BG62844B1 - Бензодиазепини като антагонисти на фибриноген, фармацевтичнисъстави, съдържащи съединенията, и метод за получаването им - Google Patents

Бензодиазепини като антагонисти на фибриноген, фармацевтичнисъстави, съдържащи съединенията, и метод за получаването им Download PDF

Info

Publication number: BG62844B1
Authority: BG; Bulgaria
Prior art keywords: carbonyl; tetrahydro; benzodiazepine; oxo; methyl
Prior art date: 1994-01-07

Application number

BG100698A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG100698A (bg

Inventor

William E. Bondinell

James F. Callahan

William F. Huffman

Richard M. Keenan

Thomas W. Ku

Kenneth A. Newlander

James M. Samanen

Irene N. Uzinskas

Original Assignee

Smithkline Beecham Corporation

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.)

1994-01-07

Filing date

1996-07-05

Publication date

2000-09-29

1996-07-05 Application filed by Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation

1997-02-28 Publication of BG100698A publication Critical patent/BG100698A/bg

2000-09-29 Publication of BG62844B1 publication Critical patent/BG62844B1/bg

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 262
238000000034 method Methods 0.000 title claims description 50
238000002360 preparation method Methods 0.000 title claims description 25
239000008194 pharmaceutical composition Substances 0.000 title claims description 10
239000005557 antagonist Substances 0.000 title description 6
229940049706 benzodiazepine Drugs 0.000 title description 5
150000001557 benzodiazepines Chemical class 0.000 title description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
239000001257 hydrogen Substances 0.000 claims abstract description 30
125000000217 alkyl group Chemical group 0.000 claims abstract description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
238000011282 treatment Methods 0.000 claims abstract description 16
208000006011 Stroke Diseases 0.000 claims abstract description 6
208000007536 Thrombosis Diseases 0.000 claims abstract description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
208000010125 myocardial infarction Diseases 0.000 claims abstract description 6
208000031481 Pathologic Constriction Diseases 0.000 claims abstract description 5
208000037804 stenosis Diseases 0.000 claims abstract description 5
206010061216 Infarction Diseases 0.000 claims abstract description 4
201000010099 disease Diseases 0.000 claims abstract description 4
230000007574 infarction Effects 0.000 claims abstract description 4
208000005189 Embolism Diseases 0.000 claims abstract 3
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract 2
-1 [4- (2-aminoethyl) -piperidin-1-yl] carbonyl Chemical group 0.000 claims description 114
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 91
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 49
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 20
208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 20
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
SXHPOBDTEYIZFL-UHFFFAOYSA-N 2-(1h-1,4-benzodiazepin-2-yl)acetic acid Chemical compound N1C(CC(=O)O)=CN=CC2=CC=CC=C21 SXHPOBDTEYIZFL-UHFFFAOYSA-N 0.000 claims description 9
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
239000011734 sodium Substances 0.000 claims description 9
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
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239000002552 dosage form Substances 0.000 claims description 8
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125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
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230000002401 inhibitory effect Effects 0.000 claims description 7
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241000124008 Mammalia Species 0.000 claims description 6
239000003153 chemical reaction reagent Substances 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
238000002399 angioplasty Methods 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
210000001367 artery Anatomy 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
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GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 3
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
BIIVGTIHIPJAHG-VWLOTQADSA-N 2-[(2s)-8-[methyl(2-piperidin-4-ylethyl)carbamoyl]-3-oxo-4-(2-phenylethyl)-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N([C@@H](CC(O)=O)C(=O)N(CCC=1C=CC=CC=1)CC1=CC=2)C1=CC=2C(=O)N(C)CCC1CCNCC1 BIIVGTIHIPJAHG-VWLOTQADSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 claims 1
FFOMBPPBROCUIJ-GOSISDBHSA-N 2-[(2r)-4-methyl-8-[methyl(2-piperidin-4-ylethyl)carbamoyl]-3-oxo-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound N([C@H](CC(O)=O)C(=O)N(C)CC1=CC=2)C1=CC=2C(=O)N(C)CCC1CCNCC1 FFOMBPPBROCUIJ-GOSISDBHSA-N 0.000 claims 1
PYZOVVQJTLOHDG-FQEVSTJZSA-N 2-[(2s)-4-methyl-3-oxo-7-(4-piperidin-4-ylpiperidine-1-carbonyl)-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound O=C([C@H](CC(O)=O)NC1=CC=2)N(C)CC1=CC=2C(=O)N(CC1)CCC1C1CCNCC1 PYZOVVQJTLOHDG-FQEVSTJZSA-N 0.000 claims 1
239000003146 anticoagulant agent Substances 0.000 claims 1
230000002537 thrombolytic effect Effects 0.000 claims 1
108010049003 Fibrinogen Proteins 0.000 abstract description 5
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230000036262 stenosis Effects 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
230000002776 aggregation Effects 0.000 abstract 1
238000004220 aggregation Methods 0.000 abstract 1
210000001772 blood platelet Anatomy 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 222
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 148
239000000243 solution Substances 0.000 description 127
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239000000203 mixture Substances 0.000 description 105
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 102
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 73
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
