JP4567439B2 - カルボン酸アミド - Google Patents
カルボン酸アミド Download PDFInfo
- Publication number
- JP4567439B2 JP4567439B2 JP2004501374A JP2004501374A JP4567439B2 JP 4567439 B2 JP4567439 B2 JP 4567439B2 JP 2004501374 A JP2004501374 A JP 2004501374A JP 2004501374 A JP2004501374 A JP 2004501374A JP 4567439 B2 JP4567439 B2 JP 4567439B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- chlorophenyl
- ureido
- phenylacetamide
- hal
- Prior art date
- 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.)
- Expired - Fee Related
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 3
- -1 azepan-1-yl Chemical group 0.000 claims description 254
- 150000001875 compounds Chemical class 0.000 claims description 109
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 98
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 83
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 43
- 239000012453 solvate Substances 0.000 claims description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 27
- 239000004480 active ingredient Substances 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 125000001544 thienyl group Chemical group 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 19
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 18
- 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 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 108010074860 Factor Xa Proteins 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 208000007536 Thrombosis Diseases 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 9
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 229930192474 thiophene Natural products 0.000 claims description 9
- 108010054265 Factor VIIa Proteins 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 238000002399 angioplasty Methods 0.000 claims description 7
- 208000010125 myocardial infarction Diseases 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 206010002383 Angina Pectoris Diseases 0.000 claims description 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 206010022562 Intermittent claudication Diseases 0.000 claims description 6
- 206010027476 Metastases Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 6
- PTQVLPWBQCFYML-HSZRJFAPSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)phenyl]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCC2)=N)C=C1 PTQVLPWBQCFYML-HSZRJFAPSA-N 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- YOKAEAHBWZYQIH-DEOSSOPVSA-N (2s)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopiperidin-1-yl)phenyl]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 YOKAEAHBWZYQIH-DEOSSOPVSA-N 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- YOKAEAHBWZYQIH-XMMPIXPASA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopiperidin-1-yl)phenyl]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 YOKAEAHBWZYQIH-XMMPIXPASA-N 0.000 claims description 3
- KWPIYPYNAZDNBS-JOCHJYFZSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-[2-(cyanoamino)-4,5-dihydroimidazol-1-yl]phenyl]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(NCC2)=NC#N)C=C1 KWPIYPYNAZDNBS-JOCHJYFZSA-N 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- HHZZUTIPNZKIAC-VQIWEWKSSA-N (2R)-2-[(4-chlorophenyl)carbamoylamino]-N-[4-(2-iminopiperidin-1-yl)-3-methylphenyl]-2-phenylacetamide hydrochloride Chemical compound Cl.N([C@@H](C(=O)NC=1C=C(C(=CC=1)N1C(CCCC1)=N)C)C=1C=CC=CC=1)C(=O)NC1=CC=C(Cl)C=C1 HHZZUTIPNZKIAC-VQIWEWKSSA-N 0.000 claims description 2
- YTGUWFABSOWYNS-NRFANRHFSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-cyanoimino-3-methylimidazolidin-1-yl)phenyl]-2-thiophen-2-ylacetamide Chemical compound N#CN=C1N(C)CCN1C(C=C1)=CC=C1NC(=O)[C@H](C=1SC=CC=1)NC(=O)NC1=CC=C(Cl)C=C1 YTGUWFABSOWYNS-NRFANRHFSA-N 0.000 claims description 2
