PT2560972T - Compostos e métodos para a modulação da quinase, e suas indicações - Google Patents
Compostos e métodos para a modulação da quinase, e suas indicações Download PDFInfo
- Publication number
- PT2560972T PT2560972T PT117726125T PT11772612T PT2560972T PT 2560972 T PT2560972 T PT 2560972T PT 117726125 T PT117726125 T PT 117726125T PT 11772612 T PT11772612 T PT 11772612T PT 2560972 T PT2560972 T PT 2560972T
- Authority
- PT
- Portugal
- Prior art keywords
- pyridyl
- fluoro
- formula
- amino
- pyrimidin
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 789
- 102000001253 Protein Kinase Human genes 0.000 title description 15
- 108060006633 protein kinase Proteins 0.000 title description 15
- 238000000034 method Methods 0.000 title description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 1002
- 125000000217 alkyl group Chemical group 0.000 claims description 752
- 229910052739 hydrogen Inorganic materials 0.000 claims description 621
- 125000003545 alkoxy group Chemical group 0.000 claims description 462
- -1 4-pyrazolyl Chemical group 0.000 claims description 301
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 282
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 271
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 152
- 239000011737 fluorine Substances 0.000 claims description 147
- 229910052731 fluorine Inorganic materials 0.000 claims description 147
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 108
- 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 89
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 89
- 150000003839 salts Chemical class 0.000 claims description 87
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 85
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 83
- 239000012453 solvate Substances 0.000 claims description 80
- 125000001246 bromo group Chemical group Br* 0.000 claims description 64
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
- 229910052799 carbon Inorganic materials 0.000 claims description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 33
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 10
- 208000002193 Pain Diseases 0.000 claims description 9
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical class 0.000 claims description 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 208000007569 Giant Cell Tumors Diseases 0.000 claims description 3
- 206010065390 Inflammatory pain Diseases 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- 206010059282 Metastases to central nervous system Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- LLQDTYOHPTWZIA-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 LLQDTYOHPTWZIA-UHFFFAOYSA-N 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000004931 neurofibromatosis Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- HHSUOQFZFBXWTK-UHFFFAOYSA-N (4-amino-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[2-chloro-6-[(4,4-difluorocyclohexyl)amino]pyridin-3-yl]methanone Chemical compound C1=2C(N)=NC=NC=2NC=C1C(=O)C(C(=N1)Cl)=CC=C1NC1CCC(F)(F)CC1 HHSUOQFZFBXWTK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000006224 2-tetrahydrofuranylmethyl group Chemical group [H]C([H])(*)C1([H])OC([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- NCVGEUDTYJBSMF-UHFFFAOYSA-N 4-[[5-[6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]piperidin-2-one Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CC(=O)NCC4)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 NCVGEUDTYJBSMF-UHFFFAOYSA-N 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 208000016192 Demyelinating disease Diseases 0.000 claims description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
- 206010027452 Metastases to bone Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 206010038468 Renal hypertrophy Diseases 0.000 claims description 2
- 206010038540 Renal tubular necrosis Diseases 0.000 claims description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- YLBZHNFWGMYDDT-UHFFFAOYSA-N [2-chloro-6-[(4,4-difluorocyclohexyl)amino]pyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)Cl)=CC=C1NC1CCC(F)(F)CC1 YLBZHNFWGMYDDT-UHFFFAOYSA-N 0.000 claims description 2
- DCMWXXAKOGADFO-UHFFFAOYSA-N [2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]-[4-(oxan-4-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1CC(F)CCC1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCOCC3)=C12 DCMWXXAKOGADFO-UHFFFAOYSA-N 0.000 claims description 2
- VLMRYRMQQFHGAS-UHFFFAOYSA-N [2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(C)C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)CC1 VLMRYRMQQFHGAS-UHFFFAOYSA-N 0.000 claims description 2
- RATANAFRZIPGTF-UHFFFAOYSA-N [2-fluoro-6-[(5-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound COC1=CN=CC(NC=2N=C(F)C(C(=O)C=3C4=C(NC(C)C)N=CN=C4NC=3)=CC=2)=C1 RATANAFRZIPGTF-UHFFFAOYSA-N 0.000 claims description 2
- WROCPEAEWKBPSQ-UHFFFAOYSA-N [2-fluoro-6-[(6-methylpyridin-3-yl)amino]pyridin-3-yl]-[4-(2,2,2-trifluoroethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(C)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NCC(F)(F)F)=C12 WROCPEAEWKBPSQ-UHFFFAOYSA-N 0.000 claims description 2
- SEHVKNHBWWPHSA-UHFFFAOYSA-N [4-(butylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1=2C(NCCCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(OC)N=C1 SEHVKNHBWWPHSA-UHFFFAOYSA-N 0.000 claims description 2
- SKFWYKIBBFEPDL-UHFFFAOYSA-N [4-(cyclobutylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CCC4)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 SKFWYKIBBFEPDL-UHFFFAOYSA-N 0.000 claims description 2
- USDGGAHPETZXCE-UHFFFAOYSA-N [4-(cyclopropylmethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NCC3CC3)=C12 USDGGAHPETZXCE-UHFFFAOYSA-N 0.000 claims description 2
- DYHZSAQXHDXWDO-LBPRGKRZSA-N [4-[[(1s)-1-cyclopropylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound N([C@@H](C)C1CC1)C(C1=2)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 DYHZSAQXHDXWDO-LBPRGKRZSA-N 0.000 claims description 2
- GQGXOAFWKBFUPX-LBPRGKRZSA-N [4-[[(2s)-butan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=2C(N[C@@H](C)CC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 GQGXOAFWKBFUPX-LBPRGKRZSA-N 0.000 claims description 2
- FBQYBWMASKYPQH-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(ethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 FBQYBWMASKYPQH-UHFFFAOYSA-N 0.000 claims description 2
- AYVPLGIMBXBDSH-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(propylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 AYVPLGIMBXBDSH-UHFFFAOYSA-N 0.000 claims description 2
- UFJCQWQNZVJFEU-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-(ethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 UFJCQWQNZVJFEU-UHFFFAOYSA-N 0.000 claims description 2
- UOHFJNMMFPVFEW-GFCCVEGCSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[[(2r)-1-methoxypropan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(N[C@H](C)COC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 UOHFJNMMFPVFEW-GFCCVEGCSA-N 0.000 claims description 2
- JWGYHEGOQZVAOT-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(2,2,2-trifluoroethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NCC(F)(F)F)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 JWGYHEGOQZVAOT-UHFFFAOYSA-N 0.000 claims description 2
- NLKKRUJTDKZYLX-UHFFFAOYSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[(6-methylpyridin-3-yl)amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC=3C=NC(C)=CC=3)=C12 NLKKRUJTDKZYLX-UHFFFAOYSA-N 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 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
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 201000006334 interstitial nephritis Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 201000008627 kidney hypertrophy Diseases 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 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 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims 43
- 150000001412 amines Chemical class 0.000 claims 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 3
- 201000002528 pancreatic cancer Diseases 0.000 claims 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 3
- INHWYJCCLKTJGY-UHFFFAOYSA-N 4-[[5-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-1-methylpiperidin-2-one Chemical compound C1C(=O)N(C)CCC1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC3CCC(F)(F)CC3)=CC=1)F)=CN2 INHWYJCCLKTJGY-UHFFFAOYSA-N 0.000 claims 2
- 206010006002 Bone pain Diseases 0.000 claims 2
- 208000000094 Chronic Pain Diseases 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 claims 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 claims 1
- MQOFXVWAFFJFJH-UHFFFAOYSA-N 4,4-difluorocyclohexan-1-amine Chemical compound NC1CCC(F)(F)CC1 MQOFXVWAFFJFJH-UHFFFAOYSA-N 0.000 claims 1
- FKJOLNNYYKMHTO-UHFFFAOYSA-N 4-[[5-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]piperidin-2-one Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CC(=O)NCC4)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 FKJOLNNYYKMHTO-UHFFFAOYSA-N 0.000 claims 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 1
- 208000010392 Bone Fractures Diseases 0.000 claims 1
- 206010017076 Fracture Diseases 0.000 claims 1
- 208000028622 Immune thrombocytopenia Diseases 0.000 claims 1
- 208000015439 Lysosomal storage disease Diseases 0.000 claims 1
- 208000003076 Osteolysis Diseases 0.000 claims 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims 1
- SSSWAWRKVQBQCT-UHFFFAOYSA-N [2-chloro-6-(cyclohexylamino)pyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)Cl)=CC=C1NC1CCCCC1 SSSWAWRKVQBQCT-UHFFFAOYSA-N 0.000 claims 1
- NRHWYWIIFWCXTO-UHFFFAOYSA-N [2-chloro-6-(cyclohexylamino)pyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(C)C)=NC=NC=2NC=C1C(=O)C(C(=N1)Cl)=CC=C1NC1CCCCC1 NRHWYWIIFWCXTO-UHFFFAOYSA-N 0.000 claims 1
- WYIDRDMKRPEKEF-UHFFFAOYSA-N [2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]-[4-(3-methoxypropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCCCOC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)CC1 WYIDRDMKRPEKEF-UHFFFAOYSA-N 0.000 claims 1
- CPDWZEWHLKZRPK-UHFFFAOYSA-N [4-(cyclobutylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]methanone Chemical compound C1CC(F)CCC1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCC3)=C12 CPDWZEWHLKZRPK-UHFFFAOYSA-N 0.000 claims 1
- MJMGSHMCTGDDFP-UHFFFAOYSA-N [4-(cyclohexylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(5-methoxypyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound COC1=CN=CC(NC=2N=C(F)C(C(=O)C=3C4=C(NC5CCCCC5)N=CN=C4NC=3)=CC=2)=C1 MJMGSHMCTGDDFP-UHFFFAOYSA-N 0.000 claims 1
- PGDNQHCNRNEZST-UHFFFAOYSA-N [4-(cyclopropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CC4)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 PGDNQHCNRNEZST-UHFFFAOYSA-N 0.000 claims 1
- QKRHXRNNIDKEBP-UHFFFAOYSA-N [4-[(1-ethylpiperidin-4-yl)amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1CN(CC)CCC1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC=3C=NC(OC)=CC=3)=CC=1)F)=CN2 QKRHXRNNIDKEBP-UHFFFAOYSA-N 0.000 claims 1
- NICCYTIXGQSYBK-UHFFFAOYSA-N [4-[(4,4-difluorocyclohexyl)amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCC(F)(F)CC3)=C12 NICCYTIXGQSYBK-UHFFFAOYSA-N 0.000 claims 1
- OKZIXHATEKJFCV-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(3-methoxypropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCCCOC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 OKZIXHATEKJFCV-UHFFFAOYSA-N 0.000 claims 1
- AIWOCBWNWVBKCK-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 AIWOCBWNWVBKCK-UHFFFAOYSA-N 0.000 claims 1
- RJGBIBYSEAIJGX-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(oxan-4-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CCOCC4)N=CN=C3NC=2)C(F)=NC=1NC1CC(F)(F)C1 RJGBIBYSEAIJGX-UHFFFAOYSA-N 0.000 claims 1
- IWAOCCCXQLRBIP-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-(4-hydroxybutan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(CCO)C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 IWAOCCCXQLRBIP-UHFFFAOYSA-N 0.000 claims 1
- QRIPRUSSGVOLQJ-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[(1,1-dioxothiolan-3-yl)amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CS(=O)(=O)CC4)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 QRIPRUSSGVOLQJ-UHFFFAOYSA-N 0.000 claims 1
- WTXNGRKDIZVULC-GFCCVEGCSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[[(2r)-1-hydroxybutan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(N[C@@H](CO)CC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 WTXNGRKDIZVULC-GFCCVEGCSA-N 0.000 claims 1
- JWCDSHIWFRMHAG-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(4-hydroxybutan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(CCO)C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 JWCDSHIWFRMHAG-UHFFFAOYSA-N 0.000 claims 1
- XNEKKGRUDFBXJS-CQSZACIVSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[[(2r)-1-hydroxybutan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(N[C@@H](CO)CC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 XNEKKGRUDFBXJS-CQSZACIVSA-N 0.000 claims 1
- IFKWVZBGWSQRNQ-GFCCVEGCSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[[(2r)-1-hydroxypropan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(N[C@@H](CO)C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 IFKWVZBGWSQRNQ-GFCCVEGCSA-N 0.000 claims 1
- ISRDIBYOJNKGJE-OAHLLOKOSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[[(1r)-1-(4-fluorophenyl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(N[C@H](C)C=3C=CC(F)=CC=3)=C12 ISRDIBYOJNKGJE-OAHLLOKOSA-N 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 125000006309 butyl amino group Chemical group 0.000 claims 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 claims 1
- 208000025113 myeloid leukemia Diseases 0.000 claims 1
- FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 claims 1
- RASPWLYDBYZRCR-UHFFFAOYSA-N pyrrolidin-1-ium-2-one;chloride Chemical compound Cl.O=C1CCCN1 RASPWLYDBYZRCR-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 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 1
- 239000001257 hydrogen Substances 0.000 description 617
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 452
- 150000002431 hydrogen Chemical class 0.000 description 163
- 235000019000 fluorine Nutrition 0.000 description 153
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 118
- 239000000460 chlorine Substances 0.000 description 118
- 229910052801 chlorine Inorganic materials 0.000 description 118
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 106
- 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 87
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 64
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 63
- 229940002612 prodrug Drugs 0.000 description 54
- 239000000651 prodrug Substances 0.000 description 54
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 37
- 150000001721 carbon Chemical group 0.000 description 35
- 108091000080 Phosphotransferase Proteins 0.000 description 33
- 102000020233 phosphotransferase Human genes 0.000 description 33
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 22
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 22
- 125000004414 alkyl thio group Chemical group 0.000 description 21
- 229910052740 iodine Inorganic materials 0.000 description 21
- 125000004076 pyridyl group Chemical group 0.000 description 12
- 125000003226 pyrazolyl group Chemical group 0.000 description 11
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 5
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 5
- 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 description 5
- 101150111783 NTRK1 gene Proteins 0.000 description 5
- 101150117329 NTRK3 gene Proteins 0.000 description 5
- 101150056950 Ntrk2 gene Proteins 0.000 description 5
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 5
- 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 description 5
- 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 description 5
- 108091008605 VEGF receptors Proteins 0.000 description 5
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 229910052741 iridium Inorganic materials 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229910052727 yttrium Inorganic materials 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- KPSBLSBABRIUJP-UHFFFAOYSA-N 4-ethoxy-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CCOC1=NC=NC2=C1C=CN2 KPSBLSBABRIUJP-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000003746 Insulin Receptor Human genes 0.000 description 3
- 108010001127 Insulin Receptor Proteins 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000003674 kinase activity assay Methods 0.000 description 3
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 3
- 125000006308 propyl amino group Chemical group 0.000 description 3
- XTUOAEWVWDYIMG-LJQANCHMSA-N (2r)-2-[[5-[6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]cyclohexan-1-one Chemical compound C=1C=C(C(=O)C=2C3=C(N[C@H]4C(CCCC4)=O)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 XTUOAEWVWDYIMG-LJQANCHMSA-N 0.000 description 2
- OLGGMDAROCVSTK-UHFFFAOYSA-N (4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[6-[(1-ethylpyrazol-4-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NN(CC)C=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(C3CC3)=C12 OLGGMDAROCVSTK-UHFFFAOYSA-N 0.000 description 2
- NAVZZWIKNNLMQX-UHFFFAOYSA-N (5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)-[2-fluoro-6-[(6-methylpyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1=NC(C)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=C(Cl)C=C12 NAVZZWIKNNLMQX-UHFFFAOYSA-N 0.000 description 2
- CSYQTHZWIIVKAB-UHFFFAOYSA-N 1-[3-[[5-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]ethanone Chemical compound C1N(C(=O)C)CCC1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC3CCC(F)(F)CC3)=CC=1)F)=CN2 CSYQTHZWIIVKAB-UHFFFAOYSA-N 0.000 description 2
- YBDPXPSYEWRZMS-UHFFFAOYSA-N 5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-(6-methoxypyridin-3-yl)pyridin-2-amine Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(C3CC3)=C12 YBDPXPSYEWRZMS-UHFFFAOYSA-N 0.000 description 2
- TVMPXRWLGGFYFJ-UHFFFAOYSA-N 5-[(4-ethoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-(6-methoxypyridin-3-yl)pyridin-2-amine Chemical compound C1=2C(OCC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(OC)N=C1 TVMPXRWLGGFYFJ-UHFFFAOYSA-N 0.000 description 2
- YKZMXHBQVNVGQB-UHFFFAOYSA-N 5-[(4-ethoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-(6-methylpyridin-3-yl)pyridin-2-amine Chemical compound C1=2C(OCC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(C)N=C1 YKZMXHBQVNVGQB-UHFFFAOYSA-N 0.000 description 2
- WVCMQNXOZJHCHQ-UHFFFAOYSA-N 5-[(4-ethoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-pyridin-3-ylpyridin-2-amine Chemical compound C1=2C(OCC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=CN=C1 WVCMQNXOZJHCHQ-UHFFFAOYSA-N 0.000 description 2
- JJDOLKAIKFSSHK-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(2-methoxyphenyl)pyrimidin-2-amine Chemical compound COC1=CC=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 JJDOLKAIKFSSHK-UHFFFAOYSA-N 0.000 description 2
- CEGNOUAQOBZYPJ-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(3-fluorophenyl)pyrimidin-2-amine Chemical compound FC1=CC=CC(NC=2N=CC(CC=3C4=CC(Cl)=CN=C4NC=3)=CN=2)=C1 CEGNOUAQOBZYPJ-UHFFFAOYSA-N 0.000 description 2
- PJMKAVKREXZLAL-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4-fluorophenyl)pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 PJMKAVKREXZLAL-UHFFFAOYSA-N 0.000 description 2
- BJXGNAHRXVZPQB-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-cyclopentylpyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1CCCC1 BJXGNAHRXVZPQB-UHFFFAOYSA-N 0.000 description 2
- SWLGDFSGMHOHOM-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(3-propan-2-yloxy-1h-pyrazol-5-yl)pyrimidin-2-amine Chemical compound N1N=C(OC(C)C)C=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 SWLGDFSGMHOHOM-UHFFFAOYSA-N 0.000 description 2
- CUBWLPRMQZFGFU-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4-methylsulfonylphenyl)pyrimidin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC=C(S(C)(=O)=O)C=C1 CUBWLPRMQZFGFU-UHFFFAOYSA-N 0.000 description 2
- KEHRPLGQSHGMFS-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-[5-(trifluoromethyl)-1h-pyrazol-3-yl]pyrimidin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC(C(F)(F)F)=NN1 KEHRPLGQSHGMFS-UHFFFAOYSA-N 0.000 description 2
- MBJXQBQBJORFLS-UHFFFAOYSA-N 6-fluoro-5-[[4-(2-methoxyethoxy)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methyl]-n-(6-methylpyridin-3-yl)pyridin-2-amine Chemical compound C1=2C(OCCOC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(C)N=C1 MBJXQBQBJORFLS-UHFFFAOYSA-N 0.000 description 2
- QUEPQIVGSQRELR-UHFFFAOYSA-N 6-fluoro-n-(6-methoxypyridin-3-yl)-5-[(4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(OC)=C12 QUEPQIVGSQRELR-UHFFFAOYSA-N 0.000 description 2
- KHOGALDQMOVCQY-UHFFFAOYSA-N 6-fluoro-n-(6-methoxypyridin-3-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=C(C)C=C12 KHOGALDQMOVCQY-UHFFFAOYSA-N 0.000 description 2
- UUVDJIWRSIJEBS-UHFFFAOYSA-N 6-methoxypyridin-3-amine Chemical compound COC1=CC=C(N)C=N1 UUVDJIWRSIJEBS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- MKDOVIIYIBYPKL-UHFFFAOYSA-N [2-fluoro-6-[(6-methylpyridin-3-yl)amino]pyridin-3-yl]-(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methanone Chemical compound C12=CC(C)=CN=C2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(C)N=C1 MKDOVIIYIBYPKL-UHFFFAOYSA-N 0.000 description 2
- PALYNWIZNNICPM-UHFFFAOYSA-N [2-methoxy-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)OC)=CC=C1NC1=CC=C(OC)N=C1 PALYNWIZNNICPM-UHFFFAOYSA-N 0.000 description 2
- HDJZCXHFPYTZSP-UHFFFAOYSA-N [4-(cyclopropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]methanone Chemical compound FC1=CC(C(=O)C=2C3=C(NC4CC4)N=CN=C3NC=2)=CN=C1NC1CCC(F)(F)CC1 HDJZCXHFPYTZSP-UHFFFAOYSA-N 0.000 description 2
- CFPRNGOMEKMWPP-UHFFFAOYSA-N [4-(cyclopropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]pyridin-3-yl]methanone Chemical compound C1CC(F)(F)CCC1NC1=CC=C(C(=O)C=2C3=C(NC4CC4)N=CN=C3NC=2)C=N1 CFPRNGOMEKMWPP-UHFFFAOYSA-N 0.000 description 2
- KOCJZTRVGCGTEF-HUUCEWRRSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[[(1r,3r)-3-hydroxycyclohexyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1[C@H](O)CCC[C@H]1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC3CCC(F)(F)CC3)=CC=1)F)=CN2 KOCJZTRVGCGTEF-HUUCEWRRSA-N 0.000 description 2
- IISIXHFYOADEAT-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]-[4-(2,2,2-trifluoroethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound FC1=CC(C(=O)C=2C3=C(NCC(F)(F)F)N=CN=C3NC=2)=CN=C1NC1CCC(F)(F)CC1 IISIXHFYOADEAT-UHFFFAOYSA-N 0.000 description 2
- DCMSOMFECLYZGI-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]-[4-(methoxymethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCOC)=NC=NC=2NC=C1C(=O)C(C=C1F)=CN=C1NC1CCC(F)(F)CC1 DCMSOMFECLYZGI-UHFFFAOYSA-N 0.000 description 2
- JNVRTALOIOWJMH-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]-[4-(oxan-4-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound FC1=CC(C(=O)C=2C3=C(NC4CCOCC4)N=CN=C3NC=2)=CN=C1NC1CCC(F)(F)CC1 JNVRTALOIOWJMH-UHFFFAOYSA-N 0.000 description 2
- HXNXXGCNBHKKGY-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]pyridin-3-yl]-[4-(2,2,2-trifluoroethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCC(F)(F)F)=NC=NC=2NC=C1C(=O)C(C=N1)=CC=C1NC1CCC(F)(F)CC1 HXNXXGCNBHKKGY-UHFFFAOYSA-N 0.000 description 2
- ICSCRMQMPQFSAP-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]pyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C=N1)=CC=C1NC1CCC(F)(F)CC1 ICSCRMQMPQFSAP-UHFFFAOYSA-N 0.000 description 2
- QOTAVWBOEXMGIL-RTBURBONSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[[(1r,2r)-2-hydroxycyclopentyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound O[C@@H]1CCC[C@H]1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC=3C=NC(=CC=3)C3CC3)=CC=1)F)=CN2 QOTAVWBOEXMGIL-RTBURBONSA-N 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- YGDCFTBYDLARQG-UHFFFAOYSA-N n-(1-ethylpyrazol-3-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound CCN1C=CC(NC=2N=CC(CC=3C4=CC(C)=CN=C4NC=3)=CN=2)=N1 YGDCFTBYDLARQG-UHFFFAOYSA-N 0.000 description 2
- QWJMTIDNHHYROL-UHFFFAOYSA-N n-(1-ethylpyrazol-4-yl)-6-fluoro-5-[(4-methyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=NN(CC)C=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(C)=C12 QWJMTIDNHHYROL-UHFFFAOYSA-N 0.000 description 2
- GJNHWDZTZMVVJV-UHFFFAOYSA-N n-(1-ethylpyrazol-4-yl)-6-fluoro-5-[[4-(2-methoxyethoxy)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methyl]pyridin-2-amine Chemical compound C1=NN(CC)C=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(OCCOC)=C12 GJNHWDZTZMVVJV-UHFFFAOYSA-N 0.000 description 2
- NHSXMJKMAMLMNP-UHFFFAOYSA-N n-(2-chlorophenyl)-5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC=CC=C1Cl NHSXMJKMAMLMNP-UHFFFAOYSA-N 0.000 description 2
- PYMKMCAACDFRHW-UHFFFAOYSA-N n-(4-chlorophenyl)-5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 PYMKMCAACDFRHW-UHFFFAOYSA-N 0.000 description 2
- LUGUTXVDCALJAX-UHFFFAOYSA-N n-(4-ethylphenyl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=CC(CC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 LUGUTXVDCALJAX-UHFFFAOYSA-N 0.000 description 2
- BTQBJHACPOFOAS-UHFFFAOYSA-N n-(4-fluorophenyl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC=C(F)C=C1 BTQBJHACPOFOAS-UHFFFAOYSA-N 0.000 description 2
- SDHHRNXTPUDSNI-UHFFFAOYSA-N n-(4-methoxyphenyl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 SDHHRNXTPUDSNI-UHFFFAOYSA-N 0.000 description 2
- USBIIGBLLFMMHI-UHFFFAOYSA-N n-(5-tert-butyl-1h-pyrazol-3-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC(C(C)(C)C)=NN1 USBIIGBLLFMMHI-UHFFFAOYSA-N 0.000 description 2
- RBYHWKDSXLIKFR-UHFFFAOYSA-N n-(6-cyclopropylpyridin-3-yl)-6-fluoro-5-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)pyridin-2-amine Chemical compound C=1C=C(CC=2C3=CC=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 RBYHWKDSXLIKFR-UHFFFAOYSA-N 0.000 description 2
- MMFSWGSQXKVGCM-UHFFFAOYSA-N n-(6-cyclopropylpyridin-3-yl)-6-fluoro-5-[(4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=2C(OC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 MMFSWGSQXKVGCM-UHFFFAOYSA-N 0.000 description 2
- IFPUCBXQDGMBBG-UHFFFAOYSA-N n-(6-cyclopropylpyridin-3-yl)-6-fluoro-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 IFPUCBXQDGMBBG-UHFFFAOYSA-N 0.000 description 2
- ZJKRVFBCMSVWGN-UHFFFAOYSA-N n-(6-ethylpyridin-3-yl)-6-fluoro-5-[(4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(OC)=C12 ZJKRVFBCMSVWGN-UHFFFAOYSA-N 0.000 description 2
- MZMVSXJYZFOORG-UHFFFAOYSA-N n-(6-methoxypyridin-3-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=NC(OC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 MZMVSXJYZFOORG-UHFFFAOYSA-N 0.000 description 2
- DLJNFSFQVQLVGS-UHFFFAOYSA-N n-cyclohexyl-6-fluoro-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C(=N1)F)=CC=C1NC1CCCCC1 DLJNFSFQVQLVGS-UHFFFAOYSA-N 0.000 description 2
- JUMJVFKLHYPKGK-UHFFFAOYSA-N n-cyclopropyl-5-[[6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1N=C(NC2CCC(F)(F)CC2)C(F)=CC=1CC(C=12)=CNC2=NC=NC=1NC1CC1 JUMJVFKLHYPKGK-UHFFFAOYSA-N 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- NJDNEOJYPDSWCL-UHFFFAOYSA-N (4-amino-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(N)=C12 NJDNEOJYPDSWCL-UHFFFAOYSA-N 0.000 description 1
- YUNLJTVRPLBFTN-UHFFFAOYSA-N 4-[[5-[6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-1-methylpiperidin-2-one Chemical compound C1C(=O)N(C)CCC1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC=3C=NC(=CC=3)C3CC3)=CC=1)F)=CN2 YUNLJTVRPLBFTN-UHFFFAOYSA-N 0.000 description 1
- QWIAHMVNMONKCU-UHFFFAOYSA-N 4-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CC1=NC=NC2=C1C=CN2 QWIAHMVNMONKCU-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- LXZGAPICQUBNFS-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-2-amine Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC=C(C(F)(F)F)N=C1 LXZGAPICQUBNFS-UHFFFAOYSA-N 0.000 description 1
- WTYADSIKJZTFJI-UHFFFAOYSA-N 5-[[6-(cyclohexylamino)-2-fluoropyridin-3-yl]methyl]-n-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C(CC=2C3=C(NC4CC4)N=CN=C3NC=2)C(F)=NC=1NC1CCCCC1 WTYADSIKJZTFJI-UHFFFAOYSA-N 0.000 description 1
- WRCVQOCGIBTZHJ-UHFFFAOYSA-N 5-[[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]methyl]-n-(2,2,2-trifluoroethyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C(CC=2C3=C(NCC(F)(F)F)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 WRCVQOCGIBTZHJ-UHFFFAOYSA-N 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010052306 Periprosthetic osteolysis Diseases 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- IVNPIZKBXPBLLI-UHFFFAOYSA-N [2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]-[4-(2,2,2-trifluoroethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1CC(F)CCC1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NCC(F)(F)F)=C12 IVNPIZKBXPBLLI-UHFFFAOYSA-N 0.000 description 1
- RCYDVLQMIRYGCY-UHFFFAOYSA-N [2-fluoro-6-[(5-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(propylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]methanone Chemical compound FC1=NC(=CC=C1C(=O)C=1N=C(C2=C(N=1)NC=C2)NCCC)NC=1C=NC=C(C=1)OC RCYDVLQMIRYGCY-UHFFFAOYSA-N 0.000 description 1
- FPHOGLJGMLSCQH-UHFFFAOYSA-N [2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-(4-morpholin-4-yl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methanone Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(N3CCOCC3)=C12 FPHOGLJGMLSCQH-UHFFFAOYSA-N 0.000 description 1
- KPWCIJXXGAIBCF-UHFFFAOYSA-N [2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(oxolan-2-ylmethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NCC3OCCC3)=C12 KPWCIJXXGAIBCF-UHFFFAOYSA-N 0.000 description 1
- NHRYYSKFZNHNKN-UHFFFAOYSA-N [2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(pentan-3-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(CC)CC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(OC)N=C1 NHRYYSKFZNHNKN-UHFFFAOYSA-N 0.000 description 1
- MTKHXWNCEKNMNS-UHFFFAOYSA-N [2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC(C)C)=C12 MTKHXWNCEKNMNS-UHFFFAOYSA-N 0.000 description 1
- UDYZZJBRHGPPKF-UHFFFAOYSA-N [2-fluoro-6-[[6-(trifluoromethyl)pyridin-3-yl]amino]pyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(C(F)(F)F)N=C1 UDYZZJBRHGPPKF-UHFFFAOYSA-N 0.000 description 1
- WIGMCZFCZCSMMW-UHFFFAOYSA-N [4-(butylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=2C(NCCCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(CC)N=C1 WIGMCZFCZCSMMW-UHFFFAOYSA-N 0.000 description 1
- UOCJEKKRDDEQOY-UHFFFAOYSA-N [4-(cyclobutylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CCC4)N=CN=C3NC=2)C(F)=NC=1NC1CC(F)(F)C1 UOCJEKKRDDEQOY-UHFFFAOYSA-N 0.000 description 1
- RZBZKNSIVHKKOV-UHFFFAOYSA-N [4-(cyclobutylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCC3)=C12 RZBZKNSIVHKKOV-UHFFFAOYSA-N 0.000 description 1
- PKIKTIUCRYUKKG-UHFFFAOYSA-N [4-(cyclohexylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(6-methylpyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1=NC(C)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCCCC3)=C12 PKIKTIUCRYUKKG-UHFFFAOYSA-N 0.000 description 1
- SWBBIIIBOYOSKX-UHFFFAOYSA-N [4-(cyclopropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(4-fluorocyclohexyl)amino]pyridin-3-yl]methanone Chemical compound C1CC(F)CCC1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CC3)=C12 SWBBIIIBOYOSKX-UHFFFAOYSA-N 0.000 description 1
- AMOXKRFYMZWTAI-UHFFFAOYSA-N [4-(cyclopropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CC3)=C12 AMOXKRFYMZWTAI-UHFFFAOYSA-N 0.000 description 1
- ZSRQKNXWSKESRS-UHFFFAOYSA-N [4-(cyclopropylmethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NCC3CC3)=C12 ZSRQKNXWSKESRS-UHFFFAOYSA-N 0.000 description 1
- PZGILXHXYSCVQW-UHFFFAOYSA-N [4-(ethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]methanone Chemical compound C1=2C(NCC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1=CC=C(OC)N=C1 PZGILXHXYSCVQW-UHFFFAOYSA-N 0.000 description 1
- WWLTXCJGKUULKE-JTQLQIEISA-N [4-[[(1s)-1-cyclopropylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound N([C@@H](C)C1CC1)C(C1=2)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 WWLTXCJGKUULKE-JTQLQIEISA-N 0.000 description 1
- KOVBGKZUQLABCR-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(methoxymethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCOC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 KOVBGKZUQLABCR-UHFFFAOYSA-N 0.000 description 1
- JCTCPKUYDKZSCR-UHFFFAOYSA-N [6-[(3,3-difluorocyclobutyl)amino]-2-fluoropyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC(C)C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CC(F)(F)C1 JCTCPKUYDKZSCR-UHFFFAOYSA-N 0.000 description 1
- BNDLGCCGTQTJAL-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-(2-methoxyethylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCCOC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 BNDLGCCGTQTJAL-UHFFFAOYSA-N 0.000 description 1
- SGSWGBQLRLNDJP-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-(3-methoxypropylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NCCCOC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC1CCC(F)(F)CC1 SGSWGBQLRLNDJP-UHFFFAOYSA-N 0.000 description 1
- CDARGWIZUNGPBX-HZPDHXFCSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[[(1r,2r)-2-hydroxycyclopentyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound O[C@@H]1CCC[C@H]1NC1=NC=NC2=C1C(C(=O)C=1C(=NC(NC3CCC(F)(F)CC3)=CC=1)F)=CN2 CDARGWIZUNGPBX-HZPDHXFCSA-N 0.000 description 1
- ZGOLZYGKOPQXNE-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(NC)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 ZGOLZYGKOPQXNE-UHFFFAOYSA-N 0.000 description 1
- CZIUOVIXFFELNX-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[(1,1-dioxothiolan-3-yl)amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CS(=O)(=O)CC4)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 CZIUOVIXFFELNX-UHFFFAOYSA-N 0.000 description 1
- XFJOFQKRWJHXTA-LLVKDONJSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[[(2r)-1,1,1-trifluoropropan-2-yl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=2C(N[C@H](C)C(F)(F)F)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 XFJOFQKRWJHXTA-LLVKDONJSA-N 0.000 description 1
- QSSQFUZJTHJXGT-UHFFFAOYSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(methylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC)=C12 QSSQFUZJTHJXGT-UHFFFAOYSA-N 0.000 description 1
- WXAOXLFSDVCIIW-UHFFFAOYSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(oxan-4-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC3CCOCC3)=C12 WXAOXLFSDVCIIW-UHFFFAOYSA-N 0.000 description 1
- BVADCBZLJPCTRQ-UHFFFAOYSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-(propan-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(NC(C)C)=C12 BVADCBZLJPCTRQ-UHFFFAOYSA-N 0.000 description 1
- HXELGNKCCDGMMN-UHFFFAOYSA-N [F].[Cl] Chemical compound [F].[Cl] HXELGNKCCDGMMN-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- IQWQSMICIKAESR-UHFFFAOYSA-N n-(1-ethylpyrazol-4-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=NN(CC)C=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 IQWQSMICIKAESR-UHFFFAOYSA-N 0.000 description 1
- QMHYNQVBMUBBBF-UHFFFAOYSA-N n-(4-ethoxyphenyl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=CC(OCC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 QMHYNQVBMUBBBF-UHFFFAOYSA-N 0.000 description 1
- OGMFZJINJBLPOB-UHFFFAOYSA-N n-(4-fluoro-3-methoxyphenyl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=C(F)C(OC)=CC(NC=2N=CC(CC=3C4=CC(C)=CN=C4NC=3)=CN=2)=C1 OGMFZJINJBLPOB-UHFFFAOYSA-N 0.000 description 1
- FFARKUYZUZJCKL-UHFFFAOYSA-N n-(6-chloropyridin-3-yl)-6-fluoro-5-[(4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=2C(OC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(Cl)N=C1 FFARKUYZUZJCKL-UHFFFAOYSA-N 0.000 description 1
- NMWKUNGZTVNVFU-UHFFFAOYSA-N n-(6-ethoxypyridin-3-yl)-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-amine Chemical compound C1=NC(OCC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 NMWKUNGZTVNVFU-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000003582 thrombocytopenic effect Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32662610P | 2010-04-21 | 2010-04-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2560972T true PT2560972T (pt) | 2017-10-09 |
Family
ID=44816304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT117726125T PT2560972T (pt) | 2010-04-21 | 2011-04-20 | Compostos e métodos para a modulação da quinase, e suas indicações |
Country Status (39)
Families Citing this family (105)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| SG183036A1 (en) | 2007-07-17 | 2012-08-30 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| US8158636B2 (en) | 2008-05-19 | 2012-04-17 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP2350075B1 (en) | 2008-09-22 | 2014-03-05 | Array Biopharma, Inc. | Substituted imidazo[1,2b]pyridazine compounds as trk kinase inhibitors |
| KR101853026B1 (ko) | 2008-10-22 | 2018-04-27 | 어레이 바이오파마 인크. | ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５ａ］ 피리미딘 화합물 |
| EA022924B1 (ru) | 2009-04-03 | 2016-03-31 | Ф.Хоффманн-Ля Рош Аг | ТВЁРДАЯ ФОРМА {3-[5-(4-ХЛОРФЕНИЛ)-1Н-ПИРРОЛО[2,3-b]ПИРИДИН-3-КАРБОНИЛ]-2,4-ДИФТОРФЕНИЛ}АМИДА ПРОПАН-1-СУЛЬФОНОВОЙ КИСЛОТЫ И ЕЁ ПРИМЕНЕНИЕ |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| MA33975B1 (fr) | 2009-11-06 | 2013-02-01 | Plexxikon Inc | Composés et méthodes de modulation des kinases et leurs indications d'emploi |
| CN105906631A (zh) | 2009-11-18 | 2016-08-31 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| RU2012131373A (ru) | 2009-12-23 | 2014-01-27 | Плексксикон, Инк. | Соединения и способы модулирования киназы, а также показания для такого модулирования |
| TWI510487B (zh) | 2010-04-21 | 2015-12-01 | Plexxikon Inc | 用於激酶調節的化合物和方法及其適應症 |
| CN105693720B (zh) | 2010-05-20 | 2019-01-18 | 阵列生物制药公司 | 作为trk激酶抑制剂的大环化合物 |
| JP5941069B2 (ja) | 2011-02-07 | 2016-06-29 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | キナーゼ調節のための化合物および方法、ならびにそれに対する適応症 |
| EP2694509B1 (en) | 2011-04-05 | 2016-05-18 | Pfizer Limited | Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of tropomyosin-related kinases |
| AU2012255275B2 (en) * | 2011-05-17 | 2016-01-28 | Plexxikon Inc. | Kinase modulation and indications therefor |
| US9358235B2 (en) * | 2012-03-19 | 2016-06-07 | Plexxikon Inc. | Kinase modulation, and indications therefor |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| US9505765B2 (en) | 2012-07-26 | 2016-11-29 | Confluence Life Sciences Inc. | 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment |
| AU2013312477B2 (en) | 2012-09-06 | 2018-05-31 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CA2885259A1 (en) | 2012-10-04 | 2014-04-10 | Pfizer Limited | Pyrrolo[3,2-c]pyridine tropomyosin-related kinase inhibitors |
| EP2903986A1 (en) | 2012-10-04 | 2015-08-12 | Pfizer Limited | Tropomyosin-related kinase inhibitors |
| CA2885253A1 (en) | 2012-10-04 | 2014-04-10 | Pfizer Limited | Pyrrolo[2,3-d]pyrimidine tropomyosin-related kinase inhibitors |
| EP2935248B1 (en) | 2012-12-21 | 2018-02-28 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| KR102244719B1 (ko) | 2013-03-15 | 2021-04-26 | 플렉시콘 인코퍼레이티드 | 헤테로시클릭 화합물 및 그의 용도 |
| BR112015028845A2 (pt) | 2013-05-30 | 2017-07-25 | Plexxikon Inc | compostos para a modulação da quinase e indicações da mesma |
| WO2015017533A1 (en) | 2013-07-30 | 2015-02-05 | Blueprint Medicines Corporation | Ntrk2 fusions |
| WO2015092610A1 (en) | 2013-12-20 | 2015-06-25 | Pfizer Limited | N-acylpiperidine ether tropomyosin-related kinase inhibitors |
| FI4176894T3 (fi) * | 2014-01-10 | 2024-05-29 | Bioverativ Therapeutics Inc | Kimeerisiä tekijä viii -proteiineja ja niiden käyttötarkoituksia |
| WO2015134536A1 (en) | 2014-03-04 | 2015-09-11 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP3131891A1 (en) | 2014-04-15 | 2017-02-22 | Pfizer Inc. | Tropomyosin-related kinase inhibitors containing both a 1h-pyrazole and a pyrimidine moiety |
| EP3140298A1 (en) | 2014-05-07 | 2017-03-15 | Pfizer Inc. | Tropomyosin-related kinase inhibitors |
| WO2016009296A1 (en) | 2014-07-16 | 2016-01-21 | Pfizer Inc. | N-acylpiperidine ether tropomyosin-related kinase inhibitors |
| WO2016020784A1 (en) | 2014-08-05 | 2016-02-11 | Pfizer Inc. | N-acylpyrrolidine ether tropomyosin-related kinase inhibitors |
| AU2015318233B2 (en) | 2014-09-15 | 2020-03-12 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| TWI746426B (zh) | 2014-11-16 | 2021-11-21 | 美商亞雷生物製藥股份有限公司 | (S)-N-(5-((R)-2-(2,5-二氟苯基)-吡咯啶-1-基)-吡唑并[1,5-a]嘧啶-3-基)-3-羥基吡咯啶-1-甲醯胺硫酸氫鹽結晶型 |
| WO2016100963A1 (en) * | 2014-12-19 | 2016-06-23 | Research Institute At Nationwide Children's Hospital | Pyruvate compounds for treatment of peripheral neuropathy |
| US9695200B2 (en) | 2015-01-23 | 2017-07-04 | Confluence Life Sciences, Inc. | Heterocyclic ITK inhibitors for treating inflammation and cancer |
| WO2016164641A1 (en) | 2015-04-08 | 2016-10-13 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP3292123B1 (en) | 2015-05-06 | 2020-07-22 | Plexxikon Inc. | Solid forms of a compound modulating kinases |
| CN112574196A (zh) | 2015-05-06 | 2021-03-30 | 普莱希科公司 | 调节激酶的1H-吡咯并[2,3-b]吡啶衍生物的合成 |
| TWI658042B (zh) | 2015-05-22 | 2019-05-01 | 美商普雷辛肯公司 | 雜環化合物的合成 |
| KR20180021745A (ko) | 2015-06-01 | 2018-03-05 | 록쏘 온콜로지, 인코포레이티드 | 암을 진단하고 치료하는 방법 |
| EP3322706B1 (en) | 2015-07-16 | 2020-11-11 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as ret kinase inhibitors |
| US10829484B2 (en) | 2015-07-28 | 2020-11-10 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CN108137585B (zh) | 2015-09-21 | 2021-10-22 | 普莱希科公司 | 杂环化合物及其应用 |
| TN2018000138A1 (en) | 2015-10-26 | 2019-10-04 | Array Biopharma Inc | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US9938273B2 (en) | 2015-12-07 | 2018-04-10 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US9630968B1 (en) | 2015-12-23 | 2017-04-25 | Arqule, Inc. | Tetrahydropyranyl amino-pyrrolopyrimidinone and methods of use thereof |
| EP3430005B1 (en) | 2016-03-16 | 2021-12-08 | Plexxikon Inc. | Compounds and methods for kinase modulation and indications therefore |
| HUE068971T2 (hu) | 2016-04-04 | 2025-02-28 | Loxo Oncology Inc | (S)-N-(5-((R)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-A]pirimidin-3-il) -3-hidroxipirrolidin-1-karboxamid folyékony készítményei |
| RS65988B1 (sr) | 2016-04-04 | 2024-10-31 | Loxo Oncology Inc | Postupak lečenja pedijatrijskih karcinoma |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| KR20190006991A (ko) * | 2016-05-11 | 2019-01-21 | 베타 파마, 인크. | 뇌암의 치료를 위한 치료제로서의 2-아닐리노피리미딘 유도체 |
| SI3458456T1 (sl) | 2016-05-18 | 2021-04-30 | Loxo Oncology, Inc. | Priprava (S)-N-(5-((R)-2-(2,5-difluorofenil) pirolidin-1-il) pirazolo (1,5-A) pirimidin-3-il)-3-hidroksipirolidin-1-karboksamida |
| RU2019108280A (ru) * | 2016-08-24 | 2020-09-25 | Аркьюл, Инк. | Аминопирролопиримидиноновые соединения и способы их применения |
| TW201815766A (zh) | 2016-09-22 | 2018-05-01 | 美商普雷辛肯公司 | 用於ｉｄｏ及ｔｄｏ調節之化合物及方法以及其適應症 |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| US12161696B2 (en) | 2016-12-02 | 2024-12-10 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| US20180153922A1 (en) | 2016-12-06 | 2018-06-07 | New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery | Inhibition of expansion and function of pathogenic age-associated b cells and use for the prevention and treatment of autoimmune disease |
| JP7193460B2 (ja) | 2016-12-23 | 2022-12-20 | プレキシコン インコーポレーテッド | Ｃｄｋ８調節およびその適応症のための化合物および方法 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| CN110267960B (zh) | 2017-01-18 | 2022-04-26 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[1,5-a]吡嗪化合物 |
| TWI752155B (zh) | 2017-02-01 | 2022-01-11 | 德商菲尼克斯製藥股份有限公司 | 芳香烴受體(AhR)調節劑化合物 |
| TWI674260B (zh) | 2017-02-01 | 2019-10-11 | 德商菲尼克斯製藥股份有限公司 | 芳基烴受體(AhR)調節劑化合物 |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| WO2018175311A1 (en) | 2017-03-20 | 2018-09-27 | Plexxikon Inc. | Crystalline forms of 4-(1-(1,1-di(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1h- pyrrolo[3,2-b]pyridin-3-yl)benzoic acid that inhibits bromodomain |
| US10428067B2 (en) | 2017-06-07 | 2019-10-01 | Plexxikon Inc. | Compounds and methods for kinase modulation |
| KR102615829B1 (ko) | 2017-07-25 | 2023-12-20 | 플렉시콘 인코퍼레이티드 | 키나제를 조정하는 화합물의 제제 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| AU2018348241B2 (en) | 2017-10-13 | 2023-01-12 | Opna Bio SA | Solid forms of a compound for modulating kinases |
| EP3700576A1 (en) | 2017-10-26 | 2020-09-02 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
| JP7175309B2 (ja) | 2017-10-27 | 2022-11-18 | プレキシコン インコーポレーテッド | キナーゼを調節する化合物の製剤 |
| CN111971286B (zh) | 2018-01-18 | 2023-04-14 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡咯并[2,3-d]嘧啶化合物 |
| TW201938169A (zh) | 2018-01-18 | 2019-10-01 | 美商亞雷生物製藥股份有限公司 | 作為RET激酶抑制劑之經取代吡唑并[3,4-d]嘧啶化合物 |
| WO2019143994A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| WO2019157119A1 (en) * | 2018-02-07 | 2019-08-15 | University Of Cincinnati | System and method for detecting small blood-tissue barrier disruption |
| WO2019183145A1 (en) | 2018-03-20 | 2019-09-26 | Plexxikon Inc. | Compounds and methods for ido and tdo modulation, and indications therefor |
| CA3095366A1 (en) | 2018-03-29 | 2019-10-03 | Loxo Oncology, Inc. | Treatment of trk-associated cancers |
| TW202015723A (zh) | 2018-05-18 | 2020-05-01 | 美商百歐維拉提夫治療公司 | 治療ａ型血友病的方法 |
| KR102129114B1 (ko) * | 2018-07-26 | 2020-07-02 | 주식회사 온코파마텍 | TrkA 저해 활성을 갖는 화합물 및 이를 유효성분으로 함유하는 통증의 예방 또는 치료용 약학적 조성물 |
| KR102653681B1 (ko) | 2018-07-31 | 2024-04-03 | 록쏘 온콜로지, 인코포레이티드 | (s)-5-아미노-3-(4-((5-플루오로-2-메톡시벤즈아미도)메틸)페닐)-1-(1,1,1-트리플루오로프로판-2-일)-1h-피라졸-4-카르복스아미드의분무-건조된 분산물 및 제제 |
| CN110833557A (zh) * | 2018-08-15 | 2020-02-25 | 广西梧州制药（集团）股份有限公司 | 吡唑并嘧啶衍生物在治疗肾小管肾炎的用途 |
| CN110833552A (zh) * | 2018-08-15 | 2020-02-25 | 广西梧州制药（集团）股份有限公司 | 吡唑并嘧啶衍生物在治疗狼疮肾炎的用途 |
| CN112888681B (zh) | 2018-08-22 | 2025-11-18 | 上海睿跃生物科技有限公司 | 原肌球蛋白受体激酶(trk)降解化合物及使用方法 |
| US11969472B2 (en) | 2018-08-22 | 2024-04-30 | Cullgen (Shanghai), Inc. | Tropomyosin receptor kinase (TRK) degradation compounds and methods of use |
| ES2922314T3 (es) | 2018-09-10 | 2022-09-13 | Array Biopharma Inc | Compuestos heterocíclicos condensados como inhibidores de cinasa RET |
| WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| EP3898626A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| CA3136224A1 (en) | 2019-04-09 | 2020-10-15 | Plexxikon Inc. | Condensed azines for ep300 or cbp modulation and indications therefor |
| CN110643672A (zh) * | 2019-10-15 | 2020-01-03 | 西安交通大学 | 高表达TrkB作为新型靶点在抑制胰腺癌转移方面的医药用途 |
| AU2021225981A1 (en) | 2020-02-26 | 2022-09-29 | Cullgen (Shanghai) , Inc. | Tropomyosin receptor kinase (TRK) degradation compounds and methods of use |
| WO2021216898A1 (en) | 2020-04-23 | 2021-10-28 | Plexxikon Inc. | Compounds and methods for cd73 modulation and indications therefor |
| IL297645B1 (en) | 2020-04-29 | 2025-09-01 | Plexxikon Inc | Synthesis of heterocyclic compounds |
| CA3192099A1 (en) | 2020-08-18 | 2022-02-24 | Incyte Corporation | Process and intermediates for preparing a jak inhibitor |
| WO2022040172A1 (en) | 2020-08-18 | 2022-02-24 | Incyte Corporation | Process and intermediates for preparing a jak1 inhibitor |
| EP4199926A1 (en) | 2020-08-21 | 2023-06-28 | Plexxikon Inc. | Combinational drug anticancer therapies |
| WO2022063241A1 (zh) * | 2020-09-25 | 2022-03-31 | 南京明德新药研发有限公司 | 1H-吡咯并[2,3-c]吡啶类化合物及其应用 |
| JP2024526762A (ja) | 2021-07-12 | 2024-07-19 | インサイト・コーポレイション | Ｊａｋ阻害剤を調製するためのプロセス及び中間体 |
| CN114920744B (zh) * | 2021-11-16 | 2024-05-07 | 中国药科大学 | 一种非共价btk激酶抑制剂及其生物用途 |
| AU2023238511B2 (en) * | 2022-03-25 | 2025-11-27 | Jumbo Drug Bank Co., Ltd. | Crystal form of 1h-pyrrolo[2,3-c]pyridine compound and preparation method therefor |
| WO2025244944A1 (en) * | 2024-05-20 | 2025-11-27 | Opna Bio SA | Crystal forms of an agent |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6316474B1 (en) * | 1999-10-29 | 2001-11-13 | Merck & Co., Inc. | 2-benzyl and 2-heteroaryl benzimidazole NMDA/NR2B antagonists |
| CN100351253C (zh) * | 2000-06-26 | 2007-11-28 | 辉瑞产品公司 | 作为免疫抑制剂的吡咯并[2,3－d]嘧啶化合物 |
| GB0107368D0 (en) * | 2001-03-23 | 2001-05-16 | Novartis Ag | Organic compounds |
| MXPA03010269A (es) | 2001-05-11 | 2004-05-05 | Vertex Pharma | Derivados de 2,5-disubstituida piridina, pirimidina, piridazina y 1,2,4-triazina para usarse como inhibidores de p38. |
| GEP20063909B (en) | 2002-01-22 | 2006-08-25 | Warner Lambert Co | 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3d] PYRIMIDIN-7-ONES |
| US20040171062A1 (en) | 2002-02-28 | 2004-09-02 | Plexxikon, Inc. | Methods for the design of molecular scaffolds and ligands |
| AU2003272548A1 (en) | 2002-09-16 | 2004-04-30 | Plexxikon, Inc. | Crystal structure of pim-1 kinase |
| GB0226370D0 (en) * | 2002-11-12 | 2002-12-18 | Novartis Ag | Organic compounds |
| US20050048573A1 (en) | 2003-02-03 | 2005-03-03 | Plexxikon, Inc. | PDE5A crystal structure and uses |
| SE0300456D0 (sv) | 2003-02-19 | 2003-02-19 | Astrazeneca Ab | Novel compounds |
| JP2007524374A (ja) | 2003-02-28 | 2007-08-30 | プレキシコン，インコーポレーテッド | Ｐｙｋ２結晶構造および使用 |
| US20050079548A1 (en) | 2003-07-07 | 2005-04-14 | Plexxikon, Inc. | Ligand development using PDE4B crystal structures |
| ATE412650T1 (de) | 2003-07-11 | 2008-11-15 | Warner Lambert Co | Isethionat salz eines selektiven cdk4 inhibitors |
| WO2005009958A1 (en) | 2003-07-17 | 2005-02-03 | Plexxikon, Inc. | Ppar active compounds |
| US7348338B2 (en) | 2003-07-17 | 2008-03-25 | Plexxikon, Inc. | PPAR active compounds |
| WO2005028624A2 (en) | 2003-09-15 | 2005-03-31 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
| ES2527118T3 (es) | 2003-12-19 | 2015-01-20 | Plexxikon Inc. | Compuestos y procedimientos de desarrollo de moduladores de Ret |
| US20070066641A1 (en) | 2003-12-19 | 2007-03-22 | Prabha Ibrahim | Compounds and methods for development of RET modulators |
| US7517970B2 (en) | 2003-12-19 | 2009-04-14 | Plexxikon, Inc. | Nucleic acids encoding kinase and phosphatase enzymes, expression vectors and cells containing same |
| EP1713806B1 (en) | 2004-02-14 | 2013-05-08 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| JP4866723B2 (ja) * | 2004-02-26 | 2012-02-01 | 協和発酵キリン株式会社 | 好中球性炎症疾患の予防及び／または治療剤 |
| WO2006078287A2 (en) | 2004-05-06 | 2006-07-27 | Plexxikon, Inc. | Pde4b inhibitors and uses therefor |
| MXPA06013805A (es) | 2004-05-27 | 2007-02-02 | Pfizer Prod Inc | Derivados de pirrolopirimidina de utilidad en el tratamiento contra el cancer. |
| TW200616632A (en) | 2004-06-17 | 2006-06-01 | Plexxikon Inc | Compounds modulating c-kit activity and uses therefor |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| WO2006026754A2 (en) | 2004-09-03 | 2006-03-09 | Plexxikon, Inc. | Bicyclic heteroaryl pde4b inhibitors |
| EP1833787A2 (en) | 2004-11-30 | 2007-09-19 | Plexxikon, Inc. | Indole derivatives for use as ppar active compounds |
| US7531568B2 (en) | 2004-11-30 | 2009-05-12 | Plexxikon, Inc. | PPAR active compounds |
| US20060160135A1 (en) | 2004-12-08 | 2006-07-20 | Weiru Wang | SF-1 and LRH-1 modulator development |
| CN101223169A (zh) * | 2005-05-17 | 2008-07-16 | 普莱希科公司 | 吡咯并[2,3-b]吡啶衍生物蛋白激酶抑制剂 |
| NZ563444A (en) * | 2005-05-17 | 2011-04-29 | Plexxikon Inc | Pyrrolo(2,3-b)pyridine derivatives as protein kinase inhibitors |
| UA95244C2 (ru) | 2005-06-22 | 2011-07-25 | Плексикон, Инк. | Соединения и способ модулирования активности киназ, и показания для их применения |
| EP1943245A2 (en) | 2005-09-07 | 2008-07-16 | Plexxikon, Inc. | 1,3-disubstituted indole derivatives for use as ppar modulators |
| TW200800872A (en) | 2005-09-07 | 2008-01-01 | Plexxikon Inc | PPAR active compounds |
| AU2006287528A1 (en) | 2005-09-07 | 2007-03-15 | Plexxikon, Inc. | 1 , 4 and 1 , 5-disubstituted indole derivatives for use as PPAR active compounds |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| US8093246B2 (en) | 2006-12-14 | 2012-01-10 | Lexicon Pharmaceuticals, Inc. | O-linked pyrimidