SK9232003A3 - Urea derivatives as integrin alpha 4 antagonists - Google Patents
Urea derivatives as integrin alpha 4 antagonists Download PDFInfo
- Publication number
- SK9232003A3 SK9232003A3 SK923-2003A SK9232003A SK9232003A3 SK 9232003 A3 SK9232003 A3 SK 9232003A3 SK 9232003 A SK9232003 A SK 9232003A SK 9232003 A3 SK9232003 A3 SK 9232003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- phenyl
- propionic acid
- ureido
- dichlorobenzoylamino
- amino
- Prior art date
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- 239000005557 antagonist Substances 0.000 title abstract description 4
- 102100032818 Integrin alpha-4 Human genes 0.000 title description 4
- 108010041012 Integrin alpha4 Proteins 0.000 title description 4
- 150000003672 ureas Chemical class 0.000 title description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 312
- -1 -ORe Chemical group 0.000 claims description 304
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 166
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 154
- 238000002360 preparation method Methods 0.000 claims description 133
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 109
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 235000019260 propionic acid Nutrition 0.000 claims description 78
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 46
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
- 150000001412 amines Chemical class 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 102000006495 integrins Human genes 0.000 claims description 27
- 108010044426 integrins Proteins 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 150000004702 methyl esters Chemical class 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
- 239000012948 isocyanate Substances 0.000 claims description 14
- 150000002513 isocyanates Chemical class 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004434 sulfur atom Chemical group 0.000 claims description 12
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
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- 229910052717 sulfur Inorganic materials 0.000 claims description 10
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
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- 125000005842 heteroatom Chemical group 0.000 claims description 7
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- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- AZMXWFMWSKVGLZ-VWLOTQADSA-N (2s)-2-[[(2-benzylphenyl)-methylcarbamoyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@H](NC(=O)N(C)C=1C(=CC=CC=1)CC=1C=CC=CC=1)C(O)=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl AZMXWFMWSKVGLZ-VWLOTQADSA-N 0.000 claims description 4
- NBUIEBPEBGHMAG-NRFANRHFSA-N (2s)-2-[[2-(benzenesulfonyl)phenyl]carbamoylamino]-3-[4-(dimethylcarbamoyloxy)phenyl]propanoic acid Chemical compound C1=CC(OC(=O)N(C)C)=CC=C1C[C@@H](C(O)=O)NC(=O)NC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1 NBUIEBPEBGHMAG-NRFANRHFSA-N 0.000 claims description 4
- DQPHOLNNUKFCLM-DEOSSOPVSA-N (2s)-2-[[5-chloro-2-(2,5-dimethoxyphenyl)sulfonylphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound COC1=CC=C(OC)C(S(=O)(=O)C=2C(=CC(Cl)=CC=2)NC(=O)N[C@@H](CC=2C=CC(NC(=O)C=3C(=CC=CC=3Cl)Cl)=CC=2)C(O)=O)=C1 DQPHOLNNUKFCLM-DEOSSOPVSA-N 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
- 206010053555 Arthritis bacterial Diseases 0.000 claims description 4
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- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 4
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
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- 231100000331 toxic Toxicity 0.000 claims description 4
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- SHUQOXZJPBSWDC-NDEPHWFRSA-N (2s)-2-[[(2-benzylphenyl)-methylcarbamoyl]amino]-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(NC=2C3=CN=CC=C3C=CN=2)=CC=1)C(O)=O)C(=O)N(C)C1=CC=CC=C1CC1=CC=CC=C1 SHUQOXZJPBSWDC-NDEPHWFRSA-N 0.000 claims description 3
- FCXDAPBRVMZHLC-VWLOTQADSA-N (2s)-2-[[2,4-dibromo-6-(cyclohexylmethylcarbamoyl)phenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC(Br)=CC=1Br)C(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl FCXDAPBRVMZHLC-VWLOTQADSA-N 0.000 claims description 3
- IOQYTEZICRUWRA-QHCPKHFHSA-N (2s)-2-[[2-(4-chlorophenyl)sulfonylpyridin-3-yl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=NC=CC=1)S(=O)(=O)C=1C=CC(Cl)=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl IOQYTEZICRUWRA-QHCPKHFHSA-N 0.000 claims description 3
- AFKXUNPCUZXWCY-DEOSSOPVSA-N (2s)-2-[[2-(benzenesulfonyl)-5-chlorophenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC=C(Cl)C=1)S(=O)(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl AFKXUNPCUZXWCY-DEOSSOPVSA-N 0.000 claims description 3
- ZYWGUAVSWBKOCQ-DEOSSOPVSA-N (2s)-2-[[2-(benzenesulfonyl)phenyl]carbamoylamino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid Chemical compound COC1=CC=CC(OC)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)NC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1 ZYWGUAVSWBKOCQ-DEOSSOPVSA-N 0.000 claims description 3
- ULADBFQCDINFOT-SANMLTNESA-N (2s)-2-[[2-(benzenesulfonyl)phenyl]carbamoylamino]-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(OC=2C3=CN=CC=C3C=CN=2)=CC=1)C(=O)O)C(=O)NC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1 ULADBFQCDINFOT-SANMLTNESA-N 0.000 claims description 3
- KDZVOYBMYHYKET-QHCPKHFHSA-N (2s)-2-[[2-(benzenesulfonyl)pyridin-3-yl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=NC=CC=1)S(=O)(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl KDZVOYBMYHYKET-QHCPKHFHSA-N 0.000 claims description 3
- SSPUQINHBDKEME-SANMLTNESA-N (2s)-2-[[2-(cyclohexylmethylcarbamoyl)-6-methylphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(NC(=O)C=2C(=CC=CC=2Cl)Cl)=CC=1)C(O)=O)C(=O)NC=1C(C)=CC=CC=1C(=O)NCC1CCCCC1 SSPUQINHBDKEME-SANMLTNESA-N 0.000 claims description 3
- JJUXOORPLAGXRN-SANMLTNESA-N (2s)-2-[[2-(cyclohexylmethylcarbamoyl)phenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC=CC=1)C(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl JJUXOORPLAGXRN-SANMLTNESA-N 0.000 claims description 3
- UCADEWFCRZSEGH-LJAQVGFWSA-N (2s)-2-[[2-[cyclohexyl(propan-2-yl)carbamoyl]-5-methoxyphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(NC(=O)C=2C(=CC=CC=2Cl)Cl)=CC=1)C(O)=O)C(=O)NC1=CC(OC)=CC=C1C(=O)N(C(C)C)C1CCCCC1 UCADEWFCRZSEGH-LJAQVGFWSA-N 0.000 claims description 3
- TYVXQMJCQHFLMU-VWLOTQADSA-N (2s)-2-[[4-(benzenesulfonyl)phenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C=CC(=CC=1)S(=O)(=O)C=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl TYVXQMJCQHFLMU-VWLOTQADSA-N 0.000 claims description 3
- QXUGFMMCKBTQNP-SANMLTNESA-N (2s)-2-[[[2-(cyclohexylmethylcarbamoyl)phenyl]-methylcarbamoyl]amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@H](NC(=O)N(C)C=1C(=CC=CC=1)C(=O)NCC1CCCCC1)C(O)=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl QXUGFMMCKBTQNP-SANMLTNESA-N 0.000 claims description 3
- HQUFMDKWKGDIDH-DEOSSOPVSA-N (2s)-3-[4-(2-methoxyphenyl)phenyl]-2-[(2-piperidin-1-ylsulfonylphenyl)carbamoylamino]propanoic acid Chemical compound COC1=CC=CC=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)NC1=CC=CC=C1S(=O)(=O)N1CCCCC1 HQUFMDKWKGDIDH-DEOSSOPVSA-N 0.000 claims description 3
- PXRCVARJYNYKOV-VWLOTQADSA-N (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[2-(phenylcarbamoyl)phenyl]carbamoylamino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC=CC=1)C(=O)NC=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl PXRCVARJYNYKOV-VWLOTQADSA-N 0.000 claims description 3
