KR20160101191A - 헤테로아릴 치환된 니코틴아미드 화합물 - Google Patents
헤테로아릴 치환된 니코틴아미드 화합물 Download PDFInfo
- Publication number
- KR20160101191A KR20160101191A KR1020167020884A KR20167020884A KR20160101191A KR 20160101191 A KR20160101191 A KR 20160101191A KR 1020167020884 A KR1020167020884 A KR 1020167020884A KR 20167020884 A KR20167020884 A KR 20167020884A KR 20160101191 A KR20160101191 A KR 20160101191A
- Authority
- KR
- South Korea
- Prior art keywords
- nicotinamide
- pyridin
- cyano
- fluoro
- amino
- 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.)
- Withdrawn
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- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 19
- 150000005480 nicotinamides Chemical class 0.000 title description 4
- -1 pyrrolo [2,3- b] pyridinyl Chemical group 0.000 claims abstract description 1466
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 238000000034 method Methods 0.000 claims abstract description 72
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 10
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 6
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 5
- 125000005899 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl group Chemical group 0.000 claims abstract description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 956
- 235000005152 nicotinamide Nutrition 0.000 claims description 339
- 239000011570 nicotinamide Substances 0.000 claims description 339
- 229960003966 nicotinamide Drugs 0.000 claims description 339
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 159
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 125000001424 substituent group Chemical group 0.000 claims description 67
- 125000005466 alkylenyl group Chemical group 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 57
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 55
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 55
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 50
- 125000003566 oxetanyl group Chemical group 0.000 claims description 46
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 41
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000002757 morpholinyl group Chemical group 0.000 claims description 34
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 33
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 32
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 30
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 125000003386 piperidinyl group Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 22
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 238000003786 synthesis reaction Methods 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 16
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- NIZFPIBTGJOVRT-UHFFFAOYSA-N bicyclo[2.2.1]heptan-4-ol Chemical compound C1CC2CCC1(O)C2 NIZFPIBTGJOVRT-UHFFFAOYSA-N 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 201000005569 Gout Diseases 0.000 claims description 12
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- IAOJIIKIDOOUEZ-UHFFFAOYSA-N 4-pyridin-2-ylpyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC=C1C1=CC=CC=N1 IAOJIIKIDOOUEZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 150000001408 amides Chemical class 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 claims description 9
- 125000002393 azetidinyl group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- IGVGARQHWLUJIO-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazol-2-amine Chemical compound C1C=CC=C2SC(N)NC21 IGVGARQHWLUJIO-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229960002428 fentanyl Drugs 0.000 claims description 7
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 206010016207 Familial Mediterranean fever Diseases 0.000 claims description 6
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000006390 chloropyrimidinyl group Chemical group 0.000 claims description 5
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 5
- WTVNFKVGGUWHQC-UHFFFAOYSA-N decane-2,4-dione Chemical compound CCCCCCC(=O)CC(C)=O WTVNFKVGGUWHQC-UHFFFAOYSA-N 0.000 claims description 5
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 4
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
- PPUNQQJLOODTRJ-UHFFFAOYSA-N C1=C2C=C(NC2=NC=C1C#N)C(=O)N Chemical compound C1=C2C=C(NC2=NC=C1C#N)C(=O)N PPUNQQJLOODTRJ-UHFFFAOYSA-N 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 208000024908 graft versus host disease Diseases 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 230000000737 periodic effect Effects 0.000 claims description 4
- 230000009885 systemic effect Effects 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
- COJGFPSLXSNWJN-UHFFFAOYSA-N 3-(2-methyl-1H-imidazol-5-yl)pyridazine Chemical compound N1=NC(=CC=C1)C=1N=C(NC=1)C COJGFPSLXSNWJN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 208000023328 Basedow disease Diseases 0.000 claims description 3
- 208000015023 Graves' disease Diseases 0.000 claims description 3
- 239000012230 colorless oil Substances 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- RUDFQVOCFDJEEF-UHFFFAOYSA-N yttrium(III) oxide Inorganic materials [O-2].[O-2].[O-2].[Y+3].[Y+3] RUDFQVOCFDJEEF-UHFFFAOYSA-N 0.000 claims description 3
- 125000006712 (C1-C4) deuteroalkyl group Chemical group 0.000 claims description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- XXUIPEKKTLXQSF-UHFFFAOYSA-N C(C1=CN=CC=C1)(=O)NNC1CC1 Chemical compound C(C1=CN=CC=C1)(=O)NNC1CC1 XXUIPEKKTLXQSF-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Chemical compound CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims 11
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 6
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 claims 4
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 claims 3
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- NKWQECORFHBKHI-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-(2-methylpropyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C)C)C(=C2)NC=2C=NN(C2)CC(F)F NKWQECORFHBKHI-UHFFFAOYSA-N 0.000 claims 2
- DXXMEKWNVCWOGJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-propan-2-ylpyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC(C)C)C(=C2)NC=2C=NN(C2)CC(F)F DXXMEKWNVCWOGJ-UHFFFAOYSA-N 0.000 claims 2
- QIDDWZFSQVWYFM-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-propylpyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC)C(=C2)NC=2C=NN(C2)CC(F)F QIDDWZFSQVWYFM-UHFFFAOYSA-N 0.000 claims 2
- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims 2
- RSMVYWKSWPOYEL-UHFFFAOYSA-N N-(2-fluoro-3-hydroxy-3-methylbutyl)pyridine-3-carboxamide Chemical compound FC(CNC(C1=CN=CC=C1)=O)C(C)(C)O RSMVYWKSWPOYEL-UHFFFAOYSA-N 0.000 claims 2
- NDMKEYPCCUCEMZ-QGZVFWFLSA-N [(3R)-4-[[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carbonyl]amino]-3-fluoro-2-methylbutan-2-yl] dihydrogen phosphate Chemical compound P(=O)(OC(C)([C@@H](CNC(C1=CN=C(C=C1NC(C)C)N1N=CC=2C1=NC=C(C2)C#N)=O)F)C)(O)O NDMKEYPCCUCEMZ-QGZVFWFLSA-N 0.000 claims 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- NQWAXHYGRQCESA-UHFFFAOYSA-N 4-pyrimidin-2-ylpyridine-3-carboxamide Chemical compound N1=C(N=CC=C1)C1=CC=NC=C1C(=O)N NQWAXHYGRQCESA-UHFFFAOYSA-N 0.000 claims 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- NZKFSOJCIGTZNS-AWEZNQCLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2S)-1-hydroxypropan-2-yl]amino]-N-(3-methylbutyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)N[C@H](CO)C NZKFSOJCIGTZNS-AWEZNQCLSA-N 0.000 claims 1
- TZAGTUBYAYQIAL-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-propylpyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC)C(=C2)NC(C)C)C#N TZAGTUBYAYQIAL-UHFFFAOYSA-N 0.000 claims 1
- PQVIAUWKCYWRRR-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-methyl-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC)C(=C2)NC(C)C)C#N PQVIAUWKCYWRRR-UHFFFAOYSA-N 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- MMRJMWNCHTVOAH-UHFFFAOYSA-N n-(6-morpholin-4-ylpyridin-3-yl)pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C=N1)=CC=C1N1CCOCC1 MMRJMWNCHTVOAH-UHFFFAOYSA-N 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims 1
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- 239000000243 solution Substances 0.000 description 73
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- 239000012071 phase Substances 0.000 description 30
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| US9546153B2 (en) | 2012-11-08 | 2017-01-17 | Bristol-Myers Squibb Company | Bicyclic heterocycle substituted pyridyl compounds useful as kinase modulators |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CA2935392C (en) | 2014-01-01 | 2022-07-26 | Medivation Technologies, Inc. | Amino pyridine derivatives for the treatment of conditions associated with excessive tgf.beta activity |
| US20180228907A1 (en) | 2014-04-14 | 2018-08-16 | Arvinas, Inc. | Cereblon ligands and bifunctional compounds comprising the same |
| CN109641906B (zh) * | 2015-06-24 | 2021-10-01 | 百时美施贵宝公司 | 杂芳基取代的氨基吡啶化合物 |
| CN107849039B (zh) | 2015-06-24 | 2020-07-03 | 百时美施贵宝公司 | 经杂芳基取代的氨基吡啶化合物 |
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| WO2023008973A1 (ko) * | 2021-07-29 | 2023-02-02 | 프라비바이오 주식회사 | 신규 벤젠 유도체 및 이의 면역억제 관련 용도 |
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| TW201609693A (zh) | 2016-03-16 |
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| WO2015103453A1 (en) | 2015-07-09 |
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| TN2016000271A1 (en) | 2017-10-06 |
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| ES2804707T3 (es) | 2021-02-09 |
| MX2016008723A (es) | 2016-09-07 |
| UY35935A (es) | 2015-06-30 |
| CN106061967A (zh) | 2016-10-26 |
| US9169252B2 (en) | 2015-10-27 |
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