JP6073931B2 - ４−（ベンゾイミダゾール−２−イル）−チアゾール化合物及び関連するアザ誘導体 - Google Patents
４−（ベンゾイミダゾール−２−イル）−チアゾール化合物及び関連するアザ誘導体 Download PDFInfo
- Publication number
- JP6073931B2 JP6073931B2 JP2014555374A JP2014555374A JP6073931B2 JP 6073931 B2 JP6073931 B2 JP 6073931B2 JP 2014555374 A JP2014555374 A JP 2014555374A JP 2014555374 A JP2014555374 A JP 2014555374A JP 6073931 B2 JP6073931 B2 JP 6073931B2
- Authority
- JP
- Japan
- Prior art keywords
- benzimidazol
- methyl
- thiazol
- piperazin
- ethanone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical class S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 title description 2
- -1 fluoroalkyl Halogen Chemical class 0.000 claims description 579
- 150000001875 compounds Chemical class 0.000 claims description 391
- 125000000217 alkyl group Chemical group 0.000 claims description 282
- 125000001424 substituent group Chemical group 0.000 claims description 214
- 125000000623 heterocyclic group Chemical group 0.000 claims description 138
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 119
- 229910052757 nitrogen Inorganic materials 0.000 claims description 107
- 229910052736 halogen Inorganic materials 0.000 claims description 101
- 150000002367 halogens Chemical class 0.000 claims description 99
- 125000001072 heteroaryl group Chemical group 0.000 claims description 96
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 93
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 89
- 229920006395 saturated elastomer Polymers 0.000 claims description 78
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 71
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 68
- 125000003545 alkoxy group Chemical group 0.000 claims description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 50
- 125000004043 oxo group Chemical group O=* 0.000 claims description 50
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 47
- 229910052760 oxygen Inorganic materials 0.000 claims description 47
- 239000001301 oxygen Substances 0.000 claims description 47
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 45
- 125000005842 heteroatom Chemical group 0.000 claims description 41
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 25
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 24
- 125000002950 monocyclic group Chemical group 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 11
- 206010016654 Fibrosis Diseases 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
- WEGYGNROSJDEIW-UHFFFAOYSA-N 3-Acetylpyridine Chemical compound CC(=O)C1=CC=CN=C1 WEGYGNROSJDEIW-UHFFFAOYSA-N 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 8
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 230000004761 fibrosis Effects 0.000 claims description 8
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 206010052779 Transplant rejections Diseases 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004536 indazol-1-yl group Chemical group N1(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims description 6
- XMZCMHSJWVCFAQ-GOSISDBHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-(methoxymethyl)piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)COC)=NC2=C1 XMZCMHSJWVCFAQ-GOSISDBHSA-N 0.000 claims description 5
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 5
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 201000000306 sarcoidosis Diseases 0.000 claims description 5
- CYLSDQBKJIONGY-OAHLLOKOSA-N 1-[(2R)-4-[4-[6-(2-hydroxyethoxy)-1H-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc2cccnc12)c1sc(nc1-c1nc2cc(OCCO)ccc2[nH]1)C(F)(F)F CYLSDQBKJIONGY-OAHLLOKOSA-N 0.000 claims description 4
- NZNVQWUDNQTVRO-GOSISDBHSA-N 1-[(2r)-2-methyl-4-[4-[6-(piperidin-1-ylmethyl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(CN4CCCCC4)=CC=C3N=2)CCN1C(=O)CN1C=CC=N1 NZNVQWUDNQTVRO-GOSISDBHSA-N 0.000 claims description 4
- WZPRXSIKEOLOJD-GOSISDBHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-ethylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)CC)=NC2=C1 WZPRXSIKEOLOJD-GOSISDBHSA-N 0.000 claims description 4
- KLPMASUPLFCEMG-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(4-phenyltriazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN(N=N1)C=C1C1=CC=CC=C1 KLPMASUPLFCEMG-QGZVFWFLSA-N 0.000 claims description 4
- JMWVCTLNDCHNCR-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[2-(hydroxymethyl)pyrrolo[2,3-b]pyridin-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3CO)C)=NC2=C1 JMWVCTLNDCHNCR-MRXNPFEDSA-N 0.000 claims description 4
- KAUAUHXGJUWWTR-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[2-(triazol-2-yl)phenyl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CC1=CC=CC=C1N1N=CC=N1 KAUAUHXGJUWWTR-QGZVFWFLSA-N 0.000 claims description 4
- ZMFVJFWPPDAJQI-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 ZMFVJFWPPDAJQI-MRXNPFEDSA-N 0.000 claims description 4
- YCXOXDIQPMMACB-GOSISDBHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(2-fluorophenyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1=CC=CC=C1F YCXOXDIQPMMACB-GOSISDBHSA-N 0.000 claims description 4
- AXYSSJYIXRNACK-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(4,6-dimethylpyridin-2-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CC1=CC(C)=CC(C)=N1 AXYSSJYIXRNACK-MRXNPFEDSA-N 0.000 claims description 4
- ZXDZWWNBSQEKTQ-CQSZACIVSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=C1 ZXDZWWNBSQEKTQ-CQSZACIVSA-N 0.000 claims description 4
- VSHOBSIPZJJYRP-CQSZACIVSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-bromo-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(Br)SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 VSHOBSIPZJJYRP-CQSZACIVSA-N 0.000 claims description 4
- NYCIVVXGRDGDMY-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-cyclopropyl-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1CC1 NYCIVVXGRDGDMY-MRXNPFEDSA-N 0.000 claims description 4
- BEMATWPFDYPDGS-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-propan-2-yl-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C(C)C)S1 BEMATWPFDYPDGS-QGZVFWFLSA-N 0.000 claims description 4
- VAERCOVIPSYJEI-OAHLLOKOSA-N 1-[(2r)-4-[4-(4-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1F VAERCOVIPSYJEI-OAHLLOKOSA-N 0.000 claims description 4
- LPGKOZKGEFZZDI-CQSZACIVSA-N 1-[(2r)-4-[4-(6-acetyl-1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(C(C)=O)C=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=C1 LPGKOZKGEFZZDI-CQSZACIVSA-N 0.000 claims description 4
- GKGKGFDQVXICKG-CYBMUJFWSA-N 1-[(2r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(Cl)C=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=C1 GKGKGFDQVXICKG-CYBMUJFWSA-N 0.000 claims description 4
- URDUAYXCJLKTDO-MRXNPFEDSA-N 1-[(2r)-4-[4-(6-cyclopropyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C=1SC=NC=1C(NC1=C2)=NC1=CC=C2C1CC1 URDUAYXCJLKTDO-MRXNPFEDSA-N 0.000 claims description 4
- DIOGWOJCJZVHGC-CQSZACIVSA-N 1-[(2r)-4-[4-[6-(dimethylamino)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(=CC=C3N=2)N(C)C)CCN1C(=O)CN1C=CC=N1 DIOGWOJCJZVHGC-CQSZACIVSA-N 0.000 claims description 4
- GJITUFZVNVJAAL-DUSLRRAJSA-N 1-[(2r)-4-[4-[6-[(3-methoxypyrrolidin-1-yl)methyl]-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C1C(OC)CCN1CC1=CC=C(N=C(N2)C3=C(SC(=N3)C(F)(F)F)N3C[C@@H](C)N(CC3)C(=O)CN3N=CC=C3)C2=C1 GJITUFZVNVJAAL-DUSLRRAJSA-N 0.000 claims description 4
- ZMFVJFWPPDAJQI-INIZCTEOSA-N 1-[(2s)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 ZMFVJFWPPDAJQI-INIZCTEOSA-N 0.000 claims description 4
- DLPPXXUNOXNAAC-OAHLLOKOSA-N 1-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3,3-difluoroindol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=CC=CC=C4C(F)(F)C3=O)C)=NC2=C1 DLPPXXUNOXNAAC-OAHLLOKOSA-N 0.000 claims description 4
- QXQPQNCYTDCRCE-QGZVFWFLSA-N 1-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3,3-dimethylindol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=CC=CC=C4C(C)(C)C3=O)C)=NC2=C1 QXQPQNCYTDCRCE-QGZVFWFLSA-N 0.000 claims description 4
- BDRMDKGDFFZADN-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-2,3-dihydroquinolin-4-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4C(=O)CC3)=O)=NC2=C1 BDRMDKGDFFZADN-UHFFFAOYSA-N 0.000 claims description 4
- NTRPDWXZPPNJEM-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3,4-dihydroquinolin-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4CCC3=O)=O)=NC2=C1 NTRPDWXZPPNJEM-UHFFFAOYSA-N 0.000 claims description 4
- BDANYOOWQHBQMA-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3h-indol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4CC3=O)=O)=NC2=C1 BDANYOOWQHBQMA-UHFFFAOYSA-N 0.000 claims description 4
- GCVYTRNWUUIZHL-UHFFFAOYSA-N 1-[2-[4-[4-(4-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1Cl GCVYTRNWUUIZHL-UHFFFAOYSA-N 0.000 claims description 4
- YBRQWDBXMPNKLF-UHFFFAOYSA-N 1-[2-[4-[4-[6-(2-hydroxyethoxy)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=C(OCCO)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 YBRQWDBXMPNKLF-UHFFFAOYSA-N 0.000 claims description 4
- RXEMPAXNECZXGS-UHFFFAOYSA-N 1-[2-[4-[4-[6-(2-methoxyethoxy)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C1=NC2=CC=C(OCCOC)C=C2N1 RXEMPAXNECZXGS-UHFFFAOYSA-N 0.000 claims description 4
- YVPPKRJCXVZZLB-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-1,4-diazepan-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCCN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 YVPPKRJCXVZZLB-UHFFFAOYSA-N 0.000 claims description 4
- RXYWJBXHDKOPST-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4OCC3)=O)=NC2=C1 RXYWJBXHDKOPST-UHFFFAOYSA-N 0.000 claims description 4
- ZOGVJPILSNMYPD-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-methylpyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=NC=CC=C4C=C3C)=NC2=C1 ZOGVJPILSNMYPD-UHFFFAOYSA-N 0.000 claims description 4
- GSQHRHIXCPPMKH-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(3-methylpyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C12=NC=CC=C2C(C)=CN1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 GSQHRHIXCPPMKH-UHFFFAOYSA-N 0.000 claims description 4
- BTZYHIMCHBMSNM-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(4-methoxyindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=4C=CC=C(C=4C=C3)OC)=NC2=C1 BTZYHIMCHBMSNM-UHFFFAOYSA-N 0.000 claims description 4
- CXOBEUJYMZUTEP-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(6-chloropyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC4=CC=C(N=C43)Cl)=NC2=C1 CXOBEUJYMZUTEP-UHFFFAOYSA-N 0.000 claims description 4
- HVJGBMMRXDCLNP-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(6-methoxypyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC4=CC=C(N=C43)OC)=NC2=C1 HVJGBMMRXDCLNP-UHFFFAOYSA-N 0.000 claims description 4
- UJBJLLNTPBFMAQ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(6-methylpyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC4=CC=C(N=C43)C)=NC2=C1 UJBJLLNTPBFMAQ-UHFFFAOYSA-N 0.000 claims description 4
- IYHUNPHDXYPKOE-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(7-fluoroindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC=4C=CC=C(C3=4)F)=NC2=C1 IYHUNPHDXYPKOE-UHFFFAOYSA-N 0.000 claims description 4
- FRHYGUPKSSETJT-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-(1-hydroxyethyl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C(O)C)S1 FRHYGUPKSSETJT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004562 2,3-dihydroindol-1-yl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- BGIPMVWYZIKOEO-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4N=C3)=O)=NC2=C1 BGIPMVWYZIKOEO-UHFFFAOYSA-N 0.000 claims description 4
- PEKODWBEGCSMPV-MRXNPFEDSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-4-[4-[6-(2-methoxyethoxy)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC(=N1)C(F)(F)F)=C1C1=NC2=CC=C(OCCOC)C=C2N1 PEKODWBEGCSMPV-MRXNPFEDSA-N 0.000 claims description 4
- IFHOVXZEIHUAOU-MRXNPFEDSA-N 3-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-4-methyl-1,3-benzoxazol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C(OC4=CC=CC(C)=C43)=O)C)=NC2=C1 IFHOVXZEIHUAOU-MRXNPFEDSA-N 0.000 claims description 4
- BYSUWLKUBDZCHP-UHFFFAOYSA-N 3-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-1h-imidazo[4,5-b]pyridin-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C(NC4=CC=CN=C43)=O)=O)=NC2=C1 BYSUWLKUBDZCHP-UHFFFAOYSA-N 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000005615 Interstitial Cystitis Diseases 0.000 claims description 4
- 208000009525 Myocarditis Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 206010046851 Uveitis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- GUACISYFMJNFES-GICMACPYSA-N 1-[(2R)-4-[4-[6-(1-hydroxyethyl)-1H-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound CC(O)c1ccc2[nH]c(nc2c1)-c1nc(sc1N1CCN([C@H](C)C1)C(=O)Cn1cnc2cccnc12)C(F)(F)F GUACISYFMJNFES-GICMACPYSA-N 0.000 claims description 3
- NCSLFCCQXGPWFZ-CQSZACIVSA-N 1-[(2r)-2-methyl-4-[4-(1-methylbenzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2N(C3=CC=CC=C3N=2)C)CCN1C(=O)CN1C=CC=N1 NCSLFCCQXGPWFZ-CQSZACIVSA-N 0.000 claims description 3
- XVWKXSFZNTWSCC-QGZVFWFLSA-N 1-[(2r)-2-methyl-4-[4-[6-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(=CC=C3N=2)N2CCN(C)CC2)CCN1C(=O)CN1C=CC=N1 XVWKXSFZNTWSCC-QGZVFWFLSA-N 0.000 claims description 3
- AXOCJQGAWLLMQP-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-ethylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)CC)=NC2=C1 AXOCJQGAWLLMQP-MRXNPFEDSA-N 0.000 claims description 3
- CCZJAXJXLVRTOE-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 CCZJAXJXLVRTOE-OAHLLOKOSA-N 0.000 claims description 3
- FLASLPWERVBSQH-LJQANCHMSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(2-methoxyphenyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound COC1=CC=CC=C1C1=NC(C=2NC3=CC=CC=C3N=2)=C(N2C[C@@H](C)N(CC2)C(=O)CN2C3=NC=CC=C3N=C2)S1 FLASLPWERVBSQH-LJQANCHMSA-N 0.000 claims description 3
- KCJXYLIKJDAZIW-HXUWFJFHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(2-methylphenyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1=CC=CC=C1C KCJXYLIKJDAZIW-HXUWFJFHSA-N 0.000 claims description 3
- IWSNSYDLJUAJNO-HXUWFJFHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(3-methylphenyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1=CC=CC(C)=C1 IWSNSYDLJUAJNO-HXUWFJFHSA-N 0.000 claims description 3
- SXZCDZZQTZDWBT-HXUWFJFHSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(4-methylphenyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1=CC=C(C)C=C1 SXZCDZZQTZDWBT-HXUWFJFHSA-N 0.000 claims description 3
- RWEYPYDCLNMMCX-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(oxetan-3-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1COC1 RWEYPYDCLNMMCX-MRXNPFEDSA-N 0.000 claims description 3
- NYZGYXUCNQEPBF-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(2,6-dimethylpyridin-4-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CC1=CC(C)=NC(C)=C1 NYZGYXUCNQEPBF-MRXNPFEDSA-N 0.000 claims description 3
- LODYPNGXMAGKTH-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(4-phenyltriazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN(N=N1)C=C1C1=CC=CC=C1 LODYPNGXMAGKTH-MRXNPFEDSA-N 0.000 claims description 3
- YVQHSLWAWYYPCD-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-ethyl-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(CC)S1 YVQHSLWAWYYPCD-MRXNPFEDSA-N 0.000 claims description 3
- XSALNAYQWZVULN-OAHLLOKOSA-N 1-[(2r)-4-[4-(5,6-dimethoxy-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC=N1)=C1C1=NC(C=C(C(=C2)OC)OC)=C2N1 XSALNAYQWZVULN-OAHLLOKOSA-N 0.000 claims description 3
- DQJDCGVYFWPJEV-CQSZACIVSA-N 1-[(2r)-4-[4-(5,6-dimethoxy-1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC(=N1)C(F)(F)F)=C1C1=NC(C=C(C(=C2)OC)OC)=C2N1 DQJDCGVYFWPJEV-CQSZACIVSA-N 0.000 claims description 3
- RPARPLJOCSXQOF-MRXNPFEDSA-N 1-[(2r)-4-[4-[1-(2-methoxyethyl)benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound N=1C2=CC=CC=C2N(CCOC)C=1C=1N=C(C(F)(F)F)SC=1N(C[C@H]1C)CCN1C(=O)CN1C=CC=N1 RPARPLJOCSXQOF-MRXNPFEDSA-N 0.000 claims description 3
- FXONERUOVVIUTD-OAHLLOKOSA-N 1-[(2r)-4-[4-[6-(1-hydroxycyclopropyl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C=1SC(C(F)(F)F)=NC=1C(NC1=C2)=NC1=CC=C2C1(O)CC1 FXONERUOVVIUTD-OAHLLOKOSA-N 0.000 claims description 3
- OHNXVUFHHKQXKE-OAHLLOKOSA-N 1-[(2r)-4-[4-[6-(hydroxymethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(CO)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 OHNXVUFHHKQXKE-OAHLLOKOSA-N 0.000 claims description 3
- XRUVZBDFYNULNQ-CQSZACIVSA-N 1-[(2r)-4-[4-[6-(hydroxymethyl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(CO)C=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=C1 XRUVZBDFYNULNQ-CQSZACIVSA-N 0.000 claims description 3
- AUNHAMUMKSZAES-OAHLLOKOSA-N 1-[(2r)-4-[4-[6-[(dimethylamino)methyl]-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(CN(C)C)=CC=C3N=2)CCN1C(=O)CN1C=CC=N1 AUNHAMUMKSZAES-OAHLLOKOSA-N 0.000 claims description 3
- CCZJAXJXLVRTOE-HNNXBMFYSA-N 1-[(2s)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 CCZJAXJXLVRTOE-HNNXBMFYSA-N 0.000 claims description 3
- ZNTQHUWUAHGPDV-GASCZTMLSA-N 1-[(2s,6r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2,6-dimethylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(Cl)C=C2NC(C=3N=CSC=3N3C[C@@H](N([C@H](C)C3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 ZNTQHUWUAHGPDV-GASCZTMLSA-N 0.000 claims description 3
- VBPUTKIGVSGJSA-OAHLLOKOSA-N 1-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]indole-2,3-dione Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=CC=CC=C4C(=O)C3=O)C)=NC2=C1 VBPUTKIGVSGJSA-OAHLLOKOSA-N 0.000 claims description 3
- DLXBKKRZSRYMDL-OAHLLOKOSA-N 1-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3h-indol-2-one Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=CC=CC=C4CC3=O)C)C(F)(F)F)=NC2=C1 DLXBKKRZSRYMDL-OAHLLOKOSA-N 0.000 claims description 3
- YTUYAVBFRAFGCB-UHFFFAOYSA-N 1-[2-[4-[4-[6-(hydroxymethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=C(CO)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 YTUYAVBFRAFGCB-UHFFFAOYSA-N 0.000 claims description 3
- WLVJMVFDAXVEBG-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-1,4-diazepan-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N(CC1)CCCN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 WLVJMVFDAXVEBG-UHFFFAOYSA-N 0.000 claims description 3
- KTHHAXJKGITINW-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-fluoro-4-methoxyphenyl)ethanone Chemical compound FC1=CC(OC)=CC=C1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 KTHHAXJKGITINW-UHFFFAOYSA-N 0.000 claims description 3
- SPCDMBWVTCWWDJ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(3,4-dihydro-2h-quinolin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4CCC3)=O)=NC2=C1 SPCDMBWVTCWWDJ-UHFFFAOYSA-N 0.000 claims description 3
- LRGJNYMKVMLWMP-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CC=3N=C4C=CC(=NN4C=3)Cl)=NC2=C1 LRGJNYMKVMLWMP-UHFFFAOYSA-N 0.000 claims description 3
- SCZVUUKBPVPDQO-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=NC=CC=C4N=C3)=O)=NC2=C1 SCZVUUKBPVPDQO-UHFFFAOYSA-N 0.000 claims description 3
- MWOOOYWWBDFWEM-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyridin-3-ylethanone Chemical compound C1CN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CC1=CC=CN=C1 MWOOOYWWBDFWEM-UHFFFAOYSA-N 0.000 claims description 3
- BEAZMTSMHQXKTE-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperidin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3C3CCN(CC3)C(CN3C4=NC=CC=C4N=C3)=O)=NC2=C1 BEAZMTSMHQXKTE-UHFFFAOYSA-N 0.000 claims description 3
- KYYFOYBZTFUJRM-UHFFFAOYSA-N 1-methyl-3-[2-oxo-2-[4-[4-[6-(trifluoromethoxy)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethyl]benzimidazol-2-one Chemical compound C1=C(OC(F)(F)F)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 KYYFOYBZTFUJRM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004463 2,4-dimethyl-thiazol-5-yl group Chemical group CC=1SC(=C(N1)C)* 0.000 claims description 3
- SXYUBRILLHMIAQ-GFCCVEGCSA-N 2-(3,5-dimethyl-1,2,4-triazol-1-yl)-1-[(2r)-2-methyl-4-[4-[6-(5-methyl-1,2,4-oxadiazol-3-yl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(=CC=C3N=2)C=2N=C(C)ON=2)CCN1C(=O)CN1N=C(C)N=C1C SXYUBRILLHMIAQ-GFCCVEGCSA-N 0.000 claims description 3
- ZGPRGZBQSUGGEI-UHFFFAOYSA-N 2-[5-[4-[2-(3-methyl-2-oxobenzimidazol-1-yl)acetyl]piperazin-1-yl]-1,3-thiazol-4-yl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 ZGPRGZBQSUGGEI-UHFFFAOYSA-N 0.000 claims description 3
- LTDSJAYCMPKAJI-MRXNPFEDSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-(6-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=C(C)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 LTDSJAYCMPKAJI-MRXNPFEDSA-N 0.000 claims description 3
- VANOQPQHNBVXJW-GFCCVEGCSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-(7h-purin-8-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=NC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=N1 VANOQPQHNBVXJW-GFCCVEGCSA-N 0.000 claims description 3
- IXKNDEKCDRZDQZ-CYBMUJFWSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-4-[4-(1h-imidazo[4,5-b]pyridin-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=N1 IXKNDEKCDRZDQZ-CYBMUJFWSA-N 0.000 claims description 3
- PSZXLPQYKNWLSY-CYBMUJFWSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-4-[4-(3h-imidazo[4,5-c]pyridin-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound C1=NC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)C(F)(F)F)=NC2=C1 PSZXLPQYKNWLSY-CYBMUJFWSA-N 0.000 claims description 3
- TWPGIBYDZPYOFV-CQSZACIVSA-N 3-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-4-fluoro-1,3-benzoxazol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C(OC4=CC=CC(F)=C43)=O)C)=NC2=C1 TWPGIBYDZPYOFV-CQSZACIVSA-N 0.000 claims description 3
- JBMKWJJTBRMXBK-CQSZACIVSA-N 3-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-[1,3]oxazolo[4,5-b]pyridin-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C(OC4=CC=CN=C43)=O)C)=NC2=C1 JBMKWJJTBRMXBK-CQSZACIVSA-N 0.000 claims description 3
- DYOFIXNFEMVOEC-CYBMUJFWSA-N 3-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-1h-imidazo[4,5-b]pyridin-2-one Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C(NC4=CC=CN=C43)=O)C)C(F)(F)F)=NC2=C1 DYOFIXNFEMVOEC-CYBMUJFWSA-N 0.000 claims description 3
- KYANNUWFRKWDMQ-CQSZACIVSA-N 3-[2-[(2r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-1,3-benzoxazol-2-one Chemical compound C1=C(Cl)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C(OC4=CC=CC=C43)=O)C)=NC2=C1 KYANNUWFRKWDMQ-CQSZACIVSA-N 0.000 claims description 3
- PZDGMWCDGMXQMZ-UHFFFAOYSA-N 4-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4OCC3=O)=O)=NC2=C1 PZDGMWCDGMXQMZ-UHFFFAOYSA-N 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- NPNZCOPQACHOOM-CQSZACIVSA-N methyl 2-[5-[(3r)-4-(2-imidazo[4,5-b]pyridin-3-ylacetyl)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazol-4-yl]-3h-benzimidazole-5-carboxylate Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC(=N1)C(F)(F)F)=C1C1=NC2=CC=C(C(=O)OC)C=C2N1 NPNZCOPQACHOOM-CQSZACIVSA-N 0.000 claims description 3
- SCVJDLUEAQOVOI-UHFFFAOYSA-N 1-(2h-pyridin-1-yl)ethanone Chemical compound CC(=O)N1CC=CC=C1 SCVJDLUEAQOVOI-UHFFFAOYSA-N 0.000 claims description 2
- GKRNFYZJVJLGFE-UHFFFAOYSA-N 1-(5-fluoroindol-1-yl)ethanone Chemical compound FC=1C=C2C=CN(C2=CC=1)C(C)=O GKRNFYZJVJLGFE-UHFFFAOYSA-N 0.000 claims description 2
- YQPCLDZGKXOPDN-GFCCVEGCSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(1,2,4-triazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cncn1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F YQPCLDZGKXOPDN-GFCCVEGCSA-N 0.000 claims description 2
- DYMSYKLLDJDGNE-CQSZACIVSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)CN1CCc2[nH]ncc2C1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F DYMSYKLLDJDGNE-CQSZACIVSA-N 0.000 claims description 2
- GQETWNSPPDJJEM-GFCCVEGCSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nc(C)nc1C)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F GQETWNSPPDJJEM-GFCCVEGCSA-N 0.000 claims description 2
- OLHGESOLUMYHMP-GFCCVEGCSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-methyl-1,2,4-triazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc(C)n1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F OLHGESOLUMYHMP-GFCCVEGCSA-N 0.000 claims description 2
- QPJFRAKVXRLOOY-CQSZACIVSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-methylpyrazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1ccc(C)n1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F QPJFRAKVXRLOOY-CQSZACIVSA-N 0.000 claims description 2
- UPOMJVFFBMUVCL-QGZVFWFLSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-phenylpyrazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1ccc(n1)-c1ccccc1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F UPOMJVFFBMUVCL-QGZVFWFLSA-N 0.000 claims description 2
- RSTJHRDIPINCJV-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc2CN(C)CCc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F RSTJHRDIPINCJV-OAHLLOKOSA-N 0.000 claims description 2
- BDUQMMQIVRMYIO-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-3-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc2CCN(C)Cc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F BDUQMMQIVRMYIO-OAHLLOKOSA-N 0.000 claims description 2
- PHGYQHBZUQJQLE-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1ncc2CN(C)CCc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F PHGYQHBZUQJQLE-OAHLLOKOSA-N 0.000 claims description 2
- NLHKMBULMFOGAN-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-2-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cc2CN(C)CCc2n1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F NLHKMBULMFOGAN-OAHLLOKOSA-N 0.000 claims description 2
- PTFZVOMXBCKEKH-CQSZACIVSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methylpyrazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nccc1C)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F PTFZVOMXBCKEKH-CQSZACIVSA-N 0.000 claims description 2
- MODKZZIVEIGIFH-QGZVFWFLSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-phenylpyrazol-1-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nccc1-c1ccccc1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F MODKZZIVEIGIFH-QGZVFWFLSA-N 0.000 claims description 2
- IWNLHWSFQQOHAB-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(6-methylpyridin-3-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cc1ccc(C)nc1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F IWNLHWSFQQOHAB-OAHLLOKOSA-N 0.000 claims description 2
- NKHWBBSTZGWYQK-GFCCVEGCSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(triazol-2-yl)ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nccn1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F NKHWBBSTZGWYQK-GFCCVEGCSA-N 0.000 claims description 2
- CUPQWUBNAFVRGV-LJQANCHMSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[2-(4-methylpiperazin-1-yl)phenyl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cc1ccccc1N1CCN(C)CC1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F CUPQWUBNAFVRGV-LJQANCHMSA-N 0.000 claims description 2
- FAROMIXDXDDMCE-MRXNPFEDSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[2-(triazol-2-yl)phenyl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cc1ccccc1-n1nccn1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F FAROMIXDXDDMCE-MRXNPFEDSA-N 0.000 claims description 2
- PVVGPJNVCWMHCI-MRXNPFEDSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[3-(triazol-2-yl)phenyl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cc1cccc(c1)-n1nccn1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F PVVGPJNVCWMHCI-MRXNPFEDSA-N 0.000 claims description 2
- YAJYRIBOXJEWBE-GFCCVEGCSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[3-(trifluoromethyl)pyrazol-1-yl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1ccc(n1)C(F)(F)F)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F YAJYRIBOXJEWBE-GFCCVEGCSA-N 0.000 claims description 2
- AUGOSSHNHBYQHS-CQSZACIVSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[3-[(dimethylamino)methyl]-5-methyl-1,2,4-triazol-1-yl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nc(CN(C)C)nc1C)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F AUGOSSHNHBYQHS-CQSZACIVSA-N 0.000 claims description 2
- HUNIUXWXOPNBDL-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[4-[(dimethylamino)methyl]-3,5-dimethylpyrazol-1-yl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1nc(C)c(CN(C)C)c1C)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F HUNIUXWXOPNBDL-OAHLLOKOSA-N 0.000 claims description 2
- RCBWGNVFXNKDSZ-OAHLLOKOSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cc(CN(C)C)c(C)n1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F RCBWGNVFXNKDSZ-OAHLLOKOSA-N 0.000 claims description 2
- VMQZDOISGACCCC-CQSZACIVSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-c]pyridin-1-ylethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc2cnccc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F VMQZDOISGACCCC-CQSZACIVSA-N 0.000 claims description 2
- CRYXEDQPNCNOKN-CYBMUJFWSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cccn1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F CRYXEDQPNCNOKN-CYBMUJFWSA-N 0.000 claims description 2
- OUMWJLAXMADJFX-MRXNPFEDSA-N 1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-quinolin-8-ylethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cc1cccc2cccnc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F OUMWJLAXMADJFX-MRXNPFEDSA-N 0.000 claims description 2
- SOSAHDDYEAPUCF-QGZVFWFLSA-N 1-[(2r)-2-methyl-4-[4-(4-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1C SOSAHDDYEAPUCF-QGZVFWFLSA-N 0.000 claims description 2
- DZRDPTHXMBOABV-MRXNPFEDSA-N 1-[(2r)-2-methyl-4-[4-(6-methylsulfonyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=C(S(C)(=O)=O)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 DZRDPTHXMBOABV-MRXNPFEDSA-N 0.000 claims description 2
- KCMDTVRCSPXXNB-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-(methoxymethyl)piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)COC)=NC2=C1 KCMDTVRCSPXXNB-MRXNPFEDSA-N 0.000 claims description 2
- HUGGOWQWJJVVCL-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-[(dimethylamino)methyl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)CN(C)C)=NC2=C1 HUGGOWQWJJVVCL-QGZVFWFLSA-N 0.000 claims description 2
- GDZIMMMZJZDSBL-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(hydroxymethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(CO)SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 GDZIMMMZJZDSBL-OAHLLOKOSA-N 0.000 claims description 2
