KR102398473B1 - Tam 패밀리 키나제 억제제로서의 아미노피리딘 유도체 - Google Patents
Tam 패밀리 키나제 억제제로서의 아미노피리딘 유도체 Download PDFInfo
- Publication number
- KR102398473B1 KR102398473B1 KR1020167016444A KR20167016444A KR102398473B1 KR 102398473 B1 KR102398473 B1 KR 102398473B1 KR 1020167016444 A KR1020167016444 A KR 1020167016444A KR 20167016444 A KR20167016444 A KR 20167016444A KR 102398473 B1 KR102398473 B1 KR 102398473B1
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- KR
- South Korea
- Prior art keywords
- pyridin
- pyrazol
- formula
- oxadiazol
- amine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 108091077436 Tam family Proteins 0.000 title abstract description 10
- 150000003927 aminopyridines Chemical class 0.000 title abstract description 3
- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 46
- 150000001875 compounds Chemical class 0.000 claims description 311
- 238000000034 method Methods 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 73
- 125000003118 aryl group Chemical group 0.000 claims description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 238000011282 treatment Methods 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 150000002431 hydrogen Chemical class 0.000 claims description 56
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 40
- 206010028980 Neoplasm Diseases 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
- 125000003386 piperidinyl group Chemical group 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 14
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 12
- 201000009273 Endometriosis Diseases 0.000 claims description 11
- 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 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 201000008482 osteoarthritis Diseases 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 208000002177 Cataract Diseases 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 9
- 208000032839 leukemia Diseases 0.000 claims description 9
- JCTRWHSQGKHHPN-UHFFFAOYSA-N 3-(3-phenyl-1,2,4-oxadiazol-5-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical class C1(=CC=CC=C1)C1=NOC(=N1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCNCC1)N JCTRWHSQGKHHPN-UHFFFAOYSA-N 0.000 claims description 8
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 208000037803 restenosis Diseases 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
- 208000001132 Osteoporosis Diseases 0.000 claims description 7
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 7
- 208000002780 macular degeneration Diseases 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 7
- 206010023439 Kidney transplant rejection Diseases 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- LMUXUZFXNUNSIF-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2-phenylethanone Chemical compound NC1=C(C=C(C=N1)C=1C=NN(C1)C1CCN(CC1)C(CC1=CC=CC=C1)=O)C=1OC(=NN1)C1=C(C=CC=C1Cl)Cl LMUXUZFXNUNSIF-UHFFFAOYSA-N 0.000 claims description 3
- JDZXATSSHQQCKE-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-4-methylpentan-1-one Chemical compound NC1=C(C=C(C=N1)C=1C=NN(C1)C1CCN(CC1)C(CCC(C)C)=O)C=1OC(=NN1)C1=C(C=CC=C1Cl)Cl JDZXATSSHQQCKE-UHFFFAOYSA-N 0.000 claims description 3
- QVQVNNUWZLJWNI-UHFFFAOYSA-N 3-(5-phenyl-1,3-oxazol-2-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound C1(=CC=CC=C1)C1=CN=C(O1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCNCC1)N QVQVNNUWZLJWNI-UHFFFAOYSA-N 0.000 claims description 3
- OGNFWOZBNYTNOL-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(Cl)C=CC=C1Cl)C1=CN(N=C1)C1CCNCC1 OGNFWOZBNYTNOL-UHFFFAOYSA-N 0.000 claims description 3
- IJLBAXYWKUBUSP-UHFFFAOYSA-N 5-(1-cyclohexylpyrazol-4-yl)-3-(5-phenyl-1,2,4-oxadiazol-3-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NOC(=N1)C1=CC=CC=C1)C1=CN(N=C1)C1CCCCC1 IJLBAXYWKUBUSP-UHFFFAOYSA-N 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 201000005969 Uveal melanoma Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 201000001514 prostate carcinoma Diseases 0.000 claims description 3
- TZHAMZFQCRXJQL-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-(3-phenyl-1,2,4-oxadiazol-5-yl)pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2-phenylethanone Chemical compound NC1=C(C=C(C=N1)C=1C=NN(C1)C1CCN(CC1)C(CC1=CC=CC=C1)=O)C1=NC(=NO1)C1=CC=CC=C1 TZHAMZFQCRXJQL-UHFFFAOYSA-N 0.000 claims description 2
- BGWDTMSGTXYLFQ-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-(3-phenyl-1,2,4-oxadiazol-5-yl)pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound NC1=C(C=C(C=N1)C=1C=NN(C1)C1CCN(CC1)C(C)=O)C1=NC(=NO1)C1=CC=CC=C1 BGWDTMSGTXYLFQ-UHFFFAOYSA-N 0.000 claims description 2
- YWKNLZNQZUWUJN-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound CC(=O)N1CCC(CC1)N1C=C(C=N1)C1=CC(C2=NN=C(O2)C2=C(Cl)C=CC=C2Cl)=C(N)N=C1 YWKNLZNQZUWUJN-UHFFFAOYSA-N 0.000 claims description 2
- BEZNVVMPNAFFQH-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(3-chlorophenyl)-1,3-oxazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2,2-dimethylpropan-1-one Chemical compound CC(C)(C)C(=O)N1CCC(CC1)N1C=C(C=N1)C1=CC(C2=NC=C(O2)C2=CC(Cl)=CC=C2)=C(N)N=C1 BEZNVVMPNAFFQH-UHFFFAOYSA-N 0.000 claims description 2
- UDJOVSNJZDGILO-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(3-chlorophenyl)-1,3-oxazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2-phenylethanone Chemical compound NC1=C(C=C(C=N1)C1=CN(N=C1)C1CCN(CC1)C(=O)CC1=CC=CC=C1)C1=NC=C(O1)C1=CC(Cl)=CC=C1 UDJOVSNJZDGILO-UHFFFAOYSA-N 0.000 claims description 2
- NQYVWMHYPZYTJQ-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(3-chlorophenyl)-1,3-oxazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound NC1=C(C=C(C=N1)C=1C=NN(C1)C1CCN(CC1)C(C)=O)C=1OC(=CN1)C1=CC(=CC=C1)Cl NQYVWMHYPZYTJQ-UHFFFAOYSA-N 0.000 claims description 2
- UTPPMYCLWHXGRC-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2-phenylethanone Chemical compound NC1=C(C=C(C=N1)C1=CN(N=C1)C1CCN(CC1)C(=O)CC1=CC=CC=C1)C1=NC=C(O1)C1=CC=C(Cl)C=C1 UTPPMYCLWHXGRC-UHFFFAOYSA-N 0.000 claims description 2
- HJCIOJLLUQLYKS-UHFFFAOYSA-N 1-[4-[4-[6-amino-5-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound CC(=O)N1CCC(CC1)N1C=C(C=N1)C1=CC(C2=NC=C(O2)C2=CC=C(Cl)C=C2)=C(N)N=C1 HJCIOJLLUQLYKS-UHFFFAOYSA-N 0.000 claims description 2
- RXYFHESTJMGSCY-UHFFFAOYSA-N 3-(3-phenyl-1,2,4-oxadiazol-5-yl)-5-(1H-pyrazol-4-yl)pyridin-2-amine Chemical compound C1(=CC=CC=C1)C1=NOC(=N1)C=1C(=NC=C(C1)C=1C=NNC1)N RXYFHESTJMGSCY-UHFFFAOYSA-N 0.000 claims description 2
- ANVAZPCRAOPQIJ-UHFFFAOYSA-N 3-(5-phenyl-1,2,4-oxadiazol-3-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical class NC1=NC=C(C=C1C1=NOC(=N1)C1=CC=CC=C1)C1=CN(N=C1)C1CCNCC1 ANVAZPCRAOPQIJ-UHFFFAOYSA-N 0.000 claims description 2
- BBAFIJXSLKRXFF-UHFFFAOYSA-N 3-(5-phenyl-1,2,4-oxadiazol-3-yl)-5-(1H-pyrazol-4-yl)pyridin-2-amine Chemical compound C1(=CC=CC=C1)C1=NC(=NO1)C=1C(=NC=C(C1)C=1C=NNC1)N BBAFIJXSLKRXFF-UHFFFAOYSA-N 0.000 claims description 2
- GTVXNXCPIWOXMW-UHFFFAOYSA-N 3-(5-phenyl-1,2-oxazol-3-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound C1(=CC=CC=C1)C1=CC(=NO1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCNCC1)N GTVXNXCPIWOXMW-UHFFFAOYSA-N 0.000 claims description 2
- OUEYCSALDJJZAE-UHFFFAOYSA-N 3-(5-phenyl-1,3,4-oxadiazol-2-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical class NC1=NC=C(C=C1C1=NN=C(O1)C1=CC=CC=C1)C1=CN(N=C1)C1CCNCC1 OUEYCSALDJJZAE-UHFFFAOYSA-N 0.000 claims description 2
- YEIHOAOJELGJES-UHFFFAOYSA-N 3-(5-phenyl-1,3,4-oxadiazol-2-yl)-5-(1H-pyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=CC=CC=C1)C1=CNN=C1 YEIHOAOJELGJES-UHFFFAOYSA-N 0.000 claims description 2
- HUDJQOWWQNOZMU-UHFFFAOYSA-N 3-(5-phenylfuran-2-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound C1(=CC=CC=C1)C1=CC=C(O1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCNCC1)N HUDJQOWWQNOZMU-UHFFFAOYSA-N 0.000 claims description 2
- HBBFYJYQLLHVLO-UHFFFAOYSA-N 3-[3-(2,6-dichlorophenyl)-1,2,4-oxadiazol-5-yl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NC(=NO1)C1=C(Cl)C=CC=C1Cl)C1=CN(N=C1)C1CCNCC1 HBBFYJYQLLHVLO-UHFFFAOYSA-N 0.000 claims description 2
- QOGFSNMJMBNROD-UHFFFAOYSA-N 3-[3-(2,6-dichlorophenyl)-1,2,4-oxadiazol-5-yl]-5-[1-(1-dodecylpiperidin-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound CCCCCCCCCCCCN1CCC(CC1)N1C=C(C=N1)C1=CN=C(N)C(=C1)C1=NC(=NO1)C1=C(Cl)C=CC=C1Cl QOGFSNMJMBNROD-UHFFFAOYSA-N 0.000 claims description 2
- QGXKCALPBVKDSW-UHFFFAOYSA-N 3-[3-(2,6-dichlorophenyl)-1,2,4-oxadiazol-5-yl]-5-[1-(1-ethylpiperidin-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound CCN1CCC(CC1)N1C=C(C=N1)C1=CN=C(N)C(=C1)C1=NC(=NO1)C1=C(Cl)C=CC=C1Cl QGXKCALPBVKDSW-UHFFFAOYSA-N 0.000 claims description 2
- VSCOLQXVVSAKLE-UHFFFAOYSA-N 3-[3-(2,6-dichlorophenyl)-1,2,4-oxadiazol-5-yl]-5-[1-(oxan-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound ClC1=C(C(=CC=C1)Cl)C1=NOC(=N1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCOCC1)N VSCOLQXVVSAKLE-UHFFFAOYSA-N 0.000 claims description 2
- LJZCRZBUFCSJRX-UHFFFAOYSA-N 3-[5-(2,5-dichlorophenyl)-1,2,4-oxadiazol-3-yl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NOC(=N1)C1=C(Cl)C=CC(Cl)=C1)C1=CN(N=C1)C1CCNCC1 LJZCRZBUFCSJRX-UHFFFAOYSA-N 0.000 claims description 2
- HJZZSPZLHHJFGM-UHFFFAOYSA-N 3-[5-(2,5-difluorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(F)C=CC(F)=C1)C1=CN(N=C1)C1CCNCC1 HJZZSPZLHHJFGM-UHFFFAOYSA-N 0.000 claims description 2
- CUCXAKDPZVGKIC-UHFFFAOYSA-N 3-[5-(2,5-difluorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1H-pyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(F)C=CC(F)=C1)C1=CNN=C1 CUCXAKDPZVGKIC-UHFFFAOYSA-N 0.000 claims description 2
- ZCLZKGMBFGLEIJ-UHFFFAOYSA-N 3-[5-(2,6-dichloro-3-fluorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(Cl)C(F)=CC=C1Cl)C1=CN(N=C1)C1CCNCC1 ZCLZKGMBFGLEIJ-UHFFFAOYSA-N 0.000 claims description 2
- DKTNXZWSOMKRAN-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1-piperidin-4-ylpyrrol-3-yl)pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(Cl)C=CC=C1Cl)C1=CN(C=C1)C1CCNCC1 DKTNXZWSOMKRAN-UHFFFAOYSA-N 0.000 claims description 2
- IMQAWWNWZMSFBP-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-(1h-pyrazol-4-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CNN=C2)C=C1C(O1)=NN=C1C1=C(Cl)C=CC=C1Cl IMQAWWNWZMSFBP-UHFFFAOYSA-N 0.000 claims description 2
- FJLRRTVVKQMQDA-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-[1-(1-dodecylpiperidin-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound CCCCCCCCCCCCN1CCC(CC1)N1C=C(C=N1)C1=CN=C(N)C(=C1)C1=NN=C(O1)C1=C(Cl)C=CC=C1Cl FJLRRTVVKQMQDA-UHFFFAOYSA-N 0.000 claims description 2
- ZBTBHQRMQLOGTA-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound CN1CCC(CC1)N1C=C(C=N1)C1=CN=C(N)C(=C1)C1=NN=C(O1)C1=C(Cl)C=CC=C1Cl ZBTBHQRMQLOGTA-UHFFFAOYSA-N 0.000 claims description 2
- LWRKYLRRDIXJHM-UHFFFAOYSA-N 3-[5-(2,6-dichlorophenyl)-1,3,4-oxadiazol-2-yl]-5-[1-(oxan-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound NC1=NC=C(C=C1C1=NN=C(O1)C1=C(Cl)C=CC=C1Cl)C1=CN(N=C1)C1CCOCC1 LWRKYLRRDIXJHM-UHFFFAOYSA-N 0.000 claims description 2
- BMUXXIXZPXPFGC-UHFFFAOYSA-N 3-[5-(3-chlorophenyl)-1,3-oxazol-2-yl]-5-(1-cyclohexylpyrazol-4-yl)pyridin-2-amine Chemical compound ClC=1C=C(C=CC1)C1=CN=C(O1)C=1C(=NC=C(C1)C=1C=NN(C1)C1CCCCC1)N BMUXXIXZPXPFGC-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
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- Transplantation (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US61/909,828 | 2013-11-27 | ||
| PCT/US2014/067709 WO2015081257A2 (en) | 2013-11-27 | 2014-11-26 | Aminopyridine derivatives as tam family kinase inhibitors |
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| WO2018224455A1 (en) | 2017-06-07 | 2018-12-13 | Basf Se | Substituted cyclopropyl derivatives |
| US11358948B2 (en) | 2017-09-22 | 2022-06-14 | Kymera Therapeutics, Inc. | CRBN ligands and uses thereof |
| WO2019060742A1 (en) | 2017-09-22 | 2019-03-28 | Kymera Therapeutics, Inc | AGENTS FOR DEGRADING PROTEINS AND USES THEREOF |
| IL315310A (en) | 2017-12-26 | 2024-10-01 | Kymera Therapeutics Inc | Irak degraders and uses thereof |
| WO2019140387A1 (en) | 2018-01-12 | 2019-07-18 | Kymera Therapeutics, Inc. | Crbn ligands and uses thereof |
| US11485743B2 (en) | 2018-01-12 | 2022-11-01 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| WO2020010177A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Tricyclic crbn ligands and uses thereof |
| US20220356185A1 (en) * | 2018-07-06 | 2022-11-10 | Kymera Therapeutics, Inc. | Mertk degraders and uses thereof |
| WO2020010227A1 (en) | 2018-07-06 | 2020-01-09 | Kymera Therapeutics, Inc. | Protein degraders and uses thereof |
| WO2020061216A1 (en) * | 2018-09-18 | 2020-03-26 | Signalchem Lifesciences Corporation | Combination therapy for treating blood cancer |
| CA3119773A1 (en) | 2018-11-30 | 2020-06-04 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| US12521438B2 (en) | 2019-06-10 | 2026-01-13 | Kymera Therapeutics, Inc. | SMARCA degraders and uses thereof |
| MX2021015995A (es) | 2019-06-28 | 2022-03-11 | Kymera Therapeutics Inc | Degradadores de cinasas asociadas al receptor de interleucina-1 (irak) y usos de los mismos. |
| US12558427B2 (en) | 2019-07-17 | 2026-02-24 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| US12551564B2 (en) | 2019-12-10 | 2026-02-17 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| CN115052627A (zh) | 2019-12-17 | 2022-09-13 | 凯麦拉医疗公司 | Irak降解剂和其用途 |
| US11591332B2 (en) | 2019-12-17 | 2023-02-28 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| BR112022012410A2 (pt) | 2019-12-23 | 2022-08-30 | Kymera Therapeutics Inc | Degradadores smarca e usos dos mesmos |
| MX2022011602A (es) | 2020-03-19 | 2023-01-04 | Kymera Therapeutics Inc | Degradadores de la proteína de homólogo de ratón de minuto 2 (mdm2) y usos de los mismos. |
| 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 |
| CN112707898A (zh) * | 2020-12-21 | 2021-04-27 | 徐新杰 | 一种杂芳基取代的吡嗪衍生物及其应用 |
| CA3202360A1 (en) | 2020-12-30 | 2022-07-07 | Nello Mainolfi | Irak degraders and uses thereof |
| JP2024505089A (ja) | 2021-02-01 | 2024-02-02 | シグナルケム・ライフサイエンシーズ・コーポレイション | 抗ウイルス治療薬としてのａｘｌ阻害剤ｓｌｃ－３９１の使用 |
| CA3207049A1 (en) | 2021-02-15 | 2022-08-18 | Jared Gollob | Irak4 degraders and uses thereof |
| KR20240020735A (ko) | 2021-05-07 | 2024-02-15 | 카이메라 쎄라퓨틱스 인코포레이티드 | Cdk2 분해제 및 그 용도 |
| CA3236265A1 (en) | 2021-10-29 | 2023-05-04 | William Leong | Irak4 degraders and synthesis thereof |
| US12091411B2 (en) | 2022-01-31 | 2024-09-17 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| TW202545523A (zh) | 2024-02-05 | 2025-12-01 | 加拿大商聖諾康生命科學公司 | 用於治療血液癌症之組合療法 |
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| PT2387395E (pt) | 2009-01-16 | 2015-02-04 | Rigel Pharmaceuticals Inc | Inibidores de axl para utilização em terapia de combinação para prevenir, tratar ou gerir cancro metastático |
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| EA201201081A1 (ru) | 2010-02-05 | 2013-03-29 | Мерк Патент Гмбх | Производные гетарил[1,8]нафтиридина |
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| EP2423208A1 (en) | 2010-08-28 | 2012-02-29 | Lead Discovery Center GmbH | Pharmaceutically active compounds as Axl inhibitors |
| WO2012087938A1 (en) | 2010-12-20 | 2012-06-28 | Glaxosmithkline Llc | Quinazolinone derivatives as antiviral agents |
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| WO2013162061A1 (ja) | 2012-04-26 | 2013-10-31 | 第一三共株式会社 | 二環性ピリミジン化合物 |
| WO2014106612A1 (en) * | 2013-01-02 | 2014-07-10 | H. Lundbeck A/S | Aminopyridine derived compounds as lrrk2 inhibitors |
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2014
- 2014-11-26 KR KR1020167016444A patent/KR102398473B1/ko active Active
- 2014-11-26 CA CA2930324A patent/CA2930324C/en active Active
- 2014-11-26 JP JP2016534735A patent/JP6496731B2/ja active Active
- 2014-11-26 EP EP14819178.6A patent/EP3074390B1/en active Active
- 2014-11-26 AU AU2014354711A patent/AU2014354711B2/en active Active
- 2014-11-26 WO PCT/US2014/067709 patent/WO2015081257A2/en not_active Ceased
- 2014-11-26 CN CN201910548630.5A patent/CN110156770B/zh active Active
- 2014-11-26 BR BR112016012146-5A patent/BR112016012146B1/pt active IP Right Grant
- 2014-11-26 MX MX2016006815A patent/MX373365B/es active IP Right Grant
- 2014-11-26 CN CN201480065032.8A patent/CN105764514B/zh active Active
- 2014-11-26 US US15/039,609 patent/US10233176B2/en active Active
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2016
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Patent Citations (3)
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|---|---|---|---|---|
| WO2009099982A1 (en) | 2008-02-04 | 2009-08-13 | Osi Pharmaceuticals, Inc. | 2-aminopyridine kinase inhibitors |
| WO2010005879A1 (en) | 2008-07-09 | 2010-01-14 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| WO2010005876A2 (en) | 2008-07-09 | 2010-01-14 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
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| AU2014354711A1 (en) | 2016-06-02 |
| US20200299288A1 (en) | 2020-09-24 |
| US11034685B2 (en) | 2021-06-15 |
| US11034686B2 (en) | 2021-06-15 |
| CN105764514B (zh) | 2019-07-12 |
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| EP3074390A2 (en) | 2016-10-05 |
| CN105764514A (zh) | 2016-07-13 |
| AU2014354711B2 (en) | 2018-10-25 |
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| US10723725B2 (en) | 2020-07-28 |
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| US10233176B2 (en) | 2019-03-19 |
| BR112016012146A2 (pt) | 2017-08-08 |
| CN110156770A (zh) | 2019-08-23 |
| US20190152965A1 (en) | 2019-05-23 |
| WO2015081257A3 (en) | 2015-07-02 |
| BR112016012146A8 (pt) | 2018-01-30 |
| CN110156770B (zh) | 2022-10-04 |
| JP2017501981A (ja) | 2017-01-19 |
| CA2930324A1 (en) | 2015-06-04 |
| IL245660A0 (en) | 2016-06-30 |
| BR112016012146B1 (pt) | 2022-11-01 |
| WO2015081257A2 (en) | 2015-06-04 |
| US20200299287A1 (en) | 2020-09-24 |
| CA2930324C (en) | 2022-01-18 |
| KR20160091358A (ko) | 2016-08-02 |
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