- SWOYJGDISFTWIU-XMMPIXPASA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)-3-methylphenyl]-2-phenylacetamide Chemical compound N([C@@H](C(=O)NC=1C=C(C(=CC=1)N1C(CCC1)=N)C)C=1C=CC=CC=1)C(=O)NC1=CC=C(Cl)C=C1 SWOYJGDISFTWIU-XMMPIXPASA-N 0.000 claims description 2
- BNEJWBQQDFVFMN-XMMPIXPASA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-methoxyiminopyrrolidin-1-yl)phenyl]-2-phenylacetamide Chemical compound CON=C1CCCN1C(C=C1)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)NC(=O)NC1=CC=C(Cl)C=C1 BNEJWBQQDFVFMN-XMMPIXPASA-N 0.000 claims description 2
- TZXWSKWLOSOZLS-JOCHJYFZSA-N (2r)-2-[(5-chlorothiophen-2-yl)carbamoylamino]-n-[4-(2-iminopiperidin-1-yl)phenyl]-2-phenylacetamide Chemical compound S1C(Cl)=CC=C1NC(=O)N[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 TZXWSKWLOSOZLS-JOCHJYFZSA-N 0.000 claims description 2
- PTQVLPWBQCFYML-QHCPKHFHSA-N (2s)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)phenyl]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCC2)=N)C=C1 PTQVLPWBQCFYML-QHCPKHFHSA-N 0.000 claims description 2
- ALINJBCGYBNJKY-SANMLTNESA-N (2s)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-methoxyiminopiperidin-1-yl)-3-methylphenyl]-2-phenylacetamide Chemical compound CON=C1CCCCN1C(C(=C1)C)=CC=C1NC(=O)[C@H](C=1C=CC=CC=1)NC(=O)NC1=CC=C(Cl)C=C1 ALINJBCGYBNJKY-SANMLTNESA-N 0.000 claims description 2
- DPVGNNOXXKLUQA-UHFFFAOYSA-N 2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopiperidin-1-yl)phenyl]-4-methylsulfonylbutanamide Chemical compound C=1C=C(N2C(CCCC2)=N)C=CC=1NC(=O)C(CCS(=O)(=O)C)NC(=O)NC1=CC=C(Cl)C=C1 DPVGNNOXXKLUQA-UHFFFAOYSA-N 0.000 claims description 2
- VEOSKUPUHOIHRF-SANMLTNESA-N CON=C1CCCCN1C(C(=C1)C)=CC=C1NC(=O)[C@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 Chemical compound CON=C1CCCCN1C(C(=C1)C)=CC=C1NC(=O)[C@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 VEOSKUPUHOIHRF-SANMLTNESA-N 0.000 claims description 2
- RYCRILJAKRTTNZ-XMMPIXPASA-N CON=C1CCCN1C(C=C1)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 Chemical compound CON=C1CCCN1C(C=C1)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 RYCRILJAKRTTNZ-XMMPIXPASA-N 0.000 claims description 2
- PPNSDJSRORWRCM-XMMPIXPASA-N [(1r)-2-[4-(2-iminopiperidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound C1=CC(Cl)=CC=C1NC(=O)O[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 PPNSDJSRORWRCM-XMMPIXPASA-N 0.000 claims description 2
- MLVFHNKOFQQYEC-HSZRJFAPSA-N [(1r)-2-[4-(2-iminopiperidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(5-chloropyridin-2-yl)carbamate Chemical compound N1=CC(Cl)=CC=C1NC(=O)O[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 MLVFHNKOFQQYEC-HSZRJFAPSA-N 0.000 claims description 2
- RXIWYMILDKEDPG-JOCHJYFZSA-N [(1r)-2-[4-(2-iminopiperidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(5-chlorothiophen-2-yl)carbamate Chemical compound S1C(Cl)=CC=C1NC(=O)O[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 RXIWYMILDKEDPG-JOCHJYFZSA-N 0.000 claims description 2
- PSVXGLKBWKRTEU-HSZRJFAPSA-N [(1r)-2-[4-(2-iminopyrrolidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound C1=CC(Cl)=CC=C1NC(=O)O[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCC2)=N)C=C1 PSVXGLKBWKRTEU-HSZRJFAPSA-N 0.000 claims description 2
- VEOSKUPUHOIHRF-AREMUKBSSA-N [(1r)-2-[4-(2-methoxyiminopiperidin-1-yl)-3-methylanilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound CON=C1CCCCN1C(C(=C1)C)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 VEOSKUPUHOIHRF-AREMUKBSSA-N 0.000 claims description 2
- PPNSDJSRORWRCM-DEOSSOPVSA-N [(1s)-2-[4-(2-iminopiperidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound C1=CC(Cl)=CC=C1NC(=O)O[C@@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(CCCC2)=N)C=C1 PPNSDJSRORWRCM-DEOSSOPVSA-N 0.000 claims description 2
- 238000010572 single replacement reaction Methods 0.000 claims 4
