DE10111842A1 - Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel - Google Patents

Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

Info

Publication number: DE10111842A1
Authority: DE; Germany
Prior art keywords: group; phenyl; methyl; hydroxy; carbamimidoyl
Prior art date: 2001-03-13
Legal status (The legal status 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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

DE10111842A

Other languages

German (de)

English (en)

Inventor

Henning Priepke

Herbert Nar

Jean Marie Stassen

Uwe Ries

Wolfgang Wienen

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Boehringer Ingelheim Pharma GmbH and Co KG

Original Assignee

Boehringer Ingelheim Pharma GmbH and Co KG

Boehringer Ingelheim Pharmaceuticals 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.)

2001-03-13

Filing date

2001-03-13

Publication date

2002-09-19

2001-03-13 Application filed by Boehringer Ingelheim Pharma GmbH and Co KG, Boehringer Ingelheim Pharmaceuticals Inc filed Critical Boehringer Ingelheim Pharma GmbH and Co KG

2001-03-13 Priority to DE10111842A priority Critical patent/DE10111842A1/de

2002-03-09 Priority to PCT/EP2002/002615 priority patent/WO2002072558A1/fr

2002-03-09 Priority to MXPA03008186A priority patent/MXPA03008186A/es

2002-03-09 Priority to CA002439231A priority patent/CA2439231A1/fr

2002-03-09 Priority to EP02732472A priority patent/EP1370540A1/fr

2002-03-09 Priority to JP2002571474A priority patent/JP2004529905A/ja

2002-03-11 Priority to US10/096,526 priority patent/US20020183519A1/en

2002-03-11 Priority to UY27202A priority patent/UY27202A1/es

2002-09-19 Publication of DE10111842A1 publication Critical patent/DE10111842A1/de

Status Withdrawn legal-status Critical Current

Links

150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 11
230000002785 anti-thrombosis Effects 0.000 title claims abstract description 6
238000002360 preparation method Methods 0.000 title claims description 13
239000003814 drug Substances 0.000 title claims 5
239000003146 anticoagulant agent Substances 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 63
150000003839 salts Chemical class 0.000 claims abstract description 34
239000000203 mixture Substances 0.000 claims abstract description 21
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract description 20
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
-1 imidazole 2-yl Chemical group 0.000 claims description 120
239000000460 chlorine Substances 0.000 claims description 41
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 34
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 24
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
229910052757 nitrogen Inorganic materials 0.000 claims description 21
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 19
229910052801 chlorine Inorganic materials 0.000 claims description 19
239000011737 fluorine Substances 0.000 claims description 19
229910052731 fluorine Inorganic materials 0.000 claims description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
239000011541 reaction mixture Substances 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 11
125000001841 imino group Chemical group [H]N=* 0.000 claims description 10
238000000034 method Methods 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 9
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 8
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
238000001727 in vivo Methods 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
125000002837 carbocyclic group Chemical group 0.000 claims description 5
125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
230000004962 physiological condition Effects 0.000 claims description 5
125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 4
FULYDTJXKWQQRK-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(4,5,6,7-tetrahydrobenzimidazol-1-yl)phenyl]acetamide Chemical compound C=1C=C(N2C=3CCCCC=3N=C2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O FULYDTJXKWQQRK-UHFFFAOYSA-N 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
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PBYSWFVUKCSQCR-UHFFFAOYSA-N 1-[4-[(5-carbamimidoyl-2-hydroxyphenyl)methylcarbamoyl]-2-(trifluoromethyl)phenyl]-N-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazole-3-carboxamide Chemical compound C1=2CCCC=2C(C(=O)NC)=NN1C(C(=C1)C(F)(F)F)=CC=C1C(=O)NCC1=CC(C(N)=N)=CC=C1O PBYSWFVUKCSQCR-UHFFFAOYSA-N 0.000 claims description 3
FYTCURARPHJFPW-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(2-pyrrolidin-1-ylbenzimidazol-1-yl)phenyl]acetamide Chemical compound C=1C=C(N2C3=CC=CC=C3N=C2N2CCCC2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O FYTCURARPHJFPW-UHFFFAOYSA-N 0.000 claims description 3
GUBKXDQNMNZITI-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-3-methylphenyl]acetamide Chemical compound C=1C=C(C=2C=3CCCC=3N=CN=2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O GUBKXDQNMNZITI-UHFFFAOYSA-N 0.000 claims description 3
125000004580 4,5-dihydroimidazol-2-yl group Chemical group N1C(=NCC1)* 0.000 claims description 3
VUVAKLISCQMEDQ-UHFFFAOYSA-N N-[(5-carbamimidoyl-2-hydroxyphenyl)methyl]-4-(1-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl)-3-(trifluoromethyl)benzamide Chemical compound C1=2CCCC=2N(C)N=C1C(C(=C1)C(F)(F)F)=CC=C1C(=O)NCC1=CC(C(N)=N)=CC=C1O VUVAKLISCQMEDQ-UHFFFAOYSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
230000032050 esterification Effects 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000006413 ring segment Chemical group 0.000 claims description 3
125000005650 substituted phenylene group Chemical group 0.000 claims description 3
QJARUSSGVYDHCV-UHFFFAOYSA-N tert-butyl N-[[1-[4-[[2-(5-carbamimidoyl-2-hydroxyphenyl)acetyl]amino]-2-methylphenyl]benzimidazol-2-yl]methyl]carbamate Chemical compound C=1C=C(N2C3=CC=CC=C3N=C2CNC(=O)OC(C)(C)C)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O QJARUSSGVYDHCV-UHFFFAOYSA-N 0.000 claims description 3
125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
OWFLWQHSBSTRNA-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)phenyl]acetamide Chemical compound C=1C=C(C=2C=3CCCC=3NN=2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O OWFLWQHSBSTRNA-UHFFFAOYSA-N 0.000 claims description 2
BYSZTUXIUVOFIC-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(1-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl)phenyl]acetamide Chemical compound C=1C=C(C=2C=3CCCC=3N(C)N=2)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O BYSZTUXIUVOFIC-UHFFFAOYSA-N 0.000 claims description 2
DTRSCQPUOKFTFP-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[3-methyl-4-(2-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazol-3-yl)phenyl]acetamide Chemical compound C=1C=C(C=2N(N=C3CCCC3=2)C)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O DTRSCQPUOKFTFP-UHFFFAOYSA-N 0.000 claims description 2
XQSPNQXHHDTKIK-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(3-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazol-1-yl)phenyl]acetamide Chemical compound C1=2CCCC=2C(C)=NN1C(C=C1)=CC=C1NC(=O)CC1=CC(C(N)=N)=CC=C1O XQSPNQXHHDTKIK-UHFFFAOYSA-N 0.000 claims description 2
MOTZIBZMLSACGE-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(4,5,6,7-tetrahydrobenzimidazol-1-yl)-3-(trifluoromethyl)phenyl]acetamide Chemical compound NC(=N)C1=CC=C(O)C(CC(=O)NC=2C=C(C(=CC=2)N2C=3CCCCC=3N=C2)C(F)(F)F)=C1 MOTZIBZMLSACGE-UHFFFAOYSA-N 0.000 claims description 2
XVJJPOMCSGQHRK-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(4,5,6,7-tetrahydrobenzimidazol-1-yl)-3-(trifluoromethyl)phenyl]propanamide Chemical compound C=1C=C(N2C=3CCCCC=3N=C2)C(C(F)(F)F)=CC=1NC(=O)C(C)C1=CC(C(N)=N)=CC=C1O XVJJPOMCSGQHRK-UHFFFAOYSA-N 0.000 claims description 2
IYFLCGWNGJQJHJ-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-(4,5-dimethyl-2-oxo-1H-imidazol-3-yl)-3-methylphenyl]acetamide Chemical compound CC1=C(C)NC(=O)N1C(C(=C1)C)=CC=C1NC(=O)CC1=CC(C(N)=N)=CC=C1O IYFLCGWNGJQJHJ-UHFFFAOYSA-N 0.000 claims description 2
COLQAJNCDMUILB-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-[2-(dimethylamino)benzimidazol-1-yl]-3-methylphenyl]acetamide Chemical compound CN(C)C1=NC2=CC=CC=C2N1C(C(=C1)C)=CC=C1NC(=O)CC1=CC(C(N)=N)=CC=C1O COLQAJNCDMUILB-UHFFFAOYSA-N 0.000 claims description 2
RPRYDPYKUVMWEW-UHFFFAOYSA-N 2-(5-carbamimidoyl-2-hydroxyphenyl)-N-[4-[3-[(dimethylamino)methyl]-5,6-dihydro-4H-cyclopenta[c]pyrazol-1-yl]-3-methylphenyl]acetamide Chemical compound C1=2CCCC=2C(CN(C)C)=NN1C(C(=C1)C)=CC=C1NC(=O)CC1=CC(C(N)=N)=CC=C1O RPRYDPYKUVMWEW-UHFFFAOYSA-N 0.000 claims description 2
YEHCAXUILFKSHD-UHFFFAOYSA-N N-[4-[2-(aminomethyl)benzimidazol-1-yl]-3-methylphenyl]-2-(5-carbamimidoyl-2-hydroxyphenyl)acetamide Chemical compound C=1C=C(N2C3=CC=CC=C3N=C2CN)C(C)=CC=1NC(=O)CC1=CC(C(N)=N)=CC=C1O YEHCAXUILFKSHD-UHFFFAOYSA-N 0.000 claims description 2
150000003855 acyl compounds Chemical class 0.000 claims description 2
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125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
BUGIDYZLIAMWSH-UHFFFAOYSA-N ethyl 1-[4-[[2-(5-carbamimidoyl-2-hydroxyphenyl)acetyl]amino]-2-methylphenyl]-5,6-dihydro-4H-cyclopenta[c]pyrazole-3-carboxylate Chemical compound C1=2CCCC=2C(C(=O)OCC)=NN1C(C(=C1)C)=CC=C1NC(=O)CC1=CC(C(N)=N)=CC=C1O BUGIDYZLIAMWSH-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
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FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
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LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
VHWJSJBTUWUEAL-UHFFFAOYSA-N propanamide;hydrochloride Chemical compound Cl.CCC(N)=O VHWJSJBTUWUEAL-UHFFFAOYSA-N 0.000 description 1
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230000000630 rising effect Effects 0.000 description 1
239000011833 salt mixture Substances 0.000 description 1
231100000241 scar Toxicity 0.000 description 1
LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
229910001958 silver carbonate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 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
235000009518 sodium iodide Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
229960000216 tenecteplase Drugs 0.000 description 1
XUTLOCQNGLJNSA-RGVLZGJSSA-N terbogrel Chemical compound CC(C)(C)\N=C(/NC#N)NC1=CC=CC(C(=C/CCCC(O)=O)\C=2C=NC=CC=2)=C1 XUTLOCQNGLJNSA-RGVLZGJSSA-N 0.000 description 1
229950006665 terbogrel Drugs 0.000 description 1
LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
230000002537 thrombolytic effect Effects 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
COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 1
229960003425 tirofiban Drugs 0.000 description 1
230000009772 tissue formation Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
239000012224 working solution Substances 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P9/10—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
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (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)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hematology (AREA)
Diabetes (AREA)
Immunology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

DE10111842A 2001-03-13 2001-03-13 Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel Withdrawn DE10111842A1 (de)

Priority Applications (8)

Application Number	Priority Date	Filing Date	Title
DE10111842A DE10111842A1 (de)	2001-03-13	2001-03-13	Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
PCT/EP2002/002615 WO2002072558A1 (fr)	2001-03-13	2002-03-09	Amides d'acide carboxylique antithrombotiques, leur production et leur utilisation comme medicaments
MXPA03008186A MXPA03008186A (es)	2001-03-13	2002-03-09	Amidas de acidos carboxilicos antitromboticas, su preparacion y su uso como medicamentos.
CA002439231A CA2439231A1 (fr)	2001-03-13	2002-03-09	Amides d'acide carboxylique antithrombotiques, leur preparation et leur utilisation comme medicaments
EP02732472A EP1370540A1 (fr)	2001-03-13	2002-03-09	Amides d'acide carboxylique antithrombotiques, leur production et leur utilisation comme medicaments
JP2002571474A JP2004529905A (ja)	2001-03-13	2002-03-09	抗血栓性カルボン酸アミド、それらの調製及び医薬組成物としてのそれらの使用
US10/096,526 US20020183519A1 (en)	2001-03-13	2002-03-11	Antithrombotic carboxylic acid amides
UY27202A UY27202A1 (es)	2001-03-13	2002-03-11	Amidas de ácidos carboxílicos antitrombóticas, su preparación y su empleo como medicamentos

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE10111842A DE10111842A1 (de)	2001-03-13	2001-03-13	Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

Publications (1)

Publication Number	Publication Date
DE10111842A1 true DE10111842A1 (de)	2002-09-19

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DE10111842A Withdrawn DE10111842A1 (de)	2001-03-13	2001-03-13	Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

Country Status (7)

Country	Link
EP (1)	EP1370540A1 (fr)
JP (1)	JP2004529905A (fr)
CA (1)	CA2439231A1 (fr)
DE (1)	DE10111842A1 (fr)
MX (1)	MXPA03008186A (fr)
UY (1)	UY27202A1 (fr)
WO (1)	WO2002072558A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2005121103A1 (fr) *	2004-06-08	2005-12-22	Boehringer Ingelheim International Gmbh	Benzimidazoles, procede de production et d'utilisation desdits benzimidazoles en tant que medicaments

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PE20040804A1 (es) *	2002-12-19	2004-12-31	Boehringer Ingelheim Pharma	DERIVADOS DE CARBOXAMIDAS COMO INHIBIDORES DEL FACTOR Xa
EP2174932B1 (fr) *	2003-03-13	2019-07-03	Idemitsu Kosan Co., Ltd.	Dérivé hétérocyclique contenant de l'azote et élément électroluminescent organique utilisant ce dérivé
SI1668014T1 (sl)	2003-09-17	2009-06-30	Janssen Pharmaceutica Nv	Kondenzirane heterociklične spojine kot modulatorji serotoninskih receptorjev
US7371743B2 (en)	2004-02-28	2008-05-13	Boehringer Ingelheim International Gmbh	Carboxylic acid amides, the preparation thereof and their use as medicaments
CA2577608A1 (fr) *	2004-09-06	2006-03-16	F. Hoffmann-La Roche Ag	Derives de 4-aminomethyl benzamidine et leur utilisation en tant qu'inhibiteurs du facteur viia
US7598255B2 (en)	2005-08-04	2009-10-06	Janssen Pharmaceutica Nv	Pyrimidine compounds as serotonin receptor modulators
NZ565334A (en) *	2005-08-04	2010-12-24	Janssen Pharmaceutica Nv	Pyrimidine compounds as serotonin receptor modulators
WO2014134391A1 (fr)	2013-02-28	2014-09-04	Bristol-Myers Squibb Company	Dérivés de phénylpyrazole en tant que puissants inhibiteurs de rock1 et rock2
TW201444798A (zh)	2013-02-28	2014-12-01	必治妥美雅史谷比公司	作爲強效ｒｏｃｋ１及ｒｏｃｋ２抑制劑之苯基吡唑衍生物
WO2020153414A1 (fr)	2019-01-24	2020-07-30	武田薬品工業株式会社	Composé hétérocyclique et son utilisation
JP2021050161A (ja)	2019-09-25	2021-04-01	武田薬品工業株式会社	複素環化合物及びその用途

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DE19912690A1 (de) *	1999-03-20	2000-09-21	Boehringer Ingelheim Pharma	Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel
DE19929787A1 (de) *	1999-06-29	2001-01-04	Bayer Ag	Neue 4-(2-Oxodihydrooxadiazinylphenyl)amide und ihre Verwendung
DE19937494A1 (de) *	1999-08-07	2001-02-08	Boehringer Ingelheim Pharma	Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

2001
- 2001-03-13 DE DE10111842A patent/DE10111842A1/de not_active Withdrawn
2002
- 2002-03-09 EP EP02732472A patent/EP1370540A1/fr not_active Withdrawn
- 2002-03-09 MX MXPA03008186A patent/MXPA03008186A/es not_active Application Discontinuation
- 2002-03-09 WO PCT/EP2002/002615 patent/WO2002072558A1/fr not_active Ceased
- 2002-03-09 JP JP2002571474A patent/JP2004529905A/ja active Pending
- 2002-03-09 CA CA002439231A patent/CA2439231A1/fr not_active Abandoned
- 2002-03-11 UY UY27202A patent/UY27202A1/es not_active Application Discontinuation

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WO2005121103A1 (fr) *	2004-06-08	2005-12-22	Boehringer Ingelheim International Gmbh	Benzimidazoles, procede de production et d'utilisation desdits benzimidazoles en tant que medicaments

Also Published As

Publication number	Publication date
JP2004529905A (ja)	2004-09-30
MXPA03008186A (es)	2004-01-29
WO2002072558A1 (fr)	2002-09-19
EP1370540A1 (fr)	2003-12-17
CA2439231A1 (fr)	2002-09-19
UY27202A1 (es)	2002-10-31

Publication	Publication Date	Title
EP1095025B1 (fr)	2002-12-11	Benzimidazoles, leur preparation et leur utilisation comme medicaments
EP1100795B1 (fr)	2004-06-09	Heterocycles bicycliques disubstitues, en particulier a effet inhibiteur de la thrombine
DE10130374A1 (de)	2003-01-02	Substituierte N-Acyl-anilinderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE10111842A1 (de)	2002-09-19	Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
EP1206446B1 (fr)	2004-05-26	Amides d'acide carboxylique, leur production et leur utilisation comme medicaments
US20020183519A1 (en)	2002-12-05	Antithrombotic carboxylic acid amides
EP1244636A1 (fr)	2002-10-02	Benzimidazoles, leur production et leur utilisation comme antithrombotiques
EP1390357A2 (fr)	2004-02-25	Composes antithrombotiques, leur preparation et leur utilisation comme produits pharmaceutiques
WO2002062748A1 (fr)	2002-08-15	Amides d'acide carboxylique, leur preparation et leur utilisation comme produit pharmaceutique
DE19912690A1 (de)	2000-09-21	Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel
DE19829964A1 (de)	2000-01-05	Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel
WO2004080970A1 (fr)	2004-09-23	Nouveaux composes bicycliques aromatiques, leur production et leur utilisation en tant que medicaments
DE10104598A1 (de)	2002-08-08	Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
EP1220845B1 (fr)	2003-08-13	Derives de benzimidazole portant comme substituant un arylsulfonamide et leur utilisation comme inhibiteurs de la tryptase
DE19937494A1 (de)	2001-02-08	Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
DE10104597A1 (de)	2002-08-08	Antithrombotische Verbindungen, deren Herstellung und deren Verwendung als Arzneimittel
DE10136434A1 (de)	2003-02-13	Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
DE19857202A1 (de)	2000-06-15	Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel
DE10260730A1 (de)	2004-07-01	Neue substituierte stickstoffhaltige Heterobicyclen, deren Herstellung und deren Verwendung als Arzneimittel
DE10136435A1 (de)	2003-02-13	Antithrombotische Verbindungen, deren Herstellung und deren Verwendung als Arzneimittel
DE10234057A1 (de)	2004-02-05	Neue Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
WO2004013128A1 (fr)	2004-02-12	Nouveaux carboxamides substitues, leur production et leur utilisation en tant que medicaments
DE10124867A1 (de)	2002-11-28	Substituierte Aryl- und Heteroarylderivate, deren Herstellung und deren Verwendung als Arzneimittel
DE10025663A1 (de)	2001-11-29	Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel
DE10335545A1 (de)	2005-06-02	Neue Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel

Legal Events

Date	Code	Title	Description
2003-04-24	8127	New person/name/address of the applicant	Owner name: BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG, 55218 IN
2006-01-05	8139	Disposal/non-payment of the annual fee

DE10111842A1 - Antithrombotische Carbonsäureamide, deren Herstellung und deren Verwendung als Arzneimittel - Google Patents

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