- YDMRIRSRIVKPNR-VWLOTQADSA-N (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[5-methoxy-2-(piperidine-1-carbonyl)phenyl]carbamoylamino]propanoic acid Chemical compound N([C@@H](CC=1C=CC(NC(=O)C=2C(=CC=CC=2Cl)Cl)=CC=1)C(O)=O)C(=O)NC1=CC(OC)=CC=C1C(=O)N1CCCCC1 YDMRIRSRIVKPNR-VWLOTQADSA-N 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
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- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
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- FMHBDVLKRKCHPG-MHZLTWQESA-N methyl (2s)-2-[(2-benzylphenyl)carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)CC=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl FMHBDVLKRKCHPG-MHZLTWQESA-N 0.000 claims description 3
- UGMJREGXVYNYBJ-LJAQVGFWSA-N methyl (2s)-2-[[(2-benzylphenyl)-methylcarbamoyl]amino]-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]propanoate Chemical compound N([C@@H](CC=1C=CC(OC=2C3=CN=CC=C3C=CN=2)=CC=1)C(=O)OC)C(=O)N(C)C1=CC=CC=C1CC1=CC=CC=C1 UGMJREGXVYNYBJ-LJAQVGFWSA-N 0.000 claims description 3
- JTRPNOJLPDTCHI-MHZLTWQESA-N methyl (2s)-2-[[2-(cyclohexylmethylcarbamoyl)phenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)C(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl JTRPNOJLPDTCHI-MHZLTWQESA-N 0.000 claims description 3
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- UFKZKWVNFMDBRS-VWLOTQADSA-N (2s)-2-[(2-anilinophenyl)carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC=CC=1)NC=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl UFKZKWVNFMDBRS-VWLOTQADSA-N 0.000 claims description 2
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- BVRXEPRCYIPBRX-DEOSSOPVSA-N (2s)-2-[[2-(benzenesulfonyl)phenyl]carbamoylamino]-3-[4-[(2-chloro-6-methylpyridine-3-carbonyl)amino]phenyl]propanoic acid Chemical compound ClC1=NC(C)=CC=C1C(=O)NC(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)NC1=CC=CC=C1S(=O)(=O)C1=CC=CC=C1 BVRXEPRCYIPBRX-DEOSSOPVSA-N 0.000 claims description 2
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- VLIUGTIYVQJBRZ-VWLOTQADSA-N (2s)-2-[[2-(cyclohexylmethylcarbamoyl)-6-methoxyphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(NC(=O)C=2C(=CC=CC=2Cl)Cl)=CC=1)C(O)=O)C(=O)NC=1C(OC)=CC=CC=1C(=O)NCC1CCCCC1 VLIUGTIYVQJBRZ-VWLOTQADSA-N 0.000 claims description 2
- ZVAOTSBOOJWZEC-VWLOTQADSA-N (2s)-2-[[2-(cyclohexylmethylcarbamoyl)phenyl]carbamoylamino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)NC=1C(=CC=CC=1)C(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl ZVAOTSBOOJWZEC-VWLOTQADSA-N 0.000 claims description 2
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- MUVFAYIVUAITJK-SANMLTNESA-N methyl (2s)-2-[[2-(cyclohexylmethylsulfamoyl)phenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)S(=O)(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl MUVFAYIVUAITJK-SANMLTNESA-N 0.000 description 1
- ILIAYJNEZDPMGE-VWLOTQADSA-N methyl (2s)-2-[[2-(cyclohexylmethylsulfamoyl)phenyl]carbamoylamino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)S(=O)(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl ILIAYJNEZDPMGE-VWLOTQADSA-N 0.000 description 1
- IKCNXPZLPVAYJV-PMERELPUSA-N methyl (2s)-2-[[2-[cyclohexyl(propan-2-yl)carbamoyl]-5-methoxyphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=C(OC)C=1)C(=O)N(C(C)C)C1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl IKCNXPZLPVAYJV-PMERELPUSA-N 0.000 description 1
- KRKVSAMBXMLPDZ-MHZLTWQESA-N methyl (2s)-2-[[2-chloro-5-(4-methylphenyl)sulfonylphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=C(C=1)S(=O)(=O)C=1C=CC(C)=CC=1)Cl)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl KRKVSAMBXMLPDZ-MHZLTWQESA-N 0.000 description 1
- NZCVQXDGRPURAG-QFIPXVFZSA-N methyl (2s)-2-[[4-(4-chlorophenyl)sulfonylthiophen-3-yl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CSC=1)S(=O)(=O)C=1C=CC(Cl)=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl NZCVQXDGRPURAG-QFIPXVFZSA-N 0.000 description 1
- VLNPCDYIKCPWRA-VWLOTQADSA-N methyl (2s)-2-[[5-chloro-2-(2,5-dimethoxyphenyl)sulfonylphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=C(Cl)C=1)S(=O)(=O)C=1C(=CC=C(OC)C=1)OC)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl VLNPCDYIKCPWRA-VWLOTQADSA-N 0.000 description 1
- WKOUBAMGZRZORQ-VWLOTQADSA-N methyl (2s)-2-[[5-chloro-2-(4-chlorophenyl)sulfonylphenyl]carbamoylamino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=C(Cl)C=1)S(=O)(=O)C=1C=CC(Cl)=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl WKOUBAMGZRZORQ-VWLOTQADSA-N 0.000 description 1
- IMYTXXPZTPCZRL-MHZLTWQESA-N methyl (2s)-2-[[[2-(cyclohexylmethylcarbamoyl)phenyl]-methylcarbamoyl]amino]-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)N(C)C=1C(=CC=CC=1)C(=O)NCC1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl IMYTXXPZTPCZRL-MHZLTWQESA-N 0.000 description 1
- VXYFARNRGZWHTJ-FVGYRXGTSA-N methyl (2s)-2-amino-3-(4-hydroxyphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VXYFARNRGZWHTJ-FVGYRXGTSA-N 0.000 description 1
- BTHMRXRBXYHLRA-FVGYRXGTSA-N methyl (2s)-2-amino-3-(4-nitrophenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 BTHMRXRBXYHLRA-FVGYRXGTSA-N 0.000 description 1
- QGYQETJVEYGQFJ-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(2,6-naphthyridin-1-ylamino)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1NC1=NC=CC2=CN=CC=C12 QGYQETJVEYGQFJ-INIZCTEOSA-N 0.000 description 1
- YQURGOVRSWWKSF-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(2,6-naphthyridin-1-yloxy)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=NC=CC2=CN=CC=C12 YQURGOVRSWWKSF-INIZCTEOSA-N 0.000 description 1
- LLAGHRASCIIHOZ-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1NC1=NC=CC2=CC=NC=C12 LLAGHRASCIIHOZ-INIZCTEOSA-N 0.000 description 1
- ZRXKUTRQFIZDAQ-INIZCTEOSA-N methyl (2s)-2-amino-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1OC1=NC=CC2=CC=NC=C12 ZRXKUTRQFIZDAQ-INIZCTEOSA-N 0.000 description 1
- QLIFBPZTJZIDAN-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-(2-cyanophenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CC=C1C#N QLIFBPZTJZIDAN-NTISSMGPSA-N 0.000 description 1
- HVHHXKSCPNBOQJ-RSAXXLAASA-N methyl (2s)-2-amino-3-[4-(2-methoxyphenyl)phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1C1=CC=CC=C1OC HVHHXKSCPNBOQJ-RSAXXLAASA-N 0.000 description 1
- GFPFUXLMONHCNC-ZDUSSCGKSA-N methyl (2s)-2-amino-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoate Chemical compound C1=CC(C[C@H](N)C(=O)OC)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl GFPFUXLMONHCNC-ZDUSSCGKSA-N 0.000 description 1
- BFLZVULIYCLNSR-NTISSMGPSA-N methyl (2s)-2-amino-3-[4-[(3-cyano-1,6-naphthyridin-2-yl)amino]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(C[C@H](N)C(=O)OC)=CC=C1NC1=NC2=CC=NC=C2C=C1C#N BFLZVULIYCLNSR-NTISSMGPSA-N 0.000 description 1
- OTYRNHIUANQYLQ-FQEVSTJZSA-N methyl (2s)-3-(4-aminophenyl)-2-[[2-(benzenesulfonyl)phenyl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)S(=O)(=O)C=1C=CC=CC=1)C1=CC=C(N)C=C1 OTYRNHIUANQYLQ-FQEVSTJZSA-N 0.000 description 1
- NQIFXJSLCUJHBB-LBPRGKRZSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 NQIFXJSLCUJHBB-LBPRGKRZSA-N 0.000 description 1
- LSHMWLGFODLMPH-SANMLTNESA-N methyl (2s)-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]-2-[(2-piperidin-1-ylsulfonylphenyl)carbamoylamino]propanoate Chemical compound N([C@@H](CC=1C=CC(NC=2C3=CN=CC=C3C=CN=2)=CC=1)C(=O)OC)C(=O)NC1=CC=CC=C1S(=O)(=O)N1CCCCC1 LSHMWLGFODLMPH-SANMLTNESA-N 0.000 description 1
- BUPZBPXMHXBFLI-SANMLTNESA-N methyl (2s)-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]-2-[(2-piperidin-1-ylsulfonylphenyl)carbamoylamino]propanoate Chemical compound N([C@@H](CC=1C=CC(OC=2C3=CN=CC=C3C=CN=2)=CC=1)C(=O)OC)C(=O)NC1=CC=CC=C1S(=O)(=O)N1CCCCC1 BUPZBPXMHXBFLI-SANMLTNESA-N 0.000 description 1
- QEFZUYPFXQBDDO-IBGZPJMESA-N methyl (2s)-3-[4-(2-cyanophenyl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1C1=CC=CC=C1C#N QEFZUYPFXQBDDO-IBGZPJMESA-N 0.000 description 1
- DEOZWDUJNHCRLW-VWLOTQADSA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[(2-phenylsulfanylphenyl)carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)SC=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl DEOZWDUJNHCRLW-VWLOTQADSA-N 0.000 description 1
- LBMVPUQWZVQKNU-VWLOTQADSA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[2-(4-methylphenyl)sulfonylpyridin-3-yl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=NC=CC=1)S(=O)(=O)C=1C=CC(C)=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl LBMVPUQWZVQKNU-VWLOTQADSA-N 0.000 description 1
- UURLFLNNHIBUBO-VWLOTQADSA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[2-(piperidine-1-carbonyl)phenyl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)C(=O)N1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl UURLFLNNHIBUBO-VWLOTQADSA-N 0.000 description 1
- ITDBOOLXBFXHJK-MHZLTWQESA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[2-[methyl(phenyl)carbamoyl]phenyl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)C(=O)N(C)C=1C=CC=CC=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl ITDBOOLXBFXHJK-MHZLTWQESA-N 0.000 description 1
- JPDBDYCTTPHNCK-SANMLTNESA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[4-(4-nitrophenyl)sulfonylphenyl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C=CC(=CC=1)S(=O)(=O)C=1C=CC(=CC=1)[N+]([O-])=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl JPDBDYCTTPHNCK-SANMLTNESA-N 0.000 description 1
- POJFCPSHDCOHNF-SANMLTNESA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[5-methoxy-2-(piperidine-1-carbonyl)phenyl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=C(OC)C=1)C(=O)N1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl POJFCPSHDCOHNF-SANMLTNESA-N 0.000 description 1
- VLRSDLCPLUBCOY-DEOSSOPVSA-N methyl (2s)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[methyl-(2-piperidin-1-ylsulfonylphenyl)carbamoyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)N(C)C=1C(=CC=CC=1)S(=O)(=O)N1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC=C1Cl VLRSDLCPLUBCOY-DEOSSOPVSA-N 0.000 description 1
- ZNJSUBDLFCWLNO-QHCPKHFHSA-N methyl (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[(2-piperidin-1-ylsulfonylphenyl)carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)NC=1C(=CC=CC=1)S(=O)(=O)N1CCCCC1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl ZNJSUBDLFCWLNO-QHCPKHFHSA-N 0.000 description 1
- MRKKPZCRAKWUKV-FQEVSTJZSA-N methyl (2s)-3-[4-[(3-cyano-1,6-naphthyridin-2-yl)amino]phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC(C[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)=CC=C1NC1=NC2=CC=NC=C2C=C1C#N MRKKPZCRAKWUKV-FQEVSTJZSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
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ES200100126A ES2200617B1 (es) | 2001-01-19 | 2001-01-19 | Derivados de urea como antagonistas de integrinas alfa 4. |
PCT/EP2002/000331 WO2002057242A2 (en) | 2001-01-19 | 2002-01-15 | Urea derivatives as integrin alpha 4 antagonists |
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CN (1) | CN100536839C (es) |
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ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
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EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
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MX2011000837A (es) | 2008-07-23 | 2011-04-05 | Vertex Pharma | Inhibidores de pirazolpiridina cinasa triciclica. |
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