239000000741 silica gel Substances 0.000 description 41
229910002027 silica gel Inorganic materials 0.000 description 41
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
238000001819 mass spectrum Methods 0.000 description 36
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 29
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239000003921 oil Substances 0.000 description 28
235000019198 oils Nutrition 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 28
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
229910052786 argon Inorganic materials 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
239000007787 solid Substances 0.000 description 21
238000000825 ultraviolet detection Methods 0.000 description 20
239000000706 filtrate Substances 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 18
235000019341 magnesium sulphate Nutrition 0.000 description 18
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
238000004587 chromatography analysis Methods 0.000 description 17
238000004458 analytical method Methods 0.000 description 16
238000004128 high performance liquid chromatography Methods 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
239000003527 fibrinolytic agent Substances 0.000 description 14
238000003818 flash chromatography Methods 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
238000010992 reflux Methods 0.000 description 12
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
239000010410 layer Substances 0.000 description 11
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
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239000000047 product Substances 0.000 description 10
238000004809 thin layer chromatography Methods 0.000 description 10
IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical group NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 9
238000002329 infrared spectrum Methods 0.000 description 9
238000001802 infusion Methods 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
235000002639 sodium chloride Nutrition 0.000 description 9
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 9
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VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
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239000012267 brine Substances 0.000 description 8
229950005499 carbon tetrachloride Drugs 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
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230000005764 inhibitory process Effects 0.000 description 8
239000000843 powder Substances 0.000 description 8
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239000012298 atmosphere Substances 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
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229910052763 palladium Inorganic materials 0.000 description 7
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 7
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VJMAITQRABEEKP-UHFFFAOYSA-N [6-(phenylmethoxymethyl)-1,4-dioxan-2-yl]methyl acetate Chemical compound O1C(COC(=O)C)COCC1COCC1=CC=CC=C1 VJMAITQRABEEKP-UHFFFAOYSA-N 0.000 description 6
229940024606 amino acid Drugs 0.000 description 6
150000001413 amino acids Chemical class 0.000 description 6
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238000005984 hydrogenation reaction Methods 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000002156 mixing Methods 0.000 description 4
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
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DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 3
229960000549 4-dimethylaminophenol Drugs 0.000 description 3
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HSQTYEUTILRRAO-UHFFFAOYSA-N tert-butyl 4-(bromomethyl)-3-nitrobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(CBr)C([N+]([O-])=O)=C1 HSQTYEUTILRRAO-UHFFFAOYSA-N 0.000 description 1
DAQVUZYHQPEMQJ-UHFFFAOYSA-N tert-butyl 4-fluoro-3-(methylaminomethyl)benzoate Chemical compound CNCC1=CC(C(=O)OC(C)(C)C)=CC=C1F DAQVUZYHQPEMQJ-UHFFFAOYSA-N 0.000 description 1
IMOHPVDDNISLPY-UHFFFAOYSA-N tert-butyl 4-fluoro-3-methylbenzoate Chemical compound CC1=CC(C(=O)OC(C)(C)C)=CC=C1F IMOHPVDDNISLPY-UHFFFAOYSA-N 0.000 description 1
QBSYXOPQDZYINE-UHFFFAOYSA-N tert-butyl 4-piperidin-4-ylpiperidine-4-carboxylate Chemical compound C1CNCCC1C1(C(=O)OC(C)(C)C)CCNCC1 QBSYXOPQDZYINE-UHFFFAOYSA-N 0.000 description 1
RQRMFFGCUUGYPC-UHFFFAOYSA-N tert-butyl n-(2-piperidin-4-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCNCC1 RQRMFFGCUUGYPC-UHFFFAOYSA-N 0.000 description 1
AJWDWZOKUIOICF-UHFFFAOYSA-N tert-butyl n-methyl-n-(2-pyridin-4-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(C)CCC1=CC=NC=C1 AJWDWZOKUIOICF-UHFFFAOYSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
239000010409 thin film Substances 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
239000003868 thrombin inhibitor Substances 0.000 description 1
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
229960005001 ticlopidine Drugs 0.000 description 1
229960000187 tissue plasminogen activator Drugs 0.000 description 1
230000008733 trauma Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
ZTWIEIFKPFJRLV-UHFFFAOYSA-K trichlororuthenium;trihydrate Chemical compound O.O.O.Cl[Ru](Cl)Cl ZTWIEIFKPFJRLV-UHFFFAOYSA-K 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
230000002792 vascular Effects 0.000 description 1
108010047303 von Willebrand Factor Proteins 0.000 description 1
102100036537 von Willebrand factor Human genes 0.000 description 1
229960001134 von willebrand factor Drugs 0.000 description 1
PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
229960005080 warfarin Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
- 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
- C07D401/14—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 three or more hetero rings
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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

