JP5807971B2 - Cxcr3受容体アンタゴニスト - Google Patents
Cxcr3受容体アンタゴニスト Download PDFInfo
- Publication number
- JP5807971B2 JP5807971B2 JP2012507460A JP2012507460A JP5807971B2 JP 5807971 B2 JP5807971 B2 JP 5807971B2 JP 2012507460 A JP2012507460 A JP 2012507460A JP 2012507460 A JP2012507460 A JP 2012507460A JP 5807971 B2 JP5807971 B2 JP 5807971B2
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- JP
- Japan
- Prior art keywords
- piperazin
- phenyl
- ethanone
- pyrimidin
- dimethyl
- 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.)
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- 108010061300 CXCR3 Receptors Proteins 0.000 title 1
- 102000011963 CXCR3 Receptors Human genes 0.000 title 1
- 239000002464 receptor antagonist Substances 0.000 title 1
- 229940044551 receptor antagonist Drugs 0.000 title 1
- -1 benzo [b] thiophenyl Chemical group 0.000 claims description 219
- 150000001875 compounds Chemical class 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 4
- RQQZFZRGHRYPHQ-UHFFFAOYSA-N 1-[4-[2-(1,3-benzoxazol-2-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2OC3=CC=CC=C3N=2)CC1 RQQZFZRGHRYPHQ-UHFFFAOYSA-N 0.000 claims description 3
- DITARGOVXVJMIV-UHFFFAOYSA-N 1-[4-[2-(1h-benzimidazol-2-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2NC3=CC=CC=C3N=2)CC1 DITARGOVXVJMIV-UHFFFAOYSA-N 0.000 claims description 3
- TVIXOCCKWVNECQ-UHFFFAOYSA-N 1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC=C3C=C2)CC1 TVIXOCCKWVNECQ-UHFFFAOYSA-N 0.000 claims description 3
- YITXQTQOTWOFER-UHFFFAOYSA-N 1-[4-[2-(2-methylsulfanylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=NC(SC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC=C3C=C2)CC1 YITXQTQOTWOFER-UHFFFAOYSA-N 0.000 claims description 3
- KPWISRQIHOZXCI-UHFFFAOYSA-N 1-[4-[2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C(C=N1)=CN=C1N1CCOCC1 KPWISRQIHOZXCI-UHFFFAOYSA-N 0.000 claims description 3
- NXZTVPNYSODMFT-UHFFFAOYSA-N 1-[4-[2-(6-chloro-1h-benzimidazol-2-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2NC3=CC=C(Cl)C=C3N=2)CC1 NXZTVPNYSODMFT-UHFFFAOYSA-N 0.000 claims description 3
- OHQQBEBGBRXYAV-UHFFFAOYSA-N 1-[4-[2-[2-(2,6-dimethylmorpholin-4-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound C1C(C)OC(C)CN1C1=NC=C(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)C=N1 OHQQBEBGBRXYAV-UHFFFAOYSA-N 0.000 claims description 3
- UCFPDSLVZZRGNC-UHFFFAOYSA-N 1-[4-[2-[2-(dimethylamino)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=NC(N(C)C)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC=C3C=C2)CC1 UCFPDSLVZZRGNC-UHFFFAOYSA-N 0.000 claims description 3
- XLSBVSNXSCACQJ-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=NC=CC=C3N=C2)C=N1 XLSBVSNXSCACQJ-UHFFFAOYSA-N 0.000 claims description 3
- XKZTYHWRHFJSGM-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=NC=CC=C3C=C2)C=N1 XKZTYHWRHFJSGM-UHFFFAOYSA-N 0.000 claims description 3
- DYTKSFKHKHTAKS-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-pyrrolo[2,3-c]pyridin-1-ylethanone Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=CN=CC=C3C=C2)C=N1 DYTKSFKHKHTAKS-UHFFFAOYSA-N 0.000 claims description 3
- NYDDBKINLWXGLH-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=NC=CC=C3N=C2)C=N1 NYDDBKINLWXGLH-UHFFFAOYSA-N 0.000 claims description 3
- JOVVYNPSVAXDBO-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=NC=CC=C3C=C2)C=N1 JOVVYNPSVAXDBO-UHFFFAOYSA-N 0.000 claims description 3
- NTFRDZBMZATPQE-UHFFFAOYSA-N 1-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-pyrrolo[2,3-c]pyridin-1-ylethanone Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C3=CN=CC=C3C=C2)C=N1 NTFRDZBMZATPQE-UHFFFAOYSA-N 0.000 claims description 3