- YAUMTVNJTLUEAT-HSZRJFAPSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-cyanoimino-3-methylimidazolidin-1-yl)phenyl]-2-phenylacetamide Chemical compound N#CN=C1N(C)CCN1C(C=C1)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)NC(=O)NC1=CC=C(Cl)C=C1 YAUMTVNJTLUEAT-HSZRJFAPSA-N 0.000 claims 1
- SIHVPTLKNPWRQS-OAQYLSRUSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-cyanoimino-3-methylimidazolidin-1-yl)phenyl]-4-methylpentanamide Chemical compound N([C@H](CC(C)C)C(=O)NC=1C=CC(=CC=1)N1C(N(C)CC1)=NC#N)C(=O)NC1=CC=C(Cl)C=C1 SIHVPTLKNPWRQS-OAQYLSRUSA-N 0.000 claims 1
- SFXCCPQNZGFPGH-HXUWFJFHSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)phenyl]-3-methylbutanamide Chemical compound N([C@H](C(C)C)C(=O)NC=1C=CC(=CC=1)N1C(CCC1)=N)C(=O)NC1=CC=C(Cl)C=C1 SFXCCPQNZGFPGH-HXUWFJFHSA-N 0.000 claims 1
- HYVDURVADYKIHB-HXUWFJFHSA-N (2r)-2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)phenyl]-4-methylpentanamide Chemical compound N([C@H](CC(C)C)C(=O)NC=1C=CC(=CC=1)N1C(CCC1)=N)C(=O)NC1=CC=C(Cl)C=C1 HYVDURVADYKIHB-HXUWFJFHSA-N 0.000 claims 1
- WNLURFHCZUMIPL-JOCHJYFZSA-N (2r)-n-[4-(2-amino-4,5-dihydroimidazol-1-yl)-3-methylphenyl]-2-[(4-chlorophenyl)carbamoylamino]-2-phenylacetamide Chemical compound N([C@@H](C(=O)NC=1C=C(C(=CC=1)N1C(NCC1)=N)C)C=1C=CC=CC=1)C(=O)NC1=CC=C(Cl)C=C1 WNLURFHCZUMIPL-JOCHJYFZSA-N 0.000 claims 1
- RJKICIJILVMNOK-OAQYLSRUSA-N (2r)-n-[4-(2-amino-4,5-dihydroimidazol-1-yl)phenyl]-2-[(4-chlorophenyl)carbamoylamino]-2-phenylacetamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)N[C@H](C=1C=CC=CC=1)C(=O)NC1=CC=C(N2C(NCC2)=N)C=C1 RJKICIJILVMNOK-OAQYLSRUSA-N 0.000 claims 1
- RZLQMZIXGWYKSD-GOSISDBHSA-N (2r)-n-[4-(2-amino-4,5-dihydroimidazol-1-yl)phenyl]-2-[(4-chlorophenyl)carbamoylamino]-3-methylbutanamide Chemical compound N([C@H](C(C)C)C(=O)NC=1C=CC(=CC=1)N1C(NCC1)=N)C(=O)NC1=CC=C(Cl)C=C1 RZLQMZIXGWYKSD-GOSISDBHSA-N 0.000 claims 1
- JPLJHLFYZMXFKW-LJQANCHMSA-N (2r)-n-[4-(2-amino-4,5-dihydroimidazol-1-yl)phenyl]-2-[(4-chlorophenyl)carbamoylamino]-4-methylpentanamide Chemical compound N([C@H](CC(C)C)C(=O)NC=1C=CC(=CC=1)N1C(NCC1)=N)C(=O)NC1=CC=C(Cl)C=C1 JPLJHLFYZMXFKW-LJQANCHMSA-N 0.000 claims 1
- JZTWIQUAGIGGMB-UHFFFAOYSA-N 2-[(4-chlorophenyl)carbamoylamino]-n-[4-(2-iminopyrrolidin-1-yl)phenyl]-3-methoxypropanamide Chemical compound C=1C=C(N2C(CCC2)=N)C=CC=1NC(=O)C(COC)NC(=O)NC1=CC=C(Cl)C=C1 JZTWIQUAGIGGMB-UHFFFAOYSA-N 0.000 claims 1
- MECBDNVKNRWPDV-UHFFFAOYSA-N 2-[(4-chlorophenyl)carbamoylamino]-n-[4-[2-(cyanoamino)-4,5-dihydroimidazol-1-yl]phenyl]-3-methoxypropanamide Chemical compound C=1C=C(N2C(NCC2)=NC#N)C=CC=1NC(=O)C(COC)NC(=O)NC1=CC=C(Cl)C=C1 MECBDNVKNRWPDV-UHFFFAOYSA-N 0.000 claims 1
- RSZMYUZNCCGNGN-HSZRJFAPSA-N ClC1=CC=C(C=C1)NC(N[C@]1(SC=CC1)CC(=O)NC1=CC=C(C=C1)N1C(CCC1)=N)=O Chemical compound ClC1=CC=C(C=C1)NC(N[C@]1(SC=CC1)CC(=O)NC1=CC=C(C=C1)N1C(CCC1)=N)=O RSZMYUZNCCGNGN-HSZRJFAPSA-N 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- AQQNXQIKZGCYLV-RUZDIDTESA-N [(1r)-2-[4-(2-iminopiperidin-1-yl)-3-methylanilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound O([C@@H](C(=O)NC=1C=C(C(=CC=1)N1C(CCCC1)=N)C)C=1C=CC=CC=1)C(=O)NC1=CC=C(Cl)C=C1 AQQNXQIKZGCYLV-RUZDIDTESA-N 0.000 claims 1
- OICJUEWQGPBRHX-XMMPIXPASA-N [(1r)-2-[4-(2-iminopyrrolidin-1-yl)-3-methylanilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound O([C@@H](C(=O)NC=1C=C(C(=CC=1)N1C(CCC1)=N)C)C=1C=CC=CC=1)C(=O)NC1=CC=C(Cl)C=C1 OICJUEWQGPBRHX-XMMPIXPASA-N 0.000 claims 1
- OMOWCRXLVOOADX-RUZDIDTESA-N [(1r)-2-[4-(2-methoxyiminopiperidin-1-yl)anilino]-2-oxo-1-phenylethyl] n-(4-chlorophenyl)carbamate Chemical compound CON=C1CCCCN1C(C=C1)=CC=C1NC(=O)[C@@H](C=1C=CC=CC=1)OC(=O)NC1=CC=C(Cl)C=C1 OMOWCRXLVOOADX-RUZDIDTESA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 238000000132 electrospray ionisation Methods 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
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- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
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- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
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- 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
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- C07D403/12—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 chain containing hetero atoms as chain links
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- 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
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2002118974 DE10218974A1 (de) | 2002-04-27 | 2002-04-27 | Carnonsäureamide |
| DE10236868A DE10236868A1 (de) | 2002-08-12 | 2002-08-12 | Carbonsäureamide |
| PCT/EP2003/003331 WO2003093235A1 (de) | 2002-04-27 | 2003-03-31 | Carbonsäureamide als inhibitoren des koagulationsfaktors xa |
Publications (3)
| Publication Number | Publication Date |
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| JP2005531547A JP2005531547A (ja) | 2005-10-20 |
| JP2005531547A5 JP2005531547A5 (enExample) | 2006-05-25 |
| JP4567439B2 true JP4567439B2 (ja) | 2010-10-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2004501374A Expired - Fee Related JP4567439B2 (ja) | 2002-04-27 | 2003-03-31 | カルボン酸アミド |
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| Country | Link |
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| EP (1) | EP1499591A1 (enExample) |
| JP (1) | JP4567439B2 (enExample) |
| AR (1) | AR039450A1 (enExample) |
| AU (1) | AU2003226755A1 (enExample) |
| CA (1) | CA2483228C (enExample) |
| WO (1) | WO2003093235A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040152741A1 (en) * | 2002-09-09 | 2004-08-05 | Nps Allelix Corporation | Arylglycine derivatives and their use as glycine transport inhibitors |
| DE10247226A1 (de) * | 2002-10-10 | 2004-04-22 | Merck Patent Gmbh | Heterocyclische Amide |
| DE10302500A1 (de) * | 2003-01-23 | 2004-07-29 | Merck Patent Gmbh | Carbonsäureamidderivate |
| DE10358539A1 (de) * | 2003-12-15 | 2005-07-07 | Merck Patent Gmbh | Carbonsäureamidderivate |
| FR2866886B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-akylcarbamates, leur preparation et leur application en therapeutique |
| WO2006089952A1 (en) * | 2005-02-24 | 2006-08-31 | Novo Nordisk Health Care Ag | Amidino-compounds por stabilizing factor vii polypeptide formulations |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2624698A1 (fr) * | 1987-12-18 | 1989-06-23 | Bernard Lyon I Universite Clau | Derives heterocycliques de n-carbamoyl-, n-thiocarbamoyl- ou n-amidino-aminomalonyl ou aminosuccinyl amides utiles comme agents edulcorants |
| EP1162194A1 (en) * | 2000-06-06 | 2001-12-12 | Aventis Pharma Deutschland GmbH | Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use |
| DE10063008A1 (de) * | 2000-12-16 | 2002-06-20 | Merck Patent Gmbh | Carbonsäureamidderivate |
| DE10102322A1 (de) * | 2001-01-19 | 2002-07-25 | Merck Patent Gmbh | Phenylderivate |
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2003
- 2003-03-31 JP JP2004501374A patent/JP4567439B2/ja not_active Expired - Fee Related
- 2003-03-31 CA CA2483228A patent/CA2483228C/en not_active Expired - Fee Related
- 2003-03-31 AU AU2003226755A patent/AU2003226755A1/en not_active Abandoned
- 2003-03-31 EP EP03747402A patent/EP1499591A1/de not_active Withdrawn
- 2003-03-31 US US10/512,478 patent/US7183277B2/en not_active Expired - Fee Related
- 2003-03-31 WO PCT/EP2003/003331 patent/WO2003093235A1/de not_active Ceased
- 2003-04-25 AR ARP030101438A patent/AR039450A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003093235A1 (de) | 2003-11-13 |
| US20050171154A1 (en) | 2005-08-04 |
| EP1499591A1 (de) | 2005-01-26 |
| US7183277B2 (en) | 2007-02-27 |
| AR039450A1 (es) | 2005-02-16 |
| CA2483228A1 (en) | 2003-11-13 |
| AU2003226755A1 (en) | 2003-11-17 |
| JP2005531547A (ja) | 2005-10-20 |
| CA2483228C (en) | 2011-07-05 |
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