- RUDFOZDSOZOPIE-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-[(dimethylamino)methyl]piperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1CN(C)C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C RUDFOZDSOZOPIE-MRXNPFEDSA-N 0.000 claims description 2
- MFAUFNKSQJGPCK-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-[(dimethylamino)methyl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)CN(C)C)C(F)(F)F)=NC2=C1 MFAUFNKSQJGPCK-MRXNPFEDSA-N 0.000 claims description 2
- XRTBLROKULPLRV-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(2-pyrazol-1-ylphenyl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CC1=CC=CC=C1N1C=CC=N1 XRTBLROKULPLRV-QGZVFWFLSA-N 0.000 claims description 2
- WJEJRGIYUYURNR-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN1N=C(C)C=C1C WJEJRGIYUYURNR-OAHLLOKOSA-N 0.000 claims description 2
- VCFWFSFQWMRPOS-LLVKDONJSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-bromo-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN1C=NC(Br)=N1 VCFWFSFQWMRPOS-LLVKDONJSA-N 0.000 claims description 2
- CYPWJHIWXFTEPD-MRXNPFEDSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(4-piperidin-4-ylpyrazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN(N=C1)C=C1C1CCNCC1 CYPWJHIWXFTEPD-MRXNPFEDSA-N 0.000 claims description 2
- KLJAEYXMUWYWNT-GFCCVEGCSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN1N=CN=C1C KLJAEYXMUWYWNT-GFCCVEGCSA-N 0.000 claims description 2
- MDOLKXWWPFVDTC-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-[4-(1-methylpiperidin-4-yl)pyrazol-1-yl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN(N=C1)C=C1C1CCN(C)CC1 MDOLKXWWPFVDTC-QGZVFWFLSA-N 0.000 claims description 2
- QHTXWILDSZAVIK-CQSZACIVSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridin-2-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(SC=3N3C[C@H](N(CC3)C(=O)CN3N=C4N=CC=CC4=C3)C)C(F)(F)F)=NC2=C1 QHTXWILDSZAVIK-CQSZACIVSA-N 0.000 claims description 2
- CJRBJYVXACGXMC-QGZVFWFLSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-[(dimethylamino)methyl]-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(CN(C)C)SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 CJRBJYVXACGXMC-QGZVFWFLSA-N 0.000 claims description 2
- SVRHNCJUFDUVQP-CYBMUJFWSA-N 1-[(2r)-4-[4-(4,5-difluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound FC1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1F SVRHNCJUFDUVQP-CYBMUJFWSA-N 0.000 claims description 2
- YXYVBEBWLPBGPS-SNVBAGLBSA-N 1-[(2r)-4-[4-(4,5-difluoro-1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=C(F)C(F)=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C YXYVBEBWLPBGPS-SNVBAGLBSA-N 0.000 claims description 2
- IMIXLMJODSSNHT-CQSZACIVSA-N 1-[(2r)-4-[4-(4-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1F IMIXLMJODSSNHT-CQSZACIVSA-N 0.000 claims description 2
- ASRHTNDMFVCZMJ-CYBMUJFWSA-N 1-[(2r)-4-[4-(5,6-difluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound FC1=C(F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 ASRHTNDMFVCZMJ-CYBMUJFWSA-N 0.000 claims description 2
- ZSYFARCCTURBGM-CQSZACIVSA-N 1-[(2r)-4-[4-(5-chloro-4-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound ClC1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1C ZSYFARCCTURBGM-CQSZACIVSA-N 0.000 claims description 2
- XPXOYMPIPXKCGW-CYBMUJFWSA-N 1-[(2r)-4-[4-(5-chloro-6-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound ClC1=C(F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 XPXOYMPIPXKCGW-CYBMUJFWSA-N 0.000 claims description 2
- AZXPJWZIDROYLV-CQSZACIVSA-N 1-[(2r)-4-[4-(5-chloro-6-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound ClC1=C(F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 AZXPJWZIDROYLV-CQSZACIVSA-N 0.000 claims description 2
- FWCTVMMNOUKNDL-OAHLLOKOSA-N 1-[(2r)-4-[4-(5-chloro-6-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound ClC1=C(C)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 FWCTVMMNOUKNDL-OAHLLOKOSA-N 0.000 claims description 2
- DJQDDTLHCBPCGG-MRXNPFEDSA-N 1-[(2r)-4-[4-(5-chloro-6-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound ClC1=C(C)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 DJQDDTLHCBPCGG-MRXNPFEDSA-N 0.000 claims description 2
- PZQMHAPTLOZMNF-OAHLLOKOSA-N 1-[(2r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=C(Cl)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 PZQMHAPTLOZMNF-OAHLLOKOSA-N 0.000 claims description 2
- TZXSPFRSJKKIHO-MRXNPFEDSA-N 1-[(2r)-4-[4-(6-ethyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC=N1)=C1C1=NC2=CC=C(CC)C=C2N1 TZXSPFRSJKKIHO-MRXNPFEDSA-N 0.000 claims description 2
- SXVAKRWMKKKLJC-CQSZACIVSA-N 1-[(2r)-4-[4-(6-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 SXVAKRWMKKKLJC-CQSZACIVSA-N 0.000 claims description 2
- MTVAHZZIVWOUEP-QGZVFWFLSA-N 1-[(2r)-4-[4-(6-tert-butyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(C(C)(C)C)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 MTVAHZZIVWOUEP-QGZVFWFLSA-N 0.000 claims description 2
- QJQBZNUWXZTKCS-GOSISDBHSA-N 1-[(2r)-4-[4-(6-tert-butyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=C(C(C)(C)C)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 QJQBZNUWXZTKCS-GOSISDBHSA-N 0.000 claims description 2
- SWADDIZTSADMDS-CYBMUJFWSA-N 1-[(2r)-4-[4-[5-chloro-6-(trifluoromethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound ClC1=C(C(F)(F)F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 SWADDIZTSADMDS-CYBMUJFWSA-N 0.000 claims description 2
- RGCMDFOKPCNRJN-CYBMUJFWSA-N 1-[(2r)-4-[4-[6-(2-aminoethyl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(CCN)=CC=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C RGCMDFOKPCNRJN-CYBMUJFWSA-N 0.000 claims description 2
- MKVNPZBCHHFZPL-CYBMUJFWSA-N 1-[(2r)-4-[4-[6-(azetidin-3-yloxy)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(OC4CNC4)=CC=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C MKVNPZBCHHFZPL-CYBMUJFWSA-N 0.000 claims description 2
- GQETWNSPPDJJEM-LBPRGKRZSA-N 1-[(2s)-4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound C([C@@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C GQETWNSPPDJJEM-LBPRGKRZSA-N 0.000 claims description 2
- AFUOHZJSVAWGAN-CQSZACIVSA-N 1-[2-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3,3-difluoroindol-2-one Chemical compound C[C@@H]1CN(CCN1C(=O)CN1C(=O)C(F)(F)c2ccccc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F AFUOHZJSVAWGAN-CQSZACIVSA-N 0.000 claims description 2
- YKMIHVJWFJSFQY-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 YKMIHVJWFJSFQY-UHFFFAOYSA-N 0.000 claims description 2
- KPKRNRYTISOSIX-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]indole-3-carbonitrile Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4C(C#N)=C3)=O)=NC2=C1 KPKRNRYTISOSIX-UHFFFAOYSA-N 0.000 claims description 2
- SANIXHCRLINTJG-UHFFFAOYSA-N 1-[2-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]indole-7-carbonitrile Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=C(C#N)C=CC=C4C=C3)=O)=NC2=C1 SANIXHCRLINTJG-UHFFFAOYSA-N 0.000 claims description 2
- MTMPGUHQBCBJDK-UHFFFAOYSA-N 1-[2-[4-[4-(4-methoxy-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C(N1)=NC2=C1C=CC=C2OC MTMPGUHQBCBJDK-UHFFFAOYSA-N 0.000 claims description 2
- WYNSUNBZSHAKJO-UHFFFAOYSA-N 1-[2-[4-[4-(5,6-dichloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound ClC1=C(Cl)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 WYNSUNBZSHAKJO-UHFFFAOYSA-N 0.000 claims description 2
- ZCXBNVYAHFUACI-UHFFFAOYSA-N 1-[2-[4-[4-(5,6-dimethoxy-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C1=NC(C=C(C(=C2)OC)OC)=C2N1 ZCXBNVYAHFUACI-UHFFFAOYSA-N 0.000 claims description 2
- PXXTXMUXFSYTBX-UHFFFAOYSA-N 1-[2-[4-[4-(5-chloro-4-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C(N1)=NC2=C1C=CC(Cl)=C2C PXXTXMUXFSYTBX-UHFFFAOYSA-N 0.000 claims description 2
- FCNACKBPZZDCHI-UHFFFAOYSA-N 1-[2-[4-[4-(6-fluoro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=C(F)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 FCNACKBPZZDCHI-UHFFFAOYSA-N 0.000 claims description 2
- IPVUFYRXDQPWGO-UHFFFAOYSA-N 1-[2-[4-[4-(6-methoxy-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C1=NC2=CC=C(OC)C=C2N1 IPVUFYRXDQPWGO-UHFFFAOYSA-N 0.000 claims description 2
- NSINNRXMHZHLTO-CQSZACIVSA-N 1-[2-[5-[(3r)-4-[2-(3,5-dimethyl-1,2,4-triazol-1-yl)acetyl]-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazol-4-yl]-3h-benzimidazol-5-yl]pyrrolidin-2-one Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(=CC=C3N=2)N2C(CCC2)=O)CCN1C(=O)CN1N=C(C)N=C1C NSINNRXMHZHLTO-CQSZACIVSA-N 0.000 claims description 2
- FJRKGRXGBKBCPH-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2,4-dimethyl-1,3-thiazol-5-yl)ethanone Chemical compound S1C(C)=NC(C)=C1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 FJRKGRXGBKBCPH-UHFFFAOYSA-N 0.000 claims description 2
- LVAVGFMFPFLFJK-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-methyl-1,3-thiazol-4-yl)ethanone Chemical compound S1C(C)=NC(CC(=O)N2CCN(CC2)C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)=C1 LVAVGFMFPFLFJK-UHFFFAOYSA-N 0.000 claims description 2
- MPXZBKLCVKNLDM-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-methylbenzimidazol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N=C3C)=NC2=C1 MPXZBKLCVKNLDM-UHFFFAOYSA-N 0.000 claims description 2
- IKSLVAGKKSLNDZ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-methylindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4C=C3C)=NC2=C1 IKSLVAGKKSLNDZ-UHFFFAOYSA-N 0.000 claims description 2
- PIAVMUPNSMEUGB-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone Chemical compound N1=C(C)N=C(C)N1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 PIAVMUPNSMEUGB-UHFFFAOYSA-N 0.000 claims description 2
- DLTKVWCOVGHZHZ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(3,5-dimethylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=C(C)N1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 DLTKVWCOVGHZHZ-UHFFFAOYSA-N 0.000 claims description 2
- CUEGGPYIWILLKJ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(3-methylpyrazol-1-yl)ethanone Chemical compound N1=C(C)C=CN1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 CUEGGPYIWILLKJ-UHFFFAOYSA-N 0.000 claims description 2
- FMZNKJLBKZFFMM-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(4-chloroindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=4C=CC=C(C=4C=C3)Cl)=NC2=C1 FMZNKJLBKZFFMM-UHFFFAOYSA-N 0.000 claims description 2
- PMQXYHUWNGWALH-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(5,6-dichloroindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC=4C=C(C(=CC=43)Cl)Cl)=NC2=C1 PMQXYHUWNGWALH-UHFFFAOYSA-N 0.000 claims description 2
- NDRFYDLJLDDNSJ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(5-chloro-6-methoxyindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=4C=C(C(=CC=4C=C3)Cl)OC)=NC2=C1 NDRFYDLJLDDNSJ-UHFFFAOYSA-N 0.000 claims description 2
- GGEUVKOZSURLRV-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(5-fluoro-3-methylindol-1-yl)ethanone Chemical compound C12=CC=C(F)C=C2C(C)=CN1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 GGEUVKOZSURLRV-UHFFFAOYSA-N 0.000 claims description 2
- ZDUYKHFZQSJNFV-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(5-methoxy-1,2-benzoxazol-3-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CC3=NOC4=CC=C(C=C43)OC)=NC2=C1 ZDUYKHFZQSJNFV-UHFFFAOYSA-N 0.000 claims description 2
- SCVSRHNPAAZGQR-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(6-fluoroindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC4=CC=C(C=C43)F)=NC2=C1 SCVSRHNPAAZGQR-UHFFFAOYSA-N 0.000 claims description 2
- HOMALBCBVVBVQX-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(7-methylindol-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC=4C=CC=C(C3=4)C)=NC2=C1 HOMALBCBVVBVQX-UHFFFAOYSA-N 0.000 claims description 2
- LWEMWERZUOBKHE-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-[2-(trifluoromethyl)benzimidazol-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N=C3C(F)(F)F)=NC2=C1 LWEMWERZUOBKHE-UHFFFAOYSA-N 0.000 claims description 2
- HJNKVIYKENHVBP-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-[3-(trifluoromethyl)pyrazol-1-yl]ethanone Chemical compound N1=C(C(F)(F)F)C=CN1CC(=O)N1CCN(C2=C(N=CS2)C=2NC3=CC=CC=C3N=2)CC1 HJNKVIYKENHVBP-UHFFFAOYSA-N 0.000 claims description 2
- RTOIAPLSSZIQHL-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-[6-(trifluoromethyl)indol-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C=CC4=CC=C(C=C43)C(F)(F)F)=NC2=C1 RTOIAPLSSZIQHL-UHFFFAOYSA-N 0.000 claims description 2
- VWQMPPWGVQVAFY-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-indol-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4C=C3)=O)=NC2=C1 VWQMPPWGVQVAFY-UHFFFAOYSA-N 0.000 claims description 2
- FZRSFOKYQJRWAB-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C(F)(F)F)S1 FZRSFOKYQJRWAB-UHFFFAOYSA-N 0.000 claims description 2
- JWULMZFPLLBNIC-UHFFFAOYSA-N 1-methyl-3-[2-[4-[4-(6-methyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]benzimidazol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)N1CC(=O)N(CC1)CCN1C(SC=N1)=C1C1=NC2=CC=C(C)C=C2N1 JWULMZFPLLBNIC-UHFFFAOYSA-N 0.000 claims description 2
- HWAONVMHZWJJNS-UHFFFAOYSA-N 1-methyl-3-[2-oxo-2-[4-[4-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethyl]benzimidazol-2-one Chemical compound C1=C(C(F)(F)F)C=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1 HWAONVMHZWJJNS-UHFFFAOYSA-N 0.000 claims description 2
- OEOHNTRTGVOMDH-CYBMUJFWSA-N 2-(3,5-dimethyl-1,2,4-triazol-1-yl)-1-[(2r)-2-methyl-4-[4-[6-(1,2,4-triazol-1-yl)-1h-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC(=CC=C3N=2)N2N=CN=C2)CCN1C(=O)CN1N=C(C)N=C1C OEOHNTRTGVOMDH-CYBMUJFWSA-N 0.000 claims description 2
- PTPLFXLDZSNCPH-LLVKDONJSA-N 2-(3,5-dimethyl-1,2,4-triazol-1-yl)-1-[(2r)-4-[4-(4-fluoro-1h-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC(F)=C3N=2)CCN1C(=O)CN1N=C(C)N=C1C PTPLFXLDZSNCPH-LLVKDONJSA-N 0.000 claims description 2
- AGOCCPOUVUKXBW-OAHLLOKOSA-N 2-(benzimidazol-1-yl)-1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound C[C@@H]1CN(CCN1C(=O)Cn1cnc2ccccc12)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F AGOCCPOUVUKXBW-OAHLLOKOSA-N 0.000 claims description 2
- FZDCGDPJOYURJH-MRXNPFEDSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-(1-methylbenzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=CC=C2N(C)C(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 FZDCGDPJOYURJH-MRXNPFEDSA-N 0.000 claims description 2
- NSNKTVMNOZLWAV-LJQANCHMSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-(6-phenyl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C=1SC=NC=1C(NC1=C2)=NC1=CC=C2C1=CC=CC=C1 NSNKTVMNOZLWAV-LJQANCHMSA-N 0.000 claims description 2
- YAEINEHECLJPQS-QGZVFWFLSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-(6-propan-2-yl-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=NC2=CC=CN=C2N1CC(=O)N([C@H](C)C1)CCN1C(SC=N1)=C1C1=NC2=CC=C(C(C)C)C=C2N1 YAEINEHECLJPQS-QGZVFWFLSA-N 0.000 claims description 2
- XTYTUXOARVNQQX-CQSZACIVSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-[4-(trifluoromethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1C(F)(F)F XTYTUXOARVNQQX-CQSZACIVSA-N 0.000 claims description 2
- RWYWRUUVNQAIPY-CQSZACIVSA-N 2-imidazo[4,5-b]pyridin-3-yl-1-[(2r)-2-methyl-4-[4-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C1=C(C(F)(F)F)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 RWYWRUUVNQAIPY-CQSZACIVSA-N 0.000 claims description 2
- DUMVKKCVINYRND-QGZVFWFLSA-N 3-[4-(1h-benzimidazol-2-yl)-5-[(3r)-3-methyl-4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]-1,3-thiazol-2-yl]propanoic acid Chemical compound C1=CC=C2NC(C=3N=C(CCC(O)=O)SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=C3)C)=NC2=C1 DUMVKKCVINYRND-QGZVFWFLSA-N 0.000 claims description 2
- ZFULQWZHHVTMAU-CQSZACIVSA-N 4-[2-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-[1,3]oxazolo[4,5-b]pyridin-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC(=O)OC4=CC=C3)C)=NC2=C1 ZFULQWZHHVTMAU-CQSZACIVSA-N 0.000 claims description 2
- YBOXTUJLDCBPEO-UHFFFAOYSA-N 6-(trifluoromethoxy)-1h-benzimidazole Chemical compound FC(F)(F)OC1=CC=C2NC=NC2=C1 YBOXTUJLDCBPEO-UHFFFAOYSA-N 0.000 claims description 2
- 206010065040 AIDS dementia complex Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 claims description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
- 201000002481 Myositis Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 claims description 2
- 206010022000 influenza Diseases 0.000 claims description 2
- 230000001394 metastastic effect Effects 0.000 claims description 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 2
- ZXNXNNGNEOZCNM-CYBMUJFWSA-N methyl 1-[2-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]pyrazole-3-carboxylate Chemical compound COC(=O)c1ccn(CC(=O)N2CCN(C[C@H]2C)c2sc(nc2-c2nc3ccccc3[nH]2)C(F)(F)F)n1 ZXNXNNGNEOZCNM-CYBMUJFWSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- QJAVQYQVZPRFTJ-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-(2-methylimidazo[1,2-a]pyridin-3-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CC=3N4C=CC=CC4=NC=3C)=NC2=C1 QJAVQYQVZPRFTJ-UHFFFAOYSA-N 0.000 claims 1
- YSIWMXKSXXVOQY-LLVKDONJSA-N 2-(3,5-dimethyl-1,2,4-triazol-1-yl)-1-[(2r)-2-methyl-4-[2-(trifluoromethyl)-4-[4-(trifluoromethyl)-1h-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethanone Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C=2NC3=CC=CC(=C3N=2)C(F)(F)F)CCN1C(=O)CN1N=C(C)N=C1C YSIWMXKSXXVOQY-LLVKDONJSA-N 0.000 claims 1
- 206010063094 Cerebral malaria Diseases 0.000 claims 1
- 208000003435 Optic Neuritis Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 206010003549 asthenia Diseases 0.000 claims 1
- HWYHDWGGACRVEH-UHFFFAOYSA-N n-methyl-n-(4-pyrrolidin-1-ylbut-2-ynyl)acetamide Chemical compound CC(=O)N(C)CC#CCN1CCCC1 HWYHDWGGACRVEH-UHFFFAOYSA-N 0.000 claims 1
- 230000002685 pulmonary effect Effects 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 361
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 358
- 238000000034 method Methods 0.000 description 194
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
- 239000002904 solvent Substances 0.000 description 136
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 101
- 239000000203 mixture Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 85
- 239000011541 reaction mixture Substances 0.000 description 84
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 69
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000012044 organic layer Substances 0.000 description 53
- 239000007787 solid Substances 0.000 description 50
- AFHSZBKDUTWXDX-UHFFFAOYSA-N 2-(benzimidazol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C=NC2=C1 AFHSZBKDUTWXDX-UHFFFAOYSA-N 0.000 description 49
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 47
- 238000010828 elution Methods 0.000 description 39
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 38
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 37
- 239000002243 precursor Substances 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000011734 sodium Substances 0.000 description 33
- 239000000725 suspension Substances 0.000 description 33
- 229910052786 argon Inorganic materials 0.000 description 32
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- 239000000460 chlorine Substances 0.000 description 25
- 239000010410 layer Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- 239000012156 elution solvent Substances 0.000 description 21
- 230000006870 function Effects 0.000 description 21
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- 239000003446 ligand Substances 0.000 description 18
- 238000002156 mixing Methods 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 17
- 238000001816 cooling Methods 0.000 description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 15
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 14
- 239000007821 HATU Substances 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 13
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- RPYQVSLCGITEHQ-UHFFFAOYSA-N 2-pyrrolo[2,3-b]pyridin-1-ylacetic acid Chemical compound C1=CN=C2N(CC(=O)O)C=CC2=C1 RPYQVSLCGITEHQ-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 11
- 229910052794 bromium Inorganic materials 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 125000001425 triazolyl group Chemical group 0.000 description 10
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 8
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000004296 chiral HPLC Methods 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000003643 water by type Substances 0.000 description 8
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 7
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 description 7
- 125000003386 piperidinyl group Chemical group 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 7
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 108010061300 CXCR3 Receptors Proteins 0.000 description 6
- 102000011963 CXCR3 Receptors Human genes 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 125000004193 piperazinyl group Chemical group 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical compound C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- 238000006069 Suzuki reaction reaction Methods 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
- 230000004064 dysfunction Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 5
- 125000001041 indolyl group Chemical group 0.000 description 5
- AUJMFWXVFMHABB-UHFFFAOYSA-N methyl 5-bromo-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=CSC=1Br AUJMFWXVFMHABB-UHFFFAOYSA-N 0.000 description 5
- 150000004702 methyl esters Chemical group 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- DATRVIMZZZVHMP-MRVPVSSYSA-N tert-butyl (2r)-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-MRVPVSSYSA-N 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- SAIXZIVDXDTYCH-UHFFFAOYSA-N 3-chlorobenzene-1,2-diamine Chemical group NC1=CC=CC(Cl)=C1N SAIXZIVDXDTYCH-UHFFFAOYSA-N 0.000 description 4
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 4
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 4
- 208000015943 Coeliac disease Diseases 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 4
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- HMVJXTUUQJUYJI-UHFFFAOYSA-N (3,4-diaminophenyl)methanol Chemical compound NC1=CC=C(CO)C=C1N HMVJXTUUQJUYJI-UHFFFAOYSA-N 0.000 description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical group C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
- FEDLEBCVFZMHBP-UHFFFAOYSA-N 2-amino-3-methylphenol Chemical compound CC1=CC=CC(O)=C1N FEDLEBCVFZMHBP-UHFFFAOYSA-N 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- DSCOSIUAQUDGJM-UHFFFAOYSA-N 6-chloro-1h-pyrrolo[2,3-b]pyridine Chemical compound ClC1=CC=C2C=CNC2=N1 DSCOSIUAQUDGJM-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102100025279 C-X-C motif chemokine 11 Human genes 0.000 description 3
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 3
- 102000009410 Chemokine receptor Human genes 0.000 description 3
- 108050000299 Chemokine receptor Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 3
- AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
- 239000000779 smoke Substances 0.000 description 3
- JPQVWIJPICIURJ-UHFFFAOYSA-N tert-butyl 1-(2-oxo-2-phenylmethoxyethyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1N=CN2CC(=O)OCC1=CC=CC=C1 JPQVWIJPICIURJ-UHFFFAOYSA-N 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical group OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 2
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- RJHDZLSJTFQULJ-UHFFFAOYSA-N 1-(2-bromophenyl)-4-methylpiperazine Chemical compound C1CN(C)CCN1C1=CC=CC=C1Br RJHDZLSJTFQULJ-UHFFFAOYSA-N 0.000 description 2
- QNDJHGODPWAKAO-UHFFFAOYSA-N 1-(2-bromophenyl)pyrazole Chemical compound BrC1=CC=CC=C1N1N=CC=C1 QNDJHGODPWAKAO-UHFFFAOYSA-N 0.000 description 2
- JTYXVQCIHWUUHK-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-chloropyrrolo[2,3-b]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C(Cl)=C3)C)=NC2=C1 JTYXVQCIHWUUHK-OAHLLOKOSA-N 0.000 description 2
- AYGNPXSYTSKYJA-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(7-chloropyrrolo[2,3-c]pyridin-1-yl)ethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=C(Cl)N=CC=C4C=C3)C)=NC2=C1 AYGNPXSYTSKYJA-OAHLLOKOSA-N 0.000 description 2
- OSVNOSAGCOHVNC-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridin-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4C=N3)C)=NC2=C1 OSVNOSAGCOHVNC-OAHLLOKOSA-N 0.000 description 2
- RDJIWCCTNIFFHR-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazolo[3,4-b]pyridin-2-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3N=C4N=CC=CC4=C3)C)=NC2=C1 RDJIWCCTNIFFHR-OAHLLOKOSA-N 0.000 description 2
- IRVSZXBHGVARHI-CQSZACIVSA-N 1-[(2r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=C(Cl)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 IRVSZXBHGVARHI-CQSZACIVSA-N 0.000 description 2
- FDBZJTIFWNJTHR-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-indazol-1-ylethanone Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(CN3C4=CC=CC=C4C=N3)=O)=NC2=C1 FDBZJTIFWNJTHR-UHFFFAOYSA-N 0.000 description 2
- UAHJMMJVSLOVSN-UHFFFAOYSA-N 1-[4-[5-(1h-benzimidazol-2-yl)-1,3-thiazol-4-yl]piperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3SC=NC=3N3CCN(CC3)C(CN3C4=NC=CC=C4N=C3)=O)=NC2=C1 UAHJMMJVSLOVSN-UHFFFAOYSA-N 0.000 description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 2
- IUHXGZHKSYYDIL-UHFFFAOYSA-N 2-(2-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1I IUHXGZHKSYYDIL-UHFFFAOYSA-N 0.000 description 2
- UTHUZYBSSBFPES-UHFFFAOYSA-N 2-(4-amino-3-nitrophenoxy)ethanol Chemical compound NC1=CC=C(OCCO)C=C1[N+]([O-])=O UTHUZYBSSBFPES-UHFFFAOYSA-N 0.000 description 2
- WFPQGQMWACGEII-UHFFFAOYSA-N 2-(5-methyl-1,2,4-triazol-1-yl)acetic acid Chemical compound CC1=NC=NN1CC(O)=O WFPQGQMWACGEII-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BHKHAZWICKSPGJ-UHFFFAOYSA-N 2-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]acetic acid Chemical compound CN(C)CC1=CN(CC(O)=O)N=C1C BHKHAZWICKSPGJ-UHFFFAOYSA-N 0.000 description 2
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 2
- ZWMULFCUVMOZMN-UHFFFAOYSA-N 2-imidazo[4,5-c]pyridin-1-ylacetic acid Chemical compound N1=CC=C2N(CC(=O)O)C=NC2=C1 ZWMULFCUVMOZMN-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 0.000 description 2
- TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 2
- HUTKDPINCSJXAA-CMDGGOBGSA-N 3-(dimethylamino)-1-phenylprop-2-en-1-one Chemical compound CN(C)\C=C\C(=O)C1=CC=CC=C1 HUTKDPINCSJXAA-CMDGGOBGSA-N 0.000 description 2
- OJSCBKGRGMBEEW-UHFFFAOYSA-N 3-fluorobenzene-1,2-diamine Chemical compound NC1=CC=CC(F)=C1N OJSCBKGRGMBEEW-UHFFFAOYSA-N 0.000 description 2
- KBEIFKMKVCDETC-UHFFFAOYSA-N 3-iodooxetane Chemical compound IC1COC1 KBEIFKMKVCDETC-UHFFFAOYSA-N 0.000 description 2
- SVSUYEJKNSMKKW-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-prop-1-en-2-yl-1,3,2-dioxaborolane Chemical compound CC(=C)B1OC(C)(C)C(C)(C)O1 SVSUYEJKNSMKKW-UHFFFAOYSA-N 0.000 description 2
- VGMJQHONPAXABH-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1h-pyrazolo[4,3-c]pyridine Chemical compound C1NCCC2=C1C=NN2 VGMJQHONPAXABH-UHFFFAOYSA-N 0.000 description 2
- ORAAOAMEUMZGGU-UHFFFAOYSA-N 4,5-dimethoxybenzene-1,2-diamine;dihydrochloride Chemical group Cl.Cl.COC1=CC(N)=C(N)C=C1OC ORAAOAMEUMZGGU-UHFFFAOYSA-N 0.000 description 2
- DIOBEQCFVVJJBU-UHFFFAOYSA-N 4-(2-methoxyethoxy)aniline Chemical compound COCCOC1=CC=C(N)C=C1 DIOBEQCFVVJJBU-UHFFFAOYSA-N 0.000 description 2
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 2
- ZCWBZRBJSPWUPG-UHFFFAOYSA-N 4-bromo-2-nitroaniline Chemical compound NC1=CC=C(Br)C=C1[N+]([O-])=O ZCWBZRBJSPWUPG-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- MPKLKOSWGGSAHW-GFCCVEGCSA-N 5-[(3r)-3-methyl-4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3C=C2)C)N1C=1SC=NC=1C(O)=O MPKLKOSWGGSAHW-GFCCVEGCSA-N 0.000 description 2
- PEDMFCHWOVJDNW-UHFFFAOYSA-N 5-fluoro-2-nitroaniline Chemical compound NC1=CC(F)=CC=C1[N+]([O-])=O PEDMFCHWOVJDNW-UHFFFAOYSA-N 0.000 description 2
- XONKJZDHGCMRRF-UHFFFAOYSA-N 7-fluoro-1h-indole Chemical compound FC1=CC=CC2=C1NC=C2 XONKJZDHGCMRRF-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101150004010 CXCR3 gene Proteins 0.000 description 2
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 101000858060 Homo sapiens C-X-C motif chemokine 11 Proteins 0.000 description 2
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 2
- 241000220317 Rosa Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 150000001336 alkenes Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- AYYSWWNQELFQKS-UHFFFAOYSA-N benzyl 2-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)acetate Chemical compound C1CC=2NN=CC=2CN1CC(=O)OCC1=CC=CC=C1 AYYSWWNQELFQKS-UHFFFAOYSA-N 0.000 description 2
- HEOXGHFAFXKMKG-UHFFFAOYSA-N benzyl 2-(3,5-dimethylpyrazol-1-yl)acetate Chemical compound N1=C(C)C=C(C)N1CC(=O)OCC1=CC=CC=C1 HEOXGHFAFXKMKG-UHFFFAOYSA-N 0.000 description 2
- UJNDNBAJYIBAAD-UHFFFAOYSA-N benzyl 2-(3-methyl-1,2,4-triazol-1-yl)acetate Chemical compound N1=C(C)N=CN1CC(=O)OCC1=CC=CC=C1 UJNDNBAJYIBAAD-UHFFFAOYSA-N 0.000 description 2
- MFMAOFVJWUAOAI-UHFFFAOYSA-N benzyl 2-(4,5,6,7-tetrahydroimidazo[4,5-c]pyridin-1-yl)acetate Chemical compound C1=NC=2CNCCC=2N1CC(=O)OCC1=CC=CC=C1 MFMAOFVJWUAOAI-UHFFFAOYSA-N 0.000 description 2
- MFDCERCHYGULQI-UHFFFAOYSA-N benzyl 2-(5-methyl-1,2,4-triazol-1-yl)acetate Chemical compound CC1=NC=NN1CC(=O)OCC1=CC=CC=C1 MFDCERCHYGULQI-UHFFFAOYSA-N 0.000 description 2
- QEQYBRCNBUKXPO-UHFFFAOYSA-N benzyl 2-(5-methyl-6,7-dihydro-4h-imidazo[4,5-c]pyridin-1-yl)acetate Chemical compound C1N(C)CCC2=C1N=CN2CC(=O)OCC1=CC=CC=C1 QEQYBRCNBUKXPO-UHFFFAOYSA-N 0.000 description 2
- UJWLOPOVXNWDPK-UHFFFAOYSA-N benzyl 2-(5-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-1-yl)acetate Chemical compound C1N(C)CCC2=C1C=NN2CC(=O)OCC1=CC=CC=C1 UJWLOPOVXNWDPK-UHFFFAOYSA-N 0.000 description 2
- ZGNWNIIULHIXKT-UHFFFAOYSA-N benzyl 2-(5-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-2-yl)acetate Chemical compound C1=C2CN(C)CCC2=NN1CC(=O)OCC1=CC=CC=C1 ZGNWNIIULHIXKT-UHFFFAOYSA-N 0.000 description 2
- VSJJZZDOBKGLIE-UHFFFAOYSA-N benzyl 2-[3-[(dimethylamino)methyl]-5-methyl-1,2,4-triazol-1-yl]acetate Chemical compound N1=C(CN(C)C)N=C(C)N1CC(=O)OCC1=CC=CC=C1 VSJJZZDOBKGLIE-UHFFFAOYSA-N 0.000 description 2
- PKKAIMYYJSHNKG-UHFFFAOYSA-N benzyl 2-[4-[(dimethylamino)methyl]-3,5-dimethylpyrazol-1-yl]acetate Chemical compound CC1=C(CN(C)C)C(C)=NN1CC(=O)OCC1=CC=CC=C1 PKKAIMYYJSHNKG-UHFFFAOYSA-N 0.000 description 2
