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CY1321A - 1,4-dihydropyridines their preparation and pharmaceutical compositions containing them - Google Patents

1,4-dihydropyridines their preparation and pharmaceutical compositions containing them Download PDF

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Publication number
CY1321A
CY1321A CY1321A CY132179A CY1321A CY 1321 A CY1321 A CY 1321A CY 1321 A CY1321 A CY 1321A CY 132179 A CY132179 A CY 132179A CY 1321 A CY1321 A CY 1321A
Authority
CY
Cyprus
Prior art keywords
compound
stated
offormula
ch2ch
compounds
Prior art date
Application number
CY1321A
Original Assignee
Sandoz Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sandoz Ltd filed Critical Sandoz Ltd
Publication of CY1321A publication Critical patent/CY1321A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Description

1
GB 2 037 766 A
1
SPECIFICATION
1,4-Dihydropyridines, their preparation and pharmaceutical compositions containing them
5 The present invention relates to 1,4-dihydropyridine derivatives.
The present invention provides compounds of formula I,
COOR.
C H.
15 wherein R,t R2, R3 and X are as defined as follows, and y indicates the ring position of the dihydropyridine moiety:-
20
CompoundR!
R 2
r3
y x
1
CH3
ch2ch(ch3)2
h
4
0
25 2
ch3
ch3
h
4
0
3
C2hs c2h5
h
5
0
4
30
5
ch2ch(ch3)2 ch2ch(ch3)2
c2h5 c2h5
h h
4 4
s
0
6
C(CH3)3
C(CH3)3
h
4
0
r-
in CO
CH2CH(CH3)2
CH2CH(CH3)2
H
4
0
8
(CH2)2OC2Hs c2h5
h
4
0
9
40
10
(CH2)2OCzH5 (CH2)2OC2H5
C2Hb c2h5
H h
4
5
s s
11
CH(CH3)2
ch3
H
4
0
45 12
<CH2)2OCH3
ch3
H
4
0
13
(CH2)2OCH{CH3)2
ch3
H
4
0
14
50
15
(CH2)2OC2H5
<0
ch3 ch3
h h
4 4
0 0
16
<CH2)2OCH3
CH(CH3)2
h
4
0
55 17
ch3
c2h5
h
4
0
18
c2h5
c2h5
ch3
4
0
19
c2h5
Q2H5
n-C3H7
4
0
60
The compounds offormula ifall under the scope of European Patent Application No. 78100165.6, but are not specifically disclosed therein. It has now been found that the compounds offormula I have particularly valuable pharmacological properties, e.g. their coronary activity is particularly long lasting and potent. Their 65 calcium antagonistic activity is particularly potent. They also possess a good tolerability.
2037766A l_>
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GB 2 037 766 A
2
The present invention also provides a process forthe production of a compound offormula I as defined above, comprising replacing the moiety -HC=Y in a compound offormula II,
-Hf no*
wherein X is as defined above and -HC=Y is i) formyl, ii) a radical offormula "
10 10
-HC=C-C(=Z)CH3
1°°*l
COOR,
15 or iii) a radial offormula -#c wherein Z and Z' are independently oxygen or NR3r and R1(R2 15
IIC-CI-IMCHj eooRj
20 and R3 are as defined above, by a moiety offormula III, 20
%A^coori
XX.
m
25 ij 25
wherein R-i, R2 and R3 are as defined above.
The process may be effected in conventional manner for analogous dihydropyridine syntheses, e.g. 30 according to Hantzsch. When the moiety -HC=Y is formyl and when it is desired to produce a compound of 30 formula I, wherein Rt is identical to R2, it is convenient to react a compound offormula II with a compound of formula IV,
CH3-CO-CH2-COOR2 IV
35 35
wherein R2 is as defined above, in the presence of a compound of formula V,
H2NR3 V
40 wherein R3 is as defined above. 40
Preferably at least 2 moles of a compound offormula IV per mole of a compound offormula II are present. Alternatively a compound offormula II may be reacted with a compound offormula VI,
CH3-C(NHR3)=CH-COORz VI
45 45
wherein R2 and R3 are as defined above.
Preferably at least 2 moles of a compound offormula VI per mole of a compound offormula II are present.
When the moiety -HC=Y is formyl and preferably when it is desired to produce a compound offormula I wherein R, is different to R2, it is also possible to react such a compound offormula II with a compound of 50 formula IV and a compound offormula VII, 50
CH3-C(NHR3}=CH-COOR, VII
wherein R1 and R3 are as defined above.
55 It will be appreciated that a compound offormula VI may be formed as an intermediate during the reaction 55 of a compound of formula IV and a compound offormula V. A compound offormula II, wherein -HC=Y is a radical ii) or iii), may be formed as an intermediate in the above reactions. They may however be produced by different processes.
Alternatively or particularly for the production of a compound offormula I, wherein R-i is different to R2, it 60 is convenient to react a compound offormula II, wherein the moiety -HC=Y is a radical ii) with a compound 60 offormula IV or VI, and where appropriate, with a compound offormula V. A compound offormula II,
wherein the moiety -HC=Y is a radical iii) may be an intermediate.
In the above reactions it is possible in certain instances when R1 and R2 are not identical that more than one isomer offormula I may be formed. If so these may be separated in conventional manner, e.g. by 65 column orthin layer chromatography. 65
BNSDOCIO: <GB 2037766A_I >
3
GB 2 037 766 A
3
When the starting material is a compound offormula II, wherein -HC=Y is a radical iii), the reaction is a ring cyclisation. When Z and 2! are both oxygen, then an amine offormula V should be present.
However, all the above reactions may be effected under the same conditions.
The reaction may be effected conveniently in solution. A suitable solvent is water, ethanol, dioxane, 5 dimethyl formamide, dimethyl sulphoxide, pyridine or glacial acetic acid. Suitable reaction temperatures may be from 20 to 160° C, preferably from 60 to 120° C.
Insofar as the production of starting materials is not particularly described these compounds are known or may be produced in analogous mannerto known compounds.
In the following Examples the temperatures given are in degrees Centigrade and are uncorrected.
10
Example 1:
4-(2,1,3-Benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydro-3-methoxycarbonyl-pyridine-5-carboxylic acidiso-butyl ester
3 g of 2,1,3-benzoxadiazole-4-aldehyde, 3.2 g of acetoacetic acid isobutyl ester, 2.3 g p-aminocrotonic acid 15 methyl ester and 10 ml of ethanol are stirred under reflux for 3 hours. The mixture is subsequently evaporated and the residue is chromatographed on silica gel with chloroform/acetic acid ethyl ester (8:1) to yield the title compound. The product is recrystallised from diisopropyl ether and methylcyclohexane, m.p. 148-158°.
By using the process described in Example 1, and corresponding starting compounds, e.g. a compound of 20 formula II, wherein -HC=Y is a radical i) and compounds of formula IV and V, and for Examples 4,5 and 8-17 a compound offormula II, wherein -HC=Yisa radical ii), wherein Z is oxygen and a compound offormula VI, the following compounds offormula I may be obtained, wherein y indicates the position of the dihydropyridine moiety:
Comp.
ri r2
r3
y x
m.p.
2
ch3
ch3
h
4
o
215-221
3
C2Hs c2h5
h
5
0
173-174
4
ch2ch{ch3)2
c2h5
h
4
s
85-95
5
ch2ch{ch3)2
c2h5
h
4
0
145-146.5
6
c(ch3)3
c(ch3)3
h
4
0
207-210
7
ch2ch(ch3)2
ch2ch{ch3)2
h
4
0
135.5-137
8
(ch2)2oc2h5
C2hs h
4
o
126-128
9
<ch2)2oc2h5
czhs h
4
s
Oel
10
(CH2)2oc2hs c2h5
h
5
s
72-78
11
ch(ch3)2
ch3
h
4
0
131-153
12
(ch2)2och3
ch3
h
4
0
151-153
13
(ch2)2och(ch3)2
ch3
h
4
0
114-120
14
(CH2)2oc2hs ch3
h
4
0
140-147
15
a ch3
h
4
0
156-163
16
<ch2)2och3
ch(ch3)2
h
4
0
119
17
ch3
c2h6
h
4
0
159
18
c2h5
c2h5
ch3
4
0
106
19
c2h5
c2h5
n-C3H7
4
0
99
The compounds of formula I exhibit pharmacological activity. In particular, they lead to a dilation of the 65 coronary vessels as demonstrated by the results of tests measuring the blood flow to the myocardium of an
BNSDOCID: <GB 2037766A_I_>
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GB 2 037 766 A
4
anaesthetised cat by means of the microsphere method {Rudolph A.M. and Heymann M.S.: Circulation Research 21,163,1967) upon administration of from 30 to 50 ng/kg i.v. or of from 50 to 150 ug/kg i.d. of the active substance.
The compounds offormula I also possess a favourable effect against angina pectoris, as shown by the 5 increase of the coronary flow of an anaesthetised cat upon administration of the active substance. 5
The compounds of formula I are therefore indicated for use in the treatment of coronary insufficiency.
The compounds offormula I increase the blood flow to limbs, e.g. leg musculature, as can be shown by means of the microsphere method on the anaesthetised cat upon administration of from 30 to 50 ug/kg i.v. or from 50 to 150 ug/kg i.d. of the compounds. *
10 The compounds offormula I are therefore indicated for use in the treatment of intermittent claudication 10 and other peripheral disturbances of blood flow to limb muscles.
The compounds of formula I increase cerebral blood flow, as can be shown by means of the microsphere method on the anaesthetised cat upon administration of from 30 to 50 ug/kg i.v. or from 50 to 150 ug/kg i.d. of the compounds.
15 The compounds offormula I aretherefore indicated for use in the treatment of cerebrovascular insults. 15
The compounds offormula I possess calcium-antagonistic activity as indicated in standard tests, for example by an inhibition of a calcium induced contraction of isolated dog coronary arteries suspended in a depolarizing solution at concentration of 10_10to 10~8 M of the compounds according to the principles of Godfraind and Kaba, Brit, J. Pharm. 36,549-560,1969.
20 The compounds offormula I aretherefore indicated for use as spasmolytic agents for the treatment of 20 spasms of muscles. For the above indications an indicated daily dose is from about 5to 100 mg,
conveniently administered in divided doses 2 to 4 times a day in unit dosage form containing from about 1.25 mg to about 50 mg, or in sustained release form.
Additionally, the compounds offormula I exhibit antihypertensive activity, as indicated in standard tests, 25 e.g. intheGrollman rat test [see A. Grollman, Proc. Soc. Expt. Biol, and Med. 57,104(1944)] on s.c. 25
administration of from 0.1 to 10 mg/kg animal body weight of the compounds.
The compounds offormula I are therefore further indicated for use as antihypertensive agents. For this use an indicated daily dose is from about 5 to about 1000 mg, conveniently given in divided doses 2 to 4 times a day in unit dosage form containing about 1.25 mg to about 500 mg, or in sustained release form. 30 The compounds offormula I may be administered in the form of a pharmaceutical composition. The 30
present invention accordingly provides pharmaceutical composition comprising a compound offormula I in association with a pharmaceutical carrier or diluent. Such compositions may be formulated by conventional techniques to be in conventional forms, for example capsules ortablets.
Compounds 1,5,11,12,13,14,15,16,17,18 and 19 are particularly interesting. Compounds 1 and 11 are 35 especially interesting. The coronary insuffiency, the intermittent claudication, the cerebrovascular insuffi- 35 ciency and the spasmolytic activities are the preferred utilities for compounds offormula 1.

Claims (23)

  1. 40 1. Aprocessfortheproductionofacompoundofformufal 40
    COOB1
    je Jl Ji x 45
    3 r3
    wherein R1f R2, Rsand X are as defined as follows, and y indicates the ring position of thedihydropyridine moiety:-
    BNSDOCID: <GB 2037766A_J_>
    5
    GB 2 037 766 A
    5
    Compound
    Ri r2
    r3
    y x
    1
    ch3
    ch2ch(ch3)2
    h
    4
    o
    5 2
    ch3
    ch3
    h
    4
    o
    3
    c2h5
    c2hs h
    5
    o
    ' 4
    ch2ch(ch3)2
    c2h5
    h
    4
    s
    10
    5
    ch2ch(ch3)2
    c2h5
    h
    4
    o
    6
    c(ch3)3
    c(ch3)3
    h
    4
    o
    15 7
    ch2ch(ch3)2
    ch2ch{ch3)2
    h
    4
    o
    8
    (ch2)2oc2h5
    c2h5
    h
    4
    o
    9
    (ch2)2oc2h5
    c2h5
    h
    4
    s
    20
    10
    (CH2)20c2hs c2h5
    h
    5
    s
    11
    ch(ch3)2
    ch3
    h
    4
    o
    25 12
    (ch2)2och3
    ch3
    h
    4
    o
    13
    (ch2)2och(ch3)2
    ch3
    h
    4
    0
    14
    (ch2)2oc2h5
    ch3
    h
    4
    0
    30
    15
    a ch3
    h
    4
    o
    16
    (ch2)2och3
    ch(ch3)2
    h
    4
    0
    35 17
    ch3
    c2h5
    h
    4
    0
    18
    c2h5
    c2hs ch3
    4
    0
    19
    c2h5
    c2h5
    n-C3H7
    4
    0
    40
    which comprises replacing the moiety -HC=Y in a compound offormula II,
    BO*;wherein X is as defined above and -HC=Yis i) formyl, ii) a radical offormula;.50;-HC=C-C(=Z)CH3;I;COOR,;or iii) a radical of formula -iic;\|C-C<-«'|CK3 COOR,;60 wherein Z and Z' are independently oxygen or NR3, and R1r R2 and R3 are as defined above, by a moiety of formula III,;MO*
    65 wherein Ri, R2 and R3 are as defined above.
    BNSDOCID: <GB 2037766A_I_>
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    60
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    GB 2 037 766 A
    6
  2. 2. A process for the production of a compound offormula I, as stated in claim 1 substantially as hereinbefore described with reference to any of the Examples.
  3. 3. A compound offormula I, whenever produced by a process according to claim 1 or2.
  4. 4. Compound 1, stated in claim 1.
  5. 5 5. Compound 2, stated in claim 1. 5
  6. 6. Compound 3, stated in claim 1.
  7. 7. Compound 4, stated in claim 1.
  8. 8. Compound 5, stated in claim 1.
  9. 9. Compound 6, stated in claim 1. = 10
  10. 10. Compound 7, stated in claim 1. 10
  11. 11. Compound 8, stated in claim 1.
  12. 12. Compound 9, stated in claim 1. 1
  13. 13. Compound 10, stated in claim 1.
  14. 14. Compound 11, stated in claim 1.
  15. 15 15. Compound 12, stated in claim 1. 15
  16. 16. Compound 13, stated in claim 1.
  17. 17. Compound 14, stated in claim 1.
  18. 18. Compound 15, stated in claim 1.
  19. 19. Compound 16, stated in claim 1.
  20. 20 20. Compound 17, stated in claim 1. 20
  21. 21. Compound 18, stated in claim 1.
  22. 22. Compound 19, stated in claim 1.
  23. 23. A pharmaceutical composition comprising a compound of any one of claims 3 to 22 in association with a pharmaceutical carrier or diluent.
    Printed for Her Majesty's Stationery Office, by Croydon Printing Company Limited, Croydon Surrey, 1980. Published by the Patent Office, 25 Southampton Buildings, London, WC2A 1AY, from which copies may be obtained.
    BNSDOCID: <GB 2037766A_l_>
CY1321A 1978-12-18 1979-12-14 1,4-dihydropyridines their preparation and pharmaceutical compositions containing them CY1321A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1283578A CH639659A5 (en) 1978-12-18 1978-12-18 NEW 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PRODUCTION AND USE.

Publications (1)

Publication Number Publication Date
CY1321A true CY1321A (en) 1986-06-27

Family

ID=4386824

Family Applications (1)

Application Number Title Priority Date Filing Date
CY1321A CY1321A (en) 1978-12-18 1979-12-14 1,4-dihydropyridines their preparation and pharmaceutical compositions containing them

Country Status (18)

Country Link
JP (1) JPS5583783A (en)
AU (1) AU536055B2 (en)
BE (1) BE880591A (en)
CH (1) CH639659A5 (en)
CY (1) CY1321A (en)
DE (1) DE2949491A1 (en)
FR (1) FR2444681A1 (en)
GB (2) GB2103203B (en)
HK (1) HK16086A (en)
IE (1) IE49496B1 (en)
IT (1) IT1164097B (en)
KE (1) KE3593A (en)
MY (1) MY8500130A (en)
NL (2) NL193066C (en)
NZ (1) NZ192422A (en)
SE (1) SE445219B (en)
SG (1) SG97585G (en)
ZA (1) ZA796842B (en)

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Publication number Priority date Publication date Assignee Title
DE3022030A1 (en) * 1980-06-12 1981-12-17 Bayer Ag, 5090 Leverkusen 4-THIAZOLE or 4-IMIDAZOLE-SUBSTITUTED, 1,4-DIHYDROPYRIDINE, METHOD FOR THE PRODUCTION THEREOF AND THE MEDICINAL PRODUCTS CONTAINING THEM
CH655658B (en) * 1980-09-18 1986-05-15
EP0080220B1 (en) * 1981-11-17 1986-02-19 FISONS plc Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals
ZA83959B (en) * 1982-03-10 1984-09-26 Sandoz Ltd 1,4-dihydropyridine derivatives,their preparation and pharmaceutical compositions containing them
US4414213A (en) * 1982-03-22 1983-11-08 Mead Johnson & Company Dihydropyridyl cyclic imidate esters and their pharmaceutical use
IL68975A (en) * 1982-06-15 1987-01-30 Sandoz Ag 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydropyridine-3,5-dicarboxylic acid ester derivatives in optically active form,their preparation and pharmaceutical compositions containing them
FR2528431B1 (en) * 1982-06-15 1986-01-10 Sandoz Sa NOVEL 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
JPS5978186A (en) * 1982-10-27 1984-05-04 Yoshitomi Pharmaceut Ind Ltd 1,4-dihydropyridine-3,5-dicarboxylic acid ester derivative
US4794111A (en) * 1984-05-23 1988-12-27 Bayer Aktiengesellschaft Dihydropyridine preparations containing β-blockers
HU198844B (en) * 1984-06-14 1989-12-28 Sandoz Ag Process for producing new galenic pharmaceutical composition ensuring retarded release of active ingredient
US5260321A (en) * 1984-11-12 1993-11-09 Sandoz Ltd. Use of 1,4-dihydropyridine derivatives and combinations thereof with calcitonins
HU197201B (en) * 1985-10-01 1989-03-28 Sandoz Ag Process for producing oral pharmaceutical compositions of controlled solubility of the active components
DE3542794A1 (en) * 1985-12-04 1987-06-11 Bayer Ag ANTI-HYPERTENSIVE COMBINATION PREPARATION
GB8626217D0 (en) * 1986-11-03 1986-12-03 Sandoz Ltd Pharmaceutical compositions
US4816263A (en) * 1987-10-02 1989-03-28 Alza Corporation Dosage form for treating cardiovascular diseases comprising isradipine
KR940003492B1 (en) * 1988-10-27 1994-04-23 주식회사 유한양행 1,4-dihydropyridine derivative and preparation method thereof
DE4222770A1 (en) * 1992-07-10 1994-01-13 Bayer Ag Light-activated 1- (2-nitrobenzyl) -substituted 1,4-dihydropyridines
KR20040088519A (en) 2002-02-22 2004-10-16 뉴 리버 파마슈티칼스, 인크. Active Agent Delivery Systems and Methods for Protecting and Administering Active Agents
WO2005023787A1 (en) * 2003-09-10 2005-03-17 Shasun Chemicals And Drugs Limited Process for the manufacture of 2,1,3-benzoxadiazole-4-carboxaldehyde
CN103613584B (en) * 2013-11-27 2016-04-27 沈阳药科大学 The method of a kind of Isrodipine synthetic product aftertreatment

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DE1670824C3 (en) * 1967-03-20 1978-08-03 Bayer Ag, 5090 Leverkusen 1,4-Dihydropyridine-33-dicarboxylic acid alkyl ester
FR2320750A1 (en) * 1975-08-12 1977-03-11 Hexachimie 1,4-DIHYDRO PYRIDINES AND THEIR THERAPEUTIC APPLICATION
DE2616991A1 (en) * 1976-04-17 1977-10-27 Bayer Ag Thio-substd. dihydro-pyridine derivs. - coronary vasodilators and antihypertensives prepd. e.g. by reacting dicarbonyl cpds. with amines and thio-substd. ketones
JPS5373327A (en) * 1976-12-13 1978-06-29 Matsushita Electric Ind Co Ltd Power source system
FI64938C (en) * 1977-06-20 1984-02-10 Sandoz Ag PROCEDURE FOR THE FRAMEWORK OF THERAPEUTIC THERAPEUTIC BENSOX A- AND OX BENZOTIADIAZOLYL-1,4-DIHYDROPYRID DERIVATIVES

Also Published As

Publication number Publication date
CH639659A5 (en) 1983-11-30
GB2037766B (en) 1983-02-16
FR2444681B1 (en) 1982-10-29
NL990014I1 (en) 1999-07-01
FR2444681A1 (en) 1980-07-18
GB2037766A (en) 1980-07-16
IT1164097B (en) 1987-04-08
GB2103203B (en) 1983-06-08
GB2103203A (en) 1983-02-16
JPH0369910B2 (en) 1991-11-05
SG97585G (en) 1986-07-18
HK16086A (en) 1986-03-14
IE49496B1 (en) 1985-10-16
KE3593A (en) 1986-02-07
NZ192422A (en) 1982-09-14
NL193066B (en) 1998-05-06
AU5389679A (en) 1980-06-26
DE2949491A1 (en) 1980-06-26
SE7910188L (en) 1980-06-19
NL193066C (en) 1998-09-08
DE2949491C2 (en) 1988-10-27
JPS5583783A (en) 1980-06-24
NL7909024A (en) 1980-06-20
MY8500130A (en) 1985-12-31
IT7951095A0 (en) 1979-12-14
BE880591A (en) 1980-06-13
AU536055B2 (en) 1984-04-19
ZA796842B (en) 1981-07-29
SE445219B (en) 1986-06-09
IE792445L (en) 1980-06-18

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