OA11062A - Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds - Google Patents

Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds Download PDF

Info

Publication number: OA11062A
Authority: OA; OAPI
Prior art keywords: sulfonic acid; oxopyrrolidin; ylmethyl; optionally substituted; chloro
Prior art date: 1996-12-13

Application number

OA9900124A

Other languages

English (en)

Inventor

Yong Mi Choi-Sledeski

Henry W Pauls

Jeffrey N Barton

William R Ewing

Daniel M Green

Michael R Becker

Original Assignee

Rhone Poulenc Rorer Pharma

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.)

1996-12-13

Filing date

1999-06-11

Publication date

2002-03-11

1999-06-11 Application filed by Rhone Poulenc Rorer Pharma filed Critical Rhone Poulenc Rorer Pharma

2002-03-11 Publication of OA11062A publication Critical patent/OA11062A/en

Links

LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title description 3
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 421
108010074860 Factor Xa Proteins 0.000 claims abstract description 30
230000000694 effects Effects 0.000 claims abstract description 28
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
CKARHIGQRRNVFD-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OC)=CC=C21 CKARHIGQRRNVFD-UHFFFAOYSA-N 0.000 claims description 118
-1 amide trifluoroacetate Chemical class 0.000 claims description 112
229910052757 nitrogen Inorganic materials 0.000 claims description 61
229910052739 hydrogen Inorganic materials 0.000 claims description 58
239000002253 acid Substances 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
125000000217 alkyl group Chemical group 0.000 claims description 34
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 31
125000003710 aryl alkyl group Chemical group 0.000 claims description 31
238000000034 method Methods 0.000 claims description 31
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
125000001072 heteroaryl group Chemical group 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 23
KTVOMLQUDMNZLK-UHFFFAOYSA-N 1-benzothiophene-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=C1 KTVOMLQUDMNZLK-UHFFFAOYSA-N 0.000 claims description 22
125000004475 heteroaralkyl group Chemical group 0.000 claims description 21
125000000547 substituted alkyl group Chemical group 0.000 claims description 20
239000003146 anticoagulant agent Substances 0.000 claims description 19
125000000623 heterocyclic group Chemical group 0.000 claims description 18
230000015572 biosynthetic process Effects 0.000 claims description 17
ZYDGKFWFDVZKMG-UHFFFAOYSA-N 6-chloro-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2SC(S(=O)(=O)O)=CC2=C1 ZYDGKFWFDVZKMG-UHFFFAOYSA-N 0.000 claims description 16
150000001408 amides Chemical class 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 12
208000007536 Thrombosis Diseases 0.000 claims description 11
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 11
125000003107 substituted aryl group Chemical group 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
238000002560 therapeutic procedure Methods 0.000 claims description 10
210000001367 artery Anatomy 0.000 claims description 9
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 9
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 9
210000003462 vein Anatomy 0.000 claims description 9
206010053567 Coagulopathies Diseases 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
230000002792 vascular Effects 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
208000035475 disorder Diseases 0.000 claims description 7
125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
230000001154 acute effect Effects 0.000 claims description 6
206010000891 acute myocardial infarction Diseases 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
125000001624 naphthyl group Chemical group 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
230000002093 peripheral effect Effects 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
206010028980 Neoplasm Diseases 0.000 claims description 5
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
201000011510 cancer Diseases 0.000 claims description 5
238000012423 maintenance Methods 0.000 claims description 5
208000037803 restenosis Diseases 0.000 claims description 5
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
210000005166 vasculature Anatomy 0.000 claims description 5
206010002388 Angina unstable Diseases 0.000 claims description 4
208000005189 Embolism Diseases 0.000 claims description 4
206010022562 Intermittent claudication Diseases 0.000 claims description 4
208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
206010040070 Septic Shock Diseases 0.000 claims description 4
208000001435 Thromboembolism Diseases 0.000 claims description 4
208000007814 Unstable Angina Diseases 0.000 claims description 4
208000036142 Viral infection Diseases 0.000 claims description 4
230000003187 abdominal effect Effects 0.000 claims description 4
230000002159 abnormal effect Effects 0.000 claims description 4
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
229940092714 benzenesulfonic acid Drugs 0.000 claims description 4
238000001631 haemodialysis Methods 0.000 claims description 4
230000000322 hemodialysis Effects 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
208000021156 intermittent vascular claudication Diseases 0.000 claims description 4
210000003127 knee Anatomy 0.000 claims description 4
230000007774 longterm Effects 0.000 claims description 4
210000003141 lower extremity Anatomy 0.000 claims description 4
XETFBTXVGCQYBD-UHFFFAOYSA-N methanamine;2,2,2-trifluoroacetic acid Chemical compound [NH3+]C.[O-]C(=O)C(F)(F)F XETFBTXVGCQYBD-UHFFFAOYSA-N 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
230000036303 septic shock Effects 0.000 claims description 4
230000001052 transient effect Effects 0.000 claims description 4
230000009385 viral infection Effects 0.000 claims description 4
150000001204 N-oxides Chemical class 0.000 claims description 3
125000005466 alkylenyl group Chemical group 0.000 claims description 3
210000005249 arterial vasculature Anatomy 0.000 claims description 3
208000015294 blood coagulation disease Diseases 0.000 claims description 3
238000010577 post-coronary angioplasty Methods 0.000 claims description 3
230000009885 systemic effect Effects 0.000 claims description 3
230000002537 thrombolytic effect Effects 0.000 claims description 3
OQMKLANOVPGNQS-YDALLXLXSA-N (3S)-3-amino-1-[(1-amino-6-methoxyisoquinolin-7-yl)methyl]pyrrolidin-2-one 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC2=CC=NC(N)=C2C=C1CN1CC[C@H](N)C1=O OQMKLANOVPGNQS-YDALLXLXSA-N 0.000 claims description 2
FCKLLRUYGATBJZ-NTISSMGPSA-N 6-chloro-n-[(3s)-2-oxo-1-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=NC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=C1 FCKLLRUYGATBJZ-NTISSMGPSA-N 0.000 claims description 2
GHJCYBFDKTZELP-KRWDZBQOSA-N 6-chloro-n-[(3s)-2-oxo-1-(1h-pyrrolo[3,2-c]pyridin-2-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound N1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=C1 GHJCYBFDKTZELP-KRWDZBQOSA-N 0.000 claims description 2
DCVXLCIPWIKDJU-BOXHHOBZSA-N 7-methoxy-n-[(3s)-2-oxo-1-(1h-pyrrolo[3,2-b]pyridin-2-ylmethyl)pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=N1 DCVXLCIPWIKDJU-BOXHHOBZSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims description 2
MGBXCZRURZLLGG-BOXHHOBZSA-N n-[(3s)-1-(3h-benzimidazol-5-ylmethyl)-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2NC=NC2=CC(CN2CC[C@@H](C2=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)=C1 MGBXCZRURZLLGG-BOXHHOBZSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
UVLKAUNUFWQFID-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=N1 UVLKAUNUFWQFID-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 8
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 3
IJZYUSAXPDDIKX-HNNXBMFYSA-N 6-chloro-n-[(3s)-1-(furo[3,2-b]pyridin-2-ylmethyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound C1=CC=C2OC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=N1 IJZYUSAXPDDIKX-HNNXBMFYSA-N 0.000 claims 2
SEYWMQRAUGNBSI-LMOVPXPDSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC=3C=CC4=CC=C(N=C4C=3)N)=CC2=C1 SEYWMQRAUGNBSI-LMOVPXPDSA-N 0.000 claims 2
238000007891 venous angioplasty Methods 0.000 claims 2
LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 claims 1
NILRJQHBKCPZCU-FYZYNONXSA-N 6-chloro-n-[(3s)-2-oxo-1-(1,2,3,4-tetrahydroisoquinolin-7-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CNCC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC=C21 NILRJQHBKCPZCU-FYZYNONXSA-N 0.000 claims 1
238000002399 angioplasty Methods 0.000 claims 1
CHHOGAXEDDUADQ-BQAIUKQQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;hydrochloride Chemical compound Cl.C1=CN=C(N)C2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 CHHOGAXEDDUADQ-BQAIUKQQSA-N 0.000 claims 1
CEPIVQSUYSIUSV-FYZYNONXSA-N n-[(3s)-1-[(4-aminothieno[2,3-d]pyrimidin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CN=C2SC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1N CEPIVQSUYSIUSV-FYZYNONXSA-N 0.000 claims 1
KJCAMNRIQLAECW-UTLKBRERSA-N n-[(3s)-2-oxo-1-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pyrrolidin-3-yl]thieno[3,2-b]pyridine-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@@H]3C(N(CC3)CC=3NC4=CN=CC=C4C=3)=O)=CC2=N1 KJCAMNRIQLAECW-UTLKBRERSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 96
239000003112 inhibitor Substances 0.000 abstract description 13
238000011282 treatment Methods 0.000 abstract description 12
230000000144 pharmacologic effect Effects 0.000 abstract description 4
230000004962 physiological condition Effects 0.000 abstract description 3
230000001668 ameliorated effect Effects 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 277
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 272
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 227
239000000243 solution Substances 0.000 description 220
239000007787 solid Substances 0.000 description 170
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 151
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 139
235000019439 ethyl acetate Nutrition 0.000 description 135
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 104
239000012043 crude product Substances 0.000 description 99
239000000047 product Substances 0.000 description 91
238000004440 column chromatography Methods 0.000 description 83
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 82
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 72
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
101150041968 CDC13 gene Proteins 0.000 description 61
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 61
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 58
239000012044 organic layer Substances 0.000 description 58
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
239000000460 chlorine Substances 0.000 description 50
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
229910052943 magnesium sulfate Inorganic materials 0.000 description 41
235000019341 magnesium sulphate Nutrition 0.000 description 41
235000002639 sodium chloride Nutrition 0.000 description 39
238000004007 reversed phase HPLC Methods 0.000 description 38
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
239000007858 starting material Substances 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
150000003839 salts Chemical class 0.000 description 32
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 28
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000010410 layer Substances 0.000 description 26
125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 22
125000003118 aryl group Chemical group 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
239000012267 brine Substances 0.000 description 21
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
229910000041 hydrogen chloride Inorganic materials 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
238000010992 reflux Methods 0.000 description 20
150000002500 ions Chemical class 0.000 description 19
229940086542 triethylamine Drugs 0.000 description 19
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 18
ZEXCZHWVXMIOFB-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(OC)=CC=C21 ZEXCZHWVXMIOFB-UHFFFAOYSA-N 0.000 description 17
239000002585 base Substances 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
238000000921 elemental analysis Methods 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