- GFFCYEIUGABTFI-UHFFFAOYSA-N benzyl 2-[5-methyl-3-[[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]-1,2,4-triazol-1-yl]acetate Chemical compound N1=C(CN(C)C(=O)OC(C)(C)C)N=C(C)N1CC(=O)OCC1=CC=CC=C1 GFFCYEIUGABTFI-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000003123 bronchiole Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- VVDUZZGYBOWDSQ-UHFFFAOYSA-M eschenmoser's salt Chemical compound [I-].C[N+](C)=C VVDUZZGYBOWDSQ-UHFFFAOYSA-M 0.000 description 2
- PPCZCRHUBFHKQG-UHFFFAOYSA-N ethyl 2-(3-methylpyrazol-1-yl)acetate Chemical compound CCOC(=O)CN1C=CC(C)=N1 PPCZCRHUBFHKQG-UHFFFAOYSA-N 0.000 description 2
- YYDDDKUXIZTYRK-UHFFFAOYSA-N ethyl 2-[4-[(dimethylamino)methyl]-3-methylpyrazol-1-yl]acetate Chemical compound CCOC(=O)CN1C=C(CN(C)C)C(C)=N1 YYDDDKUXIZTYRK-UHFFFAOYSA-N 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 125000004245 indazol-3-yl group Chemical group [H]N1N=C(*)C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- BHYPERDTLBCHAE-UHFFFAOYSA-N tert-butyl 1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1C=NN2 BHYPERDTLBCHAE-UHFFFAOYSA-N 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- DGOLMFKQDDOSPK-UHFFFAOYSA-N tert-butyl 3,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1N=CN2 DGOLMFKQDDOSPK-UHFFFAOYSA-N 0.000 description 2
- WVHXIDROFFYUDM-UHFFFAOYSA-N tert-butyl n-methyl-n-[(5-methyl-1h-1,2,4-triazol-3-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=NNC(C)=N1 WVHXIDROFFYUDM-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 2
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 2
- NQPHMXWPDCSHTE-UHFFFAOYSA-N trifluoromethanesulfonyl azide Chemical compound FC(F)(F)S(=O)(=O)N=[N+]=[N-] NQPHMXWPDCSHTE-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- RDCLVZNNBVGGFW-UHFFFAOYSA-N (4-bromo-1,3-thiazol-5-yl)methanol Chemical compound OCC=1SC=NC=1Br RDCLVZNNBVGGFW-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- BWKAYBPLDRWMCJ-UHFFFAOYSA-N 1,1-diethoxy-n,n-dimethylmethanamine Chemical compound CCOC(N(C)C)OCC BWKAYBPLDRWMCJ-UHFFFAOYSA-N 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N 1,3,5-Me3C6H3 Natural products CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- JVTRURBMYILQDA-UHFFFAOYSA-N 1-(2-bromophenyl)piperazine Chemical compound BrC1=CC=CC=C1N1CCNCC1 JVTRURBMYILQDA-UHFFFAOYSA-N 0.000 description 1
- FFVSGYAQHXJFAL-UHFFFAOYSA-N 1-(3,4-diaminophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N)C(N)=C1 FFVSGYAQHXJFAL-UHFFFAOYSA-N 0.000 description 1
- VEIXVSPCPGWULB-UHFFFAOYSA-N 1-(4-amino-3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N)C([N+]([O-])=O)=C1 VEIXVSPCPGWULB-UHFFFAOYSA-N 0.000 description 1
- BYVHYCRIGWJSOT-UHFFFAOYSA-N 1-(4-methylpyrazol-1-yl)ethanone Chemical compound CC(=O)N1C=C(C)C=N1 BYVHYCRIGWJSOT-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- IVUVEIJMNAJHAN-PHIMTYICSA-N 1-[(1S,5R)-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound O=C(Cn1cnc2cccnc12)N1[C@H]2CC[C@@H]1CNC2 IVUVEIJMNAJHAN-PHIMTYICSA-N 0.000 description 1
- CTUWPSNEZJLVDO-OAHLLOKOSA-N 1-[(2r)-4-[4-(1h-benzimidazol-2-yl)-2-methyl-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone Chemical compound C1=CC=C2NC(C=3N=C(C)SC=3N3C[C@H](N(CC3)C(=O)CN3C4=NC=CC=C4N=C3)C)=NC2=C1 CTUWPSNEZJLVDO-OAHLLOKOSA-N 0.000 description 1
- XVAOWRWKDAWWOF-MRXNPFEDSA-N 1-[(2r)-4-[4-(6-chloro-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=C(Cl)C=C2NC(C=3N=CSC=3N3C[C@H](N(CC3)C(=O)CN3C4=CC=CC=C4CC3)C)=NC2=C1 XVAOWRWKDAWWOF-MRXNPFEDSA-N 0.000 description 1
- RWVGFPUZDWIRMV-UHFFFAOYSA-N 1-[2-[4-[4-(4-hydroxy-1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-oxoethyl]-3-methylbenzimidazol-2-one Chemical compound C1=CC=C2NC(C=3N=CSC=3N3CCN(CC3)C(=O)CN3C4=CC=CC=C4N(C3=O)C)=NC2=C1O RWVGFPUZDWIRMV-UHFFFAOYSA-N 0.000 description 1
- KWYSTAZKLBIIIJ-UHFFFAOYSA-N 1-[4-[2-(1-hydroxyethyl)-4-[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound OC(C)C=1SC(=C(N1)C1=NC2=C(N1COCC[Si](C)(C)C)C=CC=C2)N2CCN(CC2)C(CN2C=CC=1C2=NC=CC1)=O KWYSTAZKLBIIIJ-UHFFFAOYSA-N 0.000 description 1
- DZQJNJBIPDJCET-UHFFFAOYSA-N 1-[4-[2-acetyl-4-[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2N(C3=CC=CC=C3N=2)COCC[Si](C)(C)C)N=C(C(=O)C)S1 DZQJNJBIPDJCET-UHFFFAOYSA-N 0.000 description 1
- SMXHUWAIPYHKPF-UHFFFAOYSA-N 1-[4-[2-bromo-4-[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound BrC=1SC(=C(N1)C1=NC2=C(N1COCC[Si](C)(C)C)C=CC=C2)N2CCN(CC2)C(CN2C=CC=1C2=NC=CC1)=O SMXHUWAIPYHKPF-UHFFFAOYSA-N 0.000 description 1
- VIRDUEBCNAWLID-UHFFFAOYSA-N 1-[4-[2-phenyl-4-[1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1(=CC=CC=C1)C=1SC(=C(N1)C1=NC2=C(N1COCC[Si](C)(C)C)C=CC=C2)N2CCN(CC2)C(CN2C=CC=1C2=NC=CC1)=O VIRDUEBCNAWLID-UHFFFAOYSA-N 0.000 description 1
- ADDKLMDMXWSFDY-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-bromo-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(Br)S1 ADDKLMDMXWSFDY-UHFFFAOYSA-N 0.000 description 1
- GESBKOWUIYJDQY-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-chloro-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(Cl)S1 GESBKOWUIYJDQY-UHFFFAOYSA-N 0.000 description 1
- KYWSSMSPIONJII-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-ethyl-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(CC)S1 KYWSSMSPIONJII-UHFFFAOYSA-N 0.000 description 1
- OEZNEYSBGWRWNR-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-methyl-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C)S1 OEZNEYSBGWRWNR-UHFFFAOYSA-N 0.000 description 1
- BLNOIZDIEKTXNA-UHFFFAOYSA-N 1-[4-[4-(1h-benzimidazol-2-yl)-2-phenyl-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone Chemical compound C1=CC2=CC=CN=C2N1CC(=O)N(CC1)CCN1C(=C(N=1)C=2NC3=CC=CC=C3N=2)SC=1C1=CC=CC=C1 BLNOIZDIEKTXNA-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 1
- VWBHMDVHVYVIAR-UHFFFAOYSA-N 1-ethyl-4-[2-[4-(4-propylcyclohexyl)phenyl]ethynyl]benzene Chemical compound C1CC(CCC)CCC1C1=CC=C(C#CC=2C=CC(CC)=CC=2)C=C1 VWBHMDVHVYVIAR-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- WJTOMXLUNDWLCY-UHFFFAOYSA-N 1-n,1-n-dimethyl-4-nitrobenzene-1,3-diamine Chemical compound CN(C)C1=CC=C([N+]([O-])=O)C(N)=C1 WJTOMXLUNDWLCY-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- XNNPFSSPGFCLLA-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridin-2-ylmethanol Chemical compound C1=CN=C2NC(CO)=CC2=C1 XNNPFSSPGFCLLA-UHFFFAOYSA-N 0.000 description 1
- XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- PCAXITAPTVOLGL-UHFFFAOYSA-N 2,3-diaminophenol Chemical group NC1=CC=CC(O)=C1N PCAXITAPTVOLGL-UHFFFAOYSA-N 0.000 description 1
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
- HRCMXYXVAWHBTH-UHFFFAOYSA-N 2,3-dihydro-1,3-benzoxazole Chemical compound C1=CC=C2OCNC2=C1 HRCMXYXVAWHBTH-UHFFFAOYSA-N 0.000 description 1
- ZFFYPGZDXUPKNK-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[2,3-b]pyridine Chemical group C1=CN=C2NCCC2=C1 ZFFYPGZDXUPKNK-UHFFFAOYSA-N 0.000 description 1
- BUWPZNOVIHAWHW-UHFFFAOYSA-N 2,3-dihydro-1h-quinolin-4-one Chemical group C1=CC=C2C(=O)CCNC2=C1 BUWPZNOVIHAWHW-UHFFFAOYSA-N 0.000 description 1
- BZKLZFBVPVMQTH-UHFFFAOYSA-N 2-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)acetic acid Chemical compound C1N(CC(=O)O)CCC2=C1C=NN2 BZKLZFBVPVMQTH-UHFFFAOYSA-N 0.000 description 1
- MKQDLENGVAZKHV-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzoxazin-4-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)CCOC2=C1 MKQDLENGVAZKHV-UHFFFAOYSA-N 0.000 description 1
- ZYKYVZPUUGVMFE-UHFFFAOYSA-N 2-(2,3-dihydroindol-1-yl)acetic acid Chemical group C1=CC=C2N(CC(=O)O)CCC2=C1 ZYKYVZPUUGVMFE-UHFFFAOYSA-N 0.000 description 1
- RRWOYYQKUJUFGL-UHFFFAOYSA-N 2-(2,3-dihydropyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C1=CN=C2N(CC(=O)O)CCC2=C1 RRWOYYQKUJUFGL-UHFFFAOYSA-N 0.000 description 1
- KYAMYNWIAQNFEG-UHFFFAOYSA-N 2-(2,3-dioxoindol-1-yl)acetic acid Chemical group C1=CC=C2N(CC(=O)O)C(=O)C(=O)C2=C1 KYAMYNWIAQNFEG-UHFFFAOYSA-N 0.000 description 1
- UDZSKYLTWZYMSX-UHFFFAOYSA-N 2-(2,6-dimethylpyridin-4-yl)acetic acid Chemical compound CC1=CC(CC(O)=O)=CC(C)=N1 UDZSKYLTWZYMSX-UHFFFAOYSA-N 0.000 description 1
- WGODSCYEKWDSAV-UHFFFAOYSA-N 2-(2-fluoro-4-methoxyphenyl)acetic acid Chemical group COC1=CC=C(CC(O)=O)C(F)=C1 WGODSCYEKWDSAV-UHFFFAOYSA-N 0.000 description 1
- NSECKCCQXANPJT-GFCCVEGCSA-N 2-(2-fluorophenyl)-5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C(O)=O)N=C(C=2C(=CC=CC=2)F)S1 NSECKCCQXANPJT-GFCCVEGCSA-N 0.000 description 1
- XBZPMGFTAGCOGU-UHFFFAOYSA-N 2-(2-methylpyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C1=CN=C2N(CC(O)=O)C(C)=CC2=C1 XBZPMGFTAGCOGU-UHFFFAOYSA-N 0.000 description 1
- PHIUXGVYFVAGTC-UHFFFAOYSA-N 2-(2-oxo-1,3-benzoxazol-3-yl)acetic acid Chemical compound C1=CC=C2OC(=O)N(CC(=O)O)C2=C1 PHIUXGVYFVAGTC-UHFFFAOYSA-N 0.000 description 1
- RQCKECZLTHIDOD-UHFFFAOYSA-N 2-(2-oxo-1h-imidazo[4,5-b]pyridin-3-yl)acetic acid Chemical compound C1=CC=C2NC(=O)N(CC(=O)O)C2=N1 RQCKECZLTHIDOD-UHFFFAOYSA-N 0.000 description 1
- LQGIKCCIECNYHT-UHFFFAOYSA-N 2-(2-oxo-3,4-dihydroquinolin-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C(=O)CCC2=C1 LQGIKCCIECNYHT-UHFFFAOYSA-N 0.000 description 1
- JKJISQOWTFXMRR-UHFFFAOYSA-N 2-(2-oxo-3h-indol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C(=O)CC2=C1 JKJISQOWTFXMRR-UHFFFAOYSA-N 0.000 description 1
- QBPZKLORFUHHAW-UHFFFAOYSA-N 2-(2-pyrazol-1-ylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1N1N=CC=C1 QBPZKLORFUHHAW-UHFFFAOYSA-N 0.000 description 1
- WJIHEGXZOMSHNO-UHFFFAOYSA-N 2-(3,3-difluoro-2-oxoindol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)C(=O)C(F)(F)C2=C1 WJIHEGXZOMSHNO-UHFFFAOYSA-N 0.000 description 1
- NAOPHBGLLPBVLR-UHFFFAOYSA-N 2-(3,3-dimethyl-2-oxoindol-1-yl)acetic acid Chemical compound C1=CC=C2C(C)(C)C(=O)N(CC(O)=O)C2=C1 NAOPHBGLLPBVLR-UHFFFAOYSA-N 0.000 description 1
- JFYNEMAXRRCTRY-UHFFFAOYSA-N 2-(3,4-diaminophenoxy)ethanol Chemical compound NC1=CC=C(OCCO)C=C1N JFYNEMAXRRCTRY-UHFFFAOYSA-N 0.000 description 1
- IBNYPYJMTVXJSZ-UHFFFAOYSA-N 2-(3,4-dihydro-2h-quinolin-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)CCCC2=C1 IBNYPYJMTVXJSZ-UHFFFAOYSA-N 0.000 description 1
- JYSWEDYPQJOEPO-UHFFFAOYSA-N 2-(3,5-dimethylpyrazol-1-yl)acetic acid Chemical compound CC=1C=C(C)N(CC(O)=O)N=1 JYSWEDYPQJOEPO-UHFFFAOYSA-N 0.000 description 1
- TYKYXRSIWMDNCQ-UHFFFAOYSA-N 2-(3-bromo-1,2,4-triazol-1-yl)acetic acid Chemical compound OC(=O)CN1C=NC(Br)=N1 TYKYXRSIWMDNCQ-UHFFFAOYSA-N 0.000 description 1
- RTDYPYFMQUULTD-UHFFFAOYSA-N 2-(3-chloropyrrolo[2,3-b]pyrazin-5-yl)acetic acid Chemical compound C1=C(Cl)N=C2N(CC(=O)O)C=CC2=N1 RTDYPYFMQUULTD-UHFFFAOYSA-N 0.000 description 1
- ZOKPVCRICOVYRK-UHFFFAOYSA-N 2-(3-chloropyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C1=CN=C2N(CC(=O)O)C=C(Cl)C2=C1 ZOKPVCRICOVYRK-UHFFFAOYSA-N 0.000 description 1
- MRSWWBAFGGGWRH-UHFFFAOYSA-N 2-(3-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(I)=C1 MRSWWBAFGGGWRH-UHFFFAOYSA-N 0.000 description 1
- STVCWVJTPWLZSP-UHFFFAOYSA-N 2-(3-methyl-1,2,4-triazol-1-yl)acetic acid Chemical compound CC=1N=CN(CC(O)=O)N=1 STVCWVJTPWLZSP-UHFFFAOYSA-N 0.000 description 1
- LAPYIDMXQINFIS-UHFFFAOYSA-N 2-(3-methyl-2-oxobenzimidazol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(O)=O)C(=O)N(C)C2=C1 LAPYIDMXQINFIS-UHFFFAOYSA-N 0.000 description 1
- JZWDFOAFMVOQKR-UHFFFAOYSA-N 2-(3-methylpyrazol-1-yl)acetic acid Chemical compound CC=1C=CN(CC(O)=O)N=1 JZWDFOAFMVOQKR-UHFFFAOYSA-N 0.000 description 1
- YALXIJVIPDXKRQ-UHFFFAOYSA-N 2-(3-methylpyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C1=CC=C2C(C)=CN(CC(O)=O)C2=N1 YALXIJVIPDXKRQ-UHFFFAOYSA-N 0.000 description 1
- QRLZFKJRNQDGFV-UHFFFAOYSA-N 2-(4-methoxyindol-1-yl)acetic acid Chemical compound COC1=CC=CC2=C1C=CN2CC(O)=O QRLZFKJRNQDGFV-UHFFFAOYSA-N 0.000 description 1
- MKWSXGBHCAKMKW-UHFFFAOYSA-N 2-(4-methyl-2-oxo-1,3-benzoxazol-3-yl)acetic acid Chemical compound CC1=CC=CC2=C1N(CC(O)=O)C(=O)O2 MKWSXGBHCAKMKW-UHFFFAOYSA-N 0.000 description 1
- DNFMIZHWDFJVOZ-UHFFFAOYSA-N 2-(4-oxo-2,3-dihydroquinolin-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(=O)O)CCC(=O)C2=C1 DNFMIZHWDFJVOZ-UHFFFAOYSA-N 0.000 description 1
- BJYCIVKSUNUGTH-UHFFFAOYSA-N 2-(5-methyl-6,7-dihydro-4h-imidazo[4,5-c]pyridin-1-yl)acetic acid Chemical compound C1N(C)CCC2=C1N=CN2CC(O)=O BJYCIVKSUNUGTH-UHFFFAOYSA-N 0.000 description 1
- HHMRMKYCCNCVTK-UHFFFAOYSA-N 2-(5-methyl-6,7-dihydro-4h-imidazo[4,5-c]pyridin-3-yl)acetic acid Chemical compound C1N(C)CCC2=C1N(CC(O)=O)C=N2 HHMRMKYCCNCVTK-UHFFFAOYSA-N 0.000 description 1
- TWSGPWDRTZEBLL-UHFFFAOYSA-N 2-(5-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-1-yl)acetic acid Chemical compound C1N(C)CCC2=C1C=NN2CC(O)=O TWSGPWDRTZEBLL-UHFFFAOYSA-N 0.000 description 1
- LKRLYIHLPXXDGM-UHFFFAOYSA-N 2-(5-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-2-yl)acetic acid Chemical compound C1N(C)CCC2=NN(CC(O)=O)C=C21 LKRLYIHLPXXDGM-UHFFFAOYSA-N 0.000 description 1
- PFAVXJYYBMOUQQ-UHFFFAOYSA-N 2-(5-phenylpyrazol-1-yl)acetic acid Chemical compound OC(=O)CN1N=CC=C1C1=CC=CC=C1 PFAVXJYYBMOUQQ-UHFFFAOYSA-N 0.000 description 1
- NXJLBOBTOLLLOJ-UHFFFAOYSA-N 2-(6-chloropyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound C1=C(Cl)N=C2N(CC(=O)O)C=CC2=C1 NXJLBOBTOLLLOJ-UHFFFAOYSA-N 0.000 description 1
- JXEVEIUBBIPFAN-UHFFFAOYSA-N 2-(6-methoxypyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound COC1=CC=C2C=CN(CC(O)=O)C2=N1 JXEVEIUBBIPFAN-UHFFFAOYSA-N 0.000 description 1
- KXZMLJNWZASBMG-UHFFFAOYSA-N 2-(6-methylpyrrolo[2,3-b]pyridin-1-yl)acetic acid Chemical compound CC1=CC=C2C=CN(CC(O)=O)C2=N1 KXZMLJNWZASBMG-UHFFFAOYSA-N 0.000 description 1
- GDOBOIUKWMRAFV-UHFFFAOYSA-N 2-(7-chloropyrrolo[2,3-c]pyridin-1-yl)acetic acid Chemical compound C1=NC(Cl)=C2N(CC(=O)O)C=CC2=C1 GDOBOIUKWMRAFV-UHFFFAOYSA-N 0.000 description 1
- XWRFQLMCZGCXQB-UHFFFAOYSA-N 2-(7-fluoroindol-1-yl)acetic acid Chemical compound C1=CC(F)=C2N(CC(=O)O)C=CC2=C1 XWRFQLMCZGCXQB-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical group CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- SAJXLJKAESCUQX-UHFFFAOYSA-N 2-[2-(4-methylpiperazin-1-yl)phenyl]acetic acid Chemical compound C1CN(C)CCN1C1=CC=CC=C1CC(O)=O SAJXLJKAESCUQX-UHFFFAOYSA-N 0.000 description 1
- VATQYQQYYSNBQV-UHFFFAOYSA-N 2-[2-(triazol-2-yl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC=C1N1N=CC=N1 VATQYQQYYSNBQV-UHFFFAOYSA-N 0.000 description 1
- HQEHSKSRMUGSTO-UHFFFAOYSA-N 2-[3-(triazol-2-yl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(N2N=CC=N2)=C1 HQEHSKSRMUGSTO-UHFFFAOYSA-N 0.000 description 1
- AYMAYXNXVGEXNN-UHFFFAOYSA-N 2-[3-[(dimethylamino)methyl]-5-methyl-1,2,4-triazol-1-yl]acetic acid Chemical compound CN(C)CC=1N=C(C)N(CC(O)=O)N=1 AYMAYXNXVGEXNN-UHFFFAOYSA-N 0.000 description 1
- UHTQHHLSGVOGQR-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-4-ium-1-yl]ethanesulfonate Chemical compound OCCN1CCN(CCS(O)(=O)=O)CC1.OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 UHTQHHLSGVOGQR-UHFFFAOYSA-N 0.000 description 1
- MYXQLITWBIBFNV-LLVKDONJSA-N 2-amino-1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone Chemical compound NCC(=O)N1[C@@H](CN(CC1)C1=C(N=CS1)C1=NC2=C(N1)C=CC=C2)C MYXQLITWBIBFNV-LLVKDONJSA-N 0.000 description 1
- QOZLOYKAFDTQNU-UHFFFAOYSA-N 2-amino-3-fluorophenol Chemical compound NC1=C(O)C=CC=C1F QOZLOYKAFDTQNU-UHFFFAOYSA-N 0.000 description 1
- BMTSZVZQNMNPCT-UHFFFAOYSA-N 2-aminopyridin-3-ol Chemical compound NC1=NC=CC=C1O BMTSZVZQNMNPCT-UHFFFAOYSA-N 0.000 description 1
- WCFISNHIHAGZOD-MRVPVSSYSA-N 2-bromo-5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C(O)=O)N=C(Br)S1 WCFISNHIHAGZOD-MRVPVSSYSA-N 0.000 description 1
- OUOPTTUFCQGFIL-UHFFFAOYSA-N 2-bromo-5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C(O)=O)N=C(Br)S1 OUOPTTUFCQGFIL-UHFFFAOYSA-N 0.000 description 1
- ILXFQOUYLMGEQL-UHFFFAOYSA-N 2-chloro-5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C(O)=O)N=C(Cl)S1 ILXFQOUYLMGEQL-UHFFFAOYSA-N 0.000 description 1
- DKPULRPERQFFIQ-SNVBAGLBSA-N 2-cyclopropyl-5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C(O)=O)N=C(C2CC2)S1 DKPULRPERQFFIQ-SNVBAGLBSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- HBVDRMMZRVBMKU-UHFFFAOYSA-N 2-imidazo[4,5-b]pyridin-3-ylacetic acid Chemical compound C1=CN=C2N(CC(=O)O)C=NC2=C1 HBVDRMMZRVBMKU-UHFFFAOYSA-N 0.000 description 1
- ZEBKRHBPTLHNRK-UHFFFAOYSA-N 2-imidazo[4,5-c]pyridin-3-ylacetic acid Chemical compound C1=NC=C2N(CC(=O)O)C=NC2=C1 ZEBKRHBPTLHNRK-UHFFFAOYSA-N 0.000 description 1
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 1
- XDHFUUVUHNOJEW-UHFFFAOYSA-N 2-methyl-1h-pyrrolo[2,3-b]pyridine Chemical group C1=CN=C2NC(C)=CC2=C1 XDHFUUVUHNOJEW-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- PKLFEINENGAXPR-UHFFFAOYSA-N 2-nitro-4-(piperidin-1-ylmethyl)aniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1CN1CCCCC1 PKLFEINENGAXPR-UHFFFAOYSA-N 0.000 description 1
- LOSKNFQZTWYZHI-UHFFFAOYSA-N 2-pyrazol-1-ylacetic acid Chemical group OC(=O)CN1C=CC=N1 LOSKNFQZTWYZHI-UHFFFAOYSA-N 0.000 description 1
- HNDSESMBMGSAFL-UHFFFAOYSA-N 2-pyrazolo[3,4-b]pyridin-1-ylacetic acid Chemical compound C1=CN=C2N(CC(=O)O)N=CC2=C1 HNDSESMBMGSAFL-UHFFFAOYSA-N 0.000 description 1
- JKDWQMXRNGZMKN-UHFFFAOYSA-N 2-pyrazolo[3,4-b]pyridin-2-ylacetic acid Chemical compound C1=CC=NC2=NN(CC(=O)O)C=C21 JKDWQMXRNGZMKN-UHFFFAOYSA-N 0.000 description 1
- UGUMHBYLVRIMRI-UHFFFAOYSA-N 2-pyrrolo[2,3-c]pyridin-1-ylacetic acid Chemical compound C1=NC=C2N(CC(=O)O)C=CC2=C1 UGUMHBYLVRIMRI-UHFFFAOYSA-N 0.000 description 1
- MWLBMGPQZJDFKZ-UHFFFAOYSA-N 23491-48-7 Chemical compound C1CN(C)CCN1C1=CC=C([N+]([O-])=O)C(N)=C1 MWLBMGPQZJDFKZ-UHFFFAOYSA-N 0.000 description 1
- 125000000850 2H-chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- AORVPBLZSJVLCI-UHFFFAOYSA-N 3,3-difluoro-1h-indol-2-one Chemical compound C1=CC=C2C(F)(F)C(=O)NC2=C1 AORVPBLZSJVLCI-UHFFFAOYSA-N 0.000 description 1
- KEZHRKOVLKUYCQ-UHFFFAOYSA-N 3,3-dimethyl-1h-indol-2-one Chemical compound C1=CC=C2C(C)(C)C(=O)NC2=C1 KEZHRKOVLKUYCQ-UHFFFAOYSA-N 0.000 description 1
- VWLLPPSBBHDXHK-UHFFFAOYSA-N 3,4-diaminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1N VWLLPPSBBHDXHK-UHFFFAOYSA-N 0.000 description 1
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical group C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- QWTQGZAUKADLTO-UHFFFAOYSA-N 3-chloro-5h-pyrrolo[2,3-b]pyrazine Chemical group ClC1=CN=C2C=CNC2=N1 QWTQGZAUKADLTO-UHFFFAOYSA-N 0.000 description 1
- SQMYKVUSWPIFEQ-UHFFFAOYSA-N 3-methoxypyrrolidine;hydrochloride Chemical compound Cl.COC1CCNC1 SQMYKVUSWPIFEQ-UHFFFAOYSA-N 0.000 description 1
- PKZDPOGLGBWEGP-UHFFFAOYSA-N 3-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC=C2C(C)=CNC2=N1 PKZDPOGLGBWEGP-UHFFFAOYSA-N 0.000 description 1
- WGNUNYPERJMVRM-UHFFFAOYSA-N 3-pyridylacetic acid Chemical compound OC(=O)CC1=CC=CN=C1 WGNUNYPERJMVRM-UHFFFAOYSA-N 0.000 description 1
- CHLFJSVTUQAGSC-UHFFFAOYSA-N 4,5,6,7-tetrahydro-3h-imidazo[4,5-c]pyridine;hydrochloride Chemical compound Cl.C1NCCC2=C1N=CN2 CHLFJSVTUQAGSC-UHFFFAOYSA-N 0.000 description 1
- PPAULTVPKLVLII-UHFFFAOYSA-N 4,5-diaminopyrimidine Chemical compound NC1=CN=CN=C1N PPAULTVPKLVLII-UHFFFAOYSA-N 0.000 description 1
- BASSHEDVDQHOJR-CYBMUJFWSA-N 4-(1H-benzimidazol-2-yl)-2-(2-fluorophenyl)-5-[(3R)-3-methylpiperazin-1-yl]-1,3-thiazole Chemical compound FC1=C(C=CC=C1)C=1SC(=C(N1)C1=NC2=C(N1)C=CC=C2)N2C[C@H](NCC2)C BASSHEDVDQHOJR-CYBMUJFWSA-N 0.000 description 1
- PDYJXRJPVAFTBE-SECBINFHSA-N 4-(1H-benzimidazol-2-yl)-2-bromo-5-[(3R)-3-methylpiperazin-1-yl]-1,3-thiazole Chemical compound BrC=1SC(=C(N1)C1=NC2=C(N1)C=CC=C2)N2C[C@H](NCC2)C PDYJXRJPVAFTBE-SECBINFHSA-N 0.000 description 1
- SSQDDGRYQCKJOB-LLVKDONJSA-N 4-(1H-benzimidazol-2-yl)-5-[(3R)-3-(methoxymethyl)piperazin-1-yl]-1,3-thiazole Chemical compound COC[C@H]1CN(CCN1)c1scnc1-c1nc2ccccc2[nH]1 SSQDDGRYQCKJOB-LLVKDONJSA-N 0.000 description 1
- GBRVWIOVCGRMAI-LLVKDONJSA-N 4-(1H-benzimidazol-2-yl)-5-[(3R)-3-ethylpiperazin-1-yl]-1,3-thiazole Chemical compound CC[C@@H]1CN(CCN1)c1scnc1-c1nc2ccccc2[nH]1 GBRVWIOVCGRMAI-LLVKDONJSA-N 0.000 description 1
- ANTOAJJYTZQZCK-SNVBAGLBSA-N 4-(1H-benzimidazol-2-yl)-5-[(3R)-3-methylpiperazin-1-yl]-1,3-thiazole Chemical compound C[C@@H]1CN(CCN1)c1scnc1-c1nc2ccccc2[nH]1 ANTOAJJYTZQZCK-SNVBAGLBSA-N 0.000 description 1
- DRMFZPAFARERQG-LLVKDONJSA-N 4-(1H-benzimidazol-2-yl)-5-[(3R)-3-methylpiperazin-1-yl]-2-(oxetan-3-yl)-1,3-thiazole Chemical compound C[C@@H]1CN(CCN1)C1=C(N=C(S1)C1COC1)C1=NC2=C(N1)C=CC=C2 DRMFZPAFARERQG-LLVKDONJSA-N 0.000 description 1
- WTTCFHFRVHRMDW-SECBINFHSA-N 4-(1H-benzimidazol-2-yl)-5-[(3R)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole Chemical compound C[C@@H]1CN(CCN1)c1sc(nc1-c1nc2ccccc2[nH]1)C(F)(F)F WTTCFHFRVHRMDW-SECBINFHSA-N 0.000 description 1
- ANTOAJJYTZQZCK-JTQLQIEISA-N 4-(1H-benzimidazol-2-yl)-5-[(3S)-3-methylpiperazin-1-yl]-1,3-thiazole Chemical compound C[C@H]1CN(CCN1)c1scnc1-c1nc2ccccc2[nH]1 ANTOAJJYTZQZCK-JTQLQIEISA-N 0.000 description 1
- HSCGHNWTTIDLKC-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-2-bromo-5-piperazin-1-yl-1,3-thiazole Chemical compound S1C(Br)=NC(C=2NC3=CC=CC=C3N=2)=C1N1CCNCC1 HSCGHNWTTIDLKC-UHFFFAOYSA-N 0.000 description 1
- XFJQGTSXELJXJE-RFVHGSKJSA-N 4-(1h-benzimidazol-2-yl)-2-cyclopropyl-5-[(3r)-3-methylpiperazin-1-yl]-1,3-thiazole;hydrochloride Chemical compound Cl.C1CN[C@H](C)CN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C2CC2)S1 XFJQGTSXELJXJE-RFVHGSKJSA-N 0.000 description 1
- FJCQIHIFDLJIQI-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-5-(1,4-diazepan-1-yl)-1,3-thiazole Chemical compound C1CCNCCN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 FJCQIHIFDLJIQI-UHFFFAOYSA-N 0.000 description 1
- SLUKHMCELQICKP-GFCCVEGCSA-N 4-(1h-benzimidazol-2-yl)-5-[(3r)-3-methylpiperazin-1-yl]-2-propan-2-yl-1,3-thiazole Chemical compound S1C(C(C)C)=NC(C=2NC3=CC=CC=C3N=2)=C1N1CCN[C@H](C)C1 SLUKHMCELQICKP-GFCCVEGCSA-N 0.000 description 1
- CJPQEXHMBKPTAX-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-5-piperazin-1-yl-1,3-thiazole Chemical compound C1CNCCN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 CJPQEXHMBKPTAX-UHFFFAOYSA-N 0.000 description 1
- VTBILGCQSDRUMZ-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-5-piperidin-4-yl-1,3-thiazole Chemical compound C1CNCCC1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 VTBILGCQSDRUMZ-UHFFFAOYSA-N 0.000 description 1
- MPTJDEWIZHQQHR-UHFFFAOYSA-N 4-(2-methoxyethoxy)-2-nitroaniline Chemical compound COCCOC1=CC=C(N)C([N+]([O-])=O)=C1 MPTJDEWIZHQQHR-UHFFFAOYSA-N 0.000 description 1
- QVPUFANJOMCUMA-UHFFFAOYSA-N 4-(2-methoxyethoxy)benzene-1,2-diamine Chemical compound COCCOC1=CC=C(N)C(N)=C1 QVPUFANJOMCUMA-UHFFFAOYSA-N 0.000 description 1
- SVUDHDDKOKWBNK-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C(N)=C1 SVUDHDDKOKWBNK-UHFFFAOYSA-N 0.000 description 1
- RTDKAEOVZXYWJW-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)benzene-1,2-diamine Chemical compound C1CN(C)CCN1C1=CC=C(N)C(N)=C1 RTDKAEOVZXYWJW-UHFFFAOYSA-N 0.000 description 1
- BICFHCWGMKRZKH-AOOOYVTPSA-N 4-(6-chloro-1H-benzimidazol-2-yl)-5-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-1,3-thiazole Chemical compound C[C@H]1CN(C[C@@H](C)N1)c1scnc1-c1nc2cc(Cl)ccc2[nH]1 BICFHCWGMKRZKH-AOOOYVTPSA-N 0.000 description 1
- WJXVXYSSQQRMMA-SECBINFHSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-5-[(3r)-3-methylpiperazin-1-yl]-1,3-thiazole Chemical compound C1CN[C@H](C)CN1C1=C(C=2NC3=CC(Cl)=CC=C3N=2)N=CS1 WJXVXYSSQQRMMA-SECBINFHSA-N 0.000 description 1
- JJVQDOCNXNUSDF-UHFFFAOYSA-N 4-(piperidin-1-ylmethyl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1CN1CCCCC1 JJVQDOCNXNUSDF-UHFFFAOYSA-N 0.000 description 1
- PIOKGAUSPFWRMD-UHFFFAOYSA-N 4-(trifluoromethoxy)benzene-1,2-diamine Chemical compound NC1=CC=C(OC(F)(F)F)C=C1N PIOKGAUSPFWRMD-UHFFFAOYSA-N 0.000 description 1
- SKLUWKYNZNXSLX-UHFFFAOYSA-N 4-Acetamidobenzaldehyde Chemical compound CC(=O)NC1=CC=C(C=O)C=C1 SKLUWKYNZNXSLX-UHFFFAOYSA-N 0.000 description 1
- NHHXZFOXLLXNNM-UHFFFAOYSA-N 4-[(3-methoxypyrrolidin-1-yl)methyl]-2-nitroaniline Chemical compound C1C(OC)CCN1CC1=CC=C(N)C([N+]([O-])=O)=C1 NHHXZFOXLLXNNM-UHFFFAOYSA-N 0.000 description 1
- KALMSTRVELSPDF-UHFFFAOYSA-N 4-[(3-methoxypyrrolidin-1-yl)methyl]benzene-1,2-diamine Chemical compound C1C(OC)CCN1CC1=CC=C(N)C(N)=C1 KALMSTRVELSPDF-UHFFFAOYSA-N 0.000 description 1
- ZVIOAVVHBYSARU-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-2-nitroaniline Chemical compound CN(C)CC1=CC=C(N)C([N+]([O-])=O)=C1 ZVIOAVVHBYSARU-UHFFFAOYSA-N 0.000 description 1
- OLMQVXWCNONAMB-UHFFFAOYSA-N 4-[(dimethylamino)methyl]benzene-1,2-diamine Chemical compound CN(C)CC1=CC=C(N)C(N)=C1 OLMQVXWCNONAMB-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- FLPSVRVLOVLWCQ-UHFFFAOYSA-N 4-bromo-1,3-thiazole-5-carbaldehyde Chemical compound BrC=1N=CSC=1C=O FLPSVRVLOVLWCQ-UHFFFAOYSA-N 0.000 description 1
- MBYVYKMAKZACJP-UHFFFAOYSA-N 4-cyclopropyl-2-nitroaniline Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1C1CC1 MBYVYKMAKZACJP-UHFFFAOYSA-N 0.000 description 1
- GPQQONRBFSTDGZ-UHFFFAOYSA-N 4-cyclopropylbenzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1CC1 GPQQONRBFSTDGZ-UHFFFAOYSA-N 0.000 description 1
- LUNOXNMCFPFPMO-UHFFFAOYSA-N 4-methoxy-1h-indole Chemical compound COC1=CC=CC2=C1C=CN2 LUNOXNMCFPFPMO-UHFFFAOYSA-N 0.000 description 1
- ZTOHIACMTGKKDU-UHFFFAOYSA-N 4-methyl-3h-1,3-benzoxazol-2-one Chemical compound CC1=CC=CC2=C1NC(=O)O2 ZTOHIACMTGKKDU-UHFFFAOYSA-N 0.000 description 1
- DGRGLKZMKWPMOH-UHFFFAOYSA-N 4-methylbenzene-1,2-diamine Chemical compound CC1=CC=C(N)C(N)=C1 DGRGLKZMKWPMOH-UHFFFAOYSA-N 0.000 description 1
- AEPYIICGYIUTCV-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,2,4-triamine Chemical compound CN(C)C1=CC=C(N)C(N)=C1 AEPYIICGYIUTCV-UHFFFAOYSA-N 0.000 description 1
- QRCGFTXRXYMJOS-UHFFFAOYSA-N 4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)COC2=C1 QRCGFTXRXYMJOS-UHFFFAOYSA-N 0.000 description 1
- ZBBBKRSADNLXAC-UHFFFAOYSA-N 5-(1h-benzimidazol-2-yl)-4-piperazin-1-yl-1,3-thiazole Chemical compound C1CNCCN1C1=C(C=2NC3=CC=CC=C3N=2)SC=N1 ZBBBKRSADNLXAC-UHFFFAOYSA-N 0.000 description 1
- NOQHPOIXPIVXCQ-SECBINFHSA-N 5-[(3r)-3-methyl-4-(2-pyrazol-1-ylacetyl)piperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H]1C)N(C2=C(N=C(S2)C(F)(F)F)C(O)=O)CCN1C(=O)CN1C=CC=N1 NOQHPOIXPIVXCQ-SECBINFHSA-N 0.000 description 1
- YZAMWRFRJRZDKO-SECBINFHSA-N 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C(O)=O)N=CS1 YZAMWRFRJRZDKO-SECBINFHSA-N 0.000 description 1
- NKWJMFPHIICFCG-SNVBAGLBSA-N 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-(oxetan-3-yl)-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C(O)=O)N=C(C2COC2)S1 NKWJMFPHIICFCG-SNVBAGLBSA-N 0.000 description 1
- WVWNFUZQKDYALN-LLVKDONJSA-N 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-propan-2-yl-1,3-thiazole-4-carboxylic acid Chemical compound S1C(C(C)C)=NC(C(O)=O)=C1N1C[C@@H](C)N(C(=O)OC(C)(C)C)CC1 WVWNFUZQKDYALN-LLVKDONJSA-N 0.000 description 1
- DLACEPDJQURKPO-SNVBAGLBSA-N 5-[(3r)-4-(2-imidazo[4,5-b]pyridin-3-ylacetyl)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylic acid Chemical compound C([C@H](N(CC1)C(=O)CN2C3=NC=CC=C3N=C2)C)N1C=1SC(C(F)(F)F)=NC=1C(O)=O DLACEPDJQURKPO-SNVBAGLBSA-N 0.000 description 1
- ZVITWZAOLJIGAT-UHFFFAOYSA-N 5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=C(C(O)=O)N=CS1 ZVITWZAOLJIGAT-UHFFFAOYSA-N 0.000 description 1
- LVNRQLWIDZAGAA-UHFFFAOYSA-N 5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C(O)=O)N=CS1 LVNRQLWIDZAGAA-UHFFFAOYSA-N 0.000 description 1
- BSUDRULOKDWNPE-UHFFFAOYSA-N 5-[4-[2-(3-methyl-2-oxobenzimidazol-1-yl)acetyl]piperazin-1-yl]-1,3-thiazole-4-carboxylic acid Chemical compound O=C1N(C)C2=CC=CC=C2N1CC(=O)N(CC1)CCN1C=1SC=NC=1C(O)=O BSUDRULOKDWNPE-UHFFFAOYSA-N 0.000 description 1
- WMPUDRHJBRXYRA-UHFFFAOYSA-N 5-bromo-2-(trifluoromethyl)-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C=1N=C(C(F)(F)F)SC=1Br WMPUDRHJBRXYRA-UHFFFAOYSA-N 0.000 description 1
- ZCWXYZBQDNFULS-UHFFFAOYSA-N 5-chloro-2-nitroaniline Chemical compound NC1=CC(Cl)=CC=C1[N+]([O-])=O ZCWXYZBQDNFULS-UHFFFAOYSA-N 0.000 description 1
- PZKFSRWSQOQYNR-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazole Chemical compound CC1=NC=NN1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- LNEHZEFKSUBWTA-UHFFFAOYSA-N 6-methoxy-1h-pyrrolo[2,3-b]pyridine Chemical compound COC1=CC=C2C=CNC2=N1 LNEHZEFKSUBWTA-UHFFFAOYSA-N 0.000 description 1
- HOHKYYCVFMEBGG-UHFFFAOYSA-N 7-chloro-1h-pyrrolo[2,3-c]pyridine Chemical compound ClC1=NC=CC2=C1NC=C2 HOHKYYCVFMEBGG-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 201000009586 Basophil Adenoma Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101710098272 C-X-C motif chemokine 11 Proteins 0.000 description 1
- 101710085500 C-X-C motif chemokine 9 Proteins 0.000 description 1
- CNFCXPRHFOXGGZ-GFCCVEGCSA-N COC(=O)C=1N=CSC1N1C[C@H](N(CC1)C(CN1C=NC=2C1=NC=CC2)=O)C Chemical compound COC(=O)C=1N=CSC1N1C[C@H](N(CC1)C(CN1C=NC=2C1=NC=CC2)=O)C CNFCXPRHFOXGGZ-GFCCVEGCSA-N 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 108010014231 Chemokine CXCL9 Proteins 0.000 description 1
- 102000016937 Chemokine CXCL9 Human genes 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 238000006050 Minisci radical substitution reaction Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028594 Myocardial fibrosis Diseases 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- DOIFOXRMYOGIEP-LLVKDONJSA-N N1=CN(C2=NC=CC=C21)CC(=O)N2[C@@H](CN(CC2)C2=C(N=CS2)C(=O)O)C Chemical compound N1=CN(C2=NC=CC=C21)CC(=O)N2[C@@H](CN(CC2)C2=C(N=CS2)C(=O)O)C DOIFOXRMYOGIEP-LLVKDONJSA-N 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 206010053395 Progressive multiple sclerosis Diseases 0.000 description 1
- 206010036832 Prolactinoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000000277 Splenic Neoplasms Diseases 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 1
- 229960004012 amifampridine Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- XYPPMCVXWVPJOY-UHFFFAOYSA-N benzyl 2-(2-oxo-3h-indol-1-yl)acetate Chemical compound O=C1CC2=CC=CC=C2N1CC(=O)OCC1=CC=CC=C1 XYPPMCVXWVPJOY-UHFFFAOYSA-N 0.000 description 1
- UJQRYUBIMPGJJM-UHFFFAOYSA-N benzyl 2-(3,3-dimethyl-2-oxoindol-1-yl)acetate Chemical compound C12=CC=CC=C2C(C)(C)C(=O)N1CC(=O)OCC1=CC=CC=C1 UJQRYUBIMPGJJM-UHFFFAOYSA-N 0.000 description 1
- SNPWPFFGJNJNPN-UHFFFAOYSA-N benzyl 2-[5-methyl-3-(methylaminomethyl)-1,2,4-triazol-1-yl]acetate Chemical compound N1=C(CNC)N=C(C)N1CC(=O)OCC1=CC=CC=C1 SNPWPFFGJNJNPN-UHFFFAOYSA-N 0.000 description 1