BG100698A 1994-01-07 1996-07-05 Бензодиазепини като антагонисти на фибриноген, фармацевтичнисъстави, съдържащи съединенията, и метод за получаването им BG62844B1 (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17901194A	1994-01-07	1994-01-07
PCT/US1995/000248 WO1995018619A1 (fr)	1994-01-07	1995-01-09	Antagonistes de fibrinogene bicycliques

Publications (2)

Publication Number	Publication Date
BG100698A BG100698A (bg)	1997-02-28
BG62844B1 true BG62844B1 (bg)	2000-09-29

Family

ID=22654859

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
BG100698A BG62844B1 (bg)	1994-01-07	1996-07-05	Бензодиазепини като антагонисти на фибриноген, фармацевтичнисъстави, съдържащи съединенията, и метод за получаването им
BG102863A BG102863A (en)	1994-01-07	1998-10-22	Benzasepins as antagonists of fibrinogen and pharmaceutical compositions containing the compounds

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
BG102863A BG102863A (en)	1994-01-07	1998-10-22	Benzasepins as antagonists of fibrinogen and pharmaceutical compositions containing the compounds

Country Status (26)

Country	Link
US (1)	US6117866A (fr)
EP (1)	EP0738150B1 (fr)
JP (1)	JPH09508620A (fr)
KR (1)	KR100388772B1 (fr)
CN (1)	CN1117569C (fr)
AP (1)	AP542A (fr)
AT (1)	ATE238993T1 (fr)
AU (1)	AU699186B2 (fr)
BG (2)	BG62844B1 (fr)
BR (1)	BR9506499A (fr)
CZ (1)	CZ292323B6 (fr)
DE (1)	DE69530571T2 (fr)
DK (1)	DK0738150T3 (fr)
ES (1)	ES2197914T3 (fr)
HU (1)	HUT76282A (fr)
IL (1)	IL112243A (fr)
MA (1)	MA23420A1 (fr)
NO (1)	NO962859L (fr)
NZ (1)	NZ279394A (fr)
OA (1)	OA10368A (fr)
PT (1)	PT738150E (fr)
SG (1)	SG64884A1 (fr)
SK (1)	SK86996A3 (fr)
TW (1)	TW420682B (fr)
WO (1)	WO1995018619A1 (fr)
ZA (1)	ZA9545B (fr)

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RU2115650C1 (ru) *	1992-11-09	1998-07-20	Дзе Бутс Компани ПЛС	2,3,4,5-тетрагидро-1,4-бензотиазепины, их стереоизомеры или их фармацевтически приемлемые соли, способ их получения, фармацевтическая композиция, обладающая противосудорожным действием
NZ259802A (en) *	1992-12-21	1997-10-24	Smithkline Beecham Corp	Bicyclic derivatives and pharmaceutical compositions
US5493020A (en) *	1993-07-29	1996-02-20	Genentech, Inc.	Tricyclic inhibitors of the GPIIb IIIa receptor
EP0762882A4 (fr) *	1994-06-29	2002-09-11	Smithkline Beecham Corp	Antagonistes du recepteur de la vibronectine

1995
- 1995-01-02 MA MA23747A patent/MA23420A1/fr unknown
- 1995-01-04 IL IL11224395A patent/IL112243A/xx not_active IP Right Cessation
- 1995-01-05 ZA ZA9545A patent/ZA9545B/xx unknown
- 1995-01-06 AP APAP/P/1995/000710A patent/AP542A/en active
- 1995-01-09 NZ NZ279394A patent/NZ279394A/en not_active IP Right Cessation
- 1995-01-09 CN CN95191991A patent/CN1117569C/zh not_active Expired - Fee Related
- 1995-01-09 JP JP7518646A patent/JPH09508620A/ja not_active Ceased
- 1995-01-09 WO PCT/US1995/000248 patent/WO1995018619A1/fr not_active Ceased
- 1995-01-09 AT AT95908006T patent/ATE238993T1/de not_active IP Right Cessation
- 1995-01-09 AU AU16001/95A patent/AU699186B2/en not_active Ceased
- 1995-01-09 EP EP95908006A patent/EP0738150B1/fr not_active Expired - Lifetime
- 1995-01-09 US US08/875,359 patent/US6117866A/en not_active Expired - Fee Related
- 1995-01-09 CZ CZ19961981A patent/CZ292323B6/cs not_active IP Right Cessation
- 1995-01-09 PT PT95908006T patent/PT738150E/pt unknown
- 1995-01-09 SK SK869-96A patent/SK86996A3/sk unknown
- 1995-01-09 ES ES95908006T patent/ES2197914T3/es not_active Expired - Lifetime
- 1995-01-09 SG SG1996004249A patent/SG64884A1/en unknown
- 1995-01-09 DK DK95908006T patent/DK0738150T3/da active
- 1995-01-09 HU HU9601849A patent/HUT76282A/hu unknown
- 1995-01-09 BR BR9506499A patent/BR9506499A/pt not_active Application Discontinuation
- 1995-01-09 DE DE69530571T patent/DE69530571T2/de not_active Expired - Fee Related
- 1995-01-09 KR KR1019960703660A patent/KR100388772B1/ko not_active Expired - Fee Related
- 1995-02-16 TW TW084101430A patent/TW420682B/zh not_active IP Right Cessation
1996
- 1996-07-05 NO NO962859A patent/NO962859L/no unknown
- 1996-07-05 BG BG100698A patent/BG62844B1/bg unknown
- 1996-07-05 OA OA60858A patent/OA10368A/en unknown
1998
- 1998-10-22 BG BG102863A patent/BG102863A/xx unknown

Also Published As

Publication number	Publication date
NZ279394A (en)	1998-05-27
KR100388772B1 (ko)	2003-11-20
OA10368A (en)	2001-11-15
CN1143323A (zh)	1997-02-19
WO1995018619A1 (fr)	1995-07-13
CZ198196A3 (en)	1997-06-11
TW420682B (en)	2001-02-01
IL112243A (en)	1999-12-31
JPH09508620A (ja)	1997-09-02
AU1600195A (en)	1995-08-01
ZA9545B (en)	1996-01-23
DE69530571T2 (de)	2004-03-04
HK1014668A1 (en)	1999-09-30
US6117866A (en)	2000-09-12
HUT76282A (en)	1997-07-28
EP0738150B1 (fr)	2003-05-02
SG64884A1 (en)	1999-05-25
DE69530571D1 (de)	2003-06-05
BG102863A (en)	1999-05-31
SK86996A3 (en)	1997-02-05
BR9506499A (pt)	1997-09-09
AU699186B2 (en)	1998-11-26
HU9601849D0 (en)	1996-09-30
WO1995018619A9 (fr)	2004-10-21
CN1117569C (zh)	2003-08-13
ES2197914T3 (es)	2004-01-16
EP0738150A4 (fr)	1997-03-19
IL112243A0 (en)	1995-03-30
PT738150E (pt)	2003-08-29
BG100698A (bg)	1997-02-28
ATE238993T1 (de)	2003-05-15
AP542A (en)	1996-10-01
NO962859L (no)	1996-09-05
NO962859D0 (no)	1996-07-05
AP9500710A0 (en)	1995-01-31
EP0738150A1 (fr)	1996-10-23
CZ292323B6 (cs)	2003-09-17
DK0738150T3 (da)	2003-08-25
MA23420A1 (fr)	1995-10-01

Publication	Publication Date	Title
BG62844B1 (bg)	2000-09-29	Бензодиазепини като антагонисти на фибриноген, фармацевтичнисъстави, съдържащи съединенията, и метод за получаването им
AU689762B2 (en)	1998-04-09	Bicyclic fibrinogen antagonists
US5693636A (en)	1997-12-02	Bicyclic fibrinogen antagonists
US6037343A (en)	2000-03-14	Fibrinogen receptor antagonists
JP2001508757A (ja)	2001-07-03	フィブリノーゲンレセプターアンタゴニスト
US5795893A (en)	1998-08-18	Fibrinogen receptor antagonists
US6127359A (en)	2000-10-03	Bicyclic fibrinogen antagonists
Bondinell et al.	1994	Design of a potent and orally active nonpeptide platelet fibrinogen receptor (GPIIb/IIIa) antagonist
US5900422A (en)	1999-05-04	Fibrinogen receptor antagonists
US5756519A (en)	1998-05-26	Fibrinogen receptor antagonists
US6403578B1 (en)	2002-06-11	Bicyclic fibrinogen antagonists
HK1014668B (en)	2003-12-24	Bicyclic fibrinogen antagonists
AU4380301A (en)	2001-07-26	Bicyclic fibrinogen antagonists