125000001309 chloro group Chemical group Cl* 0.000 description 15
238000000746 purification Methods 0.000 description 15
229920006395 saturated elastomer Polymers 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
125000005843 halogen group Chemical group 0.000 description 14
229910000104 sodium hydride Inorganic materials 0.000 description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
125000001246 bromo group Chemical group Br* 0.000 description 13
239000012312 sodium hydride Substances 0.000 description 13
238000010626 work up procedure Methods 0.000 description 13
DKSJHPRSSYLKRE-UHFFFAOYSA-N 7-(bromomethyl)-1-chloroisoquinoline Chemical compound C1=C(CBr)C=C2C(Cl)=NC=CC2=C1 DKSJHPRSSYLKRE-UHFFFAOYSA-N 0.000 description 12
150000002431 hydrogen Chemical group 0.000 description 12
239000007921 spray Substances 0.000 description 12
239000008280 blood Substances 0.000 description 11
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USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 10
108090000190 Thrombin Proteins 0.000 description 10
229940127219 anticoagulant drug Drugs 0.000 description 10
125000004104 aryloxy group Chemical group 0.000 description 10
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229940073584 methylene chloride Drugs 0.000 description 10
239000002904 solvent Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
229960004072 thrombin Drugs 0.000 description 10
PHPBFBHVSTXJOL-UHFFFAOYSA-N 6-chloro-1-benzothiophene-2-sulfonyl chloride Chemical compound ClC1=CC=C2C=C(S(Cl)(=O)=O)SC2=C1 PHPBFBHVSTXJOL-UHFFFAOYSA-N 0.000 description 9
239000005695 Ammonium acetate Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
235000019257 ammonium acetate Nutrition 0.000 description 9
229940043376 ammonium acetate Drugs 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
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239000012074 organic phase Substances 0.000 description 9
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108090000790 Enzymes Proteins 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 8
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
230000017531 blood circulation Effects 0.000 description 8
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239000000706 filtrate Substances 0.000 description 8
239000012458 free base Substances 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 7
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IKPVGHGCBQYMAE-SFHVURJKSA-N n-[(3s)-1-[(4-chlorothieno[3,2-d]pyrimidin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical group N1=CN=C2C(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CSC2=C1Cl IKPVGHGCBQYMAE-SFHVURJKSA-N 0.000 description 1
DEDKGZOVZNVTSM-JTQLQIEISA-N n-[(3s)-2-oxo-1-prop-2-ynylpyrrolidin-3-yl]thieno[3,2-b]pyridine-2-sulfonamide Chemical compound C1CN(CC#C)C(=O)[C@H]1NS(=O)(=O)C1=CC2=NC=CC=C2S1 DEDKGZOVZNVTSM-JTQLQIEISA-N 0.000 description 1
RBEDYBJZPKTQSA-UHFFFAOYSA-N n-[7-(bromomethyl)-1-chloroisoquinolin-6-yl]-1,1-diphenylmethanimine Chemical compound BrCC=1C=C2C(Cl)=NC=CC2=CC=1N=C(C=1C=CC=CC=1)C1=CC=CC=C1 RBEDYBJZPKTQSA-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000017570 negative regulation of blood coagulation Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
238000011587 new zealand white rabbit Methods 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
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150000002825 nitriles Chemical class 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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150000002895 organic esters Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
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NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
229940012957 plasmin Drugs 0.000 description 1
229940127126 plasminogen activator Drugs 0.000 description 1
229940051841 polyoxyethylene ether Drugs 0.000 description 1
229920000056 polyoxyethylene ether Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005470 propylenyl group Chemical group 0.000 description 1
229960000856 protein c Drugs 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
LOGAFLFGWNBIIG-UHFFFAOYSA-N pyridin-3-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CN=C1 LOGAFLFGWNBIIG-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
RASPWLYDBYZRCR-UHFFFAOYSA-N pyrrolidin-1-ium-2-one;chloride Chemical compound Cl.O=C1CCCN1 RASPWLYDBYZRCR-UHFFFAOYSA-N 0.000 description 1
PDAOMDFESOUGIO-UHFFFAOYSA-N pyrrolo[3,2-b]pyridin-5-one Chemical compound O=C1C=CC2=NC=CC2=N1 PDAOMDFESOUGIO-UHFFFAOYSA-N 0.000 description 1
150000005255 pyrrolopyridines Chemical class 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
238000011555 rabbit model Methods 0.000 description 1
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230000002829 reductive effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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239000012047 saturated solution Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229960002668 sodium chloride Drugs 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
230000036262 stenosis Effects 0.000 description 1
208000037804 stenosis Diseases 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
238000003860 storage Methods 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
WSKPJLPNZQUQQW-UHFFFAOYSA-N tert-butyl 2-pyrrolo[3,2-c]pyridin-1-ylacetate Chemical compound N1=CC=C2N(CC(=O)OC(C)(C)C)C=CC2=C1 WSKPJLPNZQUQQW-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
KHXSHOAPGUCQLC-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=CC2=N1 KHXSHOAPGUCQLC-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
230000002885 thrombogenetic effect Effects 0.000 description 1
239000002396 thromboxane receptor blocking agent Substances 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000004448 titration Methods 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
238000001665 trituration Methods 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
229960001322 trypsin Drugs 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
229940007718 zinc hydroxide Drugs 0.000 description 1
229910021511 zinc hydroxide Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Hematology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

