenyl 1471 S02CH3 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1472 S02CH3 2-Cl-phenyl 2-(N-pyridinium-methyl)phenyl 1473 S02CH3 2-Cl-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1474 S02CH3 2-C1-phenyl 2- (N-azatanyl-methyl)phenyl 1475 S02CH3 2-C1-phenyl 2-(N-azetidinyl-methyl)phenyl 1476 S02CH3 2-Cl-phenyl 2-(N-piperazinyl-methyl)phenyl 1477 S02CH3 2-Cl-phenyl 2-(N, N'-BOC-piperazinyl-WO 98/57934 PCTlUS98/12682 methyl)phenyl 1478 S02CH3 2-C1-phenyl 2-(N-imidazolyl-methyl)phenyl 1479 S02CH3 2-C1-phenyl 2-(N-methoxy-N-methyiamino-methyl)phenyl 1480 S02CH3 2-Cl-phenyl 2-(N-pyridonyl-methyl)phenyl 1481 S02CH3 2-C1-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1482 S02CH3 2-C1-phenyl 2-(amidinyl)phenyl 1483 S02CH3 2-C1-phenyl 2-(N-guanidinyl)phenyl 1484 S02CH3 2-C1-phenyl 2-(imidazolyl)phenyl 1485 S02CH3 2-C1-phenyl 2-(imidazolidinyl)phenyl 1486 S02CH3 2-C1-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1487 SOZCH3 2-Cl-phenyl 2-(2-pyrrolidinyl)phenyl 1488 S02CH3 2-Cl-phenyl 2-(2-piperidinyl)phenyl 1489 S02CH3 2-C1-phenyl 2-(amidinyl-methyl)phenyl 1490 S02CH3 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1491 S02CH3 2-C1-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1492 SOZCH3 2-C1-phenyl 2-dimethylaminoimidazol-1-yl 1493 S02CH3 2-C1-phenyl 2-(3-aminophenyl) 1494 S02CH3 2-C1-phenyl 2-(3-pyrrolidinylcarbonyl) 1495 SOZCH3 2-C1-phenyl 2-glycinoyl 1496 S02CH~ 2-C1-phenyl 2-(imidazol-1-ylacer_y~1 1497 SOZCH3 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1498 S02CH3 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 1499 SOZCH3 2-F-phenyl 2-(N-morpholino-methyl)phenyl 1500 S02CH3 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1501 S02CH3 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 1502 S02CH3 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1503 S02CH3 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 1504 S02CH3 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 1505 S02CH3 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 1506 S02CH3 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1507 S02CH3 2-F-phenyl 2-(N-imidazolyl-methyl)phenyl 1508 S02CH3 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1509 S02CH3 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 1510 S02CH3 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1511 S02CH3 2-F-phenyl 2-(amidinyl)phenyl 1512 SOzCH3 2-F-phenyl 2-(N-guanidinyl)phenyl 1513 S02CH3 2-F-phenyl 2-(imidazolyl)phenyl 1514 S02CH3 2-F-phenyl 2-(imidazolidinyl)phenyl 1515 S02CH3 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1516 S02CH3 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 1517 S02CH3 2-F-phenyl 2-(2-piperidinyl)phenyl 1518 SOzCH3 2-F-phenyl 2-(amidinyl-methyl)phenyl 1519 S02CH3 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1520 S02CH3 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1521 S02CH3 2-F-phenyl 2-dimethylaminoimidazol-1-yl 1522 S02CH3 2-F-phenyl 2-(3-aminophenyl) 1523 S02CH3 ?-F-phenyl 2-(3-pyrrolidinylcarbonyl) 1524 S02CH3 2-F-phenyl 2-glycinoyl 1525 S02CH3 2-F-phenyl 2-(imidazol-1-ylacetyl) 1526 S02CH3 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1527 S02CH3 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 1528 S02CH3 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 1529 S02CH3 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1530 S02CH3 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 1531 S02CH3 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1532 S02CH3 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 1533 S02CH3 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 1534 S02CH3 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 1535 S02CH3 2,S-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1536 S02CH3 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 1537 S02CH3 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1538 S02CH3 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 1539 S02CH3 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1540 SOZCH3 2,5-diF-phenyl 2-(amidinyl)phenyl 1541 S02CH3 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 1542 S02CH3 2,5-diF-phenyl 2-(imidazolyl)phenyl 1543 S02CH3 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 1544 S02CH3 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1545 S02CH3 2,5-diF-phenyl 2-(2-pyrrolidinyi)phenyl 1546 S02CH3 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 1547 S02CH3 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 1548 SOZCH3 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1549 S02CH3 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1550 S02CH3 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 1551 S02CH3 2,5-diF-phenyl 2-(3-aminophenyl) 1552 S02CH3 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 1553 S02CH3 2,5-diF-phenyl 2-glycinoyl 1554 S02CH3 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) 1555 NHS02CH3 phenyl 2-(aminosuifonyl)phenyl 1556 NHSOZCH3 phenyl 2-(methylaminosulfonyl)phenyl 1557 NHSOZCH3 phenyl ~-pyrrolidinocarbonyl 1558 NHS02CH3 phenyl 2-(methylsulfonyl)phenyl 1559 NHS02CH3 phenyl 4-morpholino 1560 NHS02CH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1561 NHS02CH3 phenyl 4-morpholinocarbonyl 1562 NHS02CH3 2-pyridyl 2-(aminosulfonyl)phenyl 1563 NHSOZCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 1564 NHS02CH3 2-pyridyl 1-pyrrolidinocarbonyl 1565 NHS02CH3 2-pyridyl 2-(methylsulfonyl)phenyl 1566 NHS02CH3 2-pyridyl 4-morpholino 1567 NHS02CH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1568 NHS02CH3 2-pyridyl 4-m~rpholinocarbonyl 1569 NHS02CH3 3-pyridyl 2-(aminosulfonyl)phenyl 1570 NHSOZCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 1571 NHSOzCH3 3-pyridyl 1-pyrrolidinocarbonyl 1572 NHS02CH3 3-pyridyl 2-(methylsulfonyl)phenyl 1573 NHS02CH3 3-pyridyl 4-morpholino 1574 NHS02CH3 3-pyridyl 2-(1'-CF3-tetrazol-2-y1)phenyl 1575 NHS02CH3 3-pyridyl 4-morpholinocarbonyl 1576 NHSOZCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 1577 NHS02CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 1578 NHS02CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 1579 NHS02CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 1580 NHS02CH3 2-pyrimidyl 4-morpholino 1581 NHSOZCH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1582 NHS02CH3 2-pyrimidyl 4-morpholinocarbonyl 1583 NHSOZCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 1584 NHS02CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 1585 NHS02CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 1586 NHSOZCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 1587 NHS02CH3 5-pyrimidyl 4-morpholino 1588 NHS02CH3 5-pyrimidyl 2-(2'-CF3-tetrazol-2-yl)phenyl 1589 NHS02CH3 5-pyrimidyl 4-morpholinocarbonyl 1590 NHS02CH3 2-C1-phenyl 2-(aminosulfonyl)phenyl 1591 NHS02CH3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 1592 NHS02CH3 2-C1-phenyl 1-pyrrolidinocarbonyl 1593 NHS02CH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 1594 NHSOZCH3 2-C1-phenyl 4-morpholino 1595 NHS02CH3 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1596 NHS02CH3 2-Cl-phenyl 4-morpholinocarbonyl 1597 NHS02CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 1598 NHS02CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 1599 NHS02CH3 2-F-phenyl 1-pyrrolidinocarbonyl 1600 NHS02CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 1601 NHS02CH3 2-F-phenyl 4-morpholino 1602 NHS02CH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1603 NHS02CH3 2-F-phenyl 4-morpholinocarbonyl 1604 NHS02CH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 1605 NHS02CH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 1606 NHS02CH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 1607 NHS02CH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 1608 NHS02CH3 2,5-diF-phenyl 4-morpholino 1609 NHS02CH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 1610 NHS02CH3 2,5-diF-phenyl 4-morpholinocarbonyl 1611 NHS02CH3 phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1612 NHS02CH3 phenyl 2-(N-piperidinyl-methyl)phenyl 1613 NHS02CH3 phenyl 2-(N-morpholino-methyl)phenyl 1614 NHS02CH3 phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1615 NHS02CH3 phenyl 2-(N-pyridinium-methyl)phenyl 1616 NHS02CH3 phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1617 NHS02CH3 phenyl 2-(N-azatanyl-methyl)phenyl 1618 NHS02CH3 phenyl 2-(N-azetidinyl-methyl)phenyl 1619 NHS02CH3 phenyl 2-(N-piperazinyl-meLiiyiiphenyl 1620 NHS02CH3 phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1621 NHS02CH3 phenyl 2-(N-imidazolyl-methyl)phenyl 1622 NHS02CH3 phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1623 NHS02CH3 phenyl 2-(N-pyridonyl-methyl)phenyl 1624 NHSOZCH3 phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1625 NHS02CH3 phenyl 2-(amidinyl)phenyl 1626 NHS02CH3 phenyl 2-(N-guanidinyl)phenyl 1627 NHS02CH3 phenyl 2-(imidazolyl)phenyl 1628 NHS02CH3 phenyl 2-(imidazolidinyl)phenyl 1629 NHS02CH3 phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1630 NHSOZCH3 phenyl 2-(2-pyrrolidinyl)phenyl 1631 NHS02CH3 phenyl 2-(2-piperidinyl)phenyl 1632 NHS02CH3 phenyl 2-(amidinyl-methy7)phenyJ_ 1633 NHS02CH3 phenyl 2-(2-imidazolidinyl-methyl)phenyl 1634 NHS02CH3 phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1635 NHS02CH3 phenyl 2-dimethylaminoimidazol-1-yl 1636 NHS02CH3 phenyl 2-(3-aminophenyl) 1637 NHS02CH3 phenyl 2-(3-pyrrolidinylcarbonyl) 1638 NHS02CH3 phenyl 2-glycinoyl 1639 NHS02CH3 phenyl 2-(imidazol-1-ylacetyl) 1640 NHS02CH3 2-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1641 NHS02CH3 2-pyridyl 2-(N-piperidinyl-methyl)phenyl 1642 NHS02CH3 2-pyridyl 2-(N-morpholino-methyl)ph,~nyl 1643 NHS02CH3 2-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1644 NHSOZCH3 2-pyridyl 2-(N-pyridinium-methyl)phenyl 1645 NHS02CH3 2-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1646 NHS02CH3 2-pyridyl 2-(N-azatanyl-methyl)phenyl 1647 NHS02CH3 2-pyridyl 2-(N-azetidinyl-methyl)phenyl 1648 NHS02CH3 2-pyridyl 2-(N-piperazinyl-methyl)phenyl 1649 NHS02CH3 2-pyridyl 2-(N,N -BOC
' -piperazinyl-methyl)phenyl 1650 NHS02CH3 2-pyridyl 2-(N-imidazolyl-methyl)phenyl 1651 NHSOZCH3 2-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1652 NHS02CH3 2-pyridyl 2-(N-pyridonyl-methyl)phenyl 1653 NHS02CH3 2-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1654 NHS02CH3 2-pyridyl 2-(amidinyl)phenyl 1655 NHS02CH3 2-pyridyl 2-(N-guanidinyl)phenyl 1656 NHS02CH3 2-pyridyl 2-(imidazolyl)phenyl 1657 NHS02CH3 2-pyridyl 2-(imidazolidinyl)phenyl 1658 NHS02CH3 2-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1659 NH~O~CH3 2-pyridyl 2-(2-pyrrolidinyl)phenyl 1660 NHS02CH3 2-pyridyl 2-(2-piperidinyl)phenyl 1661 NHS02CH3 2-pyridyl 2-(amidinyl-methyl)phenyl 1662 NHS02CH3 2-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1663 NHS02CH3 2-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1664 NHS02CH3 2-pyridyl 2-dimethylaminoimidazol-1-yl 25 1665 NHS02CH3 2-pyridyl 2-(3-aminophenyl) 1666 NHS02CH3 2-pyridyl 2-(3-pyrrolidinylcarbonyl) 1667 NHS02CH3 2-pyridyl 2-glycinoyl 1668 NHS02CH3 2-pyridyl 2-(imidazol-1-ylacetyl) 1669 NHSOZCH3 3-pyridyl 2-(N-pyrrolidinyl-methyl)phenyl 1670 NHS02CH3 3-pyridyl 2-(N-piperidinyl-methyl)phenyl 1671 NHS02CH3 3-pyridyl 2-(N-morpholino-methyl)phenyl 1672 NHS02CH3 3-pyridyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1673 NHSOZCH3 3-pyridyl 2-(N-pyridinium-methyl)phenyl 1674 NHS02CH3 3-pyridyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1675 NHSOZCH3 3-pyridyl 2-(N-azatanyl-methyl)phenyl 1676 NHS02CH3 3-pyridyl 2-(N-azetidinyl-methyl)phenyl 1677 NHS02CH3 3-pyridyl 2-(N-piperazinyl-methyl)phenyl 1678 NHS02CH3 3-pyridyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1679 NHSOZCH3 3-pyridyl 2-(N-imidazolyl-methyl)phenyl 1680 NHS02CH3 3-pyridyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1681 NHS02CH3 3-pyridyl 2-(N-pyridonyl-methyl)phenyl 1682 NHS02CH3 3-pyridyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1683 NHS02CH3 3-pyridyl 2-(amidinyl)phenyl 1684 NHS02CH3 3-pyridyl 2-(N-guanidinyl)phenyl 1685 NHS02CH3 3-pyridyl 2-(imidazolyl)phenyl 1686 NHS02CH3 3-pyridyl 2-(imidazolidinyl)phenyl 1687 NHS02CH3 3-pyridyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1688 NHS02CH3 3-pyridyl 2-(2-pyrrolidinyl)phenyl 1689 NHS02CH3 3-pyridyl 2-(2-piperidinyl)phenyl 2690 NHS02CH3 3-pyridyl 2-(amidinyl-methyl)phenyl 1691 NHS02CH3 3-pyridyl 2-(2-imidazolidinyl-methyl)phenyl 1692 NHS02CH3 3-pyridyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1693 NHS02CH3 3-pyridyl 2-dimethylaminoimidazol-1-yl 1694 NHS02CH3 3-pyridyl 2-(3-aminophenyl) 1695 NHS02CH3 3-pyridyl 2-(3-pyrrolidinylcarbonyl) 1696 NHS02CH3 3-pyridyl 2-glycinoyl 1697 NHSO~CH3 3-pyridyl 2-(imidazol-1-ylacetyl) 1698 NHSOZCH3 2-pyrimidyl 2-(N-pyrrolidinyl-methyl)phenyl 1699 NHSOZCH3 2-pyrimidyl 2-(N-piperidinyl-methyl)phenyl 1700 NHSO?CH3 2-pyrimidyl 2-(N-morpholino-methyl)phenyl 1701 NHSOZCH3 2-pyrimidyl 2-(N, N'-methylmorpholinium-methy~)phenyl 2702 NHS02CH3 2-pyrimidyl ~-(N-pyridinium-methyl)phenyl 1703 NHS02CH3 2-pyrimidyl 2-(N-4-(N, N'-dimethylarnino)-pyridinium-methyl)phenyl 1704 NHS02CH3 2-pyrimidyl 2-(N-azatanyl-methyl)phenyl 1705 NHS02CH3 2-pyrimidyl 2-(N-azetidinyl-methyl}phenyl 1706 NHSO~CH3 2-pyrimidyl 2-(N-piperazinyl-methyl)phenyl 1707 NHSO~CH3 2-pyrimidyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1708 NHS02CH3 2-pyrimidyl 2-(N-imidazolyl-methyl)phenyl 1709 NHS02CH3 2-pyrimidyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1710 NHS02CH3 2-pyrimidyl 2-(N-pyridonyl-methyl)phenyl 1711 NHSO~CH3 2-pyrimidyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1712 NHS02CH3 2-pyrimidyl 2-(amidinyl)phenyl 1713 NHS02CH3 2-pyrimidyl 2-(N-guanidinyl}phenyl 1714 NHS02CH3 2-pyrimidyl 2-(imidazolyl)phenyl 1715 NHS02CH3 2-pyrimidyl 2-(imidazolidinyl)phenyl 1716 NHS02CH3 2-pyrimidyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1717 NHS02CH3 2-pyrimidyl 2-(2-pyrrolidinyl)phenyl 1718 NHS02CH3 2-pyrimidyl 2-(2-piperidinyl)phenyl 1719 NHS02CH3 2-pyrimidyl 2-(amidinyl-methyl)phenyl 1720 NHS02CH3 2-pyrimidyl 2-(2-imidazolidinyl-methyl)phenyl 1721 NHS02CH3 2-pyrimidyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1722 NHS02CH3 2-pyrimidyl 2-dimethylaminoimidazol-1-yl 1723 NHSOZCH3 2-pyrimidyl 2-(3-aminophenyl) 1724 NHS02CH3 2-pyrimidyl 2-(3-pyrrolidinylcarbonyl) 1725 NHS02CH3 2-pyrimidyl 2-glycinoyl 1726 NHS02CH3 2-pyrimidyl 2-(imidazol-1-ylacetyl) 1727 NHS02CH3 2-Cl-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1728 NHS02CH3 2-Cl-phenyl 2-(N-piperidinyl-methyl)phenyl 1729 NHS02CH3 2-Cl-phenyl 2-(N-morpholino-methyl)phenyl 1730 NHS02CH3 2-C1-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 2731 NHS02CH3 2-C1-phenyl 2-(N-pyridinium-methyl)phenyl 1732 NHS02CH3 2-Cl-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1733 NHSOZCH3 2-C1-phenyl 2-(N-azatanyl-methyl)phenyl 1734 NHS02CH3 2-C1-phenyl 2-(N-azetidinyl-methyl)phenyl 1735 NHS02CH3 2-C1-phenyl 2-(N-piperazinyl-methyl}phenyl 1736 NHS02CH3 2-C1-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1737 NHS02CH3 2-C1-phenyl 2-(N-imidazolyl-methyl)phenyl 1738 NHS02CH3 2-Cl-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1739 NHS02CH3 2-Cl-phenyl 2-(N-pyridonyl-methyl)phenyl 1740 NHS02CH3 2-C1-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1741 NHS02CH3 2-C1-phenyl 2-(amidinyl)phenyl 1742 NHS02CH3 2-C1-phenyl 2-(N-guanidinyl)~henyl 1743 NHS02CH3 2-C1-phenyl 2-(imidazolyl)pnenyi 1744 NHS02CH3 2-C1-phenyl 2-(imidazolidinyl)phenyl 1745 NHS02CH3 2-C1-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1746 NHS02CH3 2-C1-phenyl 2-(2-pyrrolidinyl)phenyl 1747 NHS02CH3 2-Cl-phenyl 2-(2-piperidinyl)phenyl 1748 NHS02CH3 2-CI-phenyl 2-(amidinyl-methyl)phenyl 1749 NHSOZCH3 2-C1-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1750 NHS02CH3 2-C1-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1751 NHS02CH3 2-Cl-phenyl 2-dimethylaminoimidazol-1-yl 1752 NHS02CH3 2-C1-phenyl 2-(3-aminophenyl) 1753 NHS02CH3 2-Cl-phenyl 2-(3-pyrrolidinylcarbonyl) 1754 NHS02CH3 2-Cl-phenyl 2-glycinoyl 1755 NHS02CH3 2-C1-phenyl 2-(imidazol-1-ylacetyl) 1756 NHS02CH3 2-F-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1757 NHS02CH3 2-F-phenyl 2-(N-piperidinyl-methyl)phenyl 1758 NHS02CH3 2-F-phenyl 2-(N-morpholino-methyl)phenyl 1759 NHS02CH3 2-F-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1760 NHS02CH3 2-F-phenyl 2-(N-pyridinium-methyl)phenyl 1761 NHSOZCH3 2-F-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1762 NHS02CH3 2-F-phenyl 2-(N-azatanyl-methyl)phenyl 1763 NHS02CH3 2-F-phenyl 2-(N-azetidinyl-methyl)phenyl 1764 NHS02CH3 2-F-phenyl 2-(N-piperazinyl-methyl)phenyl 1765 NHS02CH3 2-F-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1766 NHSOZCH3 2-F-phenyl 2-(N-imidazolyl-meth~-1)phenyl 1767 NHS02CH3 2-F-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1768 NHS02CH3 2-F-phenyl 2-(N-pyridonyl-methyl)phenyl 1769 NHS02CH3 2-F-phenyl 2-(N-(N',N'-dimethylhydrazinyl-methyl)phenyl 1770 NHSOZCH3 2-F-phenyl 2-(amidinyl)phenyl 1771 NHS02CH3 2-F-phenyl 2-(N-guanidinyl)phenyl 1772 NHSOZCH3 2-F-phenyl 2-(imidazolyl)phenyl 1773 NHS02CH3 2-F-phenyl 2-(imidazolidinyl)phenyl 1774 NHS02CH3 2-F-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1775 NHS02CH3 2-F-phenyl 2-(2-pyrrolidinyl)phenyl 1776 NHS02CH3 2-F-phenyl 2-(2-piperidinyl)phenyl 1777 NHS02CH3 2-F-phenyl 2-(amidinyl-methyl)phenyl 1778 NHS02CH3 2-F-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1779 NHS02CH3 2-F-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1780 NHS02CH3 2-F-phenyl 2-dimethylaminoimidazol-1-yl 1781 NHS02CH3 2-F-phenyl 2-(3-aminophenyl) 1782 NHSOZCH3 2-F-phenyl 2-(3-pyrrolidinylcarbonyl) 1783 NHS02CH3 2-F-phenyl 2-glycinoyl 1784 irFiS02CH32-F-phenyl 2-(imidazol-i-ylacetyl) 1785 L~HS02CH3 2,5-diF-phenyl 2-(N-pyrrolidinyl-methyl)phenyl 1786 NHS02CH3 2,5-diF-phenyl 2-(N-piperidinyl-methyl)phenyl 1787 NHS02CH3 2,5-diF-phenyl 2-(N-morpholino-methyl)phenyl 1788 NHS02CH3 2,5-diF-phenyl 2-(N, N'-methylmorpholinium-methyl)phenyl 1789 NHS02CH3 2,5-diF-phenyl 2-(N-pyridinium-methyl)phenyl 1790 NHS02CH3 2,5-diF-phenyl 2-(N-4-(N, N'-dimethylamino)-pyridinium-methyl)phenyl 1791 NHS02CH3 2,5-diF-phenyl 2-(N-azatanyl-methyl)phenyl 1792 NHS02CH3 2,5-diF-phenyl 2-(N-azetidinyl-methyl)phenyl 1793 NHSOZCH3 2,5-diF-phenyl 2-(N-piperazinyl-methyl)phenyl 1794 NHS02CH3 2,5-diF-phenyl 2-(N, N'-BOC-piperazinyl-methyl)phenyl 1795 NHS02CH3 2,5-diF-phenyl 2-(N-imidazolyl-methyl)phenyl 1796 NHS02CH3 2,5-diF-phenyl 2-(N-methoxy-N-methylamino-methyl)phenyl 1797 NHS02CH3 2,5-diF-phenyl 2-(N-pyridonyl-methyl)phenyl 1798 NHS02CH3 2,5-diF-phenyl 2-(N-(N',N'-dimethylhydrazin~l~-methyl)phenyl 1799 NHS02CH3 2,5-diF-phenyl 2-(amidinyl)phenyl 1800 NHS02CH3 2,5-diF-phenyl 2-(N-guanidinyl)phenyl 1801 NHS02CH3 2,5-diF-phenyl 2-(imidazolyl)phenyl 1802 NHS02CH3 2,5-diF-phenyl 2-(imidazolidinyl)phenyl 1803 NHS02CH3 2,5-diF-phenyl 2-(2-imidazolidinyl-sulfonyl)phenyl 1804 NHS02CH3 2,5-diF-phenyl 2-(2-pyrrolidinyl)phenyl 1805 NHS02CH3 2,5-diF-phenyl 2-(2-piperidinyl)phenyl 1806 NHS02CH3 2,5-diF-phenyl 2-(amidinyl-methyl)phenyl 1807 NHS02CH3 2,5-diF-phenyl 2-(2-imidazolidinyl-methyl)phenyl 1808 NHS02CH3 2,5-diF-phenyl 2-(N-(2-aminoimidazolyl)-methyl)phenyl 1809 NHS02CH3 2,5-diF-phenyl 2-dimethylaminoimidazol-1-yl 1810 NHSOZCH3 2,5-diF-phenyl 2-(3-aminophenyl) 1811 NHS02CH3 2,5-diF-phenyl 2-(3-pyrrolidinylcarbonyl) 1812 NHS02CH3 2,5-diF-phenyl 2-glycinoyl 1813 NHS02CH3 2,5-diF-phenyl 2-(imidazol-1-ylacetyl) Table 3 yRib M ' H
D~E N~A~B
O
R1b R1b p ~',/ ~
w ~ w ~ w R ~ j ~ R ~ j R
D a D b D c a~R=F, D=NH2 bi R=F, D=NH2 c~ R=F, D=NH2 a2R=H, D=NH2 b2 R=H, D=NH2 c2 R=H, D=NH2 a3R=F, D=CH2NH2 b3 R=F, D=CH2NH2 c3 R=F, D=CH2NH2 a4R=H, D=CH2NH2 b4 R=H, D=CH2NH2 c4 R=H, D=CH2NH2 a5R=F, D=C(=NH)NH2b5 R=F, D=C(=NH)NH2c5 R=F, D=C(=NH)NH2 asR=H, D=C(=NH)NH2bs R=H, D=C(=NH)NH2cs R=H, D=C(=NH)NH2 a~R=F, D=C(O)NH2 b~ R=F, D=C(O)NH2 c~ R=F, D=C(O)NH2 a8R=H, D=C(O)NH2 be R=H, D=C(O)NH2 c8 R=H, D=C(O)NH2 1b tb 1b R
d1R=F, D=NH2 ei R=F, D=NH2 f~ R=F, D=NH2 d2R=H, D=NH2 e2 R=H, D=NH2 f2 R=H, D=NH2 d3R=F, D=CH2NH2 e3 R=F, D=CH2NH2 f3 R=F, D=CH2NH2 d4R=H, D=CH2NH2 e4 R=H, D=CH2NH2 f4 R=H, D=CH2NH2 d5R=F, D=C(=NH)NH2e5 R=F, D=C(=NH)NH2f5 R=F, D=C(=NH)NH2 dsR=H, D=C(=NH)NH2es R=H, D=C(=NH)NH2fs R=H, D=C(=NH)NH2 d~R=F, D=C(O)NH2e~ R=F, D=C(O)NH2f~ R=F, D=C(O)NH2 d8R=H, D=C(O)NH2e8 R=H, D=C(O)NH2fe R=H, D=C(O)NH2 R1b R1b R1b jN i~~N I ~N
I
I E ~ I E
.,."~. / ..";",.
D g R p h R i D
g ~ R=F, D=NH2 h 1 R=F, D=NH2 ii Ft=F, D=NH2 g2 R=H, D=NH2 h2 R=H, D=NH2 i2 R=H, D=NH2 g3 R=F, D=CH2NH2 h3 R=F, D=CH2NH2 i3 R=F, D=CH2NH2 g4 R=H, D=CH2NH2 h4 R=H, D=CH2NH2 i4 R=H, D=CH2NH2 g~ R=F, D=C(=NH)NH2 h5 R=F. D=C(=NH)NH2 i5 R=F, D=C(=NH)NH2 g6 R=H, D=C(=NH)NH2 h6 R=H, D=C(=NH)NH2 is R=H, D=C(=NH)NHZ
g~ R=F, D=C(O)NH2 h~ R=F, D=C(O)NH2 i~ R=F, D=C(O)NH2 g8 R=H, D=C(O)NH2 h8 R=H, D=C(O)NH2 i8 R=H, D=C(O)NH2 R1b R1b I ~1 I ~N i'N''N
~N I E ~N I E ~ Rib R ~ .""",. R ~ .""",. ~ '""""
R
D ) D k D I
j1 R=F, D=NH2 ki R=F, D=NHZ 11 R=F, D=NH2 j2 R=H, D=NH2 k2 R=H, D=NH2 12 R=H, D=NH2 j3 R=F, D=CH2NH2 k3 R=F, D=CH2NH2 13 R=F, D=CH2NH2 j4 R=H, D=CH2NH2 k4 R=H, D=CH2NH2 14 R=H, D=CH2NH2 j5 R=F, D=C(=NH)NH2 ks R=F, D=C(=NH)NH2 15 R=F, D=C(=NH}NH2 js R=H, D=C(=NH)NH2 ks R=H, D=C(=NH)NH2 I6 R=H, D=C(=NH)NH2 j~ R=F, D=C(O)NH2 k~ R=F, D=C(O)NH2 h R=F, D=C(O)NH2 j$ R=H, D=C(O)NH2 kg R=H, D=C(O)NH2 18 R=H, D=C(O)NH2 Rib N,N~RIb N~N Rib N
'' N
i i iN ~ I iN ~ I iN
R I i ~ R ~ i ~ R I i D m D n D o mi R=F, D=NH2 n~ R=F, D=NH2 0~ R=F, D=NH2 m2 R=H, D=NH2 n2 R=H, D=NH2 02 R=H, D=NH2 m3 R=F, D=CH2NH2 n3 R=F, D=CH2NH2 03 R=F, D=CH2NH2 m4 R=H, D=CH2NH2 n4 R=H, D=CH2NH2 04 R=H, D=CH2NH2 m5 R=F, D=C(=NH)NH2n5 R=F, D=C(=NH)NH205 R=F, D=C(=NH)NH2 ms R=H, D=C(=NH)NH2ns R=H, D=C(=NH)NH2os R=H, D=C(=NH)NH2 m~ R=F, D=C(O)NH2n~ R=F, D=C(O)NH20~ R=F, D=C(O}NH2 m8 R=H, D=C(O)NH2ne R=H, D=C(O)NH2oa R=H, D=C(O)NH2 /R1b ib 1b R ~ \ / R R
D P
pi R=F, D=NH2 qi R=F, D=NH2 ri R=F, D=NH2 p2 R=CI, D=NH2 q2 R=CI, D=NH2 r2 R=CI, D=NH2 p3 R=OMe, D=NH2 q3 R=OMe, D=NH2 r3 R=OMe, D=NH2 p4 R=F, D=CH2NH2 q4 R=F, D=CH2NH2 r4 R=F, D=CH2NH2 p5 R=CI D=CH2NH2 q5 R=CI, D=CH2NH2 rs R=CI, D=CH2NH2 ps R=OMe, D=CH2NH2 qs R=OMe, D=CHZNH2 rs R=OMe, D=CH2NH2 p~ R=F, D=C(=NH)NH2 q~ R=F, D=C(=NH)NH2 r~ R=F, D=C(=NH)NH2 p$ R=Cl, D=C(=NH)NH~ q8 R=CI, D=C(=NH)NH2 r$ R=Ci, D=C(=NH)NH2 p9 R=OMe, D=C(=NH)NH2 q9 R=OMe, D=C(=NH)NH2 r9 R=OMe, D=C(=NH)NH2 Pio R=F, D=C(O)NH2 qio R=F, D=C(O)NH2 rio R=F, D=C(O)NH2 P11 R=CI, D=C(O)NH2 qi1 R=C1, D=C(O)NH2 ri1 R=CI, D=C(O)NH2 P12 R=OMe, D=C(O)NH~ q12 R=OMe, D=C(O)NH2 r12 R=OMe, D=C(O)NH2 ib ib N' , R1b ~V/~~
R \ I /
D a si R=F, D=NHZ ti R=F, D=NH2 ui R=F, D=NH2 s2 R=CI, D=NH2 t2 R=CI, D=NH2 u2 R=CI, D=NH2 s3 R=OMe, D=NH2 t3 R=OMe, D=NH2 u3 R=OMe, D=NH2 s4 R=F, D=CH2NH2 t4 R=F, D=CH2NH2 u4 R=F, D=CH2NH2 ss R=CI, D=CH2NH2 t5 R=CI, D=CH2NH2 us R=CI, D=CH2NH2 ss R=OMe, D=CH2NH2 is R=OMe, D=CH2NH2 us R=OMe, D=CH2NH2 s~ R=F, D=C(=NH)NH2 t~ R=F, D=C(=NH)NH2 u~ R=F, D=C(=NH)NH2 s8 R=Cl, D=C(=NH)NH2 to R=CI, D=C(=NH)NH2 u8 R=CI, D=C(=NH)NH2 s9 R=OMe, D=C(=NH)NH2 t9 R=OMe, D=C(=NH)NH2 u9 R=OMe, D=C(=NH)NH2 sio R=F, D=C(O)NH2 do R=F, D=C(O)NH2 uio R=F, D=C(O)NH2 sii R=CI, D=C(O)NH2 tii R=Ci, D=C(O)NH2 uii R=CI, D=C(O)NH2 s12 R=OMe, D=C(O)NH~ t12 R=OMe, D=C(O)NH2 u12 R=OMe, D=C(O)NH2 R NI~~N'b 1 ib Rib /' N
\ / R \ iN R
j D v D w D x vi R=F, D=NH2 wi R=F, D=NH2 xi R=F, D=NH2 v2 R=CI, D=NH2 w2 R=CI. D=NH2 x2 R=CI, D=NH2 v3 R=OMe, D=NH2 w3 R=OMe, D=NH2 x3 R=OMe, D=NH2 v4 R=F, D=CH2NH2 w4 R=F, D=CHpNH2 x4 R=F, D=CH2NH2 vs R=CI, D=CH2NH2 w5 R=CI, D=CH2NH2 x5 R=CI, D=CH2NH2 vs R=OMe, D=CH2NH2 ws R=OMe, D=CH2NH2 xs R=OMe, D=CH2NH2 v~ R=F, D=C(=NH)NH2 w~ R=F, D=C(=NH)NH2 x~ R=F, D=C(=NH)NH2 ve R=CI, D=C(=NH)NH2 we R=CI, D=C(=NH)NH2 xe R=CI, D=C(=NH)NH2 v9 R=OMe, D=C(=NH)NH2 w9 R=OMe, D=C(=NH)NH2 x9 R=OMe, D=C(=NH)NH2 vio R=F, D=C(O)NH2 ,J,~~o R=F, D=C(O)NH2 x1o R=F, D=C(O)NH2 v> > R=CI, D=C(O)NH2 ~"~ 1 R=CI D=C(O)NH2 x> > R=CI, D=C(O)NH2 vie R=OMe, D=C(O)NH2 w~2 R=OMe, D=C(O)NH2 x~2 R=OMe, D=C(O)NH2 N. R1b tb N~N''N
~N R I E I / Rib /
/
p Y D as yi R=F D=NH2 zi R=F, D=NH2 aa~ R=F, D=NH2 y2 R=CI, D=NH2 z2 R=CI, D=NH2 aa2 R=CI, D=NH2 y3 R=OMe, D=NH2 z3 R=OMe, D=NH2 aa3 R=OMe, D=NH2 y4 R=F D=CH2NH2 z4 R=F, D=CH2NH2 aa4 R=F, D=CH2NH2 y5 R=CI D=CH2NH2 z$ R=CI, D=CH2NH2 aas R=CI, D=CH2NH2 ys R=OMe, D=CH2NH2 zs R=OMe, D=CH2NH2 aas R=OMe, D=CH2NH2 y~ R=F, D=C(=NH)NH2 z~ R=F, D=C(=NH)NH2 aa~ R=F, D=C(=NH)NH2 ys R=CI, D=C(=NH)NH2 z8 R=CI, D=C(=NH)NH2 aa8 R=CI, D=C(=NH)NH2 y9 R=OMe, D=C(=NH)NH2 z9 R=OMe, D=C(=NH)NH2 aa9 R=OMe, D=C(=NH)NH2 Y1o R=F, D=C(O)NH2 zoo R=F, D=C(O)NH2 aalo R=F, D=C(O)NH2 y1 ~ R=CI, D=C(O)NH2 zi ~ R=CI, D=C(O)NH2 aa1 y R=CI, D=C(O)NH2 yi2 R=OMe, D=C(O)NH2 ~i2 R=OMe, D=C(O)NH2 aa~2 R=OMe, D=C(O)NH2 Rib Rib N.
R I ~~' I
.".
D dd bbi R=F, D=NH2 cc~ R=F, D=NH2 dd~ R=F, D=NH2 bb2 R=CI, D=NH2 cc2 R=Cl, D=NH2 dd2 R=CI, D=NH2 bb3 R=OMe, D=NH2 cc3 R=OMe, D=NH2 dd3 R=OMe, D=NH2 bb4 R=F, D=CH2NH2 cc4 R=F, D=CH2NH2 dd4 R=F, D=CH2NH2 bb5 R=CI, D=CH2NH2 cc5 R=CI, D=CH2NH2 dd~ R=CI, D=CH2NH2 bb6 R=OMe, D=CH2NH2 ccs R=OMe, D=CH2NH2 dds R=OMe, D=CH2NH2 bb~ R=F, D=C(=NH)NH2 cc~ R=F, D=C(=NH)NH2 dd~ R=F, D=C(=NH)NH2 bbe R=CI, D=C(=NH)NH2 cce R=CI, D=C(=NH)NH2 ddb R=CI, D=C(=NH)NH2 bb9 R=OMe, D=C(=NH)NH2 cc9 R=OMe, D=C(=NH)NH2 dd9 R=OMe, D=C(=NH)NH2 bbio R=F, D=C(O)NH2 ccla R=F, D=C(O)NH2 dd~o R=F, D=C(O)NH2 bb> > R=Ci, D=C(O)NH2 cci i R=CI, D=C(O)NH2 ddi ~ R=CI, D=C(O)NH2 bbi2 R=OMe, D=C(O)NH2 ccl2 R=OMe, D=C(O)NH2 ddi2 R=OMe, D=C(O)NH2 Rib Rib Rib R I / R ~~~ R
\ / \ / \
/ .""". /
I /
D ee ff 99 eel R=F, D=CH2NH2 ffi R=F, D=CH2NH2 gg~ R=F, D=CH2NH2 ee2 R=CI, D=CH2NH2 ff2 R=CI, D=CH2NH2 gg2 R=CI, D=CH2NH2 ee3 R=OMe, D=CH2NH2 ff3 R=OMe, D=CH2NH2 gg3 R=OMe, D=CH2NH2 ee4 R=CHpNH2, ff4 R=CH2NH2, gg4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 1b R I ~N R I /1 ~b I R1b R N' \ / \ i N ,,~
I~ ~ I
D hh D ii D 1J
hh~ R=F, D=CH2NH2 iii R=F, D=CH2NH2 jj~ R=F, D=CH2NHp hh2 R=CI, D=CH2NH2 ii2 R=CI, D=CH2NH2 jj2 R=CI, D=CH2NHp hh3 R=OMe, D=CH2NH2 iii R=OMe, D=CH2NH2 jj3 R=OMe, D=CH2NH2 hh4 R=CH2NHp, ii4 R=CH2NH2, jj4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib Rib Rib N i'jN R ~ i'/N R I /' N
E
IE
.""",.
D kk D II mm D
kk~ R=F, D=CH2NH2 111 R=F, D=CH2NH2 mmi R=F, D=CH2NH2 kk2 R=CI, D=CH2NH2 112 R=CI, D=CH2NH2 mm2 R=CI, D=CH2NH2 kk3 R=OMe, D=CH2NH2 113 R=OMe, D=CH2NH2 mm3 R=OMe, D=CH2NH2 kk4 R=CH2NH2, 114 R=CH2NH2, mm4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 R I ~1 1b R I /N ~b R N,N''N
iN ~ iN ~ I
tb I ~ I ~ ~ ~ I ~ ~' 'R
D nn D oo D PP
nn~ R=F, D=CH2NH2 ooi R=F, D=CH2NH2 ppi R=F, D=CH2NH2 nn2 R=CI, D=CH2NH2 002 R=CI, D=CH2NH2 pp2 R=CI, D=CH2NH2 nn3 R=OMe, D=CH2NH2 003 R=OMe, D=CH2NH2 pp3 R=OMe, D=CH2NH2 nn4 R=CH2NH2 004 R=CH2NH2, pp4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2iJH2 Rib ,N R1b Rib N
R N ~ R N ~N R ''N
w I iN ~ I iN I i ,N
I~ 1~ I~ 1~ I, D qq D rr D ss R=F D=CH2NH2 rr1 R=F, D=CH2NH2 ss~ R=F, D=CH2NH2 qq2 R=C! D=CH2NH2 rr2 R=CI, D=CH2NH2 ss2 R=CI, D=CH2NH2 qq3 R=OMe, D=CH2NH2 rr3 R=OMe, D=CH2NH2 ss3 R=OMe, D=CH2NH2 qq4 R=CH2NH2, rr4 R=CH2NH2, ss4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NHp Ex# Ru' A g 1 H phenyl 2-((Me)2N-methyl)phenyl 2 H phenyl 2-((Me)NH-methyl)phenyl 3 H phenyl 2-(H2N-methyl)phenyl 4 H phenyl 2-HOCH2-phenyl 5 H 2-F-phenyl 2-((Me)2N-methyl)phenyl 6 H 2-F-phenyl 2-((Me)NH-methyl)phenyl 7 H 2-F-phenyl 2-(H2N-methyl)phenyl 8 H 2-F-phenyl 2-HOCH2-phenyl 9 H phenyl 2-methylimidazol-1-yl 10 H phenyl 2-ethylimidazol-1-yl 11 H phenyl 2-((Me)2N-methyl)imidazol-1-yl 12 H phenyl 2-CH3S02-imidazol-1-yl 13 H phenyl 2-CH30CH2-imidazol-1-yl 14 H 2-F-phenyl 2-methylimidazol-1-yl 15 H 2-F-phenyl 2-ethylimidazol-1-yl 16 H 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 17 H 2-F-phenyl 2-CH3S02-imidazol-1-yl 18 H 2-F-phenyl 2-CH30CH2-imidazol-1-yl 19 H 2-C~.-phenyl 2-methylimidazol-1-yl 20 H 2-C1-phenyl 2-ethylimidazol-1-yl 21 H 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 22 H 2-C1-phenyl 2-CH3S02-imidazol-1-yl 23 H 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 24 H 2-(Me)2N-phenyl 2-methylimidazol-1-yl 25 H 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 26 H 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 27 H 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 28 H 2-(Me)2N-phenyl 2-CH30CH~-imidazol-1-yl 29 H phenyl N-methylimidazol-2-yl 30 H phenyl 4-methylimidazol-5-yl 31 H phenyl 5-CF3-pyrazol-1-yl 32 H 2-F-phenyl N-methylimidazol-2-yl 33 H 2-F-phenyl 4-methylimidazol-5-yl 34 H 2-F-phenyl 5-CF3-pyrazol-1-yl 35 H phenyl guanidino 36 H phenyl 2-thiazolin-2-ylamine 37 H phenyl N-methyl-2-imidazolin-2-yl 38 H phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 39 H phenyl N-methylimidazol-2-ylthiol 40 H phenyl t-butoxycarbonylamine 41 H phenyl (N-pyrrolidino)forrnylimino 42 H phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 43 H 2-F-phenyl guanidino 44 H 2-F-phenyl 2-thiazolin-2-ylamine 45 H 2-F-phenyl N-methyl-2-imidazolin-2-yl 46 H 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 47 H 2-F-phenyl N-methylimidazol-2-ylthio 48 H 2-F-phenyl t-butoxycarbonylamine 49 H 2-F-phenyl (N-pyrrolidino)formylimino H 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 51 H 2-CH30-phenyl (N-pyrrolidino)formylimino 52 H 2-CH30-phenyl (N-pyrrolidino)formyl-N-45 (methanesuifamoyl)imino 53 -CN phenyl 2-((Me)2N-methyl)phenyl 54 -CN phenyl 2-((Me)NH-methyl)phenyl -CN phenyl 2-(H2N-methyl)phenyl 56 -CN phenyl 2-HOCH2-phenyl 50 57 -CN 2-F-phenyl 2-((Me)2N-methyl)phenyl 58 -CN 2-F-phenyl 2-((Me)NH-methyl)phenyl 59 -CN 2-F-phenyl 2-(H2N-methyl)phenyl -CN 2-F-phenyl 2-HOCH2-phenyl 61 -CN phenyl 2-methylimidazol-1-yl 55 62 -CN phenyl 2-ethylimidazol-1-yl 63 -CN phenyl 2-((Me)2N-methyl)imidazol-1-yI

64 -CN phenyl 2-CH3S02-imidazol-1-yl 65 -CN phenyl 2-CH30CH2-imidazol-1-yl 66 -CN 2-F-phenyl 2-methylimidazol-1-yl S 67 -CN 2-F-phenyl 2-ethylimidazol-1-yl 68 -CN 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 69 -CN 2-F-phenyl ?--;.H3S0~-imidazol-1-yl 70 -CN 2-F-phenyl G-~i-i30CH2-imidazol-1-yl 71 -CN 2-C1-phenyl 2-methylimidazol-1-yl 72 -CN 2-C1-phenyl 2-ethylimidazol-1-yl 73 -CN 2-C1-phenyl 2-((Me)zN-methyl)imidazol-1-yl 74 -CN 2-C1-phenyl 2-CH3S02-imidazol-1-yl 75 -CN 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 76 -CN 2-(Me)2N-phenyl 2-methylimidazol-1-yl 77 -CN 2-(Me)ZN-phenyl 2-ethylimidazol-1-yl 78 -CN 2-(Me)~N-phenyl 2-((Me)ZN-methyl)imidazol-1-yl 79 -CN 2-(Me)2N-phenyl 2-CH3S0z-imidazol-1-yl 80 -CN 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 81 -CN phenyl N-methylimidazol-2-yl 82 -CN phenyl 4-methylimidazol-5-yl 83 -CN phenyl 5-CF3-pyrazol-1-yl 84 -CN 2-F-phenyl N-methylimidazol-2-yl 85 -CN 2-F-phenyl 4-methylimidazol-5-yl 86 -CN . 2-F-phenyl 5-CF3-pyrazol-1-yl 87 -CN phenyl guanidino 88 -CN phenyl 2-thiazolin-2-ylamine 89 -CN phenyl N-methyl-2-imidazolin-2-yl 90 -CN phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 91 -CN phenyl N-methylimidazol-2-ylthiol 92 -CN phenyl t-butoxycarbonylamine 93 -CN phenyl (N-pyrrolidino)formylimino 94 -CN phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 95 -CN 2-F-phenyl guanidino 96 -CN 2-F-phenyl 2-thiazolin-2-ylamine 97 -CN 2-F-phenyl N-methyl-2-imidazolin-2-yl 98 -CN 2-F-phenyl N-met:zyl-1,4,5,6-tetrahydropyrimid-2-yl 99 -CN 2-F-phenyl N-methylimidazol-2-ylthio 100 -CN 2-F-phenyl t-butoxycarbonylamine 101 -CN 2-F-phenyl (N-pyrrolidino)formylimino 102 -CN 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 103 -CN 2-CH30-phenyl (N-pyrrolidino)formylimino 104 -CN 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 105 CF3 phenyl 2-((Me)2N-methyl)phenyl 106 CF3 phenyl 2-((Me)NH-methyl)phenyl 107 CF3 phenyl 2-(H2N-methyl)phenyl 108 CF3 phenyl 2-HOCH2-phenyl 109 CF3 2-F-phenyl 2-((Me)2N-methyl)phenyl 110 CF3 2-F-phenyl 2-((Me)NH-methyl)phenyl 111 CF3 2-F-phenyl 2-(H2N-methyl)phenyl 112 CF3 2-F-phenyl 2-HOCH2-phenyl 113 CF3 phenyl 2-methylimidazol-1-yl 114 CF3 phenyl 2-ethylimidazol-1-yl 115 CF3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 116 CF3 phenyl 2-CH3S02-imidazol-1-yl 117 CF3 phenyl 2-CH30CHZ-imidazol-1-yl lla CF3 2-F-phenyl 2-methylimidazol-1-yl 119 CF3 2-F-phenyl 2-ethylimidazol-1-yl 120 CF3 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 121 CF3 2-F~phenyl 2-CH3S02-imidazol-1-yl 122 CF3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 123 CF3 2-C1-phenyl 2-methylimidazol-1-yl 124 CF3 2-C1-phenyl 2-ethylimidazol-1-yl 125 CF3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 126 CF3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 127 CF3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 12$ CF3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 129 CF3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 130 CF3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 131 CF3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 132 CF3 2-(Me)ZN-phenyl 2-CH30CHZ-imidazol-1-yI

133 CF3 phenyl N-methylimidazol-2-yl 134 CF3 phenyl 4-methylimidazol-5-yl 135 CF3 phenyl 5-CF3-pyrazol-1-yl 136 CF3 2-F-phenyl N-methylimidazol-2-yl 137 CF3 2-F-phenyl 4-methylimidazol-5-yl 138 CF3 2-F-phenyl 5-CF3-pyrazol-1-yl 139 CF3 phenyl guanidino 140 CF3 phenyl 2-thiazolin-2-ylamine 141 CF3 phenyl N-methyl-2-imidazolin-2-yl 142 CF3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 143 CF3 phenyl N-methylimidazol-2-ylthiol 144 CF3 phenyl t-butoxycarbonylamine 145 CF3 phenyl (N-pyrrolidino)formylimino 146 CF3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 147 CF3 2-F-phenyl guanidino 148 CF3 2-F-phenyl 2-thiazolin-2-ylamine 149 CF3 2-F-phenyl N-methyl-2-imidazolin-2-yl 150 CF3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 151 CF3 2-F-phenyl N-methylimidazol-2-ylthio 152 CF3 2-F-phenyl t-butoxycarbonylamine 153 CF3 2-F-phenyl (N-pyrrolidino)formylimino 154 CF3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 155 CF3 2-CH30-phenyl (N-pyrrolidino)formylimino 156 CF3 2-Ci-i30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 157 CONHZ phenyl 2-((Me)2N-methyl)phenyl 158 CONH2 phenyl 2-((Me)NH-methyl)phenyl 159 CONH2 phenyl 2-(H2N-methyl)phenyl 160 CONH2 phenyl 2-HOCH
2-phenyl 161 CONH~ 2-F-phenyl 2-((Me)~N-methyl)phenyl 162 CONH2 2-F-phenyl 2-((Me)NH-methyl)phenyl 163 CONH2 2-F-phenyl 2-(HZN-methyl)phenyl 164 CONH2 2-F-phenyl 2-HOCH2-phenyl 165 CONH~ phenyl 2-methylimidazo.l-1-yl 166 CONH2 phenyl 2-ethylimidazol-1-yl 167 CONH2 phenyl 2-((Me)2N-methyl)imidazol-1-yl 168 CONH2 phenyl 2-CH3S02-imidazol-1-yl 169 CONH2 phenyl 2-CH30CH~-imidazol-1-yl 170 CONH2 2-F-phenyl 2-methylimidazol-1-yl 171 CONH2 2-F-phenyl 2-ethylimidazol-1-yl 172 CONH2 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 173 CONH2 2-F-phenyl 2-CH3S02-imidazol-1-yl 174 CONH2 2-F-phenyl 2-CH30CH2-imidazol-1-yl 175 CONH2 2-C1-phenyl 2-methylimidazol-1-yl 176 CONH2 2-C1-phenyl 2-ethylimidazol-1-yl 177 CONH2 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 178 CONH2 2-C1-phenyl 2-CH3S0~-imidazol-1-yl 179 CONHz 2-C1-phenyl 2-CH30CH~-imidazol-1-yl 180 CONH2 2-(Me)ZN-phenyl 2-methylimidazol-1-yl 181 CONH2 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 182 CONH2 2-(Me)2N-phenyl 2-((Me)~N-methyl)imidazol-1-yl 183 CONH2 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 184 CONH2 2-(Me)ZN-phenyl 2-CH30CH2-imidazol-1-yl 185 CONH2 phenyl N-methylimidazol-2-yl 186 CONHZ phenyl 4-methylimidazol-5-yl 187 CONH2 phenyl 5-CF3-pyrazol-1-yl 188 CONH2 2-F-phenyl N-methylimidazol-2-yl 189 CONH2 2-F-phenyl 4-methylimidazol-5-yl 190 CONH2 2-F-phenyl 5-CF3-pyrazol-1-yl 191 CONH2 phenyl guanidino 192 CONH2 phenyl 2-thiazolin-2-ylamine 193 CONH2 phenyl N-methyl-2-imidazolin-2-yl 194 CONH2 phenyl N-methyl-1,4,5,6-r m 195 CONH2 phenyl N-methylimidazol ythiol 196 CONH2 phenyl t-butoxycarbonylamine 197 CONH2 phenyl (N-pyrrolidino)formylimino 198 CONH2 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 199 CONH2 2-F-phenyl guanidino 200 CONH2 2-F-phenyl 2-thiazolin-2-ylamine 201 CONH2 2-F-phenyl N-methyl-2-imidazolin-2-yl 202 CONH2 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 203 CONH2 2-F-phenyl N-methylimidazol-2-ylthio 204 CONH2 2-F-phenyl t-butoxycarbonylamine 205 CONH2 2-F-phenyl (N-pyrrolidino)formylimino 206 CONH2 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 207 CONH2 2-CH30-phenyl (N-pyrrolidino)formylimino 208 CONHZ 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 209 SCH3 phenyl 2-((Me)2N-methyl)phenyl 210 SCH3 phenyl 2-((Me)NH-methyl)phenyl 211 SCH3 phenyl 2-(H2N-methyl)phenyl 212 SCH3 phenyl 2-HOCH2-phenyl 213 SCH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 214 SCH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 215 SCH3 2-F-phenyl 2-(H2N-methyl)phenyl 216 SCH3 2-F-phenyl 2-HOCH2-phenyl 217 SCH3 phenyl 2-methylimidazol-1-yl 218 SCH3 phenyl 2-ethylimidazol-1-yl 219 SCH3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 220 SCH3 phenyl 2-CH3S02-imidazol-1-yl 221 SCH3 phenyl 2-CH30CH2-imidazol-1-yl 222 SCH3 2-F-phenyl 2-methylimidazol-1-yl 223 SCH3 2-F-phenyl 2-ethylimidazol-1-yl 224 SCH3 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 225 SCH3 2-F-phenyl 2-CH3S02-imidazol-1-yl 226 SCH3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 227 SCH3 2-C1-phenyl 2-methylimidazol-1-yl 228 SCH3 2-C1-phenyl 2-ethylimidazol-1-yl 229 SCH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 230 SCH3 2-C1-phenyl 2-CH35u2-imidazol-1-yi 231 SCH3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 232 SCH3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 233 SCH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 234 SCH3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 235 SCH3 2-(Me)zN-phenyl 2-CH3S02-imidazol-1-yl 236 SCH3 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 237 SCH3 phenyl N-methylimidazol-2-yl 238 SCH3 phenyl 4-methylimidazol-5-yl 239 SCH3 phenyl 5-CF3-pyrazol-1-yl 240 SCH3 2-F-phenyl N-methylimidazol-2-yl 241 SCH3 2-F-phenyl 4-methylimidazol-5-yl 242 SCH3 2-F-phenyl 5-CF3-pyrazol-1-yl 243 SCH3 phenyl guanidino 244 SCH3 phenyl 2-thiazolin-2-ylamine 245 SCH3 phenyl N-methyl-2-imidazolin-2-yl 246 SCH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 247 SCH3 phenyl N-methylimidazol-2-ylthiol 248 SCH3 phenyl t-butoxycarbonylamine 249 SCH3 phenyl (N-pyrrolidino)formylimino 250 SCH3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 251 SCH3 2-F-phenyl guanidino 252 SCH3 2-F-phenyl 2-thiazolin-2-ylamine 253 SCH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 254 SCH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 255 SCH3 2-F-phenyl N-methylimidazol-2-ylthio 256 SCH3 2-F-phenyl t-butoxycarbonylamine 257 SCH3 2-F-phenyl (N-pyrrolidino)formylimino 258 SCH3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 259 SCH3 2-CH;O-phenyl (N-pyrrolidino)formylimino 260 SCH3 2-CH30-phenyl (N-pyrrolidino)for~nyl-N-(methanesultan~oyl) imino 261 S02CH3 phenyl 2-((Me)ZN-methyl)phenyl 262 S02CH3 phenyl 2-((Me)NH-methyl)phenyl 263 S02CH3 phenyl 2-(H2N-methyl)phenyl 264 S02CH3 phenyl 2-HOCH
2-phenyl 265 S02CH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 266 S02CH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 267 S02CH3 2-F-phenyl 2-(H2N-methyl)phenyl 268 S02CH3 2-F-phenyl 2-HOCH2-phenyl 269 S02CH3 phenyl 2-methylimidazol-1-yl 270 S02CH3 phenyl 2-ethylimidazol-1-yl 271 S02CH3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 272 SO2CH3 phenyl 2-CH3S02-imidazol-1-yl 273 SOZCH3 phenyl 2-CH30CH2-imidazol-1-yl 274 S02CH3 2-F-phenyl 2-methylimidazol-1-yl 275 S02CH3 2-F-phenyl 2-ethylimidazol-1-yl 276 S02CH3 2-F-phenyl 2-((Me)ZN-methyl)imidazol-1-yl 277 S02CH3 2-F-phenyl 2-CH3S02-im:iua2ol-1-yl 278 S02CH3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 279 S02CH3 2-C1-phenyl 2-methylimidazol-1-yl 280 S02CH3 2-C1-phenyl 2-ethylimidazol-1-yl 281 S02CH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 282 S02CH3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 283 S02CH3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 284 S02CH3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 285 S02CH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 286 S02CH3 2-(Me)2N-phenyl 2-((Me)zN-methyl)imidazol-1-yl 287 S02CH3 2-(Me)ZN-phenyl 2-CH3S02-imidazol-1-yl 288 S02CH3 2-(Me)zN-phenyl 2-CH30CH2-imidazol-1-yl 289 S02CH3 phenyl N-methylimidazol-2-yl 290 S02CH3 phenyl 4-methylimidazol-5-yl 291 S02CH3 phenyl 5-CF3-pyrazol-1-yl 292 SOZCH3 2-F-phenyl N-methylimidazol-2-yl 293 S02CH3 2-F-phenyl 4-methylimidazol-5-yl 294 S02CH3 2-F-phenyl 5-CF3-pyrazol-1-yl 295 S02CH3 phenyl guanidino 296 S02CH3 phenyl 2-thiazolin-2-ylamine 297 S02CH3 phenyl N-methyl-2-imidazolin-2-yl 298 S02CH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 299 S02CH3 phenyl N-methylimidazol-2-ylthiol 300 S02CH3 phenyl t-butoxycarbonylamine 301 S02CH3 phenyl (N-pyrrolidino)formylimino 302 S02CH3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 303 S02CH3 2-F-phenyl guanidino 304 S02CH3 2-F-phenyl 2-thiazolin-2-ylamine 305 S02CH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 306 S02CH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 307 S02CH3 2-F-phenyl N-methylimidazol-2-ylthio 308 302CH3 2-F-phenyl t-butoxycarbonylamine 309 S02CH3 2-F-phenyl (N-pyrrolidino)formylimino 310 S02CH3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 311 S02CH3 2-CH30-phenyl (N-pyrrolidino)formylimino 312 S02CH3 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 313 NHS02CH3 phenyl 2-((Me)2N-methyl)phenyl 314 NHS02CH3 phenyl 2-((Me)NH-methyl)phenyl 315 NHSOZCH3 phenyl 2-(H2N-methyl)phenyl 316 NHS02CH3 phenyl 2-HOCH2-phenyl 317 NHS02CH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 318 NHS02CH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 319 NHS02CH3 2-F-phenyl 2-(H2N-methyl)phenyl 320 NHS02CH3 2-F-phenyl 2-HOCH2-phenyl 321 NHS02CH3 phenyl 2-methylimidazol-1-yl 322 NHS02CH3 phenyl 2-ethylimidazol-1-yl 323 NHS02CH3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 324 NHS02CH3 phen~-1 2-CH3S02-imidazol-1-yl 325 NHS02CH3 phenyl 2-CH30CH2-imidazol-1-yl 326 NHS02CH3 2-F-phenyl 2-methylimidazol-1-yl 327 NHS02CH3 2-F-phenyl 2-ethylimidazol-1-yl 328 NHS02CH3 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 329 NHS02CH3 2-F-phenyl 2-CH3S02-imidazol-1-yl 330 NHS02CH3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 331 NHS02CH3 2-C1-phenyl 2-methylimidazol-1-yl 332 NHS02CH3 2-C1-phenyl 2-ethylimidazol-1-yl 333 NHS02CH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 334 NHS02CH3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 335 NHS02CH3 2-Cl-phenyl 2-CH30CH2-imidazol-1-yl 336 NHS02CH3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 337 N'HS02CH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 338 NHS02CH3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 339 NHS02CH3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 340 NHS02CH3 2-(Me)ZN-phenyl 2-CH30CH2-imidazol-1-yl 341 NHS02CH3 phenyl N-methylimidazol-2-yl 342 NHS02CH3 phenyl 4-methylimidazol-5-yl 343 NHS02CH3 phenyl 5-CF3-pyrazol-1-yl 344 NHS02CH3 2-F-phenyl N-methylimidazol-2-yl 345 NHS02CH3 2-F-phenyl 4-methylimidazol-5-yl 346 NHS02CH3 2-F-phenyl 5-CF3-pyrazol-1-yl 347 NHS02CH3 phenyl guanidino 348 NHS02CH3 phenyl 2-thiazolin-2-ylamine 349 NHS02CH3 phenyl N-methyl-2-irnidazolin-2-yl 350 NHS02CH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 351 NHS02CH3 phenyl N-methylimidazol-2-ylthiol 352 NHS02CH3 phenyl t-butoxycarbonylamine 353 NHS02CH3 phenyl (N-pyrrolidino)forrnylimino 354 NHS02CH3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 355 NHS02CH3 2-F-phenyl guanidino 356 NHS02CH3 2-F-phenlrl 2-thiazolin-2-ylamine 357 NHS02CH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 358 NHS02CH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 359 NHS02CH3 2-F-phenyl N-methylimidazol-2-ylthio 360 NHS02CH3 2-F-phenyl t-butoxycarbonylamine 361 NHS02CHz 2-F-phenyl (N-pyrrolidino)formylimino 362 NHS02CH3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 363 NHS02CH3 2-CH30-phenyl (N-pyrrolidino)formylimino 364 NHS02CH3 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino Table 4 yR~b M ' H
N~A~B
O
R1b Rtb Rtb I~ ~',/ I%
R R I j ~ R I j D a D b D c a~R=F, D=NH2 b~ R=F, D=NH2 c1 R=F, D=NH2 a2R=H, D=NH2 b2 R=H, D=NH2 c2 R=H, D=NH2 a3R=F, D=CH2NH2 b3 R=F, D=CH2NH2 c3 R=F, D=CH2NH2 a4R=H, D=CH2NH2 b4 R=H, D=CH2NH2 c4 R=H, D=CH2NH2 asR=F, D=C(=NH)NH2bs R=F, D=C(=NH)NH2c5 R=F, D=C(=NH)NH2 asR=H, D=C(=NH)NH2bs R=H, D=C(=NH)NH2cs R=H, D=C(=NH)NH2 a~R=F, D=C(O)NH2 b~ R=F, D=C(O)NH2 c~ R=F, D=C(O)NH2 aeR=H, D=C(O)NHZ bs R=H, D=C(O)NH2 ce R=H, D=C(O)NH2 1b 1b I ~N
I j R
D d d~R=F, D=NH2 e1 R=F, D=NH2 f~R=F, D=NH2 d2R=H, D=NH2 e2 R=H, D=NH2 f2R=H, D=NH2 d3R=F, D=CH2NH2 e3 R=F, D=CH2NH2 f3R=F, D=CH2NH2 d4R=H, D=CH2NH2 e4 R=H, 0=CH2NH2 f4R=H, D=CH2NH2 d5R=F, D=C(=NH)NH2es R=F, D=C(=NH)NH2fsR=F, D=C(=NH)NH2 dsR=H, D=C(=NH)NH2es R=H, D=C(=NH)NH2fsR=H, D=C(=NH)NH2 d~R=F, D=C(O)NH2 e~ R=F, D=C(O)NH2 f~R=F, D=C(O)NH2 dgR=H, D=C(O)NH2 ee R=H, D=C(O)NH2 fsR=H, D=C(O)NH2 N~/N ~b Rib Rib \ I ~ ~~~N I /' N
\ \
R I ~ ~ I ~ ,~~,~ I
R
D g R p h D i gi R=F, D=NH2 hi R=F, D=NH2 i~ R=F, D=NH2 g2 R=H, D=NH2 h2 R=H, D=NH2 i2 R=H, D=NH2 g3 R=F, D=CH2NH2 h3 R=F, D=CH2NH2 i3 R=F, D=CH2NH2 g4 R=H, D=CH2NH2 h4 R=H, D=CH2NH2 i4 R=H, D=CH2NH2 g5 R=F, D=C(=NH)NH2 h5 R=F, D=C(=NH)NH2 i5 R=F, D=C(=NH)NH2 gs R=H, D=C(=NH)NHp hs R=H, D=C(=NH)NH2 is R=H, D=C(=NH)NH2 g~ R=F, D=C(O)NH2 h~ R=F, D=C(O)NH2 i~ R=F, D=C(O)NH2 g8 R=H, D=C(O)NH2 hg R=H, D=C(O)NH2 i8 R=H, D=C(O)NH2 I ~1 I ~N'b N~N'~N
\ iN \ iN \ I
R ( j ~ R I j ~ R I j ~ 'R1b D 1 D k D I
R=F, D=NH2 k~ R=F, D=NH2 li R=F, D=NH2 j2 R=H, D=NHp k2 R=H, D=NH2 12 R=H, D=NH2 j3 R=F, D=CH2NH2 k3 R=F, D=CH2NH2 13 R=F, D=CH2NH2 j4 R=H, D=CH2NH2 k4 R=H, D=CH2NH2 14 R=H, D=CH2NH2 j5 R=F, D=C(=NH)NH2 k5 R=F, D=C(=NH)NH2 IS R=F, D=C(=NH)NH2 js R=H, D=C(=NH)NH2 ks R=H, D=C{=NH)NH2 I6 R=H, D=C(=NH)NH2 j~ R=F, D=C(O)NH2 k~ R=F, D=C(O)NH2 h R=F, D=C(O)NH2 ja R=H, D=C(O)NHp ke R=H, D=C(O)NH2 Ig R=H, D=C(O)NH2 1b N~N~ R1b N~N R1b N''N
i i \ I iN \ I iN \ I iN
RIj I RIj I RIj I
D m D n D o m1 R=F, D=NH2 n~ R=F, D=NH2 0~ R=F, D=NH2 m2 R=H, D=NH2 n2 R=H, D=NH2 02 R=H, D=NH2 m3 R=F, D=CH2NH2 n3 R=F, D=CH2NH2 03 R=F, D=CH2NH2 m4 R=H, D=CH2NH2 n4 R=H, D=CH2NH2 04 R=H, D=CH2NH2 ms R=F, D=C(=NH)NH2 n5 R=F, D=C(=NH)NH2 os R=F, D=C(=NH)NH2 ms R=H, D=C(=NH)NH2 ns R=H, D=C(=NH)NH2 06 R=H, D=C(=NH)NH2 m~ R=F, D=C(O)NH2 n~ R=F, D=C(O)NH2 0~ R=F, D=C(O)NH2 mB R=H, D=C(O)NH2 n8 R=H, D=C(O)NH2 08 R=H, D=C(O)NH2 1b 1b 1b piR=F, D=NH2 qt R=F, D=NH2 rt R=F, D=NH2 p2R=CI D=NH2 q2 R=CI, D=NH2 r2 R=CI, D=NH2 p3R=OMe, D=NH2 q3 R=OMe, D=NH2 r3 R=OMe, D=NH2 p4R=F, D=CH2NH2 q4 R=F, D=CH2NH2 r4 R=F, D=CH2NH2 p5R=CI D=CH2NH2 q5 R=Ci, D=CH2NH2 r~ R=CI, D=CH2NH2 psR=OMe, D=CH2NH2 qs R=OMe, D=CH2NH2 rs R=OMe, D=CH2NH2 p~R=F, D=C(=NH)NH2q~ R=F, D=C(=NH)NH2r~ R=F, D=C(=NH)NH2 peR=CI, D=C(=NH)NH2q8 R=CI, D=C(=NH)NH2r8 R=CI, D=C(=NH)NH2 p9R=OMe, D=C(=NH)NH2q9 R=OMe, D=C(=NH)NH2r9 R=OMe, D=C(=NH)NH2 ptoR=F, D=C(O)NH2 qtoR=F, D=C(O)NH2 rioR=F, D=C(O)NH2 p11R=CI, D=C(O)NH2 qitR=CI, D=C(O)NH2 riiR=CI, D=C{O)NH2 pt2R=OMe, D=C(O)NH2q12R=OMe, D=C(O)NH2rteR=OMe, D=C(O)NH2 tb ib tb siR=F, D=NH2 t1 R=F, D=NH2 ut R=F, D=NH2 s2R=CI, D=NH2 t2 R=CI, D=NH2 u2 R=CI, D=NH2 s3R=OMe, D=NH2 t3 R=OMe, D=NH2 u3 R=OMe, D=NH2 s4R=F, D=CH2NH2 t4 R=F, D=CH2NH2 u4 R=F, D=CH2NH2 s5R=CI, D=CH2NH2 t5 R=Ci, D=CH2NH2 u5 R=CI, D=CH2NH2 ssR=OMe, D=CH2NH2 is R=OMe, D=CH2NH2 us R=OMe, D=CH2NH2 s~R=F, D=C(=NH)NH2t~ R=F, D=C(=NH)NH2u~ R=F, D=C(=NH)NH2 seR=CI, D=C(=NH)NH2to R=CI, D=C{=NH)NH2ue R=CI, D=C{=NH)NH2 s9R=OMe, D=C(=NH)NH2t9 R=OMe, D=C(=NH)NH2u9 R=OMe, D=C(=NH)NH2 sioR=F, D=C(O)NH2 do R=F, D=C(O)NH2 u1oR=F, D=C(O)NH2 sitR=CI, D=C(O)NH2 t11R-_CI, D=C(O)NH2uiiR=CI, D=C(O)NH2 st2 t12R=OMe, D=C(O)NH2u12 R=OMe, R=OMe, D=C(O)NH2 D=C(O)NH2 R N~/N ~b 1 ~b Rib N ~~ /' N
\ / R \ I~N R \
I~ ~ I~
v D D w ~ x v~ R=F, D=NH2 wi R=F, D=NH2 xi R=F, D=NH2 v2 R=CI, D=NH2 w2 R=CI, D=NH2 x2 R=CI, D=NH2 v3 R=OMe, D=NH2 w3 R=OMe, D=NH2 x3 R=OMe, D=NH2 v4 R=F, D=CH2NH2 w4 R=F, D=CH2NH2 x4 R=F, D=CH2NH2 v5 R=CI, D=CH2NH2 w5 R=CI, D=CH2NH2 x5 R=CI, D=CH2NH2 v6 R=OMe, D=CH2NH2 ws R=OMe, D=CH2NH2 xs R=OMe, D=CH2NH2 v~ R=F D=C(=NH)NH2 w~ R=F, D=C(=NH)NH2 x~ R=F, D=C(=NH)NH2 va R=CI, D=C(=NH)NH2 wa R=CI, D=C(=NH)NH2 xe R=CI, D=C(=NH)NH2 v9 R=OMe, D=C(=NH)NH2 w9 R=OMe, D=C(=NH)NH2 x9 R=OMe, D=C(=NH)NH2 v~o R=F, D=C(O)NH2 ,n,~o R=F, D=C(O)NH2 x~o R=F, D=C(O)NH2 v~ i R=CI, D=C(O)NH2 ",,~ i R=CI, D=C(O)NH2 xi ~ R=CI, D=C(O)NH2 v~2 R=OMe, D=C(O)NH2 ,~,,~2 R=OMe, D=C(O)NH2 x12 R=OMe, D=C(O)NH2 N_ Rib Rib ~N N.N.~N
\ ,N R \ ,N R \ /
I ~ I I ~ ~ I ~ I R
D Y z p as y~ R=F, D=NH2 zi R=F, D=NH2 aa~ R=F, D=NH2 y2 R=CI D=NH2 z2 R=CI, D=NH2 aa2 R=CI, D=NH2 y3 R=OMe, D=NH2 z3 R=OMe, D=NH2 aa3 R=OMe, D=NH2 y4 R=F D=CH2NH2 z4 R=F, D=CH2NH2 aa4 R=F, D=CH2NH2 y5 R=CI, D=CH2NH2 z5 R=Ci, D=CH2NH2 aa5 R=CI, D=CH2NH2 ys R=OMe, D=CH2NH2 zs R=OMe, D=CH2NH2 aas R=OMe, D=CH2NH2 y~ R=F, D=C(=NH)NH2 z~ R=F, D=C(=NH)NH2 aa~ R=F, D=C(=NH)NH2 y8 R=CI, D=C(=NH)NH2 z8 R=CI, D=C(=NH)NH2 aa8 R=CI, D=C(=NH)NH2 y9 R=OMe D=C(=NH)NH2 z9 R=OMe, D=C(=NH)NH2 aa9 R=OMe, D=C(=NH)NH2 Y~o R=F, D=C(O)NH2 zio R=F, D=C(O)NH2 aa~o R=F, D=C(O)NH2 yi ~ R=CI D=C(O)NH2 z1 i R=CI, D=C(O)NH2 aa~ i R=CI, D=C(O)NH2 y~2 R=OMe, D=C(O)NH2 z~2 R=OMe, D=C(O)NH2 aa~2 R=OMe, D=C(O)NH2 Rib R1 E I I II E
bb ~ dd bbi R=F, D=NH2 cci R=F, D=NH2 ddi R=F, D=NH2 bb2 R=Ci, D=NH2 cc2 R=CI, D=NH2 dd2 R=C1, D=NH2 bb3 R=OMe, D=NH2 cc3 R=OMe, D=NH2 dd3 R=OMe, D=NH2 bb4 R=F, D=CH2NH2 cc4 R=F, D=CH2NH2 dd4 R=F, D=CH2NH2 bb5 R=CI, D=CH2NH2 cc$ R=CI, D=CH2NH2 dd5 R=CI, D=CH2NH2 bbs R=OMe, D=CH2NH2 ccs R=OMe, D=CH2NH2 dds R=OMe, D=CH2NH2 bb~ R=F, D=C(=NH)NH2 cc~ R=F, D=C(=NH)NH2 dd~ R=F, D=C(=NH)NH2 bbs R=CI, D=C(=NH)NH2 cc8 R=CI, D=C(=NH)NH2 ddb R=CI, D=C(=NH)NH2 bb9 R=OMe, D=C(=NH)NH2 cc9 R=OMe, D=C(=NH)NH2 dd9 R=OMe, D=C(=NH)NH2 bbio R=F, D=C(O)NH2 ccio R=F, D=C(O)NH2 ddio R=F, D=C(O)NH2 bbi 1 R=CI, D=C(O)NH2 cci 1 R=CI, D=C(O)NH2 ddi 1 R=CI, D=C(O)NH2 bbl2 R=OMe, D=C(O)NH2 ccl2 R=OMe, D=C(O)NH2 ddl2 R=OMe, D=C(O)NH2 Rib R1b Rib R I j R i~~ R
y ~ ~ ~ ,~.
i ~""". ~ j ~ ~ ~ T
D ee ff 99 eei R=F, D=CH2NH2 ffi R=F, D=CH2NH2 ggi R=F, D=CH2NH2 ee2 R=CI, D=CH2NH2 ff2 R=Ci, D=CH2NH2 gg2 R=CI, D=CH2NH2 ee3 R=OMe, D=CH2NH2 ff3 R=OMe, D=CH2NH2 gg3 R=OMe, D=CH2NH2 ee4 R=CH2NH2, ff4 R=CH2NH2, gg4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib Rib R1b R I ~N R I ~1 R
,~ i N ~
D hh D ii D 11 hhi R=F, D=CH2NH2 iii R=F, D=CH2NH2 jji R=F, D=CH2NH2 hh2 R=Ci, D=CH2NH2 ii2 R=Cl, D=CHpNH2 jj2 R=CI, D=CH2NH2 hh3 R=OMe, D=CH2NH2 iii R=OMe, D=CH2NH2 jj3 R=OMe, D=CH2NH2 hh4 R=CH2NH2, ii4 R=CHpNH2, jj4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib R1b R1b R N ~N R i~~l R I ~N
E iN I E
.""",. / -.,;",. / .""N.
D kk D II D mm kki R=F, D=CN2NH2 Ili R=F, D=CH2NH2 mmi R=F, D=CH2NH2 kk2 R=CI, D=CH2NH2 112 R=CI, D=CH2NH2 mm2 R=CI, D=CH2NH2 kk3 R=OMe, D=CH2NH2 113 R=OMe, D=CH2NH2 mm3 R=OMe, D=CH2NH2 kk4 R=CH2NH2, 114 R=CH2NH2, mm4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 R I ~~ ib R I /N ib R N,N''N
I E ~N E ~N E I ~ ib I ~ I ~ I R
D nn D oo D PP
nni R=F, D=CH2NH2 ooi R=F, D=CH2NH2 ppi R=F, D=CH2NH2 nn2 R=CI, D=CH2NH2 002 R=CI, D=CH2NH2 pp2 R=CI, D=CH2NH2 nn3 R=OMe, D=CH2NH2 003 R=OMe, D=CH2NH2 pp3 R=OMe, D=CH2NH2 nn4 R=CH2NH2, 004 R=CH2NH2, pp4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib ib ib R N'N~R R i ~ N R I N''N
,N ~ ,N ~ ,N
D qq D rr D ss qqi R=F D=CH2NH2 rri R=F, D=CH2NH2 ssi R=F, D=CH2NH2 qq2 R=C~I, D=CH2NH2 rr2 R=CI, D=CH2NH2 ss2 R=CI, D=CH2NH2 qq3 R=OMe, D=CH2N~i2 rr3 R=OMe, D=CH2NH2 ss3 R=OMe, D=CH2NH2 qq4 R=CH2NH2, rr4 R=CH2NH2, ss4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Ex# Rlb A g 1 H phenyl 2-(aminosulfonyl)phenyl 2 H phenyl 2-(methylaminosulfonyl)phenyl 3 H phenyl 1-pyrrolidinocarbonyl 4 H phenyl 2-(methylsulfonyl)phenyl 5 H phenyl 4-morpholino 6 H phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 7 H phenyl 4-morpholinocarbonyl 8 H 2-pyridyl 2-(aminosulfonyl)phenyl 9 H 2-pyridyl 2-(methylaminosulfonyl)phenyl 10 H 2-pyridyl 1-pyrrolidinocarbonyl 11 H 2-pyridyl 2-(methylsulfonyl)phenyl 12 H 2-pyridyl 4-morpholino 13 H 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 14 H 2-pyridyl 4-morpholinocarbonyl 15 H 3-pyridyl 2-(aminosulfonyl)phenyl 16 H 3-pyridyl 2-(methylaminosulfonyl)phenyl 17 H 3-pyridyl 1-pyrrolidinocarbonyl 18 H 3-pyridyl 2-(methylsulfonyl)phenyl 19 H 3-pyridyl 4-morpholino 20 H ~-pyridyl 2-(2'-CF3-tetrazol-2-yl)phenyl 21 H 3-pyridyl 4-morpholinocarbonyl 22 H 2-pyrimidyl 2-(aminosulfonyl)phenyl 23 H 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 24 H 2-pyrimidyl 1-pyrrolidinocarbonyl 25 H 2-pyrimidyl 2-(methylsulfonyl)phenyl 26 H 2-pyrimidyl 4-morpholino 27 H 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 28 H 2-pyrimidyl 4-morpholinocarbonyl 29 H 5-pyrimidyl 2-(aminosulfonyl)phenyl 30 H 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 31 H 5-pyrimidyl 1-pyrrolidinocarbonyl 32 H 5-pyrimidyl 2-(methylsulfonyl)phenyl 33 H 5-pyrimidyl 4-morpholino 34 H 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 35 H 5-pyrimidyl 4-morpholinocarbonyl 36 H 2-C1-phenyl 2-(aminosulfonyl)phenyl 37 H 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 38 H 2-C1-phenyl 1-pyrrolidinocarbonvl 39 H 2-C1-phenyl 2-(methylsulfonyl)phenyl 40 H 2-C1-phenyl 4-morpholino 41 H 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 42 H 2-C1-phenyl 4-morpholinocarbonyl 43 H 2-F-phenyl 2-(aminosulfonyl)phenyl 44 H 2-F-phenyl 2-(methylaminosulfonyl)phenyl 45 H 2-F~-phenyl 1-pyrrolidinocarbonyl 46 H 2-F-phenyl 2-(methylsulfonyl)phenyl 47 H 2-F-phenyl 4-morpholino 48 H 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 49 H 2-F-phenyl 4-morpholinocarbonyl 50 H 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 51 H 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 52 H 2,5-diF-phenyl 1-pyrrolidinocarbonyl 53 H 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 54 H 2,5-diF-phenyl 4-morpholino 55 H 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 56 H 2,5-diF-phenyl 4-morpholinocarbonyl 57 -CN phenyl 2-(aminosulfonyl)phenyl 58 -CN phenyl 2-(methylaminosulfonyl)phenyl 59 -CN phenyl 1-pyrrolidinocarbonyl 60 -CN phenyl 2-(methylsulfonyl)phenyl 61 -CN phenyl 4-morpholino 62 -CN phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 63 -CN phenyl 4-morpholinocarbonyl 64 -CN 2-pyridyl 2-(aminosulfonyl)phenyl 65 -CN 2-pyridyl 2-(methylaminosulfonyl)phenyl 66 -CN 2-pyridyl 1-pyrrolidinocarbonyl 67 -CN 2-pyridyl 2-(methylsulfonyl)phenyl 68 -CN 2-pyridyl 4-morpholino 69 -CN 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 70 -CN 2-pyridyl 4-morpholinocarbonyl 71 -CN 3-pyridyl 2-(aminosulfonyl)phenyl 72 -CN 3-pyridyl 2-(methylaminosulfonyl)phenyl a b 74 -CN 3-pyridyl 2-pmethyl ulfony )phenyl 75 -CN 3-pyridyl 4-morpholino 76 -CN 3-pyridyl 2-(1'-CF3-tetrazol-2-~-')prenyl 77 -CN 3-pyridyl 4-morpholinocarbonyl 78 -CN 2-pyrimidyl 2-(aminosulfonyl)phenyl 79 -CN 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 80 -CN 2-pyrimidyl 1-pyrrolidinocarbonyl 81 -CN 2-pyrimidyl 2-(methylsulfonyl)phenyl 82 -CN 2-pyrimidyl 4-morpholino 83 -CN 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 84 -CN 2-pyrimidyl 4-morpholinocarbonyl 85 -CN 5-pyrimidyl 2-(aminosulfonyl)phenyl 86 -CN 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 87 -CN 5-pyrimidyl 1-pyrrolidinocarbonyl 88 -CN 5-pyrimidyl 2-(methylsulfonyl)phenyl 89 -CN 5-pyrimidyl 4-morpholino 90 -CN 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 91 -CN 5-pyrimidyl 4-morpholinocarbonyl 92 -CN 2-Cl-phenyl 2-(aminosulfonyl)phenyl 93 -CN 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 94 -CN 2-C1-phenyl 1-pyrrolidinocarbonvl 95 -CN 2-C1-phenyl 2-(methylsulfonyl)phenyl 96 -CN 2-C1-phenyl 4-morpholino 97 -CN 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 98 -CN 2-C1-phenyl 4-morpholinocarbonyl 99 -CN 2-F-phenyl 2-(aminosulfonyl)phenyl 100 -CN 2-F-phenyl 2-(methylaminosulfonyl)phenyl 101 -CN 2-F-phenyl 1-pyrrolidinocarbonyl 102 -CN 2-F-phenyl 2-(methylsulfonyl)phenyl 103 -CN 2-F-phenyl 4-morpholino 104 -CN 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 105 -CN 2-F-phenyl 4-morpholinocarbonyl 106 -CN 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 107 -CN 2,5-diF-phenyl 2-(methylaminosulfonyl)pheiiyl 108 -CN 2,5-diF-phenyl 1-pyrrolidinocarbonyl 109 -CN 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 110 -CN 2,5-diF-phenyl 4-morpholino 111 -CN 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 112 -CN 2,5-diF-phenyl 4-morpholinocarbonyl 113 CF3 phenyl 2-(aminosulfonyl)phenyl 114 CF3 phenyl 2-(methylaminosulfonyl)phenyl 115 CF3 phenyl 1-pyrrolidinocarbonyl 116 CF3 phenyl 2-(methylsulfonyl)phenyl 117 CF3 phenyl 4-morpholino 118 CF3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 119 CF3 phenyl 4-morpholinocarbonyl 120 CF3 2-pyridyl 2-(aminosulfonyl)phenyl 121 CF3 2-pyridyl 2-(methylaminosulfonyl)phenyl 122 CF3 2-pyridyl 1-pyrrolidinocarbonyl 123 CF3 2-pyridyl 2-(methylsulfonyl)phenyl 124 CF3 2-pyridyl 4-morpholino 125 CF3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 126 CF3 2-pyridyl 4-morpholinocarbonyl 127 CF3 3-pyridyl 2-(aminosulfonyl)phenyl 128 CF3 3-pyridyl 2-(methylaminosulfonyl)phenyl 129 CF3 3-pyridyl 1-pyrrolidinocarbonyl 130 CF3 3-pyridyl 2-(methylsulfonyl)phenyl 131 CF3 3-pyridyl 4-morpholino 132 CF3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 133 CF3 3-pyridyl 4-morpholinocarbonyl 134 CF3 2-pyrimidyl 2-(aminosulfonyl)phenyl 135 CF3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 136 CF3 2-pyrimidyl 1-pyrrolidinocarbonyl 137 CF3 2-pyrimidyl 2-(methylsulfonyl)phenyl 138 CF3 2-pyrimidyl 4-morpholino 139 CF3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 140 CF3 2-pyrimidyl 4-morpholinocarbonyl 141 CF3 5-pyrimidyl 2-(aminosulfonyl)phenyl 142 CF3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 143 CF3 5-pyrimidyl 1-pyrrolidinocarbonyl 144 CF3 5-pyrimidyl 2-(methylsulfonyl)phenyl 145 CF3 5-pyrimidyl 4-morpholino 146 CF3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 147 CF3 5-pyrimidyl 4-morpholinocarbonyl 148 CF3 2-C1-phenyl 2-(aminosulfonyl)phenyl 149 CF3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 150 CF3 2-C1-phenyl 1-pyrrolidinocarbonyl 151 CF3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 152 CF3 2-C1-phenyl 4-morpholino 153 CF3 2-Cl-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 154 CF3 2-Cl-phenyl 4-morpholinocarbonyl 155 CF3 2-F-phenyl 2-(aminosulfonyl)phenyl 156 CF3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 157 CF3 2-F-phenyl 1-pyrrolidinocarbonyl 158 CF3 2-F-phenyl 2-(methylsulfonyl)phenyl 159 CF3 2-F-phenyl 4-morpholino 160 CF3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 161 CF3 2-F-phenyl 4-morpholinocarbonyl 162 CF3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 163 CF3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 164 CF3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 165 CF3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 166 CF3 2,5-diF-phenyl 4-morpholino 167 CF3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 168 CF3 2,5-diF-phenyl 4-morpholinocarbonyl 169 CONH2 phenyl 2-(aminosulfonyl)phenyl 170 CONH2 phenyl 2-(methylaminosulfonyl)phenyl 171 CONHZ phenyl 1-pyrrolidinocarbonyl 172 CONH2 phenyl 2-(methylsulfonyl)phenyl 173 CONFi2 phenyl 4-morpholino 174 CONH2 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 175 CONH2 phenyl 4-morpholinocarbonyl 176 CONH2 2-pyridyl 2-(aminosulfonyl)phenyl 177 CONH2 2-pyridyl 2-(methylaminosulfonyl)phenyl 178 CONH2 2-pyridyl 1-pyrrolicrinocarbonyl 179 CONHZ 2-pyridyl 2-(methylsalfonyl)phenyl 180 CONHZ 2-pyridyl 4-morpholino 181 CONHZ 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 182 CONH2 2-pyridyl ~-morpholinocarbonyl 183 CONH2 3-pyridyl 2-(aminosulfonyl)phenyl 184 CONH2 3-pyridyl 2-(methylaminosulfonyl)phenyl 185 CONH2 3-pyridyl 1-pyrrolidinocarbonyl 186 CONH2 3-pyridyl 2-(methylsulfonyl)phenyl 187 CONH2 3-pyridyl 4-morpholino 188 CONH2 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 189 CONH2 3-pyridyl 4-morpholinocarbonyl 190 CONHZ 2-pyrimidyl 2-(aminosulfon_,rl)phenyl 191 CONH2 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 192 CONH~ 2-pyrimidyl 1-pyrrolidinocarbonyl 193 CONH2 2-pyrimidyl 2-(methylsulfonyl)phenyl 194 CONH2 2-pyrimidyl 4-morpholino 195 CONH2 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 196 CONHZ 2-pyrimidyl 4-morpholinocarbonyl 197 CONHZ 5-pyrimidyl 2-(aminosulfonyl)phenyl 198 CONH2 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 199 CONH2 5-pyrimidyl 1-pyrrolidinocarbonyl 200 CONH2 5-pyrimidyl 2-(methylsulfonyl)phenyl 201 CONH2 5-pyrimidyl 4-morpholino 202 CONH2 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 203 CONHZ 5-pyrimidyl 4-morpholinocarbonyl 204 CONH2 2-C1-phenyl 2-(aminosulfonyl)phenyl 205 CONH2 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 206 CONH2 2-Cl-phenyl 1-pyrrolidinocarbonyl 207 CONH2 2-Cl-phenyl 2-(methylsulfonyl)phenyl 208 CONH2 2-Cl-phenyl 4-morpholino 209 CONH2 2-C1-phenyl 2-(1'-CF3-tetrazol-2-;rl)phenyl 210 CONH2 2-C1-phenyl 4-morpholinocarbonyl 211 CONH2 2-F-phenyl 2-(aminosulfonyl)phenyl 212 CONH2 2-F-phenyl 2-(methylaminosulfonyl)phenyl 213 CONH2 2-F-phenyl 1-pyrrolidinocarbonyl 214 CONH2 2-F-phenyl 2-(methylsulfonyl)phenyl 215 CONH2 2-F-phenyl 4-morpholino 216 CONH2 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 217 CONH2 2-F-phenyl 4-morpholinocarbonyl 218 CONH2 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 219 CONH2 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 220 CONHZ 2,5-diF-phenyl 1-pyrrolidinocarbonyl 221 CONH2 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 222 CONHZ 2,5-diF-phenyl 4-morpholino 223 CONH2 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 224 CONHZ 2,5-diF-phenyl 4-morpholinocarbonyl 225 SCH3 phenyl 2-(aminosulfonyl)phenyl 226 SCH3 phenyl 2-(methylaminosulfonyl)phenyl 227 SCH3 phenyl 1-pyrrolidinocarbonyl 228 SCH3 phenyl 2-(methylsulfonyl)phenyl 229 SCH3 phenyl 4-morpholino 230 SCH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 231 SCH3 phenyl 4-morpholinocarbonyl 232 SCH3 2-pyridyl 2-(aminosulfonyl)phenyl 233 SCH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 234 SCH3 2-pyridyl 1-pyrrolidinocarbonf~l 235 SCH3 2-pyridyl 2-(methylsulfonyl)phenyl 236 SCH3 2-pyridyl 4-morpholino 237 SCH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 238 SCH3 2-pyridyl 4-morpholinocarbonyl 239 SCH3 3-pyridyl 2-(aminosulfonyl)phenyl 240 SCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 241 SCH3 3-pyridyl 1-pyrrolidinocarbonyl 242 SCH3 3-pyridyl 2-(methylsulfonyl)phenyl 243 SCH3 3-pyridyl 4-morpholino 244 SCH3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 245 SCH3 3-pyridyl 4-morpholinocarbonyl 246 SCH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 247 SCH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 248 SCH3 2-pyrimidyl 1-pyrrolidinocarbonyl 249 SCH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 250 SCH3 2-pyrimidyl 4-morpholino 251 SCH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 252 SCH3 2-pyrimidyl 4-morphoiinocarbonyl 253 SCH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 254 SCH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 255 SCH3 5-pyrimidyl 1-pyrrolidinocarbonyl 256 SCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 257 SCH3 5-pyrimidyl 4-morpholino 258 SCH3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 259 SCH3 5-pyrimidyl 4-morpholinocarbonyl 260 SCH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 261 SCH3 2-Cl-phenyl 2-(methylaminosulfonyl)phenyl 262 SCH3 2-C1-phenyl 1-pyrrolidinocarbonyl 263 SCH3 2-Cl-phenyl 2-(methylsulfonyl)phenyl 264 SCH3 2-Cl-phenyl 4-morpholino 265 SCH3 2-C1-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 266 SCH3 2-C1-phenyl 4-morpholinocarbonyl 267 SCH3 2-F-phenyl 2-(aminosulfonyl)phenyl 268 SCH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 269 SCH3 2-F-phenyl 1-pyrrolidinocarbonyl 270 SCH3 2-F-phenyl 2-(methylsulfonyl)phenyl 271 SCH3 2-F-phenyl 4-morpholino 272 SCH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 273 SCH3 2-F-phenyl 4-morpholinocarbonyl 274 SCH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 275 SCH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 276 SCH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 277 SCH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 278 SCH3 2,5-diF-phenyl 4-morpholino 279 SCH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 280 SCH3 2,5-diF-phenyl 4-morpholinocarbonyl 281 S02CH3 phenyl 2-(aminosulfonyl)phenyl 282 S02CH3 phenyl 2-(methylaminosulfonyl)phenyl 283 S02CH3 phenyl 1-pyrrolidinocarbonyl 284 S02CH3 phenyl 2-(methylsulfonyl)phenyl 285 S02CH3 phenyl 4-morpholino 286 Su2CH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 287 S02CH3 phenyl 4-morpholinocarbonyl 288 S02CH3 2-pyridyl 2-(aminosulfonyl)phenyl 289 S02CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 290 S02CH3 2-pyridyl 1-pyrrolidinocarbonyl 291 S02CH3 2-pyridyl 2-(methylsulfonyl)phenyl 292 S02CH3 2-pyridyl 4-morpholino 293 S02CH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 294 S02CH3 2-pyridyl 4-morpholinocarbonyl 295 S02CH3 3-pyridyl 2-(aminosulfonyl)phenyl 296 SOZCH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 297 S02CH3 3-pyridyl 1-pyrrolidinocarbonyl 298 S02CH3 3-pyridyl 2-(methylsulfonyl)phenyl 299 S02CH3 3-pyridyl 4-morpholino 300 S02CH3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 301 SOzCH3 3-pyridyl 4-morpholinocarbonyl 302 S02CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 303 S02CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 304 S02CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 305 S02CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 306 S02CH3 2-pyrimidyl 4-morpholino 307 S02CH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 308 S02CH3 2-pyrimidyl 4-morpholinocarbonyl 309 S02CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 310 S02CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 311 S02CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 312 S02CH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 313 S02CH3 5-pyrimidyl 4-morpholino 314 S02CH3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 315 S02CH3 5-pyrimidyl 4-morpholinocarbonyl 316 S02CH3 2-Cl-phenyl 2-(aminosulfonyl)phenyl 317 S02CH3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 318 S02CH3 2-Cl-phenyl 1-pyrrolidinocarbonyl 319 S02CH3 2-C1-phenyl 2-(methylsulfonyl)phenyl 320 S02CH3 2-Cl-phenyl 4-morpholino 321 S02CH3 2-Cl-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 322 S02CH3 2-C1-phenyl 4-morpholinocarbonyl 323 S02CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 324 S02CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 325 S02CH3 2-F-phenyl 1-pyrrolidinocarbonyl 326 S02CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 327 S02CH3 2-F-phenyl 4-morpholino 328 S02CH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 329 S02CH3 2-F-phenyl 4-morpholinocarbonyl 330 S02CH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 331 S02CH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 332 S02CH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 333 S02CH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 334 S02CH3 2,5-diF-phenyl 4-morpholino 335 S02CH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 336 S02CH3 2,5-diF-phenyl 4-morpholinocarbonyl 337 NHSOzCH3 phenyl 2-(aminosulfonyl)phenyl 338 NHSOzCH3 phenyl 2-(methylaminosulfonyl)phenyl 339 NHS02CH3 phenyl 1-pyrrolidinocarbonyl 340 NHS02CH3 phenyl 2-(methylsulfonyl)phenyl 341 NHS02CH3 phenyl 4-morpholino 342 NHS02CH3 phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 343 NHS02CH3 phenyl 4-morpholinocarbonyl 344 NHS02CH3 2-pyridyl 2-(aminosulfonyl)phenyl 345 NHS02CH3 2-pyridyl 2-(methylaminosulfonyl)phenyl 346 NHSOZCH3 2-pyridyl 1-pyrrolidinocarbonyl 347 NHS02CH3 2-pyridyl 2-(methylsulfonyl)phenyl 348 NHS02CH3 2-pyridyl 4-morpholino 349 NHS02CH3 2-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 350 NHSOZCH3 2-pyridyl 4-morpholinocarbonyl 351 NHS02CH3 3-pyridyl 2-(aminosulfonyl)phenyl 352 NHS02CH3 3-pyridyl 2-(methylaminosulfonyl)phenyl 353 NHS02CH3 3-pyridyl 1-pyrrolidinocarbonyl 354 NHS02CH3 3-pyridyl 2-(methylsulfonyl)phenyl 355 NHS02CH3 3-pyridyl 4-morpholino 356 NHS02CH3 3-pyridyl 2-(1'-CF3-tetrazol-2-yl)phenyl 357 NHSOZCH3 3-pyridyl 4-morpholinocarbonyl 358 NHS02CH3 2-pyrimidyl 2-(aminosulfonyl)phenyl 359 NHS02CH3 2-pyrimidyl 2-(methylaminosulfonyl)phenyl 360 NHS02CH3 2-pyrimidyl 1-pyrrolidinocarbonyl 361 NHS02CH3 2-pyrimidyl 2-(methylsulfonyl)phenyl 362 NHS02CH3 2-pyrimidyl 4-morpholino 363 NHS02CH3 2-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 364 NHS02CH3 2-pyrimidyl 4-morpholinocarbonyl 365 NHS02CH3 5-pyrimidyl 2-(aminosulfonyl)phenyl 366 NHS02CH3 5-pyrimidyl 2-(methylaminosulfonyl)phenyl 367 NHS02CH3 5-pyrimidyl 1-pyrrolidinocarbonyl 368 NHSOzCH3 5-pyrimidyl 2-(methylsulfonyl)phenyl 369 NHS02CH3 5-pyrimidyl 4-morpholino 370 NHS02CH3 5-pyrimidyl 2-(1'-CF3-tetrazol-2-yl)phenyl 371 NHS02CH3 5-pyrimidyl 4-morpholinocarbonyl 372 NHS02CH3 2-C1-phenyl 2-(aminosulfonyl)phenyl 373 NHS02CH3 2-C1-phenyl 2-(methylaminosulfonyl)phenyl 374 NHS02CH3 2-C1-phenyl 1-pyrrolidinocarbonyl 375 NHS02CH3 2-C1-phenyl 2-(methylsulfonyl)phenyl 376 NHSOZCH3 2-C1-phenyl 4-morpholino 377 NHS02CH3 2-Ci-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 378 NHS02CH3 2-Cl-phenyl 4-morpholinocarbonyl 379 NHS02CH3 2-F-phenyl 2-(aminosulfonyl)phenyl 380 NHS02CH3 2-F-phenyl 2-(methylaminosulfonyl)phenyl 381 NHS02CH3 2-F-phenyl 1-pyrrolidinocarbonyl 382 NHS02CH3 2-F-phenyl 2-(methylsulfonyl)phenyl 383 NHS02CH3 2-F-phenyl 4-morpholino 384 NHS02CH3 2-F-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 385 NHSOZCH3 2-F-phenyl 4-morpholinocarbonyl 386 NHS02CH3 2,5-diF-phenyl 2-(aminosulfonyl)phenyl 387 NHS02CH3 2,5-diF-phenyl 2-(methylaminosulfonyl)phenyl 388 NHS02CH3 2,5-diF-phenyl 1-pyrrolidinocarbonyl 389 NHS02CH3 2,5-diF-phenyl 2-(methylsulfonyl)phenyl 390 NHS02CH3 2,5-diF-phenyl 4-morpholinc 391 NHS02CH3 2,5-diF-phenyl 2-(1'-CF3-tetrazol-2-yl)phenyl 392 NHS02CH3 2,5-diF-phenyl 4-morpholinocarbonyl Table 5 '~R~b M
H
D~E N.A~B
O
1b /R N~/Rib Rib RIj ~ ~j R ~ R .",;".
D a D b D c aiR=F, D=NH2 bi R=F, D=NH2 ci R=F, D=NH2 a2R=H, D=NH2 b2 R=H, D=NH2 c2 R=H, D=NH2 a3R=F, D=CH2NH2 b3 R=F, D=CH2NH2 c3 R=F, D=CH2NH2 a4R=H, D=CH2NH2 b4 R=H, D=CH2NH2 cQ R=H, D=CH2NH2 a5R=F, D=C(=NH)NH2b5 R=F, D=C(=NH)NH2c5 R=F, D=C(=NH)NH2 asR=H, D=C(=NH)NH2bs R=H, D=C(=NH)NH2cs R=H, D=C(=NH)NH2 a~R=F, D=C(O)NH2 b~ R=F, D=C(O)NH2 c~ R=F, D=C(O)NH2 a8R=H, D=C(O)NH2 b8 R=H, D=C(O)NH2 c$ R=H, D=C(O)NH2 1b ib ib diR=F, D=NH2 ei R=F, D=NH2 fi R=F, D=NH2 d2R=H, D=NH2 e2 R=H, D=NH2 f2 R=H, D=NH2 d3R=F, D=CH2NH2 e3 R=F, D=CH2NH2 f3 R=F, D=CH2NH2 d4R=H, D=CH2NH2 e4 R=H, D=CH2NH2 f4 R=H, D=CH2NH2 dsR=F, D=C(=NH)NH2e5 R=F, D=C(=NH)NH2f5 R=F, D=C(=NH)NH2 d6R=H, D=C(=NH)NH2es R=H, D=C(=NH)NH2f6 R=H, D=C(=NH)NHZ

d~R=F, D=C(O)NH2 e~ R=F, D=C(O)NH2 f~ R=F, D=C(O)NH2 d8R=H, D=C(O)NHz e8 R=H, D=C(O)NH2 f8 R=H, D=C(O)NH2 WO 98!57934 PCT/US98/12682 N~/N » Rib Rib N ~~ ~N
\ I ~ i ~N I
R i~ T
Ii ~ Ii D 9 R D h R ~ i D
g1 R=F, D=NH2 h~ R=F, D=NH2 ii R=F, D=NHp g2 R=H, D=NH2 h2 R=H, D=NH2 i2 R=H, D=NH2 g3 R=F, D=CH2NH2 h3 R=F, D=CH2NH2 i3 R=F, D=CH2NH2 g4 R=H, D=CH2NH2 h4 R=H, D=CH2NH2 i4 R=H, D=CH2NH2 g$ R=F, D=C(=NH)NH2 h5 R=F, D=C(=NH)NH2 i5 R=F, D=C(=NH)NH2 gs R=H, D=C(=NH)NH2 hs R=H, D=C(=NH)NH2 i6 R=H, D=C(=NH)NH2 g~ R=F, D=C(O)NH2 h~ R=F, D=C(O)NH2 i~ R=F, D=C(O)NH2 g8 R=H, D=C(O)NH2 h8 R=H, D=C(O)NH2 i8 R=H, D=C(O)NH2 N, Rib Rib ~N ~.N'~N
\ iN \ iN \
R I j R I % ~ R I j ~ Rib D l D k D I
R=F, D=NH2 k~ R=F, D=NH2 li R=F, D=NH2 j2 R=H, D=NH2 k2 R=H, D=NH2 12 R=H, D=NH2 j3 R=F, D=CH2NH2 k3 Fi=F, D=CH2NH2 13 R=F, D=CH2NH2 j4 R=H, D=CH2NH2 !c4 R=H, D=CH2NH2 14 R=H, D=CH2NH2 j5 R=F, D=C(=NH)NH2 k5 R=F, D=C(=NH)NH2 15 R=F, D=C(=NH)NH2 js R=H, D=C(=NH)NH2 ks R=H, D=C(=NH)NH2 I6 R=H, D=C(=NH)NH2 ~~ R=F, D=C(O)NH2 k~ R=F, D=C(O)NH2 h R=F, D=C(O)NH2 j$ R=H, D=C(O)NH2 kg R=H, D=C(O)NH2 18 R=H, D=C(O)NH2 Rib N,N\ Rib ~N Rib N
''N
i i \ I iN \ ~ iN \ I iN
R I i I ~ I i I R
p m p n o D
m1 R=F, D=NH2 ni R=F, D=NH2 of R=F, D=NH2 m2 R=H, D=NH2 n2 R=H, D=NH2 02 R=H, D=NH2 m3 R=F, D=CH2NH2 n3 R=F, D=CH2NH2 03 R=F, D=CH2NH2 m4 R=H, D=CH2NH2 n4 R=H, D=CH2NH2 04 R=H, D=CH2NH2 m5 R=F, D=C(=NH)NH2 n5 R=F, D=C(=NH)NH2 os R=F, D=C(=NH)NH2 ms R=H, D=C(=NH)NH2 ns R=H, D=C(=NH)NH2 os R=H, D=C(=NH)NH2 m~ R=F, D=C(O)NH2 n~ R=F, D=C(O)NH2 0~ R=F, D=C(O)NH2 m8 R=H, D=C(O)NH2 ne R=H, D=C(O)NH2 08 R=H, D=C(O)NH2 1b R
p~ R=F, D=NH2 qi R=F, D=NHp r~ R=F, D=NH2 p2 R=CI, D=NH2 q2 R=CI, D=NH2 r2 R=CI, D=NHp p3 R=OMe, D=NH2 q3 R=OMe, D=NH2 r3 R=OMe, D=NH2 p4 R=F, D=CH2NH2 q4 R=F, D=CH2NH2 r4 R=F, D=CHpNH2 p5 R=CI, D=CH2NH2 q5 R=CI, D=CH2NH2 r5 R=Ci, D=CH2NH2 ps R=OMe, D=CH2NH2 qs R=OMe, D=CH2NH2 rs R=OMe, D=CH2NH2 p~ R=F, D=C(=NH)NHp q~ R=F, D=C(=NH)NH2 r~ R=F, D=C(=NH)NH2 pe R=CI, D=C{=NH)NHz qs R=CI, D=C(=NH)NH2 r8 R=CI, D=C(=NH)NH2 p9 R=OMe D=C(=NH)NH2 q9 R=OMe, D=C(=NH)NH2 r9 R=OMe D=C(=NH)NH2 pro R=F, D=C(O)NH2 qio R=F, D=C(O)NH2 rip R=F, D=C{O)NH2 p1~ R=CI, D=C(O)NH2 q1~ R=CI, D=C(O)NH2 r» R=CI, D=C(O)NH2 pie R=OMe, D=C(O)NHz qi2 R=OMe, D=C(O)NH2 r~2 R=OMe, D~C(O)NH2 1b ~b R1b R ~
j a a s~ R=F, D=NH2 t~ R=F, D=NH2 u~ R=F, D=NH2 s2 R=CI, D=NH2 t2 R=CI, D=NH2 u2 R=CI, D=NH2 s3 R=OMe, D=NH2 t3 R=OMe, D=NH2 u3 R=OMe, D=NH2 s4 R=F, D=CH2NH2 t4 R=F, D=CH2NH2 u4 R=F, D=CH2NH2 s5 R=CI, D=CH2NH2 t5 R=CI, D=CH2NH2 u5 R=CI, D=CH2NH2 ss R=OMe, D=CH2NH2 is R=OMe, D=CH2NH2 us R=OMe, D=CH2NH2 s~ R=F, D=C(=NH)NH2 t~ R=F, D=C(=NH)NH2 u~ R=F, D=C(=NH)NH2 s8 R=CI, D=C(=NH)NH~ t8 R=CI, D=C(=NH)NH2 ue R=CI, D=C(=NH)NH2 s9 R=OMe, D=C(=NH)NH2 t9 R=OMe, D=C(=NH)NH2 u9 R=OMe, D=C(=NH)NH2 sip R=F, D=C{O)NH2 too R=F, D=C(O)NH2 u~o R=F, D=C(O)NH2 si 1 R=CI, D=C(O)NH2 t> > R=CI, D=C{O)NH2 u> > R=CI, D=C(O)NH2 s~2 R=OMe, D=C(O)NH~ t12 R°OMe, D=C(O)NH2 u~2 R=OMe, D=C(O)NH2 R1b R1b N ~~1 /' N
R ~ I iN R
j D w n x v~ R=F, D=NH2 w1 R=F, D=NH2 xi R=F, D=NH2 v2 R=CI, D=NH2 w2 R=CI, D=NH2 x2 R=CI, D=NH2 v3 R=OMe, D=NH2 w3 R=OMe, D=NH2 x3 R=OMe, D=NHZ
v4 R=F, D=CH2NH2 w4 R=F, D=CH2NH2 x4 R=F, D=CH2NH2 v5 R=CI, D=CH2NH2 w5 R=CI, D=CH2NHp x5 R=CI, D=CH2NH2 vs R=OMe, D=CH2NH2 ws R=OMe, D=CH2NH2 xs R=OMe, D=CH2NH2 v~ R=F D=C(=NH)NH2 w~ R=F, D=C(=NH)NH2 x~ R=F, D=C(=NH)NH2 vg R=CI, D=C(=NH)NH2 w8 R=CI, D=C(=NH)NH2 xe R=CI, D=C(=NH)NH2 v9 R=OMe, D=C(=NH)NH2 w9 R=OMe, D=C{=NH)NH2 x9 R=OMe, D=C(=NH)NH2 v1o R=F, D=C(O)NH2 w1o R=F, D=C(O)NH2 x~o R=F, D=C(O)NH2 v11 R=CI, D=C(O)NH2 wi ~ R=CI, D=C(O)NH2 x> > R=CI, D=C(O)NH2 vie R=OMe, D=C(O)NH2 w12 R=OMe, D=C(O)NH2 x~2 R=OMe, D=C(O)NH2 N,N' N
,N R ~ iN R ~ I ~ ib y I y I y 1 R
D y z D as y~ R=F, D=NH2 zi R=F, D=NH2 aai R=F, D=NH2 y2 R=CI, D=NH2 z2 R=CI, D=NH2 aa2 R=CI, D=NH2 y3 R=OMe, D=NH2 z3 R=OMe, D=NH2 aa3 R=OMe, D=NH2 y4 R=F D=CH2NH2 z4 R=F, D=CH2NH2 aa4 R=F, D=CH2NH2 y5 R=CI D=CH2NH2 z5 R=CI, D=CH2NH2 aa5 R=CI, D=CH2NH2 ys R=OMe. D=CH2NH2 zs R=OMe, D=CH2NH2 aas R=OMe, D=CH2NH2 y~ R=F, D=C(=NH)NH2 Z~ R=F, D=C(=NH)NH2 aa~ R=F, D=C(=NH)NH2 ye R=CI, D=C(=NH)NH2 z8 R=CI, D=C(=NH)NH2 aa8 R=CI, D=C(=NH)NH2 y9 R=OMe D=C(=NH)NH2 z9 R=OMe, D=C(=NH)NH2 aa9 R=OMe, D=C(=NH)NH2 yio R=F, D=C(O)NH2 zoo R=F, D=C(O)NH2 aaio R=F, D=C(O)NH2 y> > R=Cl D=C(O)NH2 zi 1 R=CI, D=C(O)NH2 aa1 ~ R=Ci, D=C(O)NH2 y12 R=OMe, D=C(O)NH2 z~2 R=OMe, D=C(O)NH2 aa~2 R=OMe, D=C(O)NH2 Rib .N~R~b ~ Rib N.
i R ~ ~ i R
D bb D cc D dd bbi R=F, D=NH2 cc1 R=F, D=NH2 ddi R=F, D=NH2 bb2 R=CI, D=NH2 cc2 R=CI, D=NH2 dd2 R=CI, D=NH2 bb3 R=OMe, D=NH2 cc3 R=OMe, D=NH2 dd3 R=OMe, D=NH2 bb4 R=F, D=CHpNH2 cc4 R=F, D=CH2NH2 dd4 R=F, D=CHpNH2 bbs R=CI, D=CH2NH2 cc5 R=Cl, D=CH2NH2 dd5 R=CI, D=CH2NH2 bbs R=OMe, D=CH2NH2 ccs R=OMe, D=CH2NH2 dds R=OMe, D=CH2NH2 bb~ R=F, D=C(=NH)NH2 cc~ R=F, D=C(=NH)NHz dd~ R=F, D=C(=NH)NH2 bbe R=CI, D=C(=NH)NH2 ccs R=CI, D=C(=NH)NH2 ddb R=CI, D=C(=NH)NH2 bb9 R=OMe, D=C(=NH)NH2 cc9 R=OMe, D=C(=NH)NH2 dd9 R=OMe, D=C(=NH)NH2 bb~o R=F, D=C(O)NH2 cc~o R=F, D=C(O)NHp ddio R=F, D=C(O)NH2 bbi ~ R=Cl, D=C(O)NH2 cc~ i R=CI, D=C(O)NH2 dd> > R=CI, D=C(O)NH2 bb~2 R=OMe, D=C(O)NH2 ccl2 R=OMe, D=C{O)NH2 ddl2 R=OMe, D=C(O)NH2 1b R I /R R ~/R~b R ~Rvb ee ff i r~ ~ i ee~ R=F, D=CH2NH2 ff~ R=F, D=CH2NH2 ggi R=F, D=CH2NH2 ee2 R=CI, D=CH2NH2 ff2 R=CI, D=CH2NH2 gg2 R=CI, D=CH2NH2 ee3 R=OMe, D=CH2NH2 ff3 R=OMe, D=CH2NH2 gg3 R=OMe, D=CH2NH2 ee4 R=CHpNH2, ff4 R=CH2NH2, gg4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Rib R1b R1b R I ~N R I ~1 R N
~ ,N ~
j ~ ~ j D hh D ii D jj hh1 R=F, D=CH2NH2 ii1 R=F, D=CH2NH2 jji R=F, D=CH2NH2 hh2 R=CI, D=CH2NH2 ii2 R=CI, D=CH2NH2 jj2 R=CI, D=CH2NH2 hh3 R=OMe, D=CH2NH2 iig R=OMe, D=CH2NH2 jj3 R=OMe, D=CH2NH2 hh4 R=CH2NH2, ii4 R=CH2NH2, jj4 R=CH2NH2, D=CH2NHp D=CHpNH2 D=CH2NH2 R ~~/N ~b Rib R1b R I~~N R I /' N
IE ~ IE i .".~". i ,""",.
D kk D II D mm kk~ R=F, D=CH2NH2 111 R=F, D=CH2Nh2 mm~ R=F, D=CH2NH2 kk2 R=CI, D=CH2NH2 112 R=CI, D=CH2NH2 mm2 R=Cl, D=CH2NH2 kk3 R=OMe, D=CH2NH2 113 R=OMe, D=CH2NH2 mm3 R=OMe, D=CH2NH2 kk4 R=CHpNH2, 114 R=CH2NH2, mm4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 R ( ~1 ~b R I /N ib R N,N\\N
~N E ~N E I ~ Rib I~ I I~ I I
D nn D oo D PP
nn~ R=F, D=CH2NH2 ooi R=F, D=CH2NH2 pp~ R=F, D=CH2NH2 nn2 R=Ci, D=CH2NH2 002 R=Ci, D=CH2NH2 pp2 R=CI, D=CH2NH2 nn3 R=OMe, D=CH2NH2 003 R=OMe, D=CH2NH2 pp3 R=OMe, D=CH2NH2 nn4 R=CH2NH2, 004 R=CH2NH2, pp4 R=CH2NH2, D=CH2NH2 a=~i-i2NH2 D=CH2Ni-i2 Rib 1b 1b R N'N~R R N ~ N R N~~N
iN ~ I iN ~ I iN
I~ I I
D qq D rr D ss R=F, D=CH2NH2 rr~ R=F, D=CH2NH2 ssi R=F, D=CH2NH2 qq2 R=Ci, D=CH2NH2 rr2 R=CI, D=CH2NH2 ss2 R=CI, D=CH2NH2 qq3 R=OMe D=CH2NH2 rr3 R=OMe, D=CH2Nh'.2 ss3 R=OMe, D=CH2NH2 qq4 R=CH2NH2, rr4 R=CH2NH2, ss4 R=CH2NH2, D=CH2NH2 D=CH2NH2 D=CH2NH2 Ex# R~ A B
1 H phenyl 2-((Me)2N-methyl)phenyl 2 H phenyl 2-((Me)NH-methyl)phenyl 3 H phenyl 2-(H2N-methyl)phenyl 4 H phenyl 2-HOCH2-phenyl 5 H 2-F-phenyl 2-((Me)2N-methyl)phenyl 6 H 2-F-phenyl 2-((Me)NH-methyl)phenyl 7 H 2-F-phenyl 2-(H2N-methyl)phenyl 8 H 2-F-phenyl 2-HOCH2-phenyl 9 H phenyl 2-methylimidazol-1-yl 10 H phenyl 2-ethylimidazol-1-yl 11 H phenyl 2-((Me)2N-methyl)imidazol-1-yl 12 H phenyl 2-CH3NHS02-imidazol-1-yl 13 H phenyl 2-CH30CH2-imidazol-1-yl 14 H 2-F-phenyl 2-methylimidazol-1-yl 15 H 2-F-phenyl 2-ethylimidazol-1-yl 16 H 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 17 H 2-F-phenyl 2-CH3S02-imidazol-1-yl 18 H 2-F-phenyl 2-CH30CH2-imidazol-1-yl 19 H 2-C1-phenyl 2-methylimidazol-1-yl 20 H 2-C1-phenyl 2-ethylimidazol-1-yl 21 H 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 22 H 2-C1-phenyl 2-CH3S02-imidazol-1-yl 23 H 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 24 H 2-(Me)2N-phenyl 2-methylimidazol-1-yl 25 H 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 26 H 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 27 H 2-(Me)ZN-phenyl 2-CH3S02-imidazol-1-yl 28 H 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 29 H phenyl N-methylimidazol-2-yl 30 H phenyl 4-methylimidazol-5-yl phenyl 5-CF3-pyrazol-1-yl 32 H 2-F-phenyl N-methylimidazol-2-yl 33 H 2-F-phenyl 4-methylimidazol-5-yI

34 H 2-F-phenyl 5-CF3-pyrazol-1-yl 35 H phenyl guanidino 36 H phenyl 2-thiazolin-2-ylamine 37 H phenyl N-methyl-2-imidazolin-2-yl 38 H phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 39 H phenyl N-methylimidazol-2-ylthiol 40 H phenyl t-butoxycarbonylamine 41 H phenyl (N-pyrrolidino)formylimino 42 H phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 43 H 2-F-phenyl guanidino 44 H 2-F-phenyl 2-thiazolin-2-ylamine 45 H 2-F-phenyl N-methyl-2-imidazolin-2-yl 46 H 2-F-phenyl N-methyl-1,4,5,6-y d 47 H 2-F-phenyl N-methyl midazol 2 yl thio 48 H 2-F-phenyl t-butoxycarbonylamine 49 H 2-F-phenyl (N-pyrrolidino)formylimino H 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 51 H 2-CH30-phenyl (N-pyrrolidino)formylimino 52 H 2-CH30-phenyl (N-pyrrolidino)formyl-N-45 (methanesulfamoyl)imino 53 -CN phenyl 2-((Me)2N-methyl)phenyl 54 -CN phenyl 2-((Me)NH-methyl)phenyl -CN phenyl 2-(H2N-methyl)phenyl 56 -CN phenyl 2-HOCH2-phenyl 50 57 -CN 2-F-phenyl 2-((Me)2N-methyl)phenyl 58 -CN 2-F-phenyl 2-((Me)NH-methyl)phenyl 59 -CN 2-F-phenyl 2-(HZN-methyl)phenyl -CN 2-F-phenyl 2-HOCH2-phenyl 61 -CN phenyl 2-methylimidazol-1-yl 55 62 -CN phenyl 2-ethylimidazol-1-yl 63 -CN phenyl 2-((Me)zN-methyl)imidazol-1-yl 64 -CN phenyl 2-CH3S02-imidazol-1-yl 65 -CN phenyl 2-CH30CH2-imidazol-1-yl 66 -CN 2-F-phenyl 2-methylimidazol-1-yl 67 -CN 2-F-phenyl 2-ethylimidazol-1-yl 68 -CN 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 69 -CN 2-F-phe_zyl 2-CH3S02-imidazol-1-yl 70 -CN 2-F-phenyl 2-CH30CH2-imidazol-1-yl 71 -CN 2-C1-phenyl 2-methylimidazol-1-yl 72 -CN 2-Cl-phenyl 2-ethylimidazol-1-yi 73 -CN 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 74 -CN 2-C1-phenyl 2-CH3S02-imidazol-1-yl 75 -CN 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 76 -CN 2-(Me)2N-phenyl 2-methylimidazol-1-yl 77 -CN 2-(Me)ZN-phenyl 2-ethylimidazol-1-yl 78 -CN 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 79 -CN 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 80 -CN 2-(Me}2N-phenyl 2-CH30CH2-imidazol-1-yl 81 -CN phenyl N-methylimidazol-2-yl 82 -CN phenyl 4-methylimidazol-5-yl 83 -CN phenyl 5-CF3-pyrazol-1-yl 84 -CN 2-F-phenyl N-methylimidazol-2-yl 85 -CN 2-F-phenyl 4-methylimidazol-S-yl 86 -CN 2-F-phenyl 5-CF3-pyrazol-1-yl 87 -CN phenyl guanidino 88 -CN phenyl 2-thiazolin-2-ylamine 89 -CN phenyl N-methyl-2-imidazolin-2-yl 90 -CN phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 91 -CN phenyl N-methylimidazol-2-ylthiol 92 -CN phenyl t-butoxycarbonylamine 93 -CN phenyl (N-pyrrolidino)formylimino 94 -CN phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 95 -CN 2-F-phenyl guanidino 96 -CN 2-F-phenyl 2-thiazolin-2-ylamine 97 -CN 2-F-phenyl N-methyl-2-imidazolin-2-yl 98 -CN 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 99 -CN 2-F-phenyl N-methylimidazol-2-ylthio 100 -CN 2-F-phenyl t-butoxycarbonylamine 101 -CN 2-F-phenyl (N-pyrrolidino)formylimino 102 -CN 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 103 -CN 2-CH30-phenyl (N-pyrrolidino)formylimino 104 -CN 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 105 CF3 phenyl 2-((Me)2N-methyl)phenyl 106 CF3 phenyl 2-((Me)NH-methyl)phenyl 107 CF3 phenyl 2-(H2N-methyl)phenyl 108 CF3 phenyl 2-HOCH
2-phenyl 109 CF3 2-F-phenyl 2-((Me)2N-methyl)phenyl 110 CF3 2-F-phenyl 2-((Me)NH-methyl)phenyl 111 CF3 2-F-phenyl 2-(H2N-methyl)phenyl 112 CF3 2-F-phenyl 2-HOCH2-phenyl 113 CF3 phenyl 2-methylimidazol-1-yl 114 CF3 phenyl 2-ethylimidazol-1-yl 115 CF3 phenyl 2-((Me)zN-methyl)imidazol-1-yl 116 CF3 phenyl 2-CH3S0~-imidazol-1-yl 117 CF3 phenyl 2-CH30CH2-imidazol-1-yl 118 CF3 2-F-phenyl 2-methylimidazol-1-yl 119 CF3 2-F-phenyl 2-ethylimidazol-1-yl 120 CF3 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 121 CF3 2-F-phenyl 2-CH3S02-imidazol-1-yl 122 CF3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 123 CF3 2-C1-phenyl 2-methylimidazol-1-yl 124 CF3 2-C1-phenyl 2-ethylimidazol-1-yl 125 CF3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 126 CF3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 127 CF3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 128 CF3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 129 CF3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 130 CF3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 131 CF3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 132 CF3 2-(Me)2N-phenyl 2-CH30CH~-imidazol-1-yl 133 CF3 phenyl N-methylimidazol-2-yl 134 CF3 phenyl 4-methylimidazol-5-yl 135 CF3 phenyl 5-CF3-pyrazol-1-yl 136 CF3 2-F-phenyl N-methylimidazol-2-yl 137 CF3 2-F-phenyl 4-methylimidazol-5-yl 138 CF3 2-F-phenyl 5-CF3-pyrazol-1-yl 139 CF3 phenyl guanidino 140 CF3 phenyl 2-thiazolin-2-ylamine 141 CF3 phenyl N-methyl-2-imidazolin-2-yl 142 CF3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 143 CF3 phenyl N-methylimidazol-2-ylthiol 144 CF3 phenyl t-butoxycarbonylamine 145 CF3 phenyl (N-pyrrolidino)formylimino 146 CF3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 147 CF3 2-F-phenyl guanidino 148 CF3 2-F-phenyl 2-thiazolin-2-ylamine 149 CF3 2-F-phenyl N-methyl-2-imidazolin-2-yl 150 CF3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 151 CF3 2-F-phenyl N-methylimidazol-2-ylthio 152 CF3 2-F-phenyl t-butoxycarbonylamine 153 CF3 2-F-phenyl (N-pyrrolidino)formylimino 154 CF3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 155 CF3 2-CH30-phenyl (N-pyrrolidino)formylimino 156 CF3 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 157 CONH2 phenyl 2-((Me)2N-methyl)phenyl 158 CONH2 phenyl 2-((Me)NH-methyl)phenyl 159 CONH2 phenyl 2-(H2N-methyl)phenyl 160 CONH2 phenyl 2-HOCH2-phenyl 261 CONH2 2-F-phenyl 2-((Me)~N-methyl)phenyl 162 CONH2 2-F-phenyl 2-((Me)NH-methyl)phenyl 163 CONHZ 2-F-phenyl 2-(HEN-methyl)phenyl 164 CONH2 2-F-phenyl 2-HOCH~-phenyl 165 CONHZ phenyl 2-methylimidazol-i-yl 166 CONH2 phenyl 2-ethylimidazol-1-yl 167 CONH2 phenyl 2-((Me)2N-methyl)imidazol-1-yl 168 CONH2 phenyl 2-CH3S02-imidazol-1-yl 169 CONH2 phenyl 2-CH30CH2-imidazol-1-yl 170 CONH2 2-F-phenyl 2-methylimidazol-1-yl 171 CONH2 2-F-phenyl 2-ethylimidazol-1-yl 172 CONH2 2-F-phenyl 2-((Me)ZN-methyl)imidazol-1-yl 173 CONH2 2-F-phenyl 2-CH3S02-imidazol-1-yl 174 CONH2 2-F-phenyl 2-CH30CH2-imidazol-1-yl 175 CONH2 2-Cl-phenyl 2-methylimidazol-1-yl 176 CONH2 2-C1-phenyl 2-ethylimidazol-1-yl 177 CONH2 2-C1-phenyl 2-((Me)zN-methyl)irnidazol-1-yl 178 CONH2 2-C1-phenyl 2-CH3S02-imidazol-1-yl 179 CONH2 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 180 CONH2 2-(Me)2N-phenyl 2-methylimidazol-1-yl 181 CONH2 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 182 CONH2 2-(Me)2N-phenyl 2-((Me)ZN-methyl)imidazol-1-yl 183 CONH2 2-(Me)ZN-phenyl 2-CH3S0z-imidazoi-1-y1 184 CONH2 2-{Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 185 CONH2 phenyl N-methylimidazol-2-yl 186 CONH2 phenyl 4-methylimidazol-5-yl 187 CONH2 phenyl 5-CF3-pyrazol-1-yl 188 CONH2 2-F-phenyl N-methylimidazol-2-yl 189 CONH2 2-F-phenyl 4-methylimidazol-5-yl 190 CONH2 2-F-phenyl 5-CF3-pyrazol-1-yl 191 CONH2 phenyl guanidino 192 CONH2 phenyl 2-thiazolin-2-ylamine 193 CONH2 phenyl N-methyl-2-imidazolin-2-yl 194 CONH2 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 195 CONH2 phenyl N-methylimidazol-2-ylthiol 196 CONH2 phenyl t-butoxycarbonylamine 197 CONH2 phenyl (N-pyrrolidino)formylimino 198 CONHz phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 199 CONH2 2-F-phenyl guanidino 200 CONH2 2-F-phenyl 2-thiazolin-2-ylamine 201 CONH2 2-F-phenyl N-methyl-2-imidazolin-2-yl 202 CONH2 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 203 CONH2 2-F-phenyl N-methylimidazol-2-ylthio 204 CONHZ 2-F-phenyl t-butoxycarbonylamine 205 CONH2 2-F-phenyl (N-pyrrolidino)formylimino 206 CONHZ 2-F-phenyl {N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 207 CONH2 2-CH30-phenyl (N-pyrrolidino)formylimino 208 CONH2 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 209 SCH3 phenyl 2-((Me)2N-methyl)phenyl 210 SCH3 phenyl 2-((Me)NH-methyl)phenyl 211 SCH3 phenyl 2-(H2N-methyl)phenyl 212 SCH3 phEnyl 2-HOCH
2-phenyl 213 SCH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 214 SCH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 215 SCH3 2-F-phenyl 2-(H2N-methyl)phenyl 216 SCH3 2-F-phenyl 2-HOCH2-phenyl 217 SCH3 phenyl 2-methylimidazol-1-yl 218 SCH3 phenyl 2-ethylimidazol-1-yl 219 SCH3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 220 SCH3 phenyl 2-CH3S02-imidazol-1-yl 221 SCH3 phenyl 2-CH30CH2-imidazol-1-yl 222 SCH3 2-F-phenyl 2-methylimidazol-1-yl 223 SCH3 2-F-phenyl 2-ethylimidazol-1-yl 224 SCH3 2-F-phenyl 2-((Me)zN-methyl)imidazol-1-yl 225 SCH3 2-F-phenyl 2-CH3S02-imidazol-1-yl 226 SCH3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 227 SCH3 2-C1-phenyl 2-methylimidazol-1-yl 228 SCH3 2-C1-phenyl 2-ethylimidazol-1-yl 229 SCH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 230 SCH3 2-C1-phenyl 2-CH3S02-imidazol-1-yi 231 SCH3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 232 SCH3 2-(Me)ZN-phenyl 2-methylimidazol-1-yl 233 SCH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 234 SCH3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 235 SCH3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 236 SCH3 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 237 SCH3 phenyl N-methylimidazol-2-yl 238 SCH3 phenyl 4-methylimidazol-5-yl 3 phenyl 5-CF3-pyrazol-1-yl 240 SCH3 2-F-phenyl N-methylimidazol-2-yl 241 SCH3 2-F-phenyl 4-methylimidazol-5-yl 242 SCH3 2-F-phenyl 5-CF3-pyrazol-1-yl 243 SCH3 phenyl guanidino 244 SCH3 phenyl 2-thiazolin-2-ylamine 245 SCH3 phenyl N-methyl-2-imidazolin-2-yl 246 SCH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 247 SCH phenyl N-methylimidazol-2-ylthiol 248 SCH3 phenyl t-butoxycarbonylamine 249 SCH3 phenyl (N-pyrrolidino)formylimino 250 SCH3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 251 SCH3 2-F-phenyl guanidino 252 SCH3 2-F-phenyl 2-thiazolin-2-ylamine 253 SCH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 254 SCH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 255 SCH3 2-F-phenyl N-methylimidazol-2-ylthio 256 SCH3 2-F-phenyl t-butoxycarbonylamine 257 SCH3 2-F-phenyl (N-pyrrolidino)formylimino 258 SCH3 2-F-phenyl (N-pyrrolidino)forznyl-N-(methanesulfamoyl)imino 259 SCH3 2-CH30-phenyl (N-pyrrolidino)formylimino 260 SCH3 2-CH30-p?~.enyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 261 S02CH3 phenyl 2-((Me)2N-methyl)phenyl 262 S02CH3 phenyl 2-((Me)NH-methyl)phenyl 263 S02CH3 phenyl 2-(H2N-methyl)phenyl 264 S02CH3 phenyl 2-HOCH2-phenyl 265 S02CH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 266 S02CH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 267 S02CH3 2-F-phenyl 2-(H2N-methyl)phenyl 268 SOZCH3 2-F-phenyl 2-HOCH2-phenyl 269 S02CH3 phenyl 2-methylimidazol-1-yl 270 SOZCH3 phenyl 2-ethylimidazol-1-yl 271 S02CH3 phenyl 2-((Me)ZN-methyl)imidazol-1-yl 272 S02CH3 phenyl 2-CH3S0z-imidazol-1-yl 273 S02CH3 phenyl 2-CH30CH2-imidazol-1-yl 274 S02CH3 2-F-phenyl 2-methylimidazol-1-yl 275 S02CH3 2-F-phenyl 2-ethylimidazol-1-yl 276 S02CH3 2-F-phenyl 2-((Me)ZN-methyl)imidazol-1-yl 277 SOZCH3 2-F-phenyl 2-CH3SG2-imidazol-1-yl 278 S02CH3 2-F-phenyl 2-CH30CH2-imidazol-1-yl 279 S02CH3 2-C1-phenyl 2-methylimidazol-1-yl 280 S02CH3 2-C1-phenyl 2-ethylimidazol-1-yl 281 S02CH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 282 S02CH3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 283 S02CH3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 284 S02CH3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 285 S02CH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 286 S02CH3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 287 S02CH3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 288 S02CH3 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 289 S02CH3 phenyl N-methylimidazol-2-yl 290 S02CH3 phenyl 4-methylimidazol-5-yl 291 S02CH3 phenyl 5-CF3-pyrazol-1-yl 292 S02CH3 2-F-phenyl N-methylimidazol-2-yl 293 S02CH3 2-F-phenyl 4-methylimidazol-5-yl 294 S02CH3 2-F-phenyl 5-CF3-pyrazol-1-yl 295 S02CH3 phenyl guanidino 296 S02CH3 phenyl 2-thiazolin-2-ylamine 297 S02CH3 phenyl N-methyl-2-imidazolin-2-yl 298 S02CH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 299 S02CH3 phenyl N-methylimidazol-2-ylthiol 300 S02CH3 phenyl t-butoxycarbonylamine 301 S02CH3 phenyl (N-pyrrolidino)formylimino 302 SOZCH3 phenyl (N-pyrrolidino)fornayl-N-(methanesulfamoyl)imino 303 S02CH3 2-F-phenyl guanidino 304 S02CH3 2-F-phenyl 2-thiazolin-2-ylamine 305 S02CH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 306 S02CH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 307 S02CH3 2-F-phenyl N-methylimidazol-2-ylthio 308 S02CH3 2-F-phenyl t-butoxycarb~rylamine 309 SOZCH3 2-F-phenyl (N-pyrrolictino)formylimino 310 S02CH3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 311 S02CH3 2-CH30-phenyl (N-pyrrolidino)formylimino 312 S02CH3 2-CH30-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 313 NHS02CH3 phenyl 2-((Me)2N-methyl)phenyl 314 NHS02CH3 phenyl 2-((Me)NH-methyl)phenyl 315 NHS02CH3 phenyl 2-(HZN-methyl)phenyl 316 NHSOZCH3 phenyl 2-HOCH2-phenyl 317 NHS02CH3 2-F-phenyl 2-((Me)2N-methyl)phenyl 318 NHS02CH3 2-F-phenyl 2-((Me)NH-methyl)phenyl 319 NHSOzCH3 2-F-phenyl 2-(H2N-methyl)phenyl 320 NHS02CH3 2-F-phenyl 2-HOCH2-phenyl 321 NHS02CH3 phenyl 2-methylimidazol-1-yl 322 NHS02CH3 phenyl 2-ethylimidazol-1-yl 323 NHSOZCH3 phenyl 2-((Me)2N-methyl)imidazol-1-yl 324 NHSOZCH3 phenyl 2-CH3S02-imidazol-1-yl 325 NHS02CH3 phenyl 2-CH30CH2-imidazol-1-yl 326 NHS02CH3 2-F-phenyl 2-methylimidazol-1-yl 327 NHS02CH3 2-F-phenyl 2-ethylimidazol-1-yl 328 NHS02CH3 2-F-phenyl 2-((Me)2N-methyl)imidazol-1-yl 329 NHSOZCH3 2-F-phenyl 2-CH3S02-imidazol-1-yl 330 NHS02CH3 2-F-phenyl 2-CH30CHZ-imidazol-1-yl 331 NHSOZCH3 2-C1-phenyl 2-methylimidazol-1-yl 332 NHS02CH3 2-C1-phenyl 2-ethylimidazol-1-yl 333 NHS02CH3 2-C1-phenyl 2-((Me)2N-methyl)imidazol-1-yl 334 NHS02CH3 2-C1-phenyl 2-CH3S02-imidazol-1-yl 335 NHS02CH3 2-C1-phenyl 2-CH30CH2-imidazol-1-yl 336 NHS02CH3 2-(Me)2N-phenyl 2-methylimidazol-1-yl 337 NHS02CH3 2-(Me)2N-phenyl 2-ethylimidazol-1-yl 338 NHS02CH3 2-(Me)2N-phenyl 2-((Me)2N-methyl)imidazol-1-yl 339 NHS02CH3 2-(Me)2N-phenyl 2-CH3S02-imidazol-1-yl 340 NHS02CH3 2-(Me)2N-phenyl 2-CH30CH2-imidazol-1-yl 341 NHS02CH3 phenyl N-methylimidazol-2-yl 342 NHS02CH3 phenyl 4-methylimidazol-5-yl 343 NHS02CH3 phenyl 5-CF3-pyrazol-1-yl 344 NHS02CH3 2-F-phenyl N-methylimidazol-2-yl 345 NHS02CH3 2-F-phenyl 4-methylimidazol-5-yl 346 NHS02CH3 2-F-phenyl 5-CF3-pyrazol-1-yl 347 NHS02CH3 phenyl guanidino 348 NHS02CH3 phenyl 2-thiazolin-2-ylamine 349 NHS02CH3 phenyl N-methyl-2-imidazolin-2-yl 350 NHS02CH3 phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 351 NHS02CH3 phenyl N-methylimidazol-2-ylthiol 352 NHS02CH3 phenyl t-butoxycarbonylamine 353 NHS02CH3 phenyl (N-pyrrolidino)formylimino 354 NHS02CH3 phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 355 NHS02CH3 2-F-phenyl guanidino 356 NHS02CH~ 2-F-phenyl 2-thiazolin-2-ylamine 357 NHS02CH3 2-F-phenyl N-methyl-2-imidazolin-2-yl 358 NHS02CH3 2-F-phenyl N-methyl-1,4,5,6-tetrahydropyrimid-2-yl 359 NHS02CH3 2-F-phenyl N-methylimidazol-2-ylthio 360 NHS02CH3 2-F-phenyl t-butoxycarbonylamine 361 NHS02CH3 2-F-phenyl (N-pyrrolidino)formylimino 362 NHS02CH3 2-F-phenyl (N-pyrrolidino)formyl-N-(methanesulfamoyl)imino 363 NHS02CH3 2-CH30-phenyl (N-pyrrolidino)formylimino 364 NHS02CH3 2-CH30-phenyl (N-pyrrolidino)forrnyl-N-(methanesulfamoyl)imino Utility The compounds of this invention are useful as anticoagulants for the treatment or prevention of thromboembolic disarders in mammals. The term "thromboembolic disorders" as used herein includes arterial or venous cardiovascular or cerebrovascular thromboembolic disorders, including, for example, unstable angina, first or recurrent myocardial infarction, ischemic sudden death, transient ischemic attack, stroke, atherosclerosis, venous thrombosis, deep vein thrombosis, thrombophlebitis, arterial embolism, coronary and cerebral arterial thrombosis, cerebral embolism, kidney embolisms, and pulmonary embolisms. The anticoagulant effect of compounds of the present invention is believed to be due to inhibition of factor Xa or thrombin.
The effectiveness of compounds of the present invention as inhibitors of factor Xa was determined using purified human factor Xa and synthetic substrate. The rate of factor Xa hydrolysis of chromogenic substrate S2222 (Kabi Pharmacia, Franklin, OH) was measured both in the absence and presence of compounds of the present invention. Hydrolysis of the substrate resulted in the release of pNA, which was monitored spectrophotometrically by measuring the increase in absorbance at 405 nM. A decrease in the rate of absorbance change at 405 nm in~the presence of inhibitor is indicative of enzyme inhibition. The results of this assay are expressed as inhibitory constant, Ki.
Factor Xa determinations were made in 0.10 M sodium phosphate buffer, pH 7.5, containing 0.20 M NaCl, and 0.5 ~
PEG 8000. The Michaelis constant, Km, for substrate hydrolysis was determined at 25°C using the method of Lineweaver and Burk. Values of Ki were determined by allowing 0.2-0.5 nM human factor Xa (Enzyme Research Laboratories, South Bend, IN) to react with the substrate (0.20 mM-1 mM) in the presence of inhibitor. Reactions were allowed to go for 30 minutes and the velocities (rate of absorbance change vs time) were measured in the time frame of 25-30 minutes. The following relationship was used to calculate Ki values:
(vo-vs)/vs = I/(Ki (1 + S/Km)) where:
vo is the velocity of the control in the absence of inhibitor;
vs is the velocity in the presence of inhibitor;
I is the concentration of inhibitor;
Ki is the dissociation constant of the enzyme: inhibitor complex;
S is the concentration of substrate;
Km is the Michaelis constant.
Using the methodology described above, a number of compounds of the present invention were found to exhibit a Ki of <15 ~Ni, thereby confirming the utility of the compounds of the present invention as effective Xa inhibitors.
The antithrombotic effect of compounds of the present invention can be demonstrated in a rabbit arterio-venous (AV) shunt thrombosis model. In this model, rabbits weighing 2-3 kg anesthetized with a mixture of xylazine (10 mg/kg i.m.) and ketamine (50 mg/kg i.m.) are used A saline-fi~.led AV shunt device is connected between the femoral arterial and the femoral venous cannulae. The AV shunt device consists of a piece of 6-cm tygon tubing which contains a piece of silk thread. Blood will flow from the femoral artery via the AV-shunt into the femoral vein. The exposure of flowing blood to a silk thread will induce the formation of a significant thrombus. After forty minutes, the shunt is disconnected and the silk thread covered with thrombus is weighed. Test agents or vehicle will be given (i.v., i.p., s.c., or orally) prior to the opening of the AV shunt. The percentage inhibition of thrombus formation is determined for each treatment group.
The ID50 values (dose which produces 50~ inhibition of thrombus formation) are estimated by linear regression.
The compounds of formula (I) may also be useful as inhibitors of serine proteases, notably human thrombin, plasma kallikrein and plasmin. Because of their inhibitory action, these compounds are indicated for use in the prevention or treatment of physiological reactions, blood coagulation and inflammation, catalyzed by the aforesaid class of enzymes.
Specifically, the compounds have utility as drugs for the treatment of diseases arising from elevated thrombin activity such as myocardial infarction, and as reagents used as anticoagulants in the processing of blood to plasma for diagnostic and other commercial purposes.
Some compounds of the present invention wexe shown to he direct acting inhibitors of the serine protease thrombin by their ability to inhibit the cleavage of small molecule substrates by thrombin in a purified system. In vitro inhibition constants were determined by the method described by Kettner et al. in J. Biol. Chem. 265, 18289-18297 (1990), herein incorporated by reference. In these assays, thrombin-mediated hydrolysis of the chromogenic substrate 52238 (Helena Laboratories, Beaumont, TX) was monitored spectrophotometrically. Addition of an inhibitor to the assay mixture results in decreased absorbance and is indicative of thrombin inhibition. Human thrombin (Enzyme Research Laboratories, Inc., South Bend, IN) at a concentration of 0.2 nM in 0.10 M sodium phosphate buffer, pH 7.5, 0.20 M NaCl, and 0.5~ PEG 6000, was incubated with various substrate concentrations ranging from 0.20 to 0.02 mM. After 25 to 30 minutes of incubation, thrombin activity was assayed by monitoring the rate of increase in absorbance at 405 nm which arises owing to substrate hydrolysis. Inhibition constants were derived from reciprocal plots of the reaction velocity as a function of substrate concentration using the standard method of Lineweaver and Burk. Using the methodology described above, s4me compounds of this invention were evaluated and found to exhibit a Ki of less than 15 Vim, thereby confirming the utility of the compounds of the present invention as effective Xa inhibitors.
The compounds of the present invention can be administered alone or in combination with one or more additional therapeutic agents. These include other anti-coagulant or coagulation inhibitory agents, anti-platelet or platelet inhibitory agents, thrombin inhibitors, or thrombolytic or fibrinolytic agents.
The compounds are administered to a mammal in a therapeutically effective amount. By "therapeutically effective amount" it is meant an amount of a compound of Formula I that, when administered alone or in combination with an additional therapeutic agent to a mammal, is effective to prevent or ameliorate the thromboembolic disease condition or the progression ~f the, disease.
By "administered in combination" or "combination therapy"
it is meant that the compound of Formula I and one or more additional therapeutic agents are administered concurrently to the mammal being treated. when administered in combination each component may be administered at the same time or sequentially in any order at different points in time. Thus, each component may be administered separately but sufficiently closely in time so as to provide the desired therapeutic effect. Other anticoagulant agents (or coagulation inhibitory agents) that may be used in combination with the compounds of this invention include warfarin and heparin, as well as other factor Xa inhibitors such as those described in the publications identified above under Background of the Invention.
The term anti-platelet agents (or platelet inhibitory agents), as used herein, denotes agents that inhibit platelet function such as by inhibiting the aggregation, adhesion or granular secretion of platelets. Such agents include, but are not limited to, the various known non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen, sulindac, indomethacin, mefenamate, droxicam, diclofenac, sulfinpyrazone, and piroxicam, including pharmaceutically acceptable salts or prodrugs thereof. Of the NSAIDS, aspirin (acetylsalicyclic acid or ASA), and piroxicam are preferred. Other suitable anti-platelet agents include ticlopidine, including pharmaceutically acceptable salts or prodrugs thereof. Ticlopidine is also a preferred compound since it is known to be gentle on the gastro-intestinal tract in use. Still other suitable platelet inhibitory agents include IIb/IIIa antagonists, thromboxane-A2-receptor antagonists and thromboxane-A2-synthetase inhibitors, as well as pharmaceutically acceptable salts or prodrugs thereof.

The term thrombin inhibitors (or anti-thrombin agents), as used herein, denotes inhibitors of the serine protease thrombin. By inhibiting thrombin, various thrombin-mediated processes, such as thrombin-mediated platelet activation (that is, for example, the aggregation of platelets, and/or the granular secretion of plasminogen activator inhibitor-1 and/or serotonin) and/or fibrin formation are disrupted. A number of thrombin inhibitors are known to one of skill in the art and these inhibitors are contemplated to be used in combination with the present compounds. Such inhibitors include, but are not limited to, boroarginine derivatives, boropeptides, heparins, hirudin and argatroban, including pharmaceutically acceptable salts and prodrugs thereof. Boroarginine derivatives and boropeptides include N-acetyl and peptide derivatives of boronic acid, such as C-terminal a-aminoboronic acid derivatives of lysine, ornithine, arginine, homoarginine and corresponding isothiouronium analogs thereof. The term hirudin, as used herein, includes suitable derivatives or analogs of hirudin, referred to herein as hirulogs, such as disulfatohirudin. Boropeptide thrombin inhibitors include compounds described in Kettner et al., U.S. Patent No.
5,187,157 and European Patent Application Publication Number 293 881 A2, the disclosures of which are hereby incorporated herein by reference. Other suitable boroarginine derivatives and boropeptide thrombin inhibitors include those disclosed in PCT Application Publication Number 92/07869 and European Patent Application Publication Number 471,651 A2, the disclosures of which are hereby incorporated herein by reference.
The term thrombolytics (or fibrinolytic) agents (or thrombolytics or fibrinolytics), as used herein, denotes agents that lyse blood clots (thrombi). Such agents include tissue plasminogen activator, anistreplase, urokinase or streptokinase, including pharmaceutically acceptable salts or prodrugs thereof. The term anistreplase, as used herein, refers to anisoylated plasminogen streptokinase activator complex, as described, for example, in European Patent Application No. 028,489, the disclosure of which is hereby incorporated herein by reference herein. The term urokinase, as used herein, is intended to denote both dual and single chain urokinase, the latter also being referred to herein as prourokinase.
Administration of the compounds of Formula.I of r_he invention in combination with such additional therapeutic agent, may afford an efficacy advantage over the compounds and agents alone, and may do so while permitting the use of lower doses of each. A lower dosage minimizes the potential of side effects, thereby providing an increased margin of safety.
The compounds of the present invention are also useful as standard or reference compounds, for example as a quality standard or control, in tests or assays involving the inhibition of factor Xa. Such compounds may be provided in a commercial kit, for example, for use in pharmaceutical research involving factor Xa. For example, a compound of the present invention could be used as a reference in an assay to compare its known activity to a compound with an unknown activity. This would ensure the experimenter that the assay was being performed properly and provide a basis for comparison, especially if the test compound was a derivative of the reference compound. When developing new assays or protocols, compounds according to the present invention could be used to test their effectiveness.
The compounds of the present invention may also be used in diagnostic assays involving factor Xa. For example, the presence of factor Xa in an unknown sample could be determined by addition of chromogenic substrate 52222 to a series of solutions containing test sample and optionally one of the compounds of the present invention. If production of pNA is observed in the solutions containing test sample, but no compound of the present invention, then one would conclude factor Xa was present.
Dosaae and Formulation The compounds of this invention can be administered in such oral dosage forms as tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions. They may also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts. They can be administered alone, but generally will be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice.
The dosage regimen for the compounds of the present invention will, of course, vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the species, age, sex, health, medical condition, and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration, the renal and hepatic function of the patient, and the effect desired. A physician or veterinarian can determine and prescribe the effective amount of the drug required to prevent, counter, or arrest the progress of the thromboembolic disorder.
By way of general guidance, the daily oral dosage of each active ingredient, when used for the indicated effects, will range between about 0.001 to 1000 mg/kg of body weight, preferably between about 0.01 to 100 mg/kg of body weight per day, and most preferably between about 1.0 to 20 mg/kg/day.
Intravenously, the most preferred doses will range from about 1 to about 10 mg/kg/minute during a constant rate infusion.
Compounds of this invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily.
Compounds of this invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using transdermal skin patches. When administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen.

The compounds are typically aaministered in admixture with suitable pharmaceutical diluents, excipients, or carriers (collectively referred to herein as pharmaceutical carriers) suitably selected with respect to the intended form of administration, that is, oral tablets, capsules, elixirs, syrups and trie like, and consistent with conventional pharmaceutical practices.
For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, non-toxic, pharmaceutically acceptable, inert carrier such as lactose, starch, sucrose, glucose, methyl callulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like; for oral administration in liquid form, the oral drug components can be combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Moreover, when desired or necessary, suitable binders, lubricants, disintegrating agents, and coloring agents can also be incorporated into the mixture. Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like. Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like.
Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
The compounds of the present invention can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines.
Compounds of the present invention may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, the compounds of the present invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphipathic block copolymers of hydrogels.
Dosage forms (pharmaceutical compositions) suitable for administration may contain from about 1 milligram to about 100 milligrams of active ingredient per dosage unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95o by weight based on the total weight of the composition.
Gelatin capsuies may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like.
Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar coated or film coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract.
Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.
In general, water, a suitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances. Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents. Also used are citric acid and its salts and sodium EDTA. In addition, parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.
Suitable pharmaceutical carriers are described in Reminc~ton's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field.
Representative useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows:
Capsules A large number of unit capsules can be prepared by filling standard two-piece hard gelatin capsules each with 100 milligrams of powdered active ingredient, 150 milligrams of lactose, 50 milligrams of cellulose, and 6 milligrams magnesium stearate.
Soft Gelatin Capsules A mixture of active ingredient in a digestable oil such as soybean oil, cottonseed oil or olive oil may be prepared and injected by means of a positive displacement pump into gelatin to form soft gelatin capsules containing 100 milligrams of the active ingredient. The capsules should be washed and dried.
Tablets Tablets may be prepared by conventional procedures so that the dosage unit is 100 milligrams of active ingredient, 0.2 milligrams of colloidal silicon dioxide, 5 milligrams of magnesium stearate, 275 milligrams of microcrystalline cellulose, 11 milligrams of starch and 98.8 milligrams of lactose. Appropriate coatings may be applied to increase palatability or delay absorption.
Iniectable A parenteral composition suitable for administration by injection may be prepared by stirring 1.5~ by weight of active ingredient in 10~ by volume propylene glycol and water.
The solution should be made isotonic with sodium chloride and sterilized.

Suspension An aqueous suspension can be prepared for oral administration so that each 5 mL contain 100 mg of finely divided active ingredient, 200 mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of sorbitol solution, U.S.P., and 0.025 mL of vanillin.
Where the compounds of this invention are combined with other anticoagulant agents, for example, a daily dosage may be about 0.1 to 100 milligrams of the compound of Formula I and about 1 to 7.5 milligrams of the second anticoagulant, per kilogram of patient body weight. For a tablet dosage form, the compounds of this invention generally may be present in an amount of about 5 to 10 milligrams per dosage unit, and the second anti-coagulant in an amount of about 1 to 5 milligrams per dosage unit.
Where the compounds of Formula I are administered in combination with an anti-platelet agent, by way of general guidance, typically ~ daily dosage may be about 0.01 to 25 milligrams of the compound of Formula I and about 50 to 150 milligrams of the anti-platelet agent, preferably about 0.1 to 1 milligrams of the compound of Formula I and about 1 to 3 milligrams of antiplatelet agents, per kilogram of patient body weight.
Where the compounds of Formula I are adminstered in combination with thrombolytic agent, typically a daily dosage may be about 0.1 to 1 milligrams of the compound of Formula I, per kilogram of patient body weight and, in the case of the thrombolytic agents, the usual dosage of the thrombolyic agent when administered alone may be reduced by about ?0-80~ when administered with a compound of Formula I.
Where two or more of the foregoing second therapeutic agents are administered with the compound of Formula I, generally the amount of each component in a typical daily dosage and typical dosage form may be reduced relative to the usual dosage of the agent when administered alone, in view of the additive or synergistic effect of the therapeutic agents when administered in combination.

Particularly when provided as a single dosage unit, the potential exists for a chemical interaction between the combined active ingredients. For this reason, when the compound of Formula I and a second therapeutic agent are combined in a single dosage unit they are formulated such that although the active ingredients are combined in a single dosage unit, the physical contact between the active ingredients is minimized (that is, reduced). For example, one active ingredient may be enteric coated. By enteric coating one of the active ingredients, it is possible not only to minimize the contact between the combined active ingredients, but also, it is possible to control the release of one of these components in the gastrointestinal tract such that one of these components is not released in the stomach but rather is released in the intestines. One of the active ingredients may also be coated with a material which effects a sustained-release throughout the gastrointestinal tract and also serves to minimize physical contact between the combined active ingredients. Furthermore, the sustained-released component can be additionally enteric coated such that the release of this component occurs only in the intestine. Still another approach would involve the formulation of a combination product in which the one component is coated with a sustained and/or enteric release polymer, and the other component is also coated with a polymer such as a lowviscosity grade of hydroxypropyl methylcellulose (HPMC) or other appropriate materials as known in the art, in order to further separate the active components. The polymer coating serves to form an additional barrier to interaction with the other component.
These as well as other ways of minimizing contact between the components of combination products of the present invention, whether administered in a single dosage form or administered in separate forms but at the same time by the same manner, will be readily apparent to those skilled in the art, once armed with the present disclosure.
Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise that as specifically described herein.

Claims (15)

WHAT IS CLAIMED AS NEW AND DESIRED TO BE SECURED BY LETTER
PATENT OF UNITED STATES IS:

1. A compound of formula I:
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein;
ring M contains from 0-4 N atoms;
D is selected from CN, C(=NR7)NR8R9, NHC(=NR7)NR8R9, NR8CH(=NR7), C(O)NR8R9, and (CR8R9)tNR8R9;
E is selected from phenyl, 2-pyridyl, 4-pyridyl, pyrimidyl, and piperidinyl. substituted with 1 R;
R is selected from H, F, C1, Br, I, OR3, SR3, CO2R3, NO2, and CH2OR3, and (CR8R9)t NR8R9;
alternatively, E and R combine to form methylenedioxy or ethylenedioxy;
Z is selected from a band, C1-4 alkylene, (CH2)r O(CH2)r, (CH2) r NR3 (CH2) r, (CH2) r C (O) (CH2) r C (CH2) r C (O) O (CH2) r (CH2)r OC(O)(CH2)r, (CH2)r C(O)NR3(CH2)r, (CH2) r OC (O) (CH2) r, (CH2) r OC (O) O (CH2) r, (CH2) r OC (O)NR3 (CH2) r, (CH2) r NR3C (O) O (CH2) r, (CH2)r NR3C(O)NR3(CH2)r, (CH2)r S(O)p(CH2)r, (CH2)r SO2NR3(CH2)r, (CH2)r NR3SO2(CH2)r, and (CH2)r NR3SO2NR3(CH2)r, provided that Z does not form a N-N, N-O, N-S, NCH2N, NCH2O, or NCH2S bond with ring M or group A;

R1a and R1b are independently absent or selected from -(CH2)r-R1', -CH=CH-R1', NCH2R1", OCH2R1", SCH2R1", NH(CH2)2(CH2)t R1', O(CH2)2(CH2)t R1, and S(CH2)2(CH2)t R1';
alternatively, R1a and R1b, when attached to adjacent carbon atoms, together with the atoms to which they are attached form a 5-8 membered saturated, partially saturated or unsaturated ring substituted with 0-2 R4 and which contains from 0-2 heteroatoms selected from the group consisting of N, O, and S;
alternatively, when Z is C(O)NH and R1a is attached to a ring carbon adjacent to Z, then R1a is a C(O) which replaces the amide hydrogen of Z to form a cyclic imide;
R1' is selected from H, C1-3 alkyl, F, Cl, Br, I, -CN, -CHO, (CF2)r CF3, (CH2)r OR2, NR2R2a, C(O)R2c, OC(O)R2, (CF2)r CO2R2c, S(O)p R2b NR2(CH2)r OR2, CH(=NR2c)NR2R2a, NR2C(O)R2b, NR2C(O)NHR2b, NR2C(O)2R2a, OC(O)NR2aR2b C(O) NR2R2a, C(O)NR2(CH2)r OR2, SO2NR2R2a, NR2SO2R2b, C3-6 carbocyclic residue substituted with 0-2 R4, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4;
R1" is selected from H, CH (CH2OR2)2, C(O)R2c, C (O)NR2R2a, S(O)R2b, S(O)2R2b, and SO2NR2R2a;
R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2a, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, phenethyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2c, at each occurrence, is selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl, C3-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b.
alternatively, R2 and R2a, together with the atom to which they are attached, combine to form a 5 or 6 membered saturated. partially saturated or unsaturated ring substituted with 0-2 R4b and containing from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;
R3, at each occurrence, is selected from H, C1-4 alkyl, and phenyl;
R3a, at each occurrence, is selected from H, C1-4 alkyl, and phenyl;
R3b, at each occurrence, is selected from H, C1-4 alkyl, and phenyl;
R3c, at each occurrence, is selected from C1-4 alkyl, and phenyl;
A is selected from:
C3-10 carbocyclic residue substituted with 0-2 R4, and l48 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R4;
B is selected from: H, Y, and X-Y;
X is selected from C1-4 alkylene, -CR2(CR2R2b}(CH2)t-, -C(O)-, -C(=NR1")- -CR2(NR1"R2)-, -CR2(OR2)-, -CR2(SR2)-, -C (O) CR2R2a- -CR2R2aC (O) , -S (O)p-, -S(O) p CR2R2a--CR2R2aS(O)p-, -S(O)2NR2-, -NR2S(O)2-, -NR2S(O)2CR2RZa--CR2R2aS(O)2NR2-, -NR2S(O)2NR2-, -C(O)NR2-, -NR2C(O)-, -C(O) NR2CR2R2a-, -NR2C (O) CR2R2a-, -CR2R2aC (O) NR2-, -CR2R2aNR2C (O)-, -NR2C (O) O-, -OC (O) NR2-, -NR2C (O) NR2-, -NR2- -NR2CR2R2a-, -CR2R2aNR2- O -CR2R2aO- and -OCR2R2a_;
Y is selected from:
(CH2)rNR2R2a, provided that X-Y do not form a N-N, O-N, or S-N bond, C3-10 carbocyclic residue substituted with 0-2 R4a, and 5-10 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S
substituted with 0-2 R4a;
R4, at each occurrence, is selected from H, =O, (CH2)r OR2, F, C1, Br, I, C1-4 alkyl, -CN, NO2, (CH2)rNR2R2a, (CH2) rC (O) R2c, NR2C (O) R2b, C (O) NR2R2a, NR2C (O) NR2R2a, CH(=NR2)NR2R2a, CH(=NS(O)2R5)NR2R2a, NHC(=NR2)NR2R2a C(O)NHC(=NR2)NR2R2a, SO2NR2R2a, NR2SO2NR2R2a, NR2SO2-C1-4 alkyl, NR2SO2R5, S(O)pR5, (CF2)r CF3, NCH2R1", OCH2R1", SCH2R1 " , N(CH2) 2 (CH2) tR1', O(CH2) 2 (CH2) tR1', and S(CH2)2(CH2)tR1';
alternatively, one R4 is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S;

R4a, at each occurrence, is selected from H, =O, (CH2)r OR2 (CH2)r-F, (CH2)r-Br, (CH2)r-C1, I, C1-4 alkyl, -CN, NO2, (CH2)rNR2R2a, (CH2)rNR2R2b, (CH2)r C(O)R2c NR2C(O)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a, NR2C(O)NR2R2a, CH(=NR2) NR2R2a, NHC (=NR2) NR2R2a SO2NR2R2a, NR2SO2NR2R2a NR2SO2-C1-4 alkyl, C(O)NHSO2-C1-4 alkyl, NR2SO2R5, S(O)pR5, and (CF2)r CF3;
alternatively, one R4a is a 5-6 membered aromatic heterocycle containing from 1-4 heteroatoms selected from the group consisting of N, O, and S and substituted with 0-1 R5;
R4b, at each occurrence, is selected from H, =O, (CH2)r OR3, F, C1, Br, I, C1-4 alkyl, -CN, NO2, (CH2)rNR3R3a (CH2)rC(O)R3, (CH2)rC(O)OR3c, NR3C(O)R3a, C(O)NR3R3a, NR3C(O)NR3R3a, CH(=NR3)NR3R3a, NH3C(=NR3)NR3R3a, SO2NR3R3a, NR3SO2NR3R3a, NR3SO2-C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)pCF3, S(O)p-C1-4 alkyl; S(O)p-phenyl, and (CF2)rCF3;
R5, at each occurrence, is selected from CF3, C1-6 alkyl, phenyl substituted with 0-2 R6, and benzyl substituted with 0-2 R6;
R6, at each occurrence, is selected from H, OH, (CH2)r OR2, F, C1, Br, I, C1-4 alkyl, CN, NO2, (CH2)r NR2R2a (CH2)r C(O)R2b NR2C(O)R2b, NR2C(O)NR2R2a, CH(=NH)NH2, NHC(=NH)NH2, SO2NR2R2a, NR2SO2NR2R2a, and NR2SO2C1-4 alkyl;
R7, at each occurrence, is selected from H, OH, C1-6 alkyl, C1-6 alkylcarbonyl, C1-6 alkoxy, C1-4 alkoxycarbonyl, (CH2)n-phenyl, C6-10 aryloxy, C6-10 aryloxycarbonyl, C6-10 arylmethylcarbonyl, C1-4 alkylcarbonyloxy C1-4 alkoxycarbonyl, C6-10 arylcarbonyloxy C1-4 alkoxycarbonyl, C1-6 alkylaminocarbonyl, phenylaminocarbonyl, and phenyl-C1-4 alkoxycarbonyl;
R8, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl;

alternatively, R7 and R8 combine to form a 5 or 6 membered saturated, ring which contains from 0-1 additional heteroatoms selected from the group consisting of N, O, and S;
R9, at each occurrence, is selected from H, C1-6 alkyl and (CH2)n-phenyl;
n is selected from 0, 1, 2, and 3;
m is selected from 0, 1, and 2;
p is selected from 0, 1, and 2;
r is selected from 0, 1, 2, and 3;
s is selected from 0, 1, and 2; and, t is selected from 0 and 1.

2. A compound according to Claim 1, wherein the compound is of fornnulae Ia-Io:
wherein:

Z is selected from a bond, CH2O, OCH2, CH2NH, NHCH2, CH2C(O), C(O)CH2, C(O)NH, C(O)NH, CH2S(O)2, S(O)2(CH2), SO2NH, and SO2NH;
B is selected from: Y, X-Y, and NR2R2a;
Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, benzofuran, benzothiofuran, indole, benzimidazole, benzoxazole, benzthiazole, indazole, benzisoxazole, benzisothiazole, and isoindazole;
Y may also be selected from the following bicyclic heteroaryl ring systems:
K is selected from O, S, NH, and N.

3. A compound according to Claim 2, wherein the compound is of formulae:

wherein:
D is selected from C(=NR7)NR8R9 and (CR8R9)t NR8R9;
R is selected from H, F, Cl, OR3, CH2OR3, CH2NH2;
A is selected from:
piperidinyl, piperazinyl, C5-6 carbocyclic residue substituted with 0-2 R4, and 5-6 membered heteroaryl containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4;
Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, benzimidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, and 1,3,4-triazole.

4. A compound according to Claim 3, wherein:

E is phenyl;
D is selected from C(=NH)NH2 and CH2NH2;
R is selected from H, F, Cl, and Br;
A is selected from:
C5-6 carbocyclic residue substituted with 0-2 R4, and 5-6 membered heteroaryl containing from 1-3 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4;
Y is selected from one of the following carbocyclic and heterocyclic systems which are substituted with 0-2 R4a;
phenyl, piperidinyl, piperazinyl, pyridyl, pyrimidyl, furanyl, morpholinyl, thiophenyl, pyrrolyl, pyrrolidinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, benzimidazolyl, oxadiazole, thiadiazole, triazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, and 1,3,4-triazole;
R2, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, C5-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2a, at each occurrence, is selected from H, CF3, C1-6 alkyl, benzyl, phenethyl, C5-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2b, at each occurrence, is selected from CF3, C1-4 alkoxy, C1-6 alkyl, benzyl, C5-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
R2c, at. each occurrence, is selected from CF3, OH, C1-4 alkoxy, C1-6 alkyl, benzyl, C5-6 carbocyclic residue substituted with 0-2 R4b, and 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from the group consisting of N, O, and S substituted with 0-2 R4b;
alternatively, R2 and R2a, together with the atom to which they are attached, combine to form a ring selected from imidazolyl, morpholino, piperazinyl, pyridyl, and pyrrolidinyl, substituted with 0-2 R4b;
R4, at each occurrence, is selected from H, =O, OR2, CH2OR2, F, Cl, C1-4 alkyl, NR2R2a, CH2NR2R2a, C(O)R2c, CH2C(O)R2c, C(O)NR2R2a, CH(=NR2)NR2R2a, CH(=NS(O)2R5)NR2R2a, SO2NR2R2a, NR2SO2-C1-4 alkyl, S(O)2R5, and CF3 provided that if B is H, then R4 is other than tetrazole, C(O)-alkoxy, and C(O)NR2R2a;
R4a, at each occurrence, is selected from H, =O, (CH2)r OR2, F, Cl, C1-4 alkyl, NR2R2a, CH2NR2R2a, NR2R2b, CH2NR2R2b, (CH2)r C(O)R2c, NR2C(O)R2b, C(O)NR2R2a, C(O)NH(CH2)2NR2R2a NR2C(O)NR2R2a, SO2NR2R2a, S(O)2R5, and CF3; and, R4b, at each occurrence, is selected from H, =O, (CH2)r OR3, F, Cl, C1-4 alkyl, NR3R3a, CH2NR3R3a, C(O)R3, CH2C(O)R3, C(O)OR3c, C(O)NR3R3a, CH (=NR3)NR3R3a, SO2NR3R3a, NR3SO2-C1-4 alkyl, NR3SO2CF3, NR3SO2-phenyl, S(O)2CF3, S(O)2-C1-4 alkyl, S(O)2-phenyl, and CF3.

5. A compound according to Claim 1, wherein the compound is selected from:

N-(2'-Aminosulfonyl-[1,1']biphen-4-yl)-2-(3'-amidinophenyl)nicotinamide;
N-(5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide;
N-[5-(2-t-butylaminosulfonyl)phenylpyrid-2-yl]-2-(3'-amidinophenyl)nicotinamide; and, N-[5-(2-aminosulfonyl)phenylpyrid-2-yl]-2-(3'-carboxamidophenyl)nicotinamide;
or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to Claim 1 or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to Claim 2 or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to Claim 3 or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to Claim 4 or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to Claim 5 or a pharmaceutically acceptable salt thereof.

11. A method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to Claim 1 or a pharmaceutically acceptable salt thereof.

12. A method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to Claim 2 or a pharmaceutically acceptable salt thereof.

13. A method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to Claim 3 or a pharmaceutically acceptable salt thereof.

14. A method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to Claim 4 or a pharmaceutically acceptable salt thereof.

15. A method for treating or preventing a thromboembolic disorder, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound according to Claim 5 or a pharmaceutically acceptable salt thereof.