TW201609693A - 雜芳基取代之菸鹼醯胺化合物 - Google Patents
雜芳基取代之菸鹼醯胺化合物 Download PDFInfo
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- TW201609693A TW201609693A TW103146137A TW103146137A TW201609693A TW 201609693 A TW201609693 A TW 201609693A TW 103146137 A TW103146137 A TW 103146137A TW 103146137 A TW103146137 A TW 103146137A TW 201609693 A TW201609693 A TW 201609693A
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- pyridin
- cyano
- fluoro
- hydroxy
- methylbutyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 235
- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 24
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 126
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- 125000001424 substituent group Chemical group 0.000 claims description 95
- 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 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 61
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 20
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- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 9
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- NERNEXMEYQFFHU-UHFFFAOYSA-N 1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound N1C(=O)NC(=O)C11CCCCC1 NERNEXMEYQFFHU-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
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- 239000003937 drug carrier Substances 0.000 claims description 8
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
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- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
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- 208000024908 graft versus host disease Diseases 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
- 235000001968 nicotinic acid Nutrition 0.000 claims description 6
- 239000011664 nicotinic acid Substances 0.000 claims description 6
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- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
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- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims description 4
- XEAQYABSXJFYIW-SJKOYZFVSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-1-fluoropropan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](CF)C XEAQYABSXJFYIW-SJKOYZFVSA-N 0.000 claims description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
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- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
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- WMMDEXMMBNBYRX-JOCHJYFZSA-N 4-(1,3-benzothiazol-6-ylamino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound S1C=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(=O)NC[C@H](C(C)(C)O)F)N2C=CC=1C2=NC=C(C1)C#N WMMDEXMMBNBYRX-JOCHJYFZSA-N 0.000 claims description 3
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 3
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- 230000009885 systemic effect Effects 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
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- 102100022691 NACHT, LRR and PYD domains-containing protein 3 Human genes 0.000 claims description 2
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- 125000003943 azolyl group Chemical group 0.000 claims description 2
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- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
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- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
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- DYBZYXWEMQGBKG-LEHRNKBSSA-N 4-[(3-fluorocyclopentyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)F DYBZYXWEMQGBKG-LEHRNKBSSA-N 0.000 claims 5
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
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- HKPXSYBCTAEBBC-NZAQZCIASA-N 4-(2-bicyclo[1.1.1]pentanylamino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound CC(C)(O)[C@H](F)CNC(=O)c1cnc(cc1NC1C2CC1C2)-n1ncc2cc(cnc12)C#N HKPXSYBCTAEBBC-NZAQZCIASA-N 0.000 claims 2
- KEMUCYRFZZIBDV-GOSISDBHSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCOCC2 KEMUCYRFZZIBDV-GOSISDBHSA-N 0.000 claims 2
- IOIZZRPAGUPGLO-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propan-2-ylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C(C)C IOIZZRPAGUPGLO-LJQANCHMSA-N 0.000 claims 2
- OKPCCXXZYTXSOP-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC OKPCCXXZYTXSOP-LJQANCHMSA-N 0.000 claims 2
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- HXYJSCGJGOVVRR-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCOC HXYJSCGJGOVVRR-LJQANCHMSA-N 0.000 claims 2
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- QAELJMIRDBOASW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(1-pyrimidin-2-ylpiperidin-4-yl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)C1=NC=CC=N1)C(=C2)NC(C)C QAELJMIRDBOASW-UHFFFAOYSA-N 0.000 claims 2
- KLBPPKOIYGZGRH-QLYHWAPBSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2S)-3-fluorobutan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C(C)F KLBPPKOIYGZGRH-QLYHWAPBSA-N 0.000 claims 2
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- IXKTUGRQUSWDQK-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(5-hydroxypyridin-2-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)O)C(=C2)NC(C)C IXKTUGRQUSWDQK-UHFFFAOYSA-N 0.000 claims 2
- TXXZJTQDYJOAQS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(5-morpholin-4-ylpyridin-2-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)N1CCOCC1)C(=C2)NC(C)C TXXZJTQDYJOAQS-UHFFFAOYSA-N 0.000 claims 2
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- OEYYOVDYZPNDOJ-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylsulfonylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)S(=O)(=O)C OEYYOVDYZPNDOJ-GOSISDBHSA-N 0.000 claims 2
- PKOSDQDNBPVSMM-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC PKOSDQDNBPVSMM-HXUWFJFHSA-N 0.000 claims 2
- OHOHYAKWIVIRIT-OAQYLSRUSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methyl-2-morpholin-4-ylpropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(N2CCOCC2)C OHOHYAKWIVIRIT-OAQYLSRUSA-N 0.000 claims 2
- YOLPFNYXENQSIE-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methylpyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=NN2C YOLPFNYXENQSIE-QGZVFWFLSA-N 0.000 claims 2
- SBXZUIJSOTWVRQ-NNMXDRDESA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(1R,3S)-3-(2-hydroxypropan-2-yl)cyclohexyl]amino]pyridine-3-carboxamide Chemical compound CC(C)(O)[C@H](F)CNC(=O)C1=CN=C(C=C1N[C@@H]1CCC[C@@H](C1)C(C)(C)O)N1N=CC2=C1N=CC(=C2)C#N SBXZUIJSOTWVRQ-NNMXDRDESA-N 0.000 claims 2
- CXGAKWXRURKONL-BBTUJRGHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2C[C@H](CC2)C(C)(C)O CXGAKWXRURKONL-BBTUJRGHSA-N 0.000 claims 2
- SAHXDFOXUDBXMX-RTBURBONSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-1-hydroxy-3-methylbutan-2-yl]amino]pyridine-3-carboxamide Chemical compound CC(C)[C@@H](CO)NC1=CC(=NC=C1C(=O)NC[C@@H](F)C(C)(C)O)N1N=CC2=C1N=CC(=C2)C#N SAHXDFOXUDBXMX-RTBURBONSA-N 0.000 claims 2
- JNICTEJYEKCSES-YVEFUNNKSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@H](C)F JNICTEJYEKCSES-YVEFUNNKSA-N 0.000 claims 2
- SCXQOHWTUJZMSL-WIYYLYMNSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-(5-fluoropyrimidin-2-yl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C2=NC=C(C=N2)F SCXQOHWTUJZMSL-WIYYLYMNSA-N 0.000 claims 2
- SCXQOHWTUJZMSL-GHTZIAJQSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3S)-1-(5-fluoropyrimidin-2-yl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2CN(CC2)C2=NC=C(C=N2)F SCXQOHWTUJZMSL-GHTZIAJQSA-N 0.000 claims 2
- UFEBJAKKJGACRF-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=NN(C=C2)CC(F)(F)F UFEBJAKKJGACRF-QGZVFWFLSA-N 0.000 claims 2
- YECGATBLNAMDRC-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[5-(2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2SC(=CN2)C(C)(C)O YECGATBLNAMDRC-QGZVFWFLSA-N 0.000 claims 2
- QSHWJGNNVHJYTH-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(2,2-difluoroethyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NN(C1)CC(F)F)C(=C2)NC(C)C QSHWJGNNVHJYTH-UHFFFAOYSA-N 0.000 claims 2
- KXYJRBVMSMHIMD-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(4,4-difluoro-1-hydroxycyclohexyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCC(CC1)(F)F)O)C(=C2)NC(C)C KXYJRBVMSMHIMD-UHFFFAOYSA-N 0.000 claims 2
- AHDQFUWGEYVKDP-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-fluoro-2-(3-hydroxyoxetan-3-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C1(COC1)O)F)C(=C2)NC(C)C AHDQFUWGEYVKDP-UHFFFAOYSA-N 0.000 claims 2
- MADHTMRSFJHJCD-VBKZILBWSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[[(1S)-1-cyclopropylethyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C2CC2 MADHTMRSFJHJCD-VBKZILBWSA-N 0.000 claims 2
- OKPRVZGPGATUGD-XODGURCBSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[[(2S)-3-fluorobutan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C(C)F OKPRVZGPGATUGD-XODGURCBSA-N 0.000 claims 2
- FJWNQWAVGFXJGZ-QGZVFWFLSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3,3,3-trifluoropropylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(F)(F)F FJWNQWAVGFXJGZ-QGZVFWFLSA-N 0.000 claims 2
- RCVGDDARVNZGSF-UUSAFJCLSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COCCC2 RCVGDDARVNZGSF-UUSAFJCLSA-N 0.000 claims 2
- PUZVBNZCFGDFPA-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2CCOCC2 PUZVBNZCFGDFPA-OAQYLSRUSA-N 0.000 claims 2
- MJSBQSATVRAEQB-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound CN1C=C(NC2=CC(=NC=C2C(=O)NC[C@@H](F)C(C)(C)O)N2C=CC3=C2N=CC(=C3)C#N)C=N1 MJSBQSATVRAEQB-LJQANCHMSA-N 0.000 claims 2
- JFORGMDXGMQSIF-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylsulfonylazetidin-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CN(C2)S(=O)(=O)C JFORGMDXGMQSIF-LJQANCHMSA-N 0.000 claims 2
- DITGVNQHNKVFFH-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylsulfonylpiperidin-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCN(CC2)S(=O)(=O)C DITGVNQHNKVFFH-OAQYLSRUSA-N 0.000 claims 2
- JXDGDMWIHFLTKG-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-methyloxetan-3-yl)methylamino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2(COC2)C JXDGDMWIHFLTKG-LJQANCHMSA-N 0.000 claims 2
- CYZWJXNIOTTZDS-FZKQIMNGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@@H](C)F CYZWJXNIOTTZDS-FZKQIMNGSA-N 0.000 claims 2
- CXTYGPJXWDUYRJ-SCLBCKFNSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-1-fluoropropan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](CF)C CXTYGPJXWDUYRJ-SCLBCKFNSA-N 0.000 claims 2
- NMHRLANGFQMVRW-YLJYHZDGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-methylsulfonylpyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)S(=O)(=O)C NMHRLANGFQMVRW-YLJYHZDGSA-N 0.000 claims 2
- UANKSFSMEGRREW-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(E)-3-hydroxy-3-methylbut-1-enyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=CC(C)(C)O UANKSFSMEGRREW-LJQANCHMSA-N 0.000 claims 2
- JRTPJNWNXSONLY-HSZRJFAPSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(oxan-4-yl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound CC(C)(O)[C@H](F)CNC(=O)C1=CN=C(C=C1NC1=CN(N=C1)C1CCOCC1)N1C=CC2=C1N=CC(=C2)C#N JRTPJNWNXSONLY-HSZRJFAPSA-N 0.000 claims 2
- NECVWZJWYPWQKL-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCC(=O)N1CCN(CC1)C)C(=C2)NC(C)C NECVWZJWYPWQKL-UHFFFAOYSA-N 0.000 claims 2
- DVUSWHVFVDTUEL-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(methanesulfonamido)ethyl]-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCNS(=O)(=O)C)C(=C2)NC2CCOCC2 DVUSWHVFVDTUEL-UHFFFAOYSA-N 0.000 claims 2
- XPZSXTHHZAXAFE-BDJLRTHQSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@@H](C)F)C#N XPZSXTHHZAXAFE-BDJLRTHQSA-N 0.000 claims 2
- KSECOOSTCYCUCK-QGZVFWFLSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2,3-difluoro-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC=2C=NN(C2)CC(F)F KSECOOSTCYCUCK-QGZVFWFLSA-N 0.000 claims 2
- YBQYWOIIJLUPKC-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCOC YBQYWOIIJLUPKC-LJQANCHMSA-N 0.000 claims 2
- QOVDTNCZEBZDDM-GOSISDBHSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[2-[(2-hydroxy-2-methylpropyl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1C=CC2=C1N=C(N=C2)NCC(C)(C)O)=O)C(C)(C)O QOVDTNCZEBZDDM-GOSISDBHSA-N 0.000 claims 2
- BSPUVYFGURDFHE-UHFFFAOYSA-N Nitramine Natural products CC1C(O)CCC2CCCNC12 BSPUVYFGURDFHE-UHFFFAOYSA-N 0.000 claims 2
- POCJOGNVFHPZNS-UHFFFAOYSA-N isonitramine Natural products OC1CCCCC11CNCCC1 POCJOGNVFHPZNS-UHFFFAOYSA-N 0.000 claims 2
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 claims 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- VDOMELXAOCEDDZ-CRAIPNDOSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-oxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2COCC2 VDOMELXAOCEDDZ-CRAIPNDOSA-N 0.000 claims 1
- KLMIIJJVCQXXEX-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[3-(methanesulfonamido)butyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)NS(=O)(=O)C)C(=C2)NC(C)C KLMIIJJVCQXXEX-UHFFFAOYSA-N 0.000 claims 1
- HWJXGCYEYGOGCE-DENIHFKCSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-(5-fluoropyrimidin-2-yl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C2=NC=C(C=N2)F HWJXGCYEYGOGCE-DENIHFKCSA-N 0.000 claims 1
- RUTUXFGXSFRWFD-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)(F)F RUTUXFGXSFRWFD-LJQANCHMSA-N 0.000 claims 1
- VQXUMABIUJJDCW-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2-cyanoethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC#N VQXUMABIUJJDCW-LJQANCHMSA-N 0.000 claims 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
- MJUJXFBTEFXVKU-UHFFFAOYSA-N diethyl phosphonate Chemical compound CCOP(=O)OCC MJUJXFBTEFXVKU-UHFFFAOYSA-N 0.000 claims 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
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- C07F9/02—Phosphorus compounds
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- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
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| 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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| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
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| EP3737675A4 (en) | 2018-01-12 | 2022-01-05 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
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| US11292792B2 (en) | 2018-07-06 | 2022-04-05 | Kymera Therapeutics, Inc. | Tricyclic CRBN ligands and uses thereof |
| WO2020010227A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| TWI842978B (zh) * | 2018-07-13 | 2024-05-21 | 美商基利科學股份有限公司 | 衍生物 |
| TWI727392B (zh) * | 2018-08-13 | 2021-05-11 | 美商基利科學股份有限公司 | 噻二唑irak4抑制劑 |
| KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
| US11352350B2 (en) | 2018-11-30 | 2022-06-07 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| CN114174279B (zh) * | 2019-08-06 | 2024-07-02 | 百时美施贵宝公司 | 可用作irak4抑制剂的双环杂环化合物 |
| WO2021127283A2 (en) | 2019-12-17 | 2021-06-24 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| EP4076520A4 (en) | 2019-12-17 | 2024-03-27 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| US12421230B2 (en) | 2020-02-03 | 2025-09-23 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as IRAK4 inhibitors |
| TW202210483A (zh) | 2020-06-03 | 2022-03-16 | 美商凱麥拉醫療公司 | Irak降解劑之結晶型 |
| TW202241891A (zh) | 2020-12-30 | 2022-11-01 | 美商凱麥拉醫療公司 | Irak降解劑及其用途 |
| JP2024506656A (ja) | 2021-02-15 | 2024-02-14 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋ４分解剤およびその使用 |
| US12097261B2 (en) | 2021-05-07 | 2024-09-24 | Kymera Therapeutics, Inc. | CDK2 degraders and uses thereof |
| KR20230019396A (ko) * | 2021-07-29 | 2023-02-08 | 프라비바이오 주식회사 | 신규 벤젠 유도체 및 이의 면역억제 관련 용도 |
| PT4367118T (pt) | 2021-08-18 | 2025-04-16 | Gilead Sciences Inc | Degradadores bifuncionais de quinases associadas ao recetor de interleucina-1 e sua utilização terapêutica |
| WO2023076556A1 (en) | 2021-10-29 | 2023-05-04 | Kymera Therapeutics, Inc. | Irak4 degraders and synthesis thereof |
| JP2025504059A (ja) | 2022-01-31 | 2025-02-06 | カイメラ セラピューティクス， インコーポレイテッド | Ｉｒａｋデグレーダー及びその使用 |
| WO2025151602A1 (en) * | 2024-01-11 | 2025-07-17 | Bristol-Myers Squibb Company | Heteroaryl compounds as ligand directed degraders of irak4 |
| WO2025151728A1 (en) * | 2024-01-12 | 2025-07-17 | Bristol-Myers Squibb Company | Ligand directed degrader of irak4 |
| CN118388401B (zh) * | 2024-06-28 | 2024-08-20 | 成都凯斯坦生物医药有限公司 | 一种4-氨基-2-氯烟醛的制备方法 |
| CN118641677B (zh) * | 2024-08-16 | 2024-11-05 | 北京京丰制药集团有限公司 | 尼可刹米原料中杂质的检测方法 |
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| AU2012249240A1 (en) | 2011-04-29 | 2013-11-07 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitors |
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| US8987311B2 (en) | 2012-01-13 | 2015-03-24 | Bristol-Myers Squibb Company | Triazolyl-substituted pyridyl compounds useful as kinase inhibitors |
| CN104159896B (zh) * | 2012-01-13 | 2017-05-24 | 百时美施贵宝公司 | 用作激酶抑制剂的杂环取代的吡啶基化合物 |
| ES2575604T3 (es) | 2012-01-13 | 2016-06-29 | Bristol-Myers Squibb Company | Compuestos de piridilo sustituidos con tiazolilo o tiadiazolilo útiles como inhibidores cinasa |
| SG11201503397YA (en) * | 2012-11-08 | 2015-05-28 | Bristol Myers Squibb Co | Heteroaryl substituted pyridyl compounds useful as kinase modulators |
| US9546153B2 (en) | 2012-11-08 | 2017-01-17 | Bristol-Myers Squibb Company | Bicyclic heterocycle substituted pyridyl compounds useful as kinase modulators |
| AU2013341185B2 (en) | 2012-11-08 | 2017-07-13 | Bristol-Myers Squibb Company | Alkyl-amide-substituted pyridyl compounds useful as modulators of IL-12, IL-23 and/or IFNalpha responses |
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| MX2016008723A (es) | 2016-09-07 |
| UY35935A (es) | 2015-06-30 |
| CN106061967A (zh) | 2016-10-26 |
| US9169252B2 (en) | 2015-10-27 |
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