OA9900124A 1996-12-13 1999-06-11 Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds OA11062A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US3315996P	1996-12-13	1996-12-13

Publications (1)

Publication Number	Publication Date
OA11062A true OA11062A (en)	2002-03-11

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ID=21868858

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900124A OA11062A (en)	1996-12-13	1999-06-11	Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds

Country Status (23)

Country	Link
EP (1)	EP0944386B1 (fr)
JP (1)	JP4223560B2 (fr)
KR (1)	KR20000057528A (fr)
CN (1)	CN1244798A (fr)
AP (1)	AP1032A (fr)
AT (1)	ATE224192T1 (fr)
AU (1)	AU726637B2 (fr)
BG (1)	BG103558A (fr)
BR (1)	BR9713921A (fr)
CA (1)	CA2274686C (fr)
DE (1)	DE69715658T2 (fr)
DK (1)	DK0944386T3 (fr)
EA (1)	EA002817B1 (fr)
ES (1)	ES2184145T3 (fr)
HU (1)	HUP9904188A3 (fr)
IL (1)	IL130152A0 (fr)
NO (1)	NO312416B1 (fr)
OA (1)	OA11062A (fr)
PL (1)	PL333921A1 (fr)
PT (1)	PT944386E (fr)
SK (1)	SK71299A3 (fr)
WO (1)	WO1998025611A1 (fr)
ZA (1)	ZA9711207B (fr)

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US6281227B1 (en) *	1996-12-13	2001-08-28	Aventis Pharma Deutschland Gmbh	Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
US6602864B1 (en) *	1996-12-13	2003-08-05	Aventis Pharma Deutschland Gmbh	Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds
IL123986A (en) *	1997-04-24	2011-10-31	Organon Nv	Medicinal compounds
AR016817A1 (es)	1997-08-14	2001-08-01	Smithkline Beecham Plc	Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento
AU8875798A (en)	1997-08-29	1999-03-22	Proteus Molecular Design Ltd	Meta-benzamidine derivatives as serin protease inhibitors
DE69833036T2 (de)	1997-09-30	2006-06-22	Daiichi Pharmaceutical Co., Ltd.	Sulfonylderivate
AU753675B2 (en)	1998-03-19	2002-10-24	Ajinomoto Co., Inc.	Aminoisoquinoline derivatives
CA2340100A1 (fr) *	1998-08-11	2000-02-24	Daiichi Pharmaceutical Co., Ltd.	Nouveaux derives sulfonyle
CA2408913A1 (fr)	2000-05-16	2001-11-22	Takeda Chemical Industries, Ltd.	Antagoniste de l'hormone de concentration de la melanine
GB0114004D0 (en)	2001-06-08	2001-08-01	Glaxo Group Ltd	Chemical compounds
GB0114005D0 (en)	2001-06-08	2001-08-01	Glaxo Group Ltd	Chemical compounds
GB0127568D0 (en)	2001-11-16	2002-01-09	Glaxo Group Ltd	Chemical compounds
AU2003232173A1 (en) *	2002-06-12	2003-12-31	Qsi Pharma A/S	Compounds and methods for controlling bacterial virulence
PT1569912E (pt)	2002-12-03	2015-09-15	Pharmacyclics Llc	Derivados 2-(2-hidroxibifenil-3-il)-1h-benzoimidazole-5- carboxamidina como inibidores do fator viia
EP1784410A4 (fr) *	2004-08-09	2009-07-15	Glaxo Group Ltd	Agents antibacteriens
FR2890072A1 (fr)	2005-09-01	2007-03-02	Fournier S A Sa Lab	Nouveaux composesde pyrrolopyridine
JP5147401B2 (ja) *	2005-09-06	2013-02-20	塩野義製薬株式会社	Ｐｇｄ２受容体アンタゴニスト活性を有するインドールカルボン酸誘導体
FR2955110A1 (fr)	2010-01-08	2011-07-15	Fournier Lab Sa	Nouveaux derives de type pyrrolopyridine benzoique
EP2606893A1 (fr)	2011-12-21	2013-06-26	Sanofi	Dérivés de la sulphonylaminopyrrolidinone, leur préparation et leur application thérapeutique
CN104098497B (zh) *	2014-06-17	2016-04-13	王庚禹	一种新的酰胺类化合物

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DE4121947A1 (de) *	1991-07-03	1993-01-07	Basf Ag	2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung
JPH10503176A (ja) *	1994-06-17	1998-03-24	コーバスインターナショナル，インコーポレイテッド	酵素インヒビターとしての３−アミノ−２−オキソ−１−ピペリジン酢酸誘導体
US5612353A (en) *	1995-06-07	1997-03-18	Rhone-Poulenc Rorer Pharmaceuticals Inc.	Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds

1997
- 1997-12-03 ES ES97951573T patent/ES2184145T3/es not_active Expired - Lifetime
- 1997-12-03 DK DK97951573T patent/DK0944386T3/da active
- 1997-12-03 DE DE69715658T patent/DE69715658T2/de not_active Expired - Lifetime
- 1997-12-03 EA EA199900542A patent/EA002817B1/ru not_active IP Right Cessation
- 1997-12-03 CN CN97181387A patent/CN1244798A/zh active Pending
- 1997-12-03 IL IL13015297A patent/IL130152A0/xx unknown
- 1997-12-03 JP JP52684498A patent/JP4223560B2/ja not_active Expired - Fee Related
- 1997-12-03 EP EP97951573A patent/EP0944386B1/fr not_active Expired - Lifetime
- 1997-12-03 AP APAP/P/1999/001552A patent/AP1032A/en active
- 1997-12-03 SK SK712-99A patent/SK71299A3/sk unknown
- 1997-12-03 HU HU9904188A patent/HUP9904188A3/hu unknown
- 1997-12-03 AU AU55182/98A patent/AU726637B2/en not_active Ceased
- 1997-12-03 WO PCT/US1997/022406 patent/WO1998025611A1/fr not_active Ceased
- 1997-12-03 KR KR1019990705236A patent/KR20000057528A/ko not_active Withdrawn
- 1997-12-03 AT AT97951573T patent/ATE224192T1/de not_active IP Right Cessation
- 1997-12-03 BR BR9713921A patent/BR9713921A/pt not_active IP Right Cessation
- 1997-12-03 PL PL97333921A patent/PL333921A1/xx unknown
- 1997-12-03 PT PT97951573T patent/PT944386E/pt unknown
- 1997-12-03 CA CA002274686A patent/CA2274686C/fr not_active Expired - Fee Related
- 1997-12-12 ZA ZA9711207A patent/ZA9711207B/xx unknown
1999
- 1999-06-11 NO NO19992853A patent/NO312416B1/no unknown
- 1999-06-11 OA OA9900124A patent/OA11062A/en unknown
- 1999-07-07 BG BG103558A patent/BG103558A/xx unknown

Also Published As

Publication number	Publication date
DE69715658T2 (de)	2003-05-22
CN1244798A (zh)	2000-02-16
NO312416B1 (no)	2002-05-06
NO992853D0 (no)	1999-06-11
AU726637B2 (en)	2000-11-16
NO992853L (no)	1999-08-10
ES2184145T3 (es)	2003-04-01
DK0944386T3 (da)	2003-01-27
CA2274686A1 (fr)	1998-06-18
EP0944386A4 (fr)	2001-04-11
PT944386E (pt)	2003-01-31
DE69715658D1 (de)	2002-10-24
ZA9711207B (en)	1998-07-20
CA2274686C (fr)	2009-02-03
AP1032A (en)	2001-12-24
AP9901552A0 (en)	1999-06-30
KR20000057528A (ko)	2000-09-25
PL333921A1 (en)	2000-01-31
EP0944386A1 (fr)	1999-09-29
EP0944386B1 (fr)	2002-09-18
EA199900542A1 (ru)	2000-02-28
BG103558A (en)	2000-04-28
HUP9904188A3 (en)	2003-02-28
IL130152A0 (en)	2000-06-01
SK71299A3 (en)	2000-12-11
AU5518298A (en)	1998-07-03
WO1998025611A1 (fr)	1998-06-18
HUP9904188A1 (hu)	2000-06-28
ATE224192T1 (de)	2002-10-15
EA002817B1 (ru)	2002-10-31
JP4223560B2 (ja)	2009-02-12
JP2001506630A (ja)	2001-05-22
BR9713921A (pt)	2000-03-21

Publication	Publication Date	Title
US6281227B1 (en)	2001-08-28	Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
EP0944386B1 (fr)	2002-09-18	Composes a base d'acide sulfonique ou de sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide
EP1051176B1 (fr)	2006-11-22	COMPOSES OXOAZAHETEROCYCLYLE SUBSTITUES INHIBITEURS DU FACTEUR Xa
US6602864B1 (en)	2003-08-05	Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds
KR100291711B1 (ko)	2001-09-17	3치환된(술핀산,술폰산,술포닐아미노또는술피닐아미노)n-(아미노이미노메틸)페닐알킬)-아자헤테로시클릴아미드화합물및이를포함하는약제학적조성물
US5731315A (en)	1998-03-24	Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds
JP2003529531A (ja)	2003-10-07	置換オキソアザへテロシクリルＸａ因子阻害剤
US6034093A (en)	2000-03-07	Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds
HRP20010903A2 (en)	2003-04-30	Pyrazinone thrombin inhibitors
MXPA99005483A (en)	2000-01-21	Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
CZ211599A3 (cs)	2000-09-13	Sulfonové nebo sulfonylaminové N- (heteroaralkyl)-azaheterocyklylamidové sloučeniny
MXPA00011884A (en)	2002-05-09	Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
CZ20004497A3 (en)	2001-06-13	Sulfonyl- or sulfonylamino-N-(heteroaralkyl)azaheterocyclylamide derivatives and pharmaceutical preparation containing thereof
MXPA00007250A (en)	2002-03-05	SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS
HK1030741A (en)	2001-05-18	Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds
CZ20002728A3 (cs)	2000-11-15	Substituované oxoazaheterocyklylové inhibitory faktoru Xa, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje