LV12019B - BULK CYCLIC FIBERS INHIBITORS - Google Patents

BULK CYCLIC FIBERS INHIBITORS Download PDF

Info

Publication number: LV12019B
Authority: LV; Latvia
Prior art keywords: alkyl; optionally substituted; group; aryl; compound
Prior art date: 1994-12-22

Application number

LVP-97-141A

Other languages

English (en)

Latvian (lv)

Other versions

LV12019A (lv

Inventor

John GILLARD

John Dimaio

M.Arshad SIDDIQUI

Patrice Preville

Yves St-Denis

Micheline Tarazi

Sophie Levesque

Benoit Bachand

Jeremy John Edmunds

Annette Marian Doherty

Original Assignee

Biochem Pharma Inc.

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.)

1994-12-22

Filing date

1997-07-15

Publication date

1998-07-20

1994-12-22 Priority claimed from GBGB9426038.7A external-priority patent/GB9426038D0/en

1995-05-22 Priority claimed from GBGB9510267.9A external-priority patent/GB9510267D0/en

1995-05-22 Priority claimed from GBGB9510266.1A external-priority patent/GB9510266D0/en

1995-05-22 Priority claimed from GBGB9510265.3A external-priority patent/GB9510265D0/en

1997-07-15 Application filed by Biochem Pharma Inc. filed Critical Biochem Pharma Inc.

1998-04-20 Publication of LV12019A publication Critical patent/LV12019A/xx

1998-07-20 Publication of LV12019B publication Critical patent/LV12019B/en

Links

239000003112 inhibitor Substances 0.000 title description 19
239000000835 fiber Substances 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims description 211
150000001875 compounds Chemical class 0.000 claims description 197
-1 -C0-6alkyl-CO2-C Chemical group 0.000 claims description 107
125000003118 aryl group Chemical group 0.000 claims description 106
229910052739 hydrogen Inorganic materials 0.000 claims description 84
125000000623 heterocyclic group Chemical group 0.000 claims description 81
239000001257 hydrogen Substances 0.000 claims description 71
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 67
229920006395 saturated elastomer Polymers 0.000 claims description 59
229910052757 nitrogen Inorganic materials 0.000 claims description 49
125000003710 aryl alkyl group Chemical group 0.000 claims description 47
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 46
125000004093 cyano group Chemical group *C#N 0.000 claims description 44
125000005842 heteroatom Chemical group 0.000 claims description 44
125000000753 cycloalkyl group Chemical group 0.000 claims description 41
108090000765 processed proteins & peptides Proteins 0.000 claims description 41
150000001413 amino acids Chemical class 0.000 claims description 39
238000000034 method Methods 0.000 claims description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
229910052717 sulfur Inorganic materials 0.000 claims description 31
QMPCRVWNUNHDDQ-UHFFFAOYSA-N 2-[4-amino-5-oxo-5-(1,3-thiazol-2-yl)pentyl]guanidine Chemical compound NC(N)=NCCCC(N)C(=O)C1=NC=CS1 QMPCRVWNUNHDDQ-UHFFFAOYSA-N 0.000 claims description 29
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
229910052799 carbon Inorganic materials 0.000 claims description 28
125000001165 hydrophobic group Chemical group 0.000 claims description 25
208000007536 Thrombosis Diseases 0.000 claims description 20
229910052736 halogen Inorganic materials 0.000 claims description 20
125000003545 alkoxy group Chemical group 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
DFWYZYVGPSECMA-BYPYZUCNSA-N (2s)-5-(diaminomethylideneamino)-2-nitrosopentanoic acid Chemical compound NC(=N)NCCC[C@H](N=O)C(O)=O DFWYZYVGPSECMA-BYPYZUCNSA-N 0.000 claims description 12
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 12
230000002209 hydrophobic effect Effects 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 8
239000004475 Arginine Substances 0.000 claims description 6
MRKWCHOGYWOFMG-NSHDSACASA-N CCCCOC(=O)[C@](C(O)=O)(N=O)CCCNC(N)=N Chemical compound CCCCOC(=O)[C@](C(O)=O)(N=O)CCCNC(N)=N MRKWCHOGYWOFMG-NSHDSACASA-N 0.000 claims description 6
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 6
230000001732 thrombotic effect Effects 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
206010003178 Arterial thrombosis Diseases 0.000 claims description 3
206010047249 Venous thrombosis Diseases 0.000 claims description 3
125000001931 aliphatic group Chemical group 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims description 2
208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
206010008118 cerebral infarction Diseases 0.000 claims description 2
208000026106 cerebrovascular disease Diseases 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 14
125000005843 halogen group Chemical group 0.000 claims 7
125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 6
125000003275 alpha amino acid group Chemical group 0.000 claims 6
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 1
YIUUEKWYUCHZNU-UHFFFAOYSA-N 3-amino-n-[1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-benzyl-4-oxo-2,3,6,7,8,8a-hexahydropyrrolo[2,1-b][1,3]thiazine-6-carboxamide Chemical compound S1C2CCC(C(=O)NC(CCCN=C(N)N)C(=O)C=3SC4=CC=CC=C4N=3)N2C(=O)C(N)C1CC1=CC=CC=C1 YIUUEKWYUCHZNU-UHFFFAOYSA-N 0.000 claims 1
101100441109 Arabidopsis thaliana CRR7 gene Proteins 0.000 claims 1
ONTOQLRAKPYIJS-UHFFFAOYSA-N n-[5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-6-oxo-7-(2-phenylethyl)-3,4,7,8,9,9a-hexahydro-1h-pyrido[2,1-c][1,4]thiazine-4-carboxamide Chemical compound N=1C=CSC=1C(=O)C(CCCNC(=N)N)NC(=O)C(N1C2=O)CSCC1CCC2CCC1=CC=CC=C1 ONTOQLRAKPYIJS-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 302
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 178
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 155
239000000243 solution Substances 0.000 description 153
235000019439 ethyl acetate Nutrition 0.000 description 102
239000000203 mixture Substances 0.000 description 102
229940093499 ethyl acetate Drugs 0.000 description 97
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 91
230000002829 reductive effect Effects 0.000 description 89
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 74
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
239000000741 silica gel Substances 0.000 description 44
229910002027 silica gel Inorganic materials 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 43
239000012267 brine Substances 0.000 description 38
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
239000002904 solvent Substances 0.000 description 38
235000019270 ammonium chloride Nutrition 0.000 description 36
239000007787 solid Substances 0.000 description 36
108090000190 Thrombin Proteins 0.000 description 33
229910052943 magnesium sulfate Inorganic materials 0.000 description 33
229960004072 thrombin Drugs 0.000 description 32
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
0 C*(C[C@@](C(*)=O)NC)NC(C(N)=N)=N Chemical compound C*(C[C@@](C(*)=O)NC)NC(C(N)=N)=N 0.000 description 29
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
238000003756 stirring Methods 0.000 description 29
229940024606 amino acid Drugs 0.000 description 28
235000001014 amino acid Nutrition 0.000 description 28
229960000583 acetic acid Drugs 0.000 description 27
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
150000002431 hydrogen Chemical class 0.000 description 25
239000012044 organic layer Substances 0.000 description 24
239000000543 intermediate Substances 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 21
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
239000000047 product Substances 0.000 description 20
239000007858 starting material Substances 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 18
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 17
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 17
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 16
125000002619 bicyclic group Chemical group 0.000 description 16
239000013058 crude material Substances 0.000 description 16
229910001868 water Inorganic materials 0.000 description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 14
238000005406 washing Methods 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
239000002253 acid Substances 0.000 description 13
150000001299 aldehydes Chemical class 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 13
239000000706 filtrate Substances 0.000 description 13
238000001914 filtration Methods 0.000 description 13
150000002367 halogens Chemical group 0.000 description 13
230000002401 inhibitory effect Effects 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
101150041968 CDC13 gene Proteins 0.000 description 12
GEZDNKVNPSUCSU-UHFFFAOYSA-N N-[5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]pyrazine-2-carboxamide Chemical compound N(C(=N)N)CCCC(C(=O)C=1SC=CN=1)NC(=O)C1=CN=CC=N1 GEZDNKVNPSUCSU-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000003054 catalyst Substances 0.000 description 12
230000000694 effects Effects 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
108090000790 Enzymes Proteins 0.000 description 11
102000004190 Enzymes Human genes 0.000 description 11
229940122388 Thrombin inhibitor Drugs 0.000 description 11
229940088598 enzyme Drugs 0.000 description 11
239000003868 thrombin inhibitor Substances 0.000 description 11
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
238000001035 drying Methods 0.000 description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
239000003921 oil Substances 0.000 description 10
MAJHCCQPIDXPAN-UHFFFAOYSA-N 2-[4-amino-5-(1,3-benzothiazol-2-yl)-5-oxopentyl]guanidine Chemical compound C1=CC=C2SC(C(=O)C(CCCNC(N)=N)N)=NC2=C1 MAJHCCQPIDXPAN-UHFFFAOYSA-N 0.000 description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
230000003197 catalytic effect Effects 0.000 description 9
LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
239000000725 suspension Substances 0.000 description 9
238000010792 warming Methods 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
239000003146 anticoagulant agent Substances 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
CGAMNSKIHXUDMK-UHFFFAOYSA-N benzyl n-[methylsulfanyl(phenylmethoxycarbonylamino)methylidene]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N=C(SC)NC(=O)OCC1=CC=CC=C1 CGAMNSKIHXUDMK-UHFFFAOYSA-N 0.000 description 8
239000012043 crude product Substances 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
235000001968 nicotinic acid Nutrition 0.000 description 8
239000011664 nicotinic acid Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
238000000746 purification Methods 0.000 description 8
238000011282 treatment Methods 0.000 description 8
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
238000000605 extraction Methods 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 description 6
PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 6
HIIOOJGGMVEBBE-UHFFFAOYSA-N 6-oxo-8-(3-phenylpropanoyl)-1,3,4,7,9,9a-hexahydropyrazino[2,1-c][1,4]thiazine-4-carboxylic acid Chemical compound C1C(=O)N2C(C(=O)O)CSCC2CN1C(=O)CCC1=CC=CC=C1 HIIOOJGGMVEBBE-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
102000009123 Fibrin Human genes 0.000 description 6
108010073385 Fibrin Proteins 0.000 description 6
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 6
108010049003 Fibrinogen Proteins 0.000 description 6
102000008946 Fibrinogen Human genes 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
150000001336 alkenes Chemical class 0.000 description 6
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
239000000284 extract Substances 0.000 description 6
229950003499 fibrin Drugs 0.000 description 6
229940012952 fibrinogen Drugs 0.000 description 6
239000007789 gas Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000005897 peptide coupling reaction Methods 0.000 description 6
230000008569 process Effects 0.000 description 6
102000004196 processed proteins & peptides Human genes 0.000 description 6
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
239000012279 sodium borohydride Substances 0.000 description 6
229910000033 sodium borohydride Inorganic materials 0.000 description 6
239000000126 substance Substances 0.000 description 6
ZAQFUFHPCDFIOR-UHFFFAOYSA-N 5-methoxy-5-oxopentanoic acid;hydrochloride Chemical compound Cl.COC(=O)CCCC(O)=O ZAQFUFHPCDFIOR-UHFFFAOYSA-N 0.000 description 5
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
101150052863 THY1 gene Proteins 0.000 description 5
229910001115 Zinc-copper couple Inorganic materials 0.000 description 5
238000003556 assay Methods 0.000 description 5
238000006664 bond formation reaction Methods 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 5
150000002148 esters Chemical group 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
150000002466 imines Chemical class 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
239000000758 substrate Substances 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 5
238000010626 work up procedure Methods 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
208000027418 Wounds and injury Diseases 0.000 description 4
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238000011160 research Methods 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
238000012552 review Methods 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
HKSZLNNOFSGOKW-HMWZOHBLSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@@H]1C[C@H](NC)[C@H](OC)[C@@]4(C)O1 HKSZLNNOFSGOKW-HMWZOHBLSA-N 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
125000004962 sulfoxyl group Chemical group 0.000 description 1
FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
GZHRJEYBUUYERI-UHFFFAOYSA-N tert-butyl 2-(phenylmethoxycarbonylamino)hex-4-enoate Chemical compound CC=CCC(C(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 GZHRJEYBUUYERI-UHFFFAOYSA-N 0.000 description 1
FXRLWSYREBUSNL-UHFFFAOYSA-N tert-butyl 4-hydroxy-2-(phenylmethoxycarbonylamino)butanoate Chemical compound CC(C)(C)OC(=O)C(CCO)NC(=O)OCC1=CC=CC=C1 FXRLWSYREBUSNL-UHFFFAOYSA-N 0.000 description 1
JOHVKIPGBIKFLE-UHFFFAOYSA-N tert-butyl 4-iodo-2-(phenylmethoxycarbonylamino)butanoate Chemical compound CC(C)(C)OC(=O)C(CCI)NC(=O)OCC1=CC=CC=C1 JOHVKIPGBIKFLE-UHFFFAOYSA-N 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
206010043554 thrombocytopenia Diseases 0.000 description 1
101150068774 thyX gene Proteins 0.000 description 1
230000036964 tight binding Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
230000005945 translocation Effects 0.000 description 1
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000002604 ultrasonography Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
150000004799 α-ketoamides Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- 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
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pulmonology (AREA)
Hematology (AREA)
Diabetes (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Crystallography & Structural Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Peptides Or Proteins (AREA)

LVP-97-141A 1994-12-22 1997-07-15 BULK CYCLIC FIBERS INHIBITORS LV12019B (en)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GBGB9426038.7A GB9426038D0 (en)	1994-12-22	1994-12-22	Low molecular weight bicyclic thrombin inhibitors
GBGB9503136.5A GB9503136D0 (en)	1994-12-22	1995-02-17	Low molecular weight bicyclic thrombin inhibitors
GBGB9510267.9A GB9510267D0 (en)	1995-05-22	1995-05-22	Low molecular weight thiobicyclic thrombin inhibitors
GBGB9510266.1A GB9510266D0 (en)	1995-05-22	1995-05-22	Low molecular weight bicyclic thrombin inhibitors
GBGB9510265.3A GB9510265D0 (en)	1995-05-22	1995-05-22	Low molecular weight diaminobicyclic thrombin inhibitors
PCT/CA1995/000708 WO1996019483A1 (en)	1994-12-22	1995-12-21	Low molecular weight bicyclic thrombin inhibitors

Publications (2)

Publication Number	Publication Date
LV12019A LV12019A (lv)	1998-04-20
LV12019B true LV12019B (en)	1998-07-20

Family

ID=27517273

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
LVP-97-141A LV12019B (en)	1994-12-22	1997-07-15	BULK CYCLIC FIBERS INHIBITORS

Country Status (22)

Country	Link
EP (1)	EP0802916A1 (no)
JP (1)	JPH11508535A (no)
CN (1)	CN1175259A (no)
AP (1)	AP9701004A0 (no)
AU (2)	AU4250596A (no)
BG (1)	BG101647A (no)
CA (1)	CA2208772A1 (no)
CZ (1)	CZ189997A3 (no)
EE (1)	EE9700113A (no)
FI (1)	FI972466L (no)
HU (1)	HUT77651A (no)
IL (1)	IL116503A0 (no)
IS (1)	IS4504A (no)
LV (1)	LV12019B (no)
MD (1)	MD970253A (no)
MX (1)	MX9704718A (no)
NO (1)	NO972892L (no)
NZ (1)	NZ297360A (no)
OA (1)	OA10493A (no)
PL (1)	PL320965A1 (no)
SK (1)	SK83897A3 (no)
WO (1)	WO1996019483A1 (no)

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US6020331A (en) *	1995-03-24	2000-02-01	Molecumetics, Ltd.	β-sheet mimetics and use thereof as protease inhibitors
IT1277405B1 (it) *	1995-08-01	1997-11-10	Menarini Farma Ind	Derivati di lattami biciclici come inibitori della trombina
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BR9707501A (pt) *	1996-02-13	1999-07-27	Akzo Nobel Nv	Composto composição farmacêutica e uso do composto
TW523513B (en) *	1996-03-01	2003-03-11	Akzo Nobel Nv	Serine protease inhibitors
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US6117896A (en) *	1997-02-10	2000-09-12	Molecumetics Ltd.	Methods for regulating transcription factors
EP1661566A3 (en) *	1996-08-05	2008-04-16	Myriad Genetics, Inc.	Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors
WO1998005333A1 (en) *	1996-08-05	1998-02-12	Molecumetics Ltd.	Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors
AU4172397A (en) *	1996-09-06	1998-03-26	Biochem Pharma Inc.	Lactam inhibitors of thrombin
US6194435B1 (en)	1996-10-11	2001-02-27	Cor Therapeutics, Inc.	Lactams as selective factor Xa inhibitors
US6063794A (en)	1996-10-11	2000-05-16	Cor Therapeutics Inc.	Selective factor Xa inhibitors
US6369080B2 (en)	1996-10-11	2002-04-09	Cor Therapeutics, Inc.	Selective factor Xa inhibitors
US6262047B1 (en)	1996-10-11	2001-07-17	Cor Therapeutics, Inc.	Selective factor Xa inhibitors
WO1998028326A1 (en) *	1996-12-23	1998-07-02	Biochem Pharma Inc.	Bicyclic thrombin inhibitors
AU6896398A (en)	1997-04-14	1998-11-11	Cor Therapeutics, Inc.	Selective factor xa inhibitors
EP0975659A1 (en) *	1997-04-14	2000-02-02	Cor Therapeutics, Inc.	SELECTIVE FACTOR Xa INHIBITORS
NZ500353A (en)	1997-04-14	2002-02-01	Cor Therapeutics Inc	Cyclic diaza compounds that are selective inhibitors of factor Xa
US6333321B1 (en)	1997-08-11	2001-12-25	Cor Therapeutics, Inc.	Selective factor Xa inhibitors
US6228854B1 (en)	1997-08-11	2001-05-08	Cor Therapeutics, Inc.	Selective factor Xa inhibitors
US6218382B1 (en)	1997-08-11	2001-04-17	Cor Therapeutics, Inc	Selective factor Xa inhibitors
WO1999015169A1 (en) *	1997-09-23	1999-04-01	Merck & Co., Inc.	Thrombin inhibitors
ES2192764T3 (es) *	1998-02-12	2003-10-16	Molecumetics Ltd	Mimeticos de lamina beta y metodos relacionados con el uso de los mismos.
US6323219B1 (en)	1998-04-02	2001-11-27	Ortho-Mcneil Pharmaceutical, Inc.	Methods for treating immunomediated inflammatory disorders
US8106094B2 (en)	1998-07-06	2012-01-31	Johnson & Johnson Consumer Companies, Inc.	Compositions and methods for treating skin conditions
US8093293B2 (en)	1998-07-06	2012-01-10	Johnson & Johnson Consumer Companies, Inc.	Methods for treating skin conditions
AU3127900A (en)	1998-12-23	2000-07-31	Du Pont Pharmaceuticals Company	Thrombin or factor xa inhibitors
BR0007778A (pt)	1999-01-27	2002-06-04	Ortho Mcneil Pharm Inc	Peptidila cetonas heterocìclicas úteis como inibidores de triptase
FR2795072B1 (fr) *	1999-06-15	2001-07-27	Adir	Nouveaux derives bicycliques d'amino-pyrazinones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US7309688B2 (en)	2000-10-27	2007-12-18	Johnson & Johnson Consumer Companies	Topical anti-cancer compositions and methods of use thereof
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US6586418B2 (en)	2000-06-29	2003-07-01	Bristol-Myers Squibb Company	Thrombin or factor Xa inhibitors
US8431550B2 (en)	2000-10-27	2013-04-30	Johnson & Johnson Consumer Companies, Inc.	Topical anti-cancer compositions and methods of use thereof
FR2818277B1 (fr) *	2000-12-14	2003-01-24	Servier Lab	Nouveaux derives bicycliques d'amino-pyrazinones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
US7192615B2 (en)	2001-02-28	2007-03-20	J&J Consumer Companies, Inc.	Compositions containing legume products
US7053214B2 (en)	2002-02-14	2006-05-30	Myriad Genetics, Inc.	β-sheet mimetics and composition and methods relating thereto
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JP6642948B2 (ja)	2014-10-06	2020-02-12	コーテクシーミー，インコーポレイテッド	リシンジンジパインの阻害剤
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TW201932470A (zh)	2017-11-29	2019-08-16	愛爾蘭商健生科學愛爾蘭無限公司	具有抗ｒｓｖ活性之吡唑并嘧啶
EA202091835A1 (ru)	2018-01-31	2020-10-20	Янссен Сайенсиз Айрлэнд Анлимитед Компани	Замещенные циклоалкилом пиразолопиримидины, обладающие активностью против rsv
MX2020011200A (es)	2018-04-23	2020-11-13	Janssen Sciences Ireland Unlimited Co	Compuestos heteroaromaticos que tienen actividad contra vrs.

1995
- 1995-12-21 AU AU42505/96A patent/AU4250596A/en not_active Abandoned
- 1995-12-21 AP APAP/P/1997/001004A patent/AP9701004A0/en unknown
- 1995-12-21 EE EE9700113A patent/EE9700113A/xx unknown
- 1995-12-21 PL PL95320965A patent/PL320965A1/xx unknown
- 1995-12-21 CN CN95197614A patent/CN1175259A/zh active Pending
- 1995-12-21 JP JP8519383A patent/JPH11508535A/ja active Pending
- 1995-12-21 SK SK838-97A patent/SK83897A3/sk unknown
- 1995-12-21 MD MD97-0253A patent/MD970253A/ro unknown
- 1995-12-21 CA CA002208772A patent/CA2208772A1/en not_active Abandoned
- 1995-12-21 NZ NZ297360A patent/NZ297360A/xx unknown
- 1995-12-21 WO PCT/CA1995/000708 patent/WO1996019483A1/en not_active Application Discontinuation
- 1995-12-21 HU HU9800216A patent/HUT77651A/hu unknown
- 1995-12-21 CZ CZ971899A patent/CZ189997A3/cs unknown
- 1995-12-21 EP EP95940923A patent/EP0802916A1/en not_active Ceased
- 1995-12-22 AU AU40628/95A patent/AU715378B2/en not_active Ceased
- 1995-12-22 IL IL11650395D patent/IL116503A0/xx unknown
1997
- 1997-06-11 IS IS4504A patent/IS4504A/is unknown
- 1997-06-11 FI FI972466A patent/FI972466L/fi unknown
- 1997-06-18 OA OA70029A patent/OA10493A/en unknown
- 1997-06-20 BG BG101647A patent/BG101647A/xx unknown
- 1997-06-20 NO NO972892A patent/NO972892L/no unknown
- 1997-06-23 MX MX9704718A patent/MX9704718A/es unknown
- 1997-07-15 LV LVP-97-141A patent/LV12019B/en unknown

Also Published As

Publication number	Publication date
AU4250596A (en)	1996-07-10
FI972466A0 (fi)	1997-06-11
MD970253A (ro)	1999-05-31
IL116503A0 (en)	1996-03-31
NO972892L (no)	1997-08-20
NZ297360A (en)	2000-03-27
BG101647A (en)	1998-03-31
LV12019A (lv)	1998-04-20
AP9701004A0 (en)	1997-07-31
WO1996019483A1 (en)	1996-06-27
FI972466L (fi)	1997-08-19
SK83897A3 (en)	1998-05-06
NO972892D0 (no)	1997-06-20
AU715378B2 (en)	2000-02-03
AU4062895A (en)	1996-07-04
CN1175259A (zh)	1998-03-04
CZ189997A3 (cs)	1998-09-16
PL320965A1 (en)	1997-11-24
EP0802916A1 (en)	1997-10-29
CA2208772A1 (en)	1996-06-27
MX9704718A (es)	1998-06-28
EE9700113A (et)	1997-12-15
IS4504A (is)	1997-06-11
JPH11508535A (ja)	1999-07-27
OA10493A (en)	2002-04-10
HUT77651A (hu)	1998-07-28

Publication	Publication Date	Title
LV12019B (en)	1998-07-20	BULK CYCLIC FIBERS INHIBITORS
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