- LZDSDKNDVWRRID-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[2-(2-pyrrolidin-1-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=NC=2)N2CCCC2)CC1 LZDSDKNDVWRRID-UHFFFAOYSA-N 0.000 claims description 3
- VNXHYJHVPDAUHY-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[2-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]phenyl]piperazin-1-yl]ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2NC3=CC=C(C=C3N=2)C(F)(F)F)CC1 VNXHYJHVPDAUHY-UHFFFAOYSA-N 0.000 claims description 3
- KGEUNAZEQRRDLP-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(C3=CC=CC=C3C2)=O)C=N1 KGEUNAZEQRRDLP-UHFFFAOYSA-N 0.000 claims description 3
- GLWMODWQRYHHAQ-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(C3=CC=CC=C3C2)=O)C=N1 GLWMODWQRYHHAQ-UHFFFAOYSA-N 0.000 claims description 3
- GDPWWOUZDHKUHD-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(NC3=CC=CC=C32)=O)C=N1 GDPWWOUZDHKUHD-UHFFFAOYSA-N 0.000 claims description 3
- JVNDDBDHDJVWQQ-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(NC3=CC=CC=C32)=O)C=N1 JVNDDBDHDJVWQQ-UHFFFAOYSA-N 0.000 claims description 3
- ZWQLSSCUWNHOJX-UHFFFAOYSA-N 5-[2-[4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]phenyl]pyridine-2-carbonitrile Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C1=CC=C(C#N)N=C1 ZWQLSSCUWNHOJX-UHFFFAOYSA-N 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- RDKIRFGAYOHJNN-HSZRJFAPSA-N (2r)-1-[5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyrimidin-2-yl]pyrrolidine-2-carboxamide Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=NC=2)N2[C@H](CCC2)C(N)=O)CC1 RDKIRFGAYOHJNN-HSZRJFAPSA-N 0.000 claims description 2
- QYEYJURGTVYHGD-DEOSSOPVSA-N (2s)-1-[5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyrimidin-2-yl]-n-methylpyrrolidine-2-carboxamide Chemical compound CNC(=O)[C@@H]1CCCN1C1=NC=C(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)C=N1 QYEYJURGTVYHGD-DEOSSOPVSA-N 0.000 claims description 2
- ICGUJVMBPMMDFF-UHFFFAOYSA-N 1-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(N(C)C3=CC=CC=C32)=O)CC1 ICGUJVMBPMMDFF-UHFFFAOYSA-N 0.000 claims description 2
- SYSDOWKKMOZCTE-UHFFFAOYSA-N 1-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]indole-2,3-dione Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC=CC=C3C(=O)C2=O)CC1 SYSDOWKKMOZCTE-UHFFFAOYSA-N 0.000 claims description 2
- DUDZYSJSFRYINK-UHFFFAOYSA-N 1-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]pyrrolo[2,3-b]pyridine-4-carbonitrile Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC(=C3C=C2)C#N)CC1 DUDZYSJSFRYINK-UHFFFAOYSA-N 0.000 claims description 2
- WXAYGXGWQNSLGW-UHFFFAOYSA-N 1-[2-[4-[2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]imidazolidin-2-one Chemical compound C1CN(C=2C(=CC=CC=2)C=2C=NC(=NC=2)N2CCOCC2)CCN1C(=O)CN1CCNC1=O WXAYGXGWQNSLGW-UHFFFAOYSA-N 0.000 claims description 2
- NQNLMGMGISGHQM-UHFFFAOYSA-N 1-[2-[4-[4-fluoro-2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]piperidin-2-one Chemical compound C1=NC(OC)=NC=C1C1=CC(F)=CC=C1N1CCN(C(=O)CN2C(CCCC2)=O)CC1 NQNLMGMGISGHQM-UHFFFAOYSA-N 0.000 claims description 2
- UBRKNSVFCODKFV-UHFFFAOYSA-N 1-[2-[4-[4-fluoro-2-(2-pyrrolidin-1-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]piperidin-2-one Chemical compound C=1N=C(N2CCCC2)N=CC=1C1=CC(F)=CC=C1N(CC1)CCN1C(=O)CN1CCCCC1=O UBRKNSVFCODKFV-UHFFFAOYSA-N 0.000 claims description 2
- FNUXPBHOLKUTQC-UHFFFAOYSA-N 1-[2-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]piperidin-2-one Chemical compound C1CC(O)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(CCCC2)=O)C=N1 FNUXPBHOLKUTQC-UHFFFAOYSA-N 0.000 claims description 2
- WYJZCORHTVDUMN-UHFFFAOYSA-N 1-[2-[4-[4-fluoro-2-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]piperidin-2-one Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(CCCC2)=O)C=N1 WYJZCORHTVDUMN-UHFFFAOYSA-N 0.000 claims description 2
- BFZWEEHDSHVFKB-UHFFFAOYSA-N 1-[2-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]piperidin-2-one Chemical compound C1CC(S(=O)(=O)C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(CCCC2)=O)C=N1 BFZWEEHDSHVFKB-UHFFFAOYSA-N 0.000 claims description 2
- RDYDUKMIMQRBFN-UHFFFAOYSA-N 1-[4-(2-phenylphenyl)piperazin-1-yl]-2-piperidin-1-ylethanone Chemical compound C1CN(C=2C(=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)CN1CCCCC1 RDYDUKMIMQRBFN-UHFFFAOYSA-N 0.000 claims description 2
- IJEOVXZDBQKOIW-UHFFFAOYSA-N 1-[4-(2-phenylphenyl)piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C1=CC=CC=C1 IJEOVXZDBQKOIW-UHFFFAOYSA-N 0.000 claims description 2
- WFZYOFTVLWCNEH-UHFFFAOYSA-N 1-[4-[2-(1-benzothiophen-2-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2SC3=CC=CC=C3C=2)CC1 WFZYOFTVLWCNEH-UHFFFAOYSA-N 0.000 claims description 2
- UYBXZPVAECDWHY-UHFFFAOYSA-N 1-[4-[2-(1-benzothiophen-3-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C3=CC=CC=C3SC=2)CC1 UYBXZPVAECDWHY-UHFFFAOYSA-N 0.000 claims description 2
- KABZREWJNIWKAJ-UHFFFAOYSA-N 1-[4-[2-(1-benzylpyrazol-4-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C2=CN(CC=3C=CC=CC=3)N=C2)CC1 KABZREWJNIWKAJ-UHFFFAOYSA-N 0.000 claims description 2
- AHHXPKIXPMLCBZ-UHFFFAOYSA-N 1-[4-[2-(2-aminopyrimidin-5-yl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(N)=NC=2)CC1 AHHXPKIXPMLCBZ-UHFFFAOYSA-N 0.000 claims description 2
- YWRYDWAWWCJNHA-UHFFFAOYSA-N 1-[4-[2-(2-chlorophenyl)phenyl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C(=CC=CC=2)Cl)CC1 YWRYDWAWWCJNHA-UHFFFAOYSA-N 0.000 claims description 2
- ZKRGLGDZVBLNAU-UHFFFAOYSA-N 1-[4-[2-(2-methoxypyridin-4-yl)phenyl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=NC(OC)=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C3=NC=CC=C3C=C2)=C1 ZKRGLGDZVBLNAU-UHFFFAOYSA-N 0.000 claims description 2
- NCWYPQJRBXRZMX-UHFFFAOYSA-N 1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-(3,4,5-trimethylpyrazol-1-yl)ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=C(C)C(C)=N2)C)CC1 NCWYPQJRBXRZMX-UHFFFAOYSA-N 0.000 claims description 2
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- ADQKSSRMMVOPSO-UHFFFAOYSA-N 1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-pyrrolo[2,3-c]pyridin-1-ylethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CN=CC=C3C=C2)CC1 ADQKSSRMMVOPSO-UHFFFAOYSA-N 0.000 claims description 2
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- HNLWFFKETLWJRJ-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[4-fluoro-2-(2-pyrrolidin-1-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC(F)=CC=2)C=2C=NC(=NC=2)N2CCCC2)CC1 HNLWFFKETLWJRJ-UHFFFAOYSA-N 0.000 claims description 2
- PUTFTNTZMOPNFO-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[4-fluoro-2-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC(F)=CC=2)C=2C=NC(=NC=2)N2CCC(O)CC2)CC1 PUTFTNTZMOPNFO-UHFFFAOYSA-N 0.000 claims description 2
- AGCLIWAYFCOAKG-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[4-fluoro-2-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)C=N1 AGCLIWAYFCOAKG-UHFFFAOYSA-N 0.000 claims description 2
- NKWRKJUGTKMGIX-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)-1-[4-[4-fluoro-2-[2-(4-methylsulfonylpiperidin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC(F)=CC=2)C=2C=NC(=NC=2)N2CCC(CC2)S(C)(=O)=O)CC1 NKWRKJUGTKMGIX-UHFFFAOYSA-N 0.000 claims description 2
- LYIRDUYIOVOAKX-UHFFFAOYSA-N 2-(4,5-dichloroimidazol-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=C(Cl)N=C2)Cl)CC1 LYIRDUYIOVOAKX-UHFFFAOYSA-N 0.000 claims description 2
- SLQLLMBRHUJGQZ-UHFFFAOYSA-N 2-(4-chloro-3,5-dimethylpyrazol-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=C(Cl)C(C)=N2)C)CC1 SLQLLMBRHUJGQZ-UHFFFAOYSA-N 0.000 claims description 2
- NTZFHTAQPOUYEH-UHFFFAOYSA-N 2-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=NC(Cl)=C3C=C2)CC1 NTZFHTAQPOUYEH-UHFFFAOYSA-N 0.000 claims description 2
- LQMKQBMHGRDJNE-UHFFFAOYSA-N 2-(4-chloropyrrolo[3,2-c]pyridin-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC=NC(Cl)=C3C=C2)CC1 LQMKQBMHGRDJNE-UHFFFAOYSA-N 0.000 claims description 2
- WQMHRKFENHWYFC-UHFFFAOYSA-N 2-(5-chloropyrrolo[3,2-b]pyridin-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC=C(Cl)N=C3C=C2)CC1 WQMHRKFENHWYFC-UHFFFAOYSA-N 0.000 claims description 2
- WEQDEIHUGCDHTR-UHFFFAOYSA-N 2-(5-fluoropyrrolo[2,3-b]pyridin-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=C(F)C=C3C=C2)CC1 WEQDEIHUGCDHTR-UHFFFAOYSA-N 0.000 claims description 2
- MBBVLUDKRZIATE-UHFFFAOYSA-N 2-(6-bromopyrrolo[3,2-c]pyridin-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC(Br)=NC=C3C=C2)CC1 MBBVLUDKRZIATE-UHFFFAOYSA-N 0.000 claims description 2
- FNARAKAZGOTMOS-UHFFFAOYSA-N 2-(7-chloropyrrolo[2,3-c]pyridin-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=C(Cl)N=CC=C3C=C2)CC1 FNARAKAZGOTMOS-UHFFFAOYSA-N 0.000 claims description 2
- YAKCAHNTYWHUFQ-UHFFFAOYSA-N 2-(benzotriazol-1-yl)-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC=CC=C3N=N2)CC1 YAKCAHNTYWHUFQ-UHFFFAOYSA-N 0.000 claims description 2
- PCWDVUVSIUXIBX-UHFFFAOYSA-N 2-[2-[4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]phenyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1=CC=CC=C1N(CC1)CCN1C(=O)CN1C2=NC=CC=C2C=C1 PCWDVUVSIUXIBX-UHFFFAOYSA-N 0.000 claims description 2
- LITVBQLGNXGAMU-UHFFFAOYSA-N 2-[2-[4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]phenyl]isoquinolin-1-one Chemical compound C1=CC2=CC=CC=C2C(=O)N1C1=CC=CC=C1N(CC1)CCN1C(=O)CN1C2=NC=CC=C2C=C1 LITVBQLGNXGAMU-UHFFFAOYSA-N 0.000 claims description 2
- ADKVOTNNJXAFKJ-UHFFFAOYSA-N 2-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(C3=CC=CC=C3C2)=O)CC1 ADKVOTNNJXAFKJ-UHFFFAOYSA-N 0.000 claims description 2
- QZLBTTGDKMDJPE-UHFFFAOYSA-N 2-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]phthalazin-1-one Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(C3=CC=CC=C3C=N2)=O)CC1 QZLBTTGDKMDJPE-UHFFFAOYSA-N 0.000 claims description 2
- PQTUFUHIXYVIJG-UHFFFAOYSA-N 2-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]-3h-benzimidazole-5-carbonitrile Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2NC3=CC=C(C=C3N=2)C#N)CC1 PQTUFUHIXYVIJG-UHFFFAOYSA-N 0.000 claims description 2
- RQYPSOJCFGZJFB-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C=1C(F)=CC=C(N2CCN(CC2)C(=O)CN2C(C3=CC=CC=C3C2)=O)C=1C(C=N1)=CN=C1N1CCOCC1 RQYPSOJCFGZJFB-UHFFFAOYSA-N 0.000 claims description 2
- AUCLOCSETOTKRD-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-2-(2-pyrrolidin-1-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C=1C(F)=CC=C(N2CCN(CC2)C(=O)CN2C(C3=CC=CC=C3C2)=O)C=1C(C=N1)=CN=C1N1CCCC1 AUCLOCSETOTKRD-UHFFFAOYSA-N 0.000 claims description 2
- GJEKFPUIEIRZHK-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-2-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-3h-isoindol-1-one Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(C3=CC=CC=C3C2)=O)C=N1 GJEKFPUIEIRZHK-UHFFFAOYSA-N 0.000 claims description 2
- JBIFTNIARJMJOQ-UHFFFAOYSA-N 2-imidazo[4,5-b]pyridin-1-yl-1-[4-(2-phenylphenyl)piperazin-1-yl]ethanone Chemical compound C1=NC2=NC=CC=C2N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C1=CC=CC=C1 JBIFTNIARJMJOQ-UHFFFAOYSA-N 0.000 claims description 2
- JDHSVAYNOQKEJB-UHFFFAOYSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC=C3N=C2)CC1 JDHSVAYNOQKEJB-UHFFFAOYSA-N 0.000 claims description 2
- VFJSXYFLHXLKQA-UHFFFAOYSA-N 2-indazol-1-yl-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=CC=CC=C3C=N2)CC1 VFJSXYFLHXLKQA-UHFFFAOYSA-N 0.000 claims description 2
- CSTZLXPKJHMYIV-UHFFFAOYSA-N 2-indazol-2-yl-1-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]ethanone Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2N=C3C=CC=CC3=C2)CC1 CSTZLXPKJHMYIV-UHFFFAOYSA-N 0.000 claims description 2
- OPRLKBAVVKLTGJ-UHFFFAOYSA-N 3-[2-[4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]quinazolin-4-one Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(C3=CC=CC=C3N=C2)=O)CC1 OPRLKBAVVKLTGJ-UHFFFAOYSA-N 0.000 claims description 2
- UZPZUPLRBPDDFD-UHFFFAOYSA-N 3-[2-[4-[2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C12=CC=CC=C2NC(=O)N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C(C=N1)=CN=C1N1CCOCC1 UZPZUPLRBPDDFD-UHFFFAOYSA-N 0.000 claims description 2
- BKTDHNAFXRMGER-UHFFFAOYSA-N 3-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)=C1 BKTDHNAFXRMGER-UHFFFAOYSA-N 0.000 claims description 2
- WSCQPSUDXIPMCI-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-(2-methoxypyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C1=NC(OC)=NC=C1C1=CC(F)=CC=C1N1CCN(C(=O)CN2C(NC3=CC=CC=C32)=O)CC1 WSCQPSUDXIPMCI-UHFFFAOYSA-N 0.000 claims description 2
- DYMDYOLOPDBOTP-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-(2-methylsulfonylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C1=NC(S(=O)(=O)C)=NC=C1C1=CC(F)=CC=C1N1CCN(C(=O)CN2C(NC3=CC=CC=C32)=O)CC1 DYMDYOLOPDBOTP-UHFFFAOYSA-N 0.000 claims description 2
- AHIIYDIUZYZTSE-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C=1C(F)=CC=C(N2CCN(CC2)C(=O)CN2C(NC3=CC=CC=C32)=O)C=1C(C=N1)=CN=C1N1CCOCC1 AHIIYDIUZYZTSE-UHFFFAOYSA-N 0.000 claims description 2
- YCHBQMNYZBVURG-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-(2-pyrrolidin-1-ylpyrimidin-5-yl)phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C=1C(F)=CC=C(N2CCN(CC2)C(=O)CN2C(NC3=CC=CC=C32)=O)C=1C(C=N1)=CN=C1N1CCCC1 YCHBQMNYZBVURG-UHFFFAOYSA-N 0.000 claims description 2
- KQODTJNYCXCBPZ-UHFFFAOYSA-N 3-[2-[4-[4-fluoro-2-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]phenyl]piperazin-1-yl]-2-oxoethyl]-1h-benzimidazol-2-one Chemical compound C1CN(C)CCN1C1=NC=C(C=2C(=CC=C(F)C=2)N2CCN(CC2)C(=O)CN2C(NC3=CC=CC=C32)=O)C=N1 KQODTJNYCXCBPZ-UHFFFAOYSA-N 0.000 claims description 2
- UCOAQSJCJMSYND-UHFFFAOYSA-N 3-[2-oxo-2-[4-(2-phenylphenyl)piperazin-1-yl]ethyl]-1h-benzimidazol-2-one Chemical compound C12=CC=CC=C2NC(=O)N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C1=CC=CC=C1 UCOAQSJCJMSYND-UHFFFAOYSA-N 0.000 claims description 2
- JRPAILBDUXSHMO-UHFFFAOYSA-N 4-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=CC(C)=N2)C)CC1 JRPAILBDUXSHMO-UHFFFAOYSA-N 0.000 claims description 2
- HREDURYUMMCZSQ-UHFFFAOYSA-N 4-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)=C1 HREDURYUMMCZSQ-UHFFFAOYSA-N 0.000 claims description 2
- CDNZPLTYSYBZNL-UHFFFAOYSA-N 4-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]benzenesulfonamide Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=CC(=CC=2)S(N)(=O)=O)CC1 CDNZPLTYSYBZNL-UHFFFAOYSA-N 0.000 claims description 2
- WHLPSWUIVJSSFN-UHFFFAOYSA-N 5-[2-[4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]phenyl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C3=NC=CC=C3C=C2)CC1 WHLPSWUIVJSSFN-UHFFFAOYSA-N 0.000 claims description 2
- KTWKOMWBIVEFTC-UHFFFAOYSA-N 5-[2-[4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]phenyl]pyrimidine-2-carbonitrile Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=CC=CC=C1C1=CN=C(C#N)N=C1 KTWKOMWBIVEFTC-UHFFFAOYSA-N 0.000 claims description 2
- VLIIOWVDUHIGQJ-UHFFFAOYSA-N 5-[2-[4-[2-(2,4-dimethylimidazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyridine-2-carbonitrile Chemical compound CC1=NC(C)=CN1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=CC=2)C#N)CC1 VLIIOWVDUHIGQJ-UHFFFAOYSA-N 0.000 claims description 2
- XRQBWDHJACMHGO-UHFFFAOYSA-N 5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=CC(C)=N2)C)CC1 XRQBWDHJACMHGO-UHFFFAOYSA-N 0.000 claims description 2
- VKUTZPGOSMWPBF-UHFFFAOYSA-N 5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyridine-2-carbonitrile Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=CC=2)C#N)CC1 VKUTZPGOSMWPBF-UHFFFAOYSA-N 0.000 claims description 2
- OBBSEVNENHJKGE-UHFFFAOYSA-N 5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyrimidine-2-carbonitrile Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=NC=2)C#N)CC1 OBBSEVNENHJKGE-UHFFFAOYSA-N 0.000 claims description 2
- WTKIYWSMDZSOCG-UHFFFAOYSA-N 5-[2-[4-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperazin-1-yl]phenyl]pyridine-2-carbonitrile Chemical compound CC1=CC(C(F)(F)F)=NN1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=CC=2)C#N)CC1 WTKIYWSMDZSOCG-UHFFFAOYSA-N 0.000 claims description 2
- WRYAUHPVLGFDTI-UHFFFAOYSA-N 5-[2-[4-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]piperazin-1-yl]phenyl]pyridine-2-carboxamide Chemical compound CC1=CC(C(F)(F)F)=NN1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=NC(=CC=2)C(N)=O)CC1 WRYAUHPVLGFDTI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005872 benzooxazolyl group Chemical group 0.000 claims description 2
- 125000005509 dibenzothiophenyl group Chemical group 0.000 claims description 2
- XGNZJFYQWVUGEH-UHFFFAOYSA-N ethyl 5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)=C1 XGNZJFYQWVUGEH-UHFFFAOYSA-N 0.000 claims description 2
- JTLNKMGJFWUIDT-UHFFFAOYSA-N methyl 4-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)=C1 JTLNKMGJFWUIDT-UHFFFAOYSA-N 0.000 claims description 2
- GXMLTLNDQZEAHE-UHFFFAOYSA-N methyl 5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=CC(C)=N2)C)CC1 GXMLTLNDQZEAHE-UHFFFAOYSA-N 0.000 claims description 2
- OQUJDMXFGBAQOU-UHFFFAOYSA-N n-[3-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(C=2C(=CC=CC=2)N2CCN(CC2)C(=O)CN2C(=CC(C)=N2)C)=C1 OQUJDMXFGBAQOU-UHFFFAOYSA-N 0.000 claims description 2
- IVFWYDJLZPVBPK-UHFFFAOYSA-N n-[4-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]phenyl]methanesulfonamide Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C=2C(=CC=CC=2)C=2C=CC(NS(C)(=O)=O)=CC=2)CC1 IVFWYDJLZPVBPK-UHFFFAOYSA-N 0.000 claims description 2
- FAKNPIHVTCDNRA-UHFFFAOYSA-N n-[5-[2-[4-[2-(3,5-dimethylpyrazol-1-yl)acetyl]piperazin-1-yl]phenyl]pyrimidin-2-yl]-n-methylacetamide Chemical compound C1=NC(N(C(C)=O)C)=NC=C1C1=CC=CC=C1N1CCN(C(=O)CN2C(=CC(C)=N2)C)CC1 FAKNPIHVTCDNRA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- BYVHYCRIGWJSOT-UHFFFAOYSA-N 1-(4-methylpyrazol-1-yl)ethanone Chemical compound CC(=O)N1C=C(C)C=N1 BYVHYCRIGWJSOT-UHFFFAOYSA-N 0.000 claims 1
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- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- FGJACYJASSSXNJ-UHFFFAOYSA-N tert-butyl 4-(2-formylphenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC=C1C=O FGJACYJASSSXNJ-UHFFFAOYSA-N 0.000 description 1
- VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 1
- WCNUHAITMHJUAN-UHFFFAOYSA-N tert-butyl 4-[2-(2-methoxypyrimidin-5-yl)phenyl]piperazine-1-carboxylate Chemical compound C1=NC(OC)=NC=C1C1=CC=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 WCNUHAITMHJUAN-UHFFFAOYSA-N 0.000 description 1
- KBRRKNCIGDFBSS-UHFFFAOYSA-N tert-butyl 4-[2-(2-morpholin-4-ylpyrimidin-5-yl)phenyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C(=CC=CC=2)C=2C=NC(=NC=2)N2CCOCC2)=C1 KBRRKNCIGDFBSS-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D213/00—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
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- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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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
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- 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
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- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
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Applications Claiming Priority (5)
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| US17287309P | 2009-04-27 | 2009-04-27 | |
| US61/172,873 | 2009-04-27 | ||
| US31948210P | 2010-03-31 | 2010-03-31 | |
| US61/319,482 | 2010-03-31 | ||
| PCT/US2010/032347 WO2010126811A1 (en) | 2009-04-27 | 2010-04-26 | Cxcr3 receptor antagonists |
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| JP2012525332A JP2012525332A (ja) | 2012-10-22 |
| JP2012525332A5 JP2012525332A5 (enExample) | 2013-06-20 |
| JP5807971B2 true JP5807971B2 (ja) | 2015-11-10 |
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| EP (1) | EP2424840B1 (enExample) |
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| WO (1) | WO2010126811A1 (enExample) |
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| AU2009289649B2 (en) | 2008-09-03 | 2016-05-05 | Biomarin Pharmaceutical Inc. | Compositions including 6-aminohexanoic acid derivatives as HDAC inhibitors |
| US8362249B2 (en) * | 2009-04-27 | 2013-01-29 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
| WO2010126811A1 (en) | 2009-04-27 | 2010-11-04 | Boehringer Ingelheim International Gmbh | Cxcr3 receptor antagonists |
| JP2011057661A (ja) * | 2009-08-14 | 2011-03-24 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
| US8952004B2 (en) | 2010-01-07 | 2015-02-10 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
| US10059723B2 (en) | 2011-02-28 | 2018-08-28 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| JP6250403B2 (ja) | 2011-02-28 | 2017-12-20 | バイオマリン ファーマシューティカル インク | ヒストン脱アセチル化酵素阻害剤 |
| US8957066B2 (en) | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US8822464B2 (en) | 2011-11-28 | 2014-09-02 | Boehringer Ingelheim International Gmbh | N-aryl-piperazine derivatives and their use as positive allosteric modulators of mGluR5 receptors |
| US8741892B2 (en) | 2011-12-05 | 2014-06-03 | Boehringer Ingelheim International Gmbh | Compounds |
| US8642774B2 (en) | 2011-12-08 | 2014-02-04 | Boehringer Ingelheim International Gmbh | Compounds |
| US8796467B2 (en) | 2011-12-13 | 2014-08-05 | Boehringer Ingelheim International Gmbh | Compounds |
| US8846948B2 (en) | 2011-12-13 | 2014-09-30 | Boehringer Ingelheim International Gmbh | Compounds |
| US8716277B2 (en) | 2011-12-14 | 2014-05-06 | Boehringer Ingelheim International Gmbh | Substituted imidazole compounds useful as positive allosteric modulators of mGlu5 receptor activity |
| US8937176B2 (en) | 2011-12-14 | 2015-01-20 | Boehringer Ingelheim International Gmbh | Compounds |
| US8883789B2 (en) | 2011-12-14 | 2014-11-11 | Boehringer Ingelheim International Gmbh | Piperazine derivatives and their use as positive allosteric modulators of mGluR5 receptors |
| US8889677B2 (en) | 2012-01-17 | 2014-11-18 | Boehringer Ingellheim International GmbH | Substituted triazoles useful as mGlu5 receptor modulators |
| AU2013216354B2 (en) * | 2012-02-02 | 2017-08-31 | Idorsia Pharmaceuticals Ltd | 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives |
| JP6503338B2 (ja) | 2013-03-15 | 2019-04-17 | バイオマリン ファーマシューティカル インコーポレイテッド | Hdac阻害剤 |
| PL3024832T3 (pl) * | 2013-07-22 | 2018-10-31 | Idorsia Pharmaceuticals Ltd | Pochodne 1-(piperazyn-1-ylo)-2-([1,2,4]triazol-1-ilo)-etanonu |
| AR099789A1 (es) * | 2014-03-24 | 2016-08-17 | Actelion Pharmaceuticals Ltd | Derivados de 8-(piperazin-1-il)-1,2,3,4-tetrahidro-isoquinolina |
| PL3245203T3 (pl) * | 2015-01-15 | 2019-05-31 | Idorsia Pharmaceuticals Ltd | Pochodne hydroksyalkilopiperazyny jako modulatory receptora cxcr3 |
| AR103399A1 (es) | 2015-01-15 | 2017-05-10 | Actelion Pharmaceuticals Ltd | Derivados de (r)-2-metil-piperazina como moduladores del receptor cxcr3 |
| WO2018011265A1 (en) | 2016-07-13 | 2018-01-18 | Idorsia Pharmaceuticals Ltd | Hydroxyalkyl-piperazine derivatives as cxcr3 receptor modulators |
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| WO1997038992A1 (en) * | 1996-04-12 | 1997-10-23 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyramidine derivatives |
| US5948786A (en) * | 1996-04-12 | 1999-09-07 | Sumitomo Pharmaceuticals Company, Limited | Piperidinylpyrimidine derivatives |
| PE20030739A1 (es) * | 2001-11-30 | 2003-08-28 | Schering Corp | Antagonistas del receptor de adenosina a2a |
| CN100343255C (zh) | 2002-04-23 | 2007-10-17 | 盐野义制药株式会社 | 吡唑并[1,5-a]嘧啶衍生物和含有该衍生物的NAD(P)H氧化酶抑制剂 |
| AU2003236500B9 (en) * | 2002-06-12 | 2009-07-02 | Chemocentryx, Inc. | 1-aryl-4-substituted piperazine derivatives for use as CCR1 antagonists for the treatment of inflammation and immune disorders |
| US20040192728A1 (en) * | 2003-02-03 | 2004-09-30 | Ellen Codd | Quinoline-derived amide modulators of vanilloid VR1 receptor |
| HRP20150832T1 (hr) * | 2005-06-22 | 2015-09-25 | Chemocentryx, Inc. | Spojevi azaindazola i postupci njihove upotrebe |
| US20080312215A1 (en) | 2005-06-28 | 2008-12-18 | Pharmacopeia Drug Discovery, Inc. | Substituted [1,4]-diazepanes as CXCR3 antagonists and their use in the treatment of inflammatory disorders |
| US7790726B2 (en) * | 2005-08-16 | 2010-09-07 | Chemocentryx, Inc. | Monocyclic and bicyclic compounds and methods of use |
| US20090030012A1 (en) * | 2006-02-23 | 2009-01-29 | Adams Alan D | Pyridine, Pyrimidine and Pyrazine Derivatives as Cxcr3 Receptor Modulators |
| CN101426774B (zh) | 2006-04-19 | 2012-04-25 | 安斯泰来制药有限公司 | 唑类甲酰胺衍生物 |
| US7807671B2 (en) * | 2006-04-25 | 2010-10-05 | Bristol-Myers Squibb Company | Diketo-piperazine and piperidine derivatives as antiviral agents |
| US9206142B2 (en) | 2006-10-31 | 2015-12-08 | Merck Sharp & Dohme Corp. | Anilinopiperazine derivatives and methods of use thereof |
| US20090099201A1 (en) * | 2007-05-22 | 2009-04-16 | David Robert Bolin | Diacylglycerol Acyltransferase Inhibitors |
| JO2972B1 (en) | 2007-06-08 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Piperidine / piperazine derivatives |
| EA017918B1 (ru) * | 2007-12-13 | 2013-04-30 | СИЕНА БИОТЕК С.п.А. | Антагонисты пути hedgehog и их терапевтические применения |
| PE20091576A1 (es) | 2008-02-19 | 2009-11-05 | Sanofi Aventis | DERIVADOS DE 3-(AMIDO O SULFAMIDO)-4-(4-AZINIL SUSTITUIDO)BENZAMIDA COMO INHIBIDORES DEL RECEPTOR DE QUIMIOQUINAS CxCR3 |
| WO2010126811A1 (en) | 2009-04-27 | 2010-11-04 | Boehringer Ingelheim International Gmbh | Cxcr3 receptor antagonists |
| US8362249B2 (en) | 2009-04-27 | 2013-01-29 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
| US8952004B2 (en) * | 2010-01-07 | 2015-02-10 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
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- 2010-04-26 EP EP10715470.0A patent/EP2424840B1/en active Active
- 2010-04-26 JP JP2012507460A patent/JP5807971B2/ja active Active
- 2010-04-27 US US12/768,268 patent/US8450317B2/en active Active
Also Published As
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| US8450317B2 (en) | 2013-05-28 |
| US20100280028A1 (en) | 2010-11-04 |
| EP2424840A1 (en) | 2012-03-07 |
| EP2424840B1 (en) | 2014-08-06 |
| WO2010126811A1 (en) | 2010-11-04 |
| JP2012525332A (ja) | 2012-10-22 |
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