JP2005533803A5 - - Google Patents
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- JP2005533803A5 JP2005533803A5 JP2004515328A JP2004515328A JP2005533803A5 JP 2005533803 A5 JP2005533803 A5 JP 2005533803A5 JP 2004515328 A JP2004515328 A JP 2004515328A JP 2004515328 A JP2004515328 A JP 2004515328A JP 2005533803 A5 JP2005533803 A5 JP 2005533803A5
- Authority
- JP
- Japan
- Prior art keywords
- amino
- carbonitrile
- alkyl
- chlorophenyl
- morpholin
- 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.)
- Pending
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- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 38
- -1 amino, hydroxy Chemical group 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 29
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 108090000613 Cathepsin S Proteins 0.000 claims description 2
- 102100035654 Cathepsin S Human genes 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 241001024304 Mino Species 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- HRXPLNARFGLXAV-UHFFFAOYSA-N 1-(4-cyano-6-morpholin-4-yl-1,3,5-triazin-2-yl)-n,n-diethylpiperidine-3-carboxamide Chemical compound C1C(C(=O)N(CC)CC)CCCN1C1=NC(C#N)=NC(N2CCOCC2)=N1 HRXPLNARFGLXAV-UHFFFAOYSA-N 0.000 claims 1
- CMRHBNMOCLQRSF-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(NC=2C=C3OCCOC3=CC=2)=NC=1N1CCOCC1 CMRHBNMOCLQRSF-UHFFFAOYSA-N 0.000 claims 1
- XWCQLQFUUUVLRU-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-6-(4-chloroanilino)-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCC(N)CC2)C(OC)=C1NC1=CC=C(Cl)C=C1 XWCQLQFUUUVLRU-UHFFFAOYSA-N 0.000 claims 1
- YPDSLCXUIXJXNJ-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-6-(4-chloroanilino)pyrimidine-2-carbonitrile Chemical compound C1CC(N)CCN1C1=CC(NC=2C=CC(Cl)=CC=2)=NC(C#N)=N1 YPDSLCXUIXJXNJ-UHFFFAOYSA-N 0.000 claims 1
- NMABGHZGYRXDKI-UHFFFAOYSA-N 4-(4-chloroanilino)-5-methoxy-6-(3-oxopiperazin-1-yl)pyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CC(=O)NCC2)C(OC)=C1NC1=CC=C(Cl)C=C1 NMABGHZGYRXDKI-UHFFFAOYSA-N 0.000 claims 1
- BTZKIHBFNQJXTB-UHFFFAOYSA-N 4-(4-chloroanilino)-5-methoxy-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCOCC2)C(OC)=C1NC1=CC=C(Cl)C=C1 BTZKIHBFNQJXTB-UHFFFAOYSA-N 0.000 claims 1
- WUUXAWFBPPBXII-UHFFFAOYSA-N 4-(4-chloroanilino)-5-methoxy-6-piperazin-1-ylpyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCNCC2)C(OC)=C1NC1=CC=C(Cl)C=C1 WUUXAWFBPPBXII-UHFFFAOYSA-N 0.000 claims 1
- PQVMVGGJDJIQEL-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(2-piperidin-1-ylethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(NCCN2CCCCC2)=NC(C#N)=N1 PQVMVGGJDJIQEL-UHFFFAOYSA-N 0.000 claims 1
- ZPTOAFOTEBXFRX-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(3-hydroxypyrrolidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound C1C(O)CCN1C1=NC(NC=2C=CC(Cl)=CC=2)=NC(C#N)=N1 ZPTOAFOTEBXFRX-UHFFFAOYSA-N 0.000 claims 1
- LNLMQGVSOHPCFR-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(3-pyrrolidin-1-ylpropylamino)pyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(NCCCN2CCCC2)=NC(C#N)=N1 LNLMQGVSOHPCFR-UHFFFAOYSA-N 0.000 claims 1
- XFOOFOWYROOZEA-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(4-methylpiperazin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound C1CN(C)CCN1C1=NC(NC=2C=CC(Cl)=CC=2)=NC(C#N)=N1 XFOOFOWYROOZEA-UHFFFAOYSA-N 0.000 claims 1
- XJKDWNYTZZEYQD-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(4-phenylpiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCC(CC2)C=2C=CC=CC=2)=N1 XJKDWNYTZZEYQD-UHFFFAOYSA-N 0.000 claims 1
- BBAKVKGWOAPQKH-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCC(CC2)N2CCCC2)=NC(C#N)=N1 BBAKVKGWOAPQKH-UHFFFAOYSA-N 0.000 claims 1
- NMWMRLWGNJUBRC-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N#CC1=NC(N(C)C)=NC(NC=2C=CC(Cl)=CC=2)=N1 NMWMRLWGNJUBRC-UHFFFAOYSA-N 0.000 claims 1
- FKNPVHLJQRYZPP-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N(C)C)C(OC)=C1NC1=CC=C(Cl)C=C1 FKNPVHLJQRYZPP-UHFFFAOYSA-N 0.000 claims 1
- VCUKMSHUJDBTKR-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(dimethylamino)pyrimidine-2-carbonitrile Chemical compound N#CC1=NC(N(C)C)=CC(NC=2C=CC(Cl)=CC=2)=N1 VCUKMSHUJDBTKR-UHFFFAOYSA-N 0.000 claims 1
- CFTYWZFVQURLDD-UHFFFAOYSA-N 4-(4-chloroanilino)-6-(ethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N#CC1=NC(NCC)=NC(NC=2C=CC(Cl)=CC=2)=N1 CFTYWZFVQURLDD-UHFFFAOYSA-N 0.000 claims 1
- VSBXRTMJVIITDW-UHFFFAOYSA-N 4-(4-chloroanilino)-6-[4-[3-(dimethylamino)propyl]piperazin-1-yl]-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCN(CCCN(C)C)CC2)C(OC)=C1NC1=CC=C(Cl)C=C1 VSBXRTMJVIITDW-UHFFFAOYSA-N 0.000 claims 1
- GKWVLGLOAVNKNN-UHFFFAOYSA-N 4-(4-chloroanilino)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCOCC2)=N1 GKWVLGLOAVNKNN-UHFFFAOYSA-N 0.000 claims 1
- ARIOMJSONVMVHM-UHFFFAOYSA-N 4-(4-chloroanilino)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCOCC2)=NC(C#N)=N1 ARIOMJSONVMVHM-UHFFFAOYSA-N 0.000 claims 1
- PHRFVDJKWANIIJ-UHFFFAOYSA-N 4-(4-chloroanilino)-6-piperazin-1-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCNCC2)=NC(C#N)=N1 PHRFVDJKWANIIJ-UHFFFAOYSA-N 0.000 claims 1
- XUABEUVVOXVCEQ-UHFFFAOYSA-N 4-(4-chloroanilino)-6-piperidin-1-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCCCC2)=N1 XUABEUVVOXVCEQ-UHFFFAOYSA-N 0.000 claims 1
- FNIDFZPHGCXTQD-UHFFFAOYSA-N 4-(4-chloroanilino)-6-pyrrolidin-1-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCCC2)=N1 FNIDFZPHGCXTQD-UHFFFAOYSA-N 0.000 claims 1
- JBJHOQKLHPKKNE-UHFFFAOYSA-N 4-(4-chloroanilino)-6-pyrrolidin-1-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCCC2)=NC(C#N)=N1 JBJHOQKLHPKKNE-UHFFFAOYSA-N 0.000 claims 1
- RCCAPSQQOVDJIJ-UHFFFAOYSA-N 4-(4-chlorophenoxy)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1OC1=CC(N2CCOCC2)=NC(C#N)=N1 RCCAPSQQOVDJIJ-UHFFFAOYSA-N 0.000 claims 1
- ICWNIFGBCIVBTL-UHFFFAOYSA-N 4-(4-imidazol-1-ylpiperidin-1-yl)-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1N1C=CN=C1 ICWNIFGBCIVBTL-UHFFFAOYSA-N 0.000 claims 1
- NLPJWWPRAXCQIW-UHFFFAOYSA-N 4-(7-azabicyclo[2.2.1]heptan-7-yl)-6-(4-chloroanilino)-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2C3CCC2CC3)=N1 NLPJWWPRAXCQIW-UHFFFAOYSA-N 0.000 claims 1
- ZOZJTLLDGHUBPY-UHFFFAOYSA-N 4-(azetidin-1-yl)-6-(4-chloroanilino)-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCC2)=N1 ZOZJTLLDGHUBPY-UHFFFAOYSA-N 0.000 claims 1
- JACOZRXEUWTVOP-UHFFFAOYSA-N 4-(cyclohexylamino)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C=1C(N2CCOCC2)=NC(C#N)=NC=1NC1CCCCC1 JACOZRXEUWTVOP-UHFFFAOYSA-N 0.000 claims 1
- SWHVKIKRWPLXPK-UHFFFAOYSA-N 4-[(1-methylpiperidin-4-yl)amino]-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1CN(C)CCC1NC1=CC(N2CCOCC2)=NC(C#N)=N1 SWHVKIKRWPLXPK-UHFFFAOYSA-N 0.000 claims 1
- WOXKHFVEAVYTRX-UHFFFAOYSA-N 4-[(3-chlorophenyl)methylamino]-6-(dimethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N#CC1=NC(N(C)C)=NC(NCC=2C=C(Cl)C=CC=2)=N1 WOXKHFVEAVYTRX-UHFFFAOYSA-N 0.000 claims 1
- KJLDVJFLNOBWQC-NSHDSACASA-N 4-[(3s)-3-aminopyrrolidin-1-yl]-6-(4-chloroanilino)-5-methoxypyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2C[C@@H](N)CC2)C(OC)=C1NC1=CC=C(Cl)C=C1 KJLDVJFLNOBWQC-NSHDSACASA-N 0.000 claims 1
- QTUPPQQZNILLGV-UHFFFAOYSA-N 4-[(4-methylcyclohexyl)amino]-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1CC(C)CCC1NC1=CC(N2CCOCC2)=NC(C#N)=N1 QTUPPQQZNILLGV-UHFFFAOYSA-N 0.000 claims 1
- FBBDIKHSVMXWNJ-UHFFFAOYSA-N 4-[(6-chloropyridin-3-yl)amino]-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1=NC(Cl)=CC=C1NC1=CC(N2CCOCC2)=NC(C#N)=N1 FBBDIKHSVMXWNJ-UHFFFAOYSA-N 0.000 claims 1
- HKYNATOIQKWVMA-UHFFFAOYSA-N 4-[2-(furan-2-yl)ethylamino]-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(N2CCOCC2)=NC(C#N)=NC=1NCCC1=CC=CO1 HKYNATOIQKWVMA-UHFFFAOYSA-N 0.000 claims 1
- AGZVGTBMPVFJME-UHFFFAOYSA-N 4-[4-(2-methoxyphenyl)piperazin-1-yl]-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound COC1=CC=CC=C1N1CCN(C=2N=C(N=C(N=2)C#N)N2CCOCC2)CC1 AGZVGTBMPVFJME-UHFFFAOYSA-N 0.000 claims 1
- QBVCDJOMJPOECH-UHFFFAOYSA-N 4-[4-(4-chlorobenzoyl)piperidin-1-yl]-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)C1CCN(C=2N=C(N=C(N=2)C#N)N2CCOCC2)CC1 QBVCDJOMJPOECH-UHFFFAOYSA-N 0.000 claims 1
- NSXYUBSJTLTVOX-UHFFFAOYSA-N 4-[4-(5-chloropyridin-2-yl)piperazin-1-yl]-6-morpholin-4-yl-1,3,5-triazine-2-carbonitrile Chemical compound N1=CC(Cl)=CC=C1N1CCN(C=2N=C(N=C(N=2)C#N)N2CCOCC2)CC1 NSXYUBSJTLTVOX-UHFFFAOYSA-N 0.000 claims 1
- VVFZSWNCOHTYQS-UHFFFAOYSA-N 4-morpholin-4-yl-6-(2-pyridin-3-ylethylamino)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(N2CCOCC2)=NC(C#N)=NC=1NCCC1=CC=CN=C1 VVFZSWNCOHTYQS-UHFFFAOYSA-N 0.000 claims 1
- ACPGGAROWYBYCA-UHFFFAOYSA-N 4-morpholin-4-yl-6-(3-phenylpiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(C1)CCCC1C1=CC=CC=C1 ACPGGAROWYBYCA-UHFFFAOYSA-N 0.000 claims 1
- RSBVTQNOBXLYGL-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-morpholin-4-ylanilino)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(N2CCOCC2)=NC(C#N)=NC=1NC(C=C1)=CC=C1N1CCOCC1 RSBVTQNOBXLYGL-UHFFFAOYSA-N 0.000 claims 1
- KHPHMGJSXDODOC-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-phenoxypiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1OC1=CC=CC=C1 KHPHMGJSXDODOC-UHFFFAOYSA-N 0.000 claims 1
- URMHHFDWPPZHIV-UHFFFAOYSA-N 4-morpholin-4-yl-6-(4-piperidin-1-ylpiperidin-1-yl)-1,3,5-triazine-2-carbonitrile Chemical compound N=1C(C#N)=NC(N2CCOCC2)=NC=1N(CC1)CCC1N1CCCCC1 URMHHFDWPPZHIV-UHFFFAOYSA-N 0.000 claims 1
- JORNRTNWRASXHW-UHFFFAOYSA-N 4-morpholin-4-yl-6-[3-(2-oxopyrrolidin-1-yl)propylamino]-1,3,5-triazine-2-carbonitrile Chemical compound O=C1CCCN1CCCNC1=NC(C#N)=NC(N2CCOCC2)=N1 JORNRTNWRASXHW-UHFFFAOYSA-N 0.000 claims 1
- HLVUUIRENGTYML-UHFFFAOYSA-N 5-amino-4-(4-chloroanilino)-6-(ethylamino)pyrimidine-2-carbonitrile Chemical compound CCNC1=NC(C#N)=NC(NC=2C=CC(Cl)=CC=2)=C1N HLVUUIRENGTYML-UHFFFAOYSA-N 0.000 claims 1
- GJHNZJNXSKYROP-UHFFFAOYSA-N 5-amino-4-(4-chloroanilino)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C(N2CCOCC2)C(N)=C1NC1=CC=C(Cl)C=C1 GJHNZJNXSKYROP-UHFFFAOYSA-N 0.000 claims 1
- JLEVFFZEGQVAOR-UHFFFAOYSA-N 5-chloro-4-(4-chloroanilino)-6-morpholin-4-ylpyrimidine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1NC1=NC(C#N)=NC(N2CCOCC2)=C1Cl JLEVFFZEGQVAOR-UHFFFAOYSA-N 0.000 claims 1
- HXDJGRYZPYELDQ-UHFFFAOYSA-N C(#N)C1=NC(=NC(=N1)N1CCOCC1)N(CC(=O)N1C(COCC1)NCC(=O)NC(C)(C)C)CC(C)C Chemical compound C(#N)C1=NC(=NC(=N1)N1CCOCC1)N(CC(=O)N1C(COCC1)NCC(=O)NC(C)(C)C)CC(C)C HXDJGRYZPYELDQ-UHFFFAOYSA-N 0.000 claims 1
- 108010005843 Cysteine Proteases Proteins 0.000 claims 1
- 102000005927 Cysteine Proteases Human genes 0.000 claims 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims 1
- 150000002780 morpholines Chemical class 0.000 claims 1
- 125000004193 piperazinyl group Chemical class 0.000 claims 1
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000001174 sulfone group Chemical group 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
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| PCT/SE2003/001078 WO2004000819A1 (en) | 2002-06-24 | 2003-06-23 | New use of pyrimidine - or triazine- 2-carbonitiles for treating diseases associated with cysteine protease activity and novel pyrimidine-2-carbonitile derivatives |
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| JP2005533803A JP2005533803A (ja) | 2005-11-10 |
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| ES (1) | ES2280794T3 (enExample) |
| SE (1) | SE0201976D0 (enExample) |
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| AR036375A1 (es) | 2001-08-30 | 2004-09-01 | Novartis Ag | Compuestos pirrolo [2,3-d] pirimidina -2- carbonitrilo, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de medicamentos |
| SE0201980D0 (sv) * | 2002-06-24 | 2002-06-24 | Astrazeneca Ab | Novel compounds |
| GB0220187D0 (en) * | 2002-08-30 | 2002-10-09 | Novartis Ag | Organic compounds |
| DE602004009295T2 (de) * | 2003-01-14 | 2008-07-03 | Arena Pharmaceuticals, Inc., San Diego | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| EP1927594A1 (en) | 2003-01-14 | 2008-06-04 | Arena Pharmaceuticals, Inc. | 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| KR20050122220A (ko) | 2003-03-25 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 디펩티딜 펩티다제 억제제 |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| EP2292620A3 (en) | 2003-07-14 | 2011-06-22 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prohylaxis and treatment of disorders related thereto |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| US7790734B2 (en) * | 2003-09-08 | 2010-09-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
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| EA013427B1 (ru) * | 2004-03-15 | 2010-04-30 | Такеда Фармасьютикал Компани Лимитед | Ингибиторы дипептидилпептидазы |
| TW200614993A (en) * | 2004-06-11 | 2006-05-16 | Akzo Nobel Nv | 4-phenyl-pyrimidine-2-carbonitrile derivatives |
| GB0418353D0 (en) * | 2004-08-17 | 2004-09-22 | Novartis Ag | Organic compounds |
| CN101090724A (zh) | 2004-09-20 | 2007-12-19 | 泽农医药公司 | 用于抑制人硬脂酰CoA去饱和酶的吡啶衍生物 |
| WO2006040300A1 (en) * | 2004-10-12 | 2006-04-20 | N.V. Organon | 4-cycloalkyl-pyrimidine-2-carbonitrile derivatives |
| EP1828192B1 (en) | 2004-12-21 | 2014-12-03 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| GB0514684D0 (en) * | 2005-07-18 | 2005-08-24 | Novartis Ag | Organic compounds |
| PT1942898E (pt) | 2005-09-14 | 2011-12-20 | Takeda Pharmaceutical | Inibidores da dipeptidilpeptidase para o tratamento da diabetes |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| TW200745055A (en) * | 2005-09-23 | 2007-12-16 | Organon Nv | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
| US7326715B2 (en) | 2005-09-23 | 2008-02-05 | N.V. Organon | 4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives |
| US7687515B2 (en) | 2006-01-17 | 2010-03-30 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| US8324383B2 (en) * | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| BRPI0716971A2 (pt) * | 2006-09-13 | 2013-10-15 | Takeda Pharmaceutical | Uso de 2-6(3-amino-piperini-l-il)-3-metil-2,4-dioxo-3,4-dihidro-2 h-pirimidin-1ilmetil-4-fluoro-benxonitrila |
| US20090118274A1 (en) * | 2007-02-15 | 2009-05-07 | Darin Allen | Monocyclic aminopropyl tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20080269241A1 (en) * | 2007-02-15 | 2008-10-30 | Darin Allen | Bicyclic aminopropyl tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20080207683A1 (en) * | 2007-02-15 | 2008-08-28 | Darin Allen | Biaryl-substituted tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US20090099157A1 (en) * | 2007-02-15 | 2009-04-16 | Ameriks Michael K | Tetrahydro-pyrazolo-pyridine thioether modulators of cathepsin s |
| US20080200454A1 (en) * | 2007-02-15 | 2008-08-21 | Ameriks Michael K | Carbon-linked tetrahydro-pyrazolo-pyridine modulators of cathepsin s |
| US8093236B2 (en) * | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| US7932251B2 (en) | 2007-07-16 | 2011-04-26 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| US20100144140A1 (en) * | 2008-12-10 | 2010-06-10 | Novellus Systems, Inc. | Methods for depositing tungsten films having low resistivity for gapfill applications |
| US8026236B2 (en) | 2009-01-16 | 2011-09-27 | N.V. Organon | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| TW201035094A (en) | 2009-01-16 | 2010-10-01 | Organon Nv | 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives |
| US9115126B2 (en) | 2010-01-15 | 2015-08-25 | Merck Sharp & Dohme B.V. | 1H-[1,2,3]triazolo[4,5-c]pyridine-4-carbonitrile derivatives |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US8524710B2 (en) * | 2010-11-05 | 2013-09-03 | Hoffmann-La Roche Inc. | Pyrrolidine derivatives |
| ES2995737T3 (en) | 2015-01-06 | 2025-02-11 | Arena Pharm Inc | Compound for use in treating conditions related to the s1p1 receptor |
| MA42807A (fr) | 2015-06-22 | 2018-07-25 | Arena Pharm Inc | Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1 |
| WO2018151873A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| EP3801459B1 (en) | 2018-06-06 | 2024-08-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| WO2020201572A1 (en) | 2019-04-05 | 2020-10-08 | Université De Bretagne Occidentale | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
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| DE1172684B (de) * | 1962-09-15 | 1964-06-25 | Degussa | Verfahren zur Herstellung von substituierten 2, 4-Bis-alkylamino-1, 3, 5-triazinverbindungen |
| NL284584A (enExample) * | 1962-11-22 | |||
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| BR6915234D0 (pt) * | 1969-05-22 | 1973-06-07 | American Cyanamid Co | Novos derivados de melamina e processo para sua preparaca |
| CH627919A5 (de) * | 1977-04-14 | 1982-02-15 | Ciba Geigy Ag | Herbizide mittel. |
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| DE10111649A1 (de) * | 2001-03-12 | 2002-09-19 | Bayer Ag | Substituierte Fluoralkoxyphenylsulfonylharnstoffe |
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-
2002
- 2002-06-24 SE SE0201976A patent/SE0201976D0/xx unknown
-
2003
- 2003-06-23 AU AU2003243095A patent/AU2003243095A1/en not_active Abandoned
- 2003-06-23 EP EP03761001A patent/EP1532121B1/en not_active Expired - Lifetime
- 2003-06-23 AT AT03761001T patent/ATE353880T1/de not_active IP Right Cessation
- 2003-06-23 US US10/518,817 patent/US7125881B2/en not_active Expired - Fee Related
- 2003-06-23 WO PCT/SE2003/001078 patent/WO2004000819A1/en not_active Ceased
- 2003-06-23 JP JP2004515328A patent/JP2005533803A/ja active Pending
- 2003-06-23 ES ES03761001T patent/ES2280794T3/es not_active Expired - Lifetime
- 2003-06-23 DE DE60311820T patent/DE60311820T2/de not_active Expired - Fee Related
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