- KYPANHYTALROSM-UHFFFAOYSA-N benzyl 2-imidazo[4,5-b]pyridin-3-ylacetate Chemical compound C1=NC2=CC=CN=C2N1CC(=O)OCC1=CC=CC=C1 KYPANHYTALROSM-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229940047583 cetamide Drugs 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- BOBUBHOXRCYKLI-UHFFFAOYSA-N ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene Chemical compound [Fe+2].CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.C1=CC=CC=C1C1=C(C=2C=CC=CC=2)[C-](C=2C=CC=CC=2)C(C=2C=CC=CC=2)=C1C1=CC=CC=C1 BOBUBHOXRCYKLI-UHFFFAOYSA-N 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- ZXDDITJXZPTHFE-BQYQJAHWSA-N ethyl (e)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-enoate Chemical compound CCOC(=O)\C=C\B1OC(C)(C)C(C)(C)O1 ZXDDITJXZPTHFE-BQYQJAHWSA-N 0.000 description 1
- WFWCPJYCYMXPRA-UHFFFAOYSA-N ethyl 2-(2,3-dihydro-1,4-benzoxazin-4-yl)acetate Chemical compound C1=CC=C2N(CC(=O)OCC)CCOC2=C1 WFWCPJYCYMXPRA-UHFFFAOYSA-N 0.000 description 1
- SRNLYJMYWJNXNE-UHFFFAOYSA-N ethyl 2-(2-oxo-3,4-dihydroquinolin-1-yl)acetate Chemical compound C1=CC=C2N(CC(=O)OCC)C(=O)CCC2=C1 SRNLYJMYWJNXNE-UHFFFAOYSA-N 0.000 description 1
- ZCBQGBGXIARHHN-UHFFFAOYSA-N ethyl 2-(3,4-dihydro-2h-quinolin-1-yl)acetate Chemical compound C1=CC=C2N(CC(=O)OCC)CCCC2=C1 ZCBQGBGXIARHHN-UHFFFAOYSA-N 0.000 description 1
- PBUXBPCBEQVRST-UHFFFAOYSA-N ethyl 2-(3-bromo-1,2,4-triazol-1-yl)acetate Chemical compound CCOC(=O)CN1C=NC(Br)=N1 PBUXBPCBEQVRST-UHFFFAOYSA-N 0.000 description 1
- CFUNNLVEVPHXSV-UHFFFAOYSA-N ethyl 2-(4-oxo-2,3-dihydroquinolin-1-yl)acetate Chemical compound C1=CC=C2N(CC(=O)OCC)CCC(=O)C2=C1 CFUNNLVEVPHXSV-UHFFFAOYSA-N 0.000 description 1
- QAXPGSLPVBUFEW-UHFFFAOYSA-N ethyl 2-(7-fluoroindol-1-yl)acetate Chemical compound C1=CC(F)=C2N(CC(=O)OCC)C=CC2=C1 QAXPGSLPVBUFEW-UHFFFAOYSA-N 0.000 description 1
- WFUNYBAJYAWHLX-UHFFFAOYSA-N ethyl 2-(trifluoromethyl)-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(C(F)(F)F)=N1 WFUNYBAJYAWHLX-UHFFFAOYSA-N 0.000 description 1
- HZZRIIPYFPIKHR-UHFFFAOYSA-N ethyl 2-hydrazinylacetate;hydron;chloride Chemical compound Cl.CCOC(=O)CNN HZZRIIPYFPIKHR-UHFFFAOYSA-N 0.000 description 1
- CWBPDAREDFJTOB-UHFFFAOYSA-N ethyl 2-indazol-1-ylacetate Chemical compound C1=CC=C2N(CC(=O)OCC)N=CC2=C1 CWBPDAREDFJTOB-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- MKSYCFYYDLTUNQ-UHFFFAOYSA-N heptylbenzene Chemical compound [CH2]CCCCCCC1=CC=CC=C1 MKSYCFYYDLTUNQ-UHFFFAOYSA-N 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229950007593 homonicotinic acid Drugs 0.000 description 1
- 102000055771 human CXCR3 Human genes 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 208000031424 hyperprolactinemia Diseases 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 208000016332 liver symptom Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- HWOQCGSIDCQVRM-UHFFFAOYSA-N methyl 1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CN=C2NC(C(=O)OC)=CC2=C1 HWOQCGSIDCQVRM-UHFFFAOYSA-N 0.000 description 1
- MPCBOKFGJRMGQX-SECBINFHSA-N methyl 2-bromo-5-[(3R)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)c1nc(Br)sc1N1CCN([C@H](C)C1)C(=O)OC(C)(C)C MPCBOKFGJRMGQX-SECBINFHSA-N 0.000 description 1
- PUMLEZMGSXUDRR-UHFFFAOYSA-N methyl 2-bromo-5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(Br)SC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC PUMLEZMGSXUDRR-UHFFFAOYSA-N 0.000 description 1
- RWZDEAVQQGKNPV-UHFFFAOYSA-N methyl 2-chloro-5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=C(Cl)SC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC RWZDEAVQQGKNPV-UHFFFAOYSA-N 0.000 description 1
- SGRJXBJGQDUPSW-LLVKDONJSA-N methyl 2-cyclopropyl-5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2CC2)SC=1N1CCN(C(=O)OC(C)(C)C)[C@H](C)C1 SGRJXBJGQDUPSW-LLVKDONJSA-N 0.000 description 1
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
- UOBGEPCHQWPBHH-SNVBAGLBSA-N methyl 5-[(3R)-3-methyl-4-(2-pyrazol-1-ylacetyl)piperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)c1nc(sc1N1CCN([C@H](C)C1)C(=O)Cn1cccn1)C(F)(F)F UOBGEPCHQWPBHH-SNVBAGLBSA-N 0.000 description 1
- YVYKCOFALXGQIU-GFCCVEGCSA-N methyl 5-[(3R)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-propan-2-yl-1,3-thiazole-4-carboxylate Chemical compound COC(=O)c1nc(sc1N1CCN([C@H](C)C1)C(=O)OC(C)(C)C)C(C)C YVYKCOFALXGQIU-GFCCVEGCSA-N 0.000 description 1
- IDYUQGGOQWQHNK-LLVKDONJSA-N methyl 5-[(3R)-4-(2-imidazo[4,5-b]pyridin-3-ylacetyl)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)c1nc(sc1N1CCN([C@H](C)C1)C(=O)Cn1cnc2cccnc12)C(F)(F)F IDYUQGGOQWQHNK-LLVKDONJSA-N 0.000 description 1
- IWHDSMSAHFXIDR-CYBMUJFWSA-N methyl 5-[(3r)-3-methyl-4-(2-pyrrolo[2,3-b]pyridin-1-ylacetyl)piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(N2C[C@@H](C)N(CC2)C(=O)CN2C3=NC=CC=C3C=C2)=C1C(=O)OC IWHDSMSAHFXIDR-CYBMUJFWSA-N 0.000 description 1
- IDYMSLVIASPPGV-SNVBAGLBSA-N methyl 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(N2C[C@@H](C)N(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC IDYMSLVIASPPGV-SNVBAGLBSA-N 0.000 description 1
- XBNRAILVLKLDFF-LLVKDONJSA-N methyl 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-(oxetan-3-yl)-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C=1N=C(C2COC2)SC=1N1CCN(C(=O)OC(C)(C)C)[C@H](C)C1 XBNRAILVLKLDFF-LLVKDONJSA-N 0.000 description 1
- BKNPCORAOZIKTL-SECBINFHSA-N methyl 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C(F)(F)F)SC(N2C[C@@H](C)N(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC BKNPCORAOZIKTL-SECBINFHSA-N 0.000 description 1
- DEOPBPQOBIIBIH-GFCCVEGCSA-N methyl 5-[(3r)-3-methyl-4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-2-prop-1-en-2-yl-1,3-thiazole-4-carboxylate Chemical compound N1=C(C(C)=C)SC(N2C[C@@H](C)N(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC DEOPBPQOBIIBIH-GFCCVEGCSA-N 0.000 description 1
- XINYLZUKHJOLCF-SSDOTTSWSA-N methyl 5-[(3r)-3-methylpiperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(N2C[C@@H](C)NCC2)=C1C(=O)OC XINYLZUKHJOLCF-SSDOTTSWSA-N 0.000 description 1
- FJUDXSZPWULNDT-ZCFIWIBFSA-N methyl 5-[(3r)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazole-4-carboxylate Chemical compound N1=C(C(F)(F)F)SC(N2C[C@@H](C)NCC2)=C1C(=O)OC FJUDXSZPWULNDT-ZCFIWIBFSA-N 0.000 description 1
- IYQAXBLJUZCAAL-UHFFFAOYSA-N methyl 5-[1-[(2-methylpropan-2-yl)oxycarbonyl]-3,6-dihydro-2h-pyridin-4-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C=2CCN(CC=2)C(=O)OC(C)(C)C)=C1C(=O)OC IYQAXBLJUZCAAL-UHFFFAOYSA-N 0.000 description 1
- FOQRYRVIYJWEOJ-UHFFFAOYSA-N methyl 5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(C2CCN(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC FOQRYRVIYJWEOJ-UHFFFAOYSA-N 0.000 description 1
- CXSFWDFVSROIJH-UHFFFAOYSA-N methyl 5-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound N1=CSC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1C(=O)OC CXSFWDFVSROIJH-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- WECHHDJTILFYQT-UHFFFAOYSA-N n-(4-acetylphenyl)acetamide Chemical group CC(=O)NC1=CC=C(C(C)=O)C=C1 WECHHDJTILFYQT-UHFFFAOYSA-N 0.000 description 1
- WQTKNBPCJKRYPA-OAQYLSRUSA-N n-[(1r)-1-[3-(4-ethoxyphenyl)-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-n-(pyridin-3-ylmethyl)-2-[4-(trifluoromethoxy)phenyl]acetamide Chemical compound C1=CC(OCC)=CC=C1N1C(=O)C2=CC=CN=C2N=C1[C@@H](C)N(C(=O)CC=1C=CC(OC(F)(F)F)=CC=1)CC1=CC=CN=C1 WQTKNBPCJKRYPA-OAQYLSRUSA-N 0.000 description 1
- BCIINLWUHTURMF-UHFFFAOYSA-N n-[2-nitro-4-(piperidin-1-ylmethyl)phenyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NC(=O)C)=CC=C1CN1CCCCC1 BCIINLWUHTURMF-UHFFFAOYSA-N 0.000 description 1
- VPGSUKDVDCTGQU-UHFFFAOYSA-N n-[4-(piperidin-1-ylmethyl)phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CN1CCCCC1 VPGSUKDVDCTGQU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 150000004986 phenylenediamines Chemical group 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 208000020351 pituitary gland basophil adenoma Diseases 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000030153 prolactin-producing pituitary gland adenoma Diseases 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 201000002471 spleen cancer Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- PSDAEKDIOQXLLC-DTORHVGOSA-N tert-butyl (1r,5s)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate Chemical group C1N(C(=O)OC(C)(C)C)C[C@@]2([H])CC[C@]1([H])N2 PSDAEKDIOQXLLC-DTORHVGOSA-N 0.000 description 1
- YZUWUDFMARRGOM-MRXNPFEDSA-N tert-butyl (2R)-4-[4-(1H-benzimidazol-2-yl)-2-(2-fluorophenyl)-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(CCN1C(=O)OC(C)(C)C)c1sc(nc1-c1nc2ccccc2[nH]1)-c1ccccc1F YZUWUDFMARRGOM-MRXNPFEDSA-N 0.000 description 1
- PNEZXHFTVSMIAH-CQSZACIVSA-N tert-butyl (2R)-4-[4-(1H-benzimidazol-2-yl)-2-(oxetan-3-yl)-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(CCN1C(=O)OC(C)(C)C)c1sc(nc1-c1nc2ccccc2[nH]1)C1COC1 PNEZXHFTVSMIAH-CQSZACIVSA-N 0.000 description 1
- ODOJNXXZXCRBCC-SECBINFHSA-N tert-butyl (2r)-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound COC[C@H]1CNCCN1C(=O)OC(C)(C)C ODOJNXXZXCRBCC-SECBINFHSA-N 0.000 description 1
- CTCGRXDGXGUOTE-SECBINFHSA-N tert-butyl (2r)-2-ethylpiperazine-1-carboxylate Chemical compound CC[C@@H]1CNCCN1C(=O)OC(C)(C)C CTCGRXDGXGUOTE-SECBINFHSA-N 0.000 description 1
- BIGWKROPEKEJEZ-CYBMUJFWSA-N tert-butyl (2r)-4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 BIGWKROPEKEJEZ-CYBMUJFWSA-N 0.000 description 1
- GPDMCZUBSRXQTJ-GFCCVEGCSA-N tert-butyl (2r)-4-[4-(1h-benzimidazol-2-yl)-2-bromo-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(Br)S1 GPDMCZUBSRXQTJ-GFCCVEGCSA-N 0.000 description 1
- XTIOROICPVFIMH-CQSZACIVSA-N tert-butyl (2r)-4-[4-(1h-benzimidazol-2-yl)-2-cyclopropyl-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(C2CC2)S1 XTIOROICPVFIMH-CQSZACIVSA-N 0.000 description 1
- PDSTVLSOVMBJNR-OAHLLOKOSA-N tert-butyl (2r)-4-[4-(1h-benzimidazol-2-yl)-2-propan-2-yl-1,3-thiazol-5-yl]-2-methylpiperazine-1-carboxylate Chemical compound S1C(C(C)C)=NC(C=2NC3=CC=CC=C3N=2)=C1N1CCN(C(=O)OC(C)(C)C)[C@H](C)C1 PDSTVLSOVMBJNR-OAHLLOKOSA-N 0.000 description 1
- DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical group C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
- RBOGBIZGALIITO-DTORHVGOSA-N tert-butyl (2s,6r)-2,6-dimethylpiperazine-1-carboxylate Chemical compound C[C@H]1CNC[C@@H](C)N1C(=O)OC(C)(C)C RBOGBIZGALIITO-DTORHVGOSA-N 0.000 description 1
- WDPWEXWMQDRXAL-UHFFFAOYSA-N tert-butyl 1,4-diazepane-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCCNCC1 WDPWEXWMQDRXAL-UHFFFAOYSA-N 0.000 description 1
- SIURBZDHAXKALD-UHFFFAOYSA-N tert-butyl 2-(2-oxo-1h-imidazo[4,5-b]pyridin-3-yl)acetate Chemical compound C1=CC=C2NC(=O)N(CC(=O)OC(C)(C)C)C2=N1 SIURBZDHAXKALD-UHFFFAOYSA-N 0.000 description 1
- ORIGRCOIINNWCH-UHFFFAOYSA-N tert-butyl 2-(2-pyrazol-1-ylphenyl)acetate Chemical group CC(C)(C)OC(=O)CC1=CC=CC=C1N1N=CC=C1 ORIGRCOIINNWCH-UHFFFAOYSA-N 0.000 description 1
- AMGYOCAQQAKLAR-UHFFFAOYSA-N tert-butyl 2-(3,3-difluoro-2-oxoindol-1-yl)acetate Chemical compound C1=CC=C2N(CC(=O)OC(C)(C)C)C(=O)C(F)(F)C2=C1 AMGYOCAQQAKLAR-UHFFFAOYSA-N 0.000 description 1
- UAHIRYUGRNVXDS-UHFFFAOYSA-N tert-butyl 2-(4-methyl-2-oxo-1,3-benzoxazol-3-yl)acetate Chemical compound CC1=CC=CC2=C1N(CC(=O)OC(C)(C)C)C(=O)O2 UAHIRYUGRNVXDS-UHFFFAOYSA-N 0.000 description 1
- CKQOXJDLGANQGJ-UHFFFAOYSA-N tert-butyl 2-(6-chloropyrrolo[2,3-b]pyridin-1-yl)acetate Chemical compound CC(C)(C)OC(=O)Cn1ccc2ccc(Cl)nc12 CKQOXJDLGANQGJ-UHFFFAOYSA-N 0.000 description 1
- OJGROBZLDRKKFT-UHFFFAOYSA-N tert-butyl 2-(6-methylpyrrolo[2,3-b]pyridin-1-yl)acetate Chemical compound Cc1ccc2ccn(CC(=O)OC(C)(C)C)c2n1 OJGROBZLDRKKFT-UHFFFAOYSA-N 0.000 description 1
- VITNPTFZXVIXSJ-UHFFFAOYSA-N tert-butyl 2-(7-chloropyrrolo[2,3-c]pyridin-1-yl)acetate Chemical compound C1=NC(Cl)=C2N(CC(=O)OC(C)(C)C)C=CC2=C1 VITNPTFZXVIXSJ-UHFFFAOYSA-N 0.000 description 1
- XWPZVRFRXKGEHE-UHFFFAOYSA-N tert-butyl 2-[(3-aminopyridin-2-yl)amino]acetate Chemical compound CC(C)(C)OC(=O)CNC1=NC=CC=C1N XWPZVRFRXKGEHE-UHFFFAOYSA-N 0.000 description 1
- YJYJATIUIUXMHI-UHFFFAOYSA-N tert-butyl 2-[(3-nitropyridin-2-yl)amino]acetate Chemical compound CC(C)(C)OC(=O)CNC1=NC=CC=C1[N+]([O-])=O YJYJATIUIUXMHI-UHFFFAOYSA-N 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
- UVGFHRAETUSQAK-UHFFFAOYSA-N tert-butyl 2-pyrazolo[3,4-b]pyridin-1-ylacetate Chemical compound C1=CN=C2N(CC(=O)OC(C)(C)C)N=CC2=C1 UVGFHRAETUSQAK-UHFFFAOYSA-N 0.000 description 1
- VWYKHNUBUCHGMP-UHFFFAOYSA-N tert-butyl 2-pyrazolo[3,4-b]pyridin-2-ylacetate Chemical compound C1=CC=NC2=NN(CC(=O)OC(C)(C)C)C=C21 VWYKHNUBUCHGMP-UHFFFAOYSA-N 0.000 description 1
- ODVRZBKPMQDYKH-UHFFFAOYSA-N tert-butyl 3-(2-oxo-2-phenylmethoxyethyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1=2CN(C(=O)OC(C)(C)C)CCC=2N=CN1CC(=O)OCC1=CC=CC=C1 ODVRZBKPMQDYKH-UHFFFAOYSA-N 0.000 description 1
- BJEFDZGXBHRKJL-UHFFFAOYSA-N tert-butyl 4-(5-formyl-1,3-thiazol-4-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=O)SC=N1 BJEFDZGXBHRKJL-UHFFFAOYSA-N 0.000 description 1
- PLWCDWUJKUEWMR-UHFFFAOYSA-N tert-butyl 4-[4-(1h-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=CS1 PLWCDWUJKUEWMR-UHFFFAOYSA-N 0.000 description 1
- PCYXHVWEVQCKIU-UHFFFAOYSA-N tert-butyl 4-[4-(1h-benzimidazol-2-yl)-2-chloro-1,3-thiazol-5-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=2NC3=CC=CC=C3N=2)N=C(Cl)S1 PCYXHVWEVQCKIU-UHFFFAOYSA-N 0.000 description 1
- MWRBWPQBGGARAY-UHFFFAOYSA-M tert-butyl acetate;chlorozinc(1+) Chemical compound [Zn+]Cl.CC(C)(C)OC([CH2-])=O MWRBWPQBGGARAY-UHFFFAOYSA-M 0.000 description 1
- VQWBYKYBNLFIPX-UHFFFAOYSA-N tert-butyl n-(2-hydrazinyl-2-oxoethyl)-n-methylcarbamate Chemical compound NNC(=O)CN(C)C(=O)OC(C)(C)C VQWBYKYBNLFIPX-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
- 201000003120 testicular cancer Diseases 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 150000007979 thiazole derivatives Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Psychology (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IBPCT/IB2012/050489 | 2012-02-02 | ||
| IBPCT/IB2012/050489 | 2012-02-02 | ||
| PCT/IB2013/050870 WO2013114332A1 (en) | 2012-02-02 | 2013-02-01 | 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2015506957A JP2015506957A (ja) | 2015-03-05 |
| JP6073931B2 true JP6073931B2 (ja) | 2017-02-01 |
Family
ID=48014121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014555374A Expired - Fee Related JP6073931B2 (ja) | 2012-02-02 | 2013-02-01 | ４−（ベンゾイミダゾール−２−イル）−チアゾール化合物及び関連するアザ誘導体 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US9266876B2 (https=) |
| EP (1) | EP2809668B1 (https=) |
| JP (1) | JP6073931B2 (https=) |
| KR (1) | KR101800607B1 (https=) |
| CN (1) | CN104093715B (https=) |
| AU (1) | AU2013216354B2 (https=) |
| BR (1) | BR112014018714A8 (https=) |
| CA (1) | CA2861020C (https=) |
| CL (1) | CL2014002048A1 (https=) |
| EA (1) | EA027595B1 (https=) |
| ES (1) | ES2632237T3 (https=) |
| IL (1) | IL233872A (https=) |
| MX (1) | MX352181B (https=) |
| MY (1) | MY170524A (https=) |
| NZ (1) | NZ629795A (https=) |
| PH (1) | PH12014501540A1 (https=) |
| PL (1) | PL2809668T3 (https=) |
| SG (1) | SG11201404144PA (https=) |
| UA (1) | UA113638C2 (https=) |
| WO (1) | WO2013114332A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA030067B1 (ru) | 2013-07-22 | 2018-06-29 | Идорсиа Фармасьютиклз Лтд | Производные 1-(пиперазин-1-ил)-2-([1,2,4]триазол-1-ил)этанона |
| US10087151B2 (en) | 2014-01-09 | 2018-10-02 | The J. David Gladstone Institutes, A Testimentary Trust Established Under The Will Of J. David Gladstone | Substituted benzoxazine and related compounds |
| AR099789A1 (es) | 2014-03-24 | 2016-08-17 | Actelion Pharmaceuticals Ltd | Derivados de 8-(piperazin-1-il)-1,2,3,4-tetrahidro-isoquinolina |
| AR103399A1 (es) * | 2015-01-15 | 2017-05-10 | Actelion Pharmaceuticals Ltd | Derivados de (r)-2-metil-piperazina como moduladores del receptor cxcr3 |
| JP6337218B2 (ja) * | 2015-01-15 | 2018-06-06 | イドーシア ファーマシューティカルズ リミテッドＩｄｏｒｓｉａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｌｔｄ | Ｃｘｃｒ３受容体調節剤としてのヒドロキシアルキル−ピペラジン誘導体 |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| WO2018011265A1 (en) | 2016-07-13 | 2018-01-18 | Idorsia Pharmaceuticals Ltd | Hydroxyalkyl-piperazine derivatives as cxcr3 receptor modulators |
| FR3067028B1 (fr) | 2017-06-06 | 2019-07-12 | Adpuerivitam | Modulateurs de recepteurs nmda, compositions les comprenant et utilisation de ces composes dans le traitement de maladies impliquant le systeme nerveux central |
| AU2021324684A1 (en) * | 2020-08-11 | 2023-04-20 | Board Of Trustees Of Michigan State University | Proteasome enhancers and uses thereof |
| EP4228632A4 (en) * | 2020-10-16 | 2025-02-19 | Saint Louis University | Rev-erb agonists |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002059117A1 (en) | 2001-01-23 | 2002-08-01 | Eli Lilly And Company | Piperazine- and piperidine-derivatives as melanocortin receptor agonists |
| JP2004532838A (ja) | 2001-03-02 | 2004-10-28 | ブリストル−マイヤーズ スクイブ カンパニー | メラノコルチン受容体のモデュレーターとして有用な化合物及びそれを含む製薬組成物 |
| GB0229618D0 (en) * | 2002-12-19 | 2003-01-22 | Cancer Rec Tech Ltd | Pyrazole compounds |
| GB0315203D0 (en) | 2003-06-28 | 2003-08-06 | Celltech R&D Ltd | Chemical compounds |
| WO2005035534A1 (ja) | 2003-10-08 | 2005-04-21 | Ono Pharmaceutical Co., Ltd. | 複素ビシクロ環および複素トリシクロ環化合物およびその医薬 |
| US20050124625A1 (en) | 2003-10-21 | 2005-06-09 | Salvati Mark E. | Piperazine derivatives and their use as modulators of nuclear hormone receptor function |
| US20050119252A1 (en) | 2003-10-22 | 2005-06-02 | Neurocrine Biosciences, Inc. | Ligands of melanocortin receptors and compositions and methods related thereto |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| CA2546754A1 (en) | 2003-11-21 | 2005-06-09 | Array Biopharma Inc. | Akt protein kinase inhibitors |
| US20060276465A1 (en) | 2003-12-26 | 2006-12-07 | Eisai R&D Management Co., Ltd. | 1,2-di(cyclic) substituted benzene compounds |
| MY140489A (en) | 2003-12-26 | 2009-12-31 | Eisai R&D Man Co Ltd | 1,2-di (cyclic) substituted benzene compounds |
| CA2598456A1 (en) | 2005-02-16 | 2006-08-24 | Schering Corporation | Heterocyclic substituted piperazines with cxcr3 antagonist activity |
| BRPI0607946A2 (pt) | 2005-02-16 | 2009-10-20 | Schering Corp | piperazina-piperidinas substituìdas por pirazinila com atividade de antagonista cxcr3 |
| CN101146793A (zh) | 2005-02-16 | 2008-03-19 | 先灵公司 | 具有cxcr3拮抗剂活性的新的杂环取代了的吡啶或苯基化合物 |
| MX2007009949A (es) | 2005-02-16 | 2007-09-26 | Schering Corp | Pirazinil-piperazin-piperidinas sustituidas con heteroarilo con actividad antagonista de cxcr3. |
| EP1853583B1 (en) | 2005-02-16 | 2011-09-07 | Schering Corporation | Amine-linked pyridyl and phenyl substituted piperazine-piperidines with cxcr3 antagonist activity |
| CA2598489A1 (en) | 2005-02-16 | 2006-08-24 | Schering Corporation | Piperazine-piperidines with cxcr3 antagonist activity |
| AU2006214378A1 (en) | 2005-02-16 | 2006-08-24 | Pharmacopeia, Inc. | Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity |
| NZ561613A (en) * | 2005-02-18 | 2010-12-24 | Astrazeneca Ab | Antibacterial piperidine derivatives |
| WO2007002742A1 (en) | 2005-06-28 | 2007-01-04 | Pharmacopeia, Inc. | Substituted [1,4]-diazepanes as cxcr3 antagonists and their use in the treatment of inflammatory disorders |
| US7754724B2 (en) | 2005-06-30 | 2010-07-13 | Dow Agrosciences Llc | N-substituted piperazines |
| TW200738701A (en) | 2005-07-26 | 2007-10-16 | Du Pont | Fungicidal carboxamides |
| JP2009511582A (ja) | 2005-10-11 | 2009-03-19 | シェーリング コーポレイション | Ｃｘｃｒ３拮抗薬活性を有する置換複素環式化合物 |
| EP1957076A2 (en) * | 2005-11-29 | 2008-08-20 | Merck & Co., Inc. | Thiazole derivatives as cxcr3 receptor modulators |
| EP1962605A2 (en) * | 2005-12-12 | 2008-09-03 | Merck & Co., Inc. | 2-arylthiazole derivatives as cxcr3 receptor modulators |
| WO2007076318A2 (en) | 2005-12-21 | 2007-07-05 | Smithkline Beecham Corporation | Camphor-derived cxcr3 antagonists |
| EP1988900A2 (en) | 2006-02-23 | 2008-11-12 | Merck & Co., Inc. | Pyridine, pyrimidine and pyrazine derivatives as cxcr3 receptor modulators |
| CN101460482B (zh) | 2006-03-21 | 2013-03-27 | 默沙东公司 | 具有cxcr3拮抗剂活性的杂环取代的吡啶化合物 |
| FR2903405B1 (fr) | 2006-07-04 | 2011-09-09 | Pasteur Institut | Composes a effet potentialisateur de l'activite de l'ethionamide et leurs applications |
| MX2009000577A (es) | 2006-07-14 | 2009-03-09 | Schering Corp | Compuestos de piperazina sustituida heterociclica con actividad antagonista de cxcr3. |
| WO2008013622A2 (en) | 2006-07-27 | 2008-01-31 | E. I. Du Pont De Nemours And Company | Fungicidal azocyclic amides |
| CN101558066A (zh) * | 2006-08-17 | 2009-10-14 | 阿斯利康(瑞典)有限公司 | 具有抗菌活性的吡咯衍生物 |
| AR064609A1 (es) | 2006-12-22 | 2009-04-15 | Schering Corp | Piperazinas sustituidas, composiciones farmaceuticas que las comprenden y su uso en el tratamiento de enfermedades mediadas por el receptor de quimiocinas cxcr3. |
| EP2125893A2 (en) | 2007-01-23 | 2009-12-02 | Xencor, Inc. | Optimized cd40 antibodies and methods of using the same |
| JP5337711B2 (ja) | 2007-01-25 | 2013-11-06 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー | 殺菌性アミド |
| EP2185154A2 (en) | 2007-08-03 | 2010-05-19 | Schering Corporation | Method of treating cxcr3 mediated diseases using heterocyclic substituted piperazines |
| TWI428091B (zh) * | 2007-10-23 | 2014-03-01 | Du Pont | 殺真菌劑混合物 |
| WO2009079490A1 (en) | 2007-12-18 | 2009-06-25 | Schering Corporation | Process and intermediates for the synthesis of heterocyclic substituted piperazines with cxcr3 antagonist activity |
| CN101965347B (zh) * | 2008-01-09 | 2013-01-02 | 阵列生物制药公司 | 作为激酶抑制剂的吡唑并吡啶 |
| EP2238133A2 (en) | 2008-01-25 | 2010-10-13 | E. I. du Pont de Nemours and Company | Fungicidal amides |
| US8349870B2 (en) | 2008-01-25 | 2013-01-08 | E I Du Pont De Nemours And Company | Fungicidal hetercyclic compounds |
| 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 |
| BRPI0910837B1 (pt) | 2008-04-30 | 2017-03-07 | Bayer Cropscience Ag | ésteres e tioésteres tiazol-4-carboxílicos, seus usos, e método e composição para controlar fungos fitopatogênicos prejudiciais |
| JP5654467B2 (ja) * | 2008-09-11 | 2015-01-14 | ケモセントリックス，インコーポレイティド | ４−アミノ−３−（イミダゾリル）−ピラゾロ［３，４−ｄ］ピリミジン |
| EP2334669B1 (de) | 2008-10-01 | 2015-12-23 | Bayer Intellectual Property GmbH | Heterocyclyl substituierte thiazole als pflanzenschutzmittel |
| KR101052065B1 (ko) | 2008-10-15 | 2011-07-27 | 한국과학기술연구원 | 칼슘이온 채널 조절제로서 유효한 피라졸릴메틸아민-피페라진 유도체와 이의 제조방법 |
| AU2009322486A1 (en) | 2008-12-02 | 2010-06-10 | E. I. Du Pont De Nemours And Company | Fungicidal heterocyclic compounds |
| CN102292334A (zh) | 2008-12-11 | 2011-12-21 | 拜尔农作物科学股份公司 | 噻唑基肟醚和腙植物保护剂 |
| EP2424840B1 (en) * | 2009-04-27 | 2014-08-06 | Boehringer Ingelheim International GmbH | Cxcr3 receptor antagonists |
| US8362249B2 (en) | 2009-04-27 | 2013-01-29 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
| EP2272846A1 (de) | 2009-06-23 | 2011-01-12 | Bayer CropScience AG | Thiazolylpiperidin Derivate als Fungizide |
| EP2464643A1 (en) | 2009-08-12 | 2012-06-20 | Syngenta Participations AG | Microbiocidal heterocycles |
| UA107938C2 (en) | 2009-08-12 | 2015-03-10 | Syngenta Participations Ag | Heterocycles with microbicidal properties |
| WO2011051243A1 (en) | 2009-10-29 | 2011-05-05 | Bayer Cropscience Ag | Active compound combinations |
| KR20120101019A (ko) | 2009-10-30 | 2012-09-12 | 바이엘 크롭사이언스 아게 | 헤테로아릴피페리딘 및 -피페라진 유도체 |
| MX2012007200A (es) | 2009-12-21 | 2012-07-10 | Bayer Cropscience Ag | Bis(difluorometil)pirazoles como fungicidas. |
| US8952004B2 (en) | 2010-01-07 | 2015-02-10 | Boehringer Ingelheim International Gmbh | CXCR3 receptor antagonists |
| BR112012027762B1 (pt) | 2010-04-28 | 2018-06-05 | Bayer Intellectual Property Gmbh | Derivados de cetoheteroarilpiperidina e - piperazina como fungicidas |
| US8815775B2 (en) | 2010-05-18 | 2014-08-26 | Bayer Cropscience Ag | Bis(difluoromethyl)pyrazoles as fungicides |
| BR112012026708A2 (pt) | 2010-05-20 | 2015-09-22 | Du Pont | composto selecionado, composição fungicida e método para controlar doenças vegetais |
| EP2576539B1 (de) | 2010-05-27 | 2017-12-13 | Bayer CropScience AG | Pyridinylcarbonsäure derivate als fungizide |
| US20120122928A1 (en) | 2010-08-11 | 2012-05-17 | Bayer Cropscience Ag | Heteroarylpiperidine and -Piperazine Derivatives as Fungicides |
| US8759527B2 (en) | 2010-08-25 | 2014-06-24 | Bayer Cropscience Ag | Heteroarylpiperidine and -piperazine derivatives as fungicides |
| EP2632922B1 (de) | 2010-10-27 | 2019-02-27 | Bayer CropScience Aktiengesellschaft | Heteroarylpiperidin und -piperazinderivate als fungizide |
| BR112013012621A2 (pt) | 2010-11-25 | 2016-07-12 | Syngenta Participations Ag | heterociclos microbicidas |
| CN103384470A (zh) | 2010-12-17 | 2013-11-06 | 纳幕尔杜邦公司 | 杀真菌偶氮环酰胺 |
| WO2012104273A1 (de) | 2011-02-01 | 2012-08-09 | Bayer Cropscience Ag | Heteroarylpiperidin und -piperazinderivate als fungizide |
| BR112013020419A2 (pt) | 2011-02-10 | 2016-07-12 | Syngenta Participations Ag | microbicidas derivados de pirazol |
| BR112013020270A2 (pt) | 2011-02-10 | 2016-07-12 | Syngenta Participations Ag | derivados de pirazol microbicidas |
| CN102827073A (zh) | 2011-06-17 | 2012-12-19 | 安吉奥斯医药品有限公司 | 治疗活性组合物和它们的使用方法 |
| US10004232B2 (en) | 2011-09-15 | 2018-06-26 | Bayer Intellectual Property Gmbh | Piperidine pyrazoles as fungicides |
| US20140243371A1 (en) | 2011-10-18 | 2014-08-28 | Syngenta Participations Ag | Microbiocidal pyrazole derivatives |
| CN103889982A (zh) | 2011-10-18 | 2014-06-25 | 先正达参股股份有限公司 | 杀微生物的吡唑衍生物 |
| US8642774B2 (en) | 2011-12-08 | 2014-02-04 | Boehringer Ingelheim International Gmbh | Compounds |
| WO2013127808A1 (en) | 2012-03-02 | 2013-09-06 | Syngenta Participations Ag | Microbiocidal pyrazole derivatives |
| EP2820012A1 (en) | 2012-03-02 | 2015-01-07 | Syngenta Participations AG | Microbiocidal pyrazole derivatives |
| US10035790B2 (en) | 2012-10-19 | 2018-07-31 | Exelixis, Inc. | RORγ modulators |
| WO2014075874A1 (en) | 2012-11-13 | 2014-05-22 | Syngenta Participations Ag | Microbiocidal pyrazole derivatives |
| WO2014075873A1 (en) | 2012-11-13 | 2014-05-22 | Syngenta Participations Ag | Microbiocidal pyrazole derivatives |
-
2013
- 2013-02-01 US US14/376,307 patent/US9266876B2/en active Active
- 2013-02-01 NZ NZ629795A patent/NZ629795A/en not_active IP Right Cessation
- 2013-02-01 EP EP13712913.6A patent/EP2809668B1/en active Active
- 2013-02-01 MY MYPI2014702122A patent/MY170524A/en unknown
- 2013-02-01 AU AU2013216354A patent/AU2013216354B2/en not_active Ceased
- 2013-02-01 EA EA201400854A patent/EA027595B1/ru not_active IP Right Cessation
- 2013-02-01 BR BR112014018714A patent/BR112014018714A8/pt not_active IP Right Cessation
- 2013-02-01 UA UAA201409420A patent/UA113638C2/uk unknown
- 2013-02-01 ES ES13712913.6T patent/ES2632237T3/es active Active
- 2013-02-01 JP JP2014555374A patent/JP6073931B2/ja not_active Expired - Fee Related
- 2013-02-01 WO PCT/IB2013/050870 patent/WO2013114332A1/en not_active Ceased
- 2013-02-01 CN CN201380007926.7A patent/CN104093715B/zh not_active Expired - Fee Related
- 2013-02-01 SG SG11201404144PA patent/SG11201404144PA/en unknown
- 2013-02-01 MX MX2014009355A patent/MX352181B/es active IP Right Grant
- 2013-02-01 CA CA2861020A patent/CA2861020C/en active Active
- 2013-02-01 KR KR1020147024508A patent/KR101800607B1/ko not_active Expired - Fee Related
- 2013-02-01 PL PL13712913T patent/PL2809668T3/pl unknown
-
2014
- 2014-07-03 PH PH12014501540A patent/PH12014501540A1/en unknown
- 2014-07-30 IL IL233872A patent/IL233872A/en not_active IP Right Cessation
- 2014-07-31 CL CL2014002048A patent/CL2014002048A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013216354A1 (en) | 2014-09-25 |
| MY170524A (en) | 2019-08-09 |
| MX2014009355A (es) | 2014-09-01 |
| PL2809668T3 (pl) | 2018-02-28 |
| CA2861020A1 (en) | 2013-08-08 |
| PH12014501540B1 (en) | 2014-09-22 |
| US9266876B2 (en) | 2016-02-23 |
| UA113638C2 (xx) | 2017-02-27 |
| CN104093715B (zh) | 2017-04-26 |
| SG11201404144PA (en) | 2014-10-30 |
| KR20140120364A (ko) | 2014-10-13 |
| EP2809668A1 (en) | 2014-12-10 |
| BR112014018714A8 (pt) | 2017-12-26 |
| EA201400854A1 (ru) | 2015-04-30 |
| CA2861020C (en) | 2018-07-17 |
| ES2632237T3 (es) | 2017-09-12 |
| AU2013216354B2 (en) | 2017-08-31 |
| PH12014501540A1 (en) | 2014-09-22 |
| CL2014002048A1 (es) | 2014-11-14 |
| JP2015506957A (ja) | 2015-03-05 |
| EP2809668B1 (en) | 2017-04-12 |
| IL233872A (en) | 2017-05-29 |
| EA027595B1 (ru) | 2017-08-31 |
| MX352181B (es) | 2017-11-13 |
| CN104093715A (zh) | 2014-10-08 |
| KR101800607B1 (ko) | 2017-11-23 |
| WO2013114332A1 (en) | 2013-08-08 |
| NZ629795A (en) | 2016-06-24 |
| BR112014018714A2 (https=) | 2017-06-20 |
| US20140371204A1 (en) | 2014-12-18 |
| HK1203939A1 (en) | 2015-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6073931B2 (ja) | ４−（ベンゾイミダゾール−２−イル）−チアゾール化合物及び関連するアザ誘導体 | |
| JP7265554B2 (ja) | 置換インドール化合物 | |
| TWI471326B (zh) | 作為ｃＦＭＳ抑制劑之經取代之Ｎ－（１Ｈ－吲唑－４－基）咪唑［１，２－ａ］吡啶－３－羧醯胺化合物 | |
| CN104349777B (zh) | 用于治疗脊髓性肌萎缩的化合物 | |
| AU2021232727A1 (en) | Nuclear receptor modulators | |
| JP6424234B2 (ja) | ８−（ピペラジン−１−イル）−１，２，３，４−テトラヒドロ−イソキノリン誘導体 | |
| HUE025416T2 (en) | Substituted n- (1H-indazol-4-yl) imidazo [1,2-a] pyridine-3-carboxamide compounds as Type III receptor tyrosine kinase inhibitors | |
| CA3038280A1 (en) | Heteroaryl derivatives as sepiapterin reductase inhibitors | |
| WO2011072694A1 (en) | Heteroaromatic phenylimidazole derivatives as pde10a enzyme inhibitors | |
| AU2013269800A1 (en) | Triazolo compounds as PDE10 inhibitors | |
| CN117836297A (zh) | (s)-1-(5-((吡啶-3-基)硫代)吡嗪-2-基)-4'h,6'h-螺[哌啶-4,5'-吡咯并[1,2-b]吡唑]-4'-胺衍生物和类似化合物作为shp2抑制剂用于例如癌症的治疗 | |
| CA3194376A1 (en) | Hsd17b13 inhibitors and uses thereof | |
| CA3117510A1 (en) | 5-azaindazole derivatives as adenosine receptor antagonists | |
| CA3182500A1 (en) | Competitive and noncompetitive inhibitors of the muscarinic acetylcholine receptor m5 | |
| CA3236550A1 (en) | Spirotricycle ripk1 inhibitors and methods of uses thereof | |
| HK1203939B (en) | 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives | |
| WO2024121013A1 (en) | Sulfonyl derivatives as ccr6 inhibitors | |
| HK40121516A (zh) | 作为ccr6抑制剂的磺酰基衍生物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160126 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160721 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160810 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161109 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161214 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170105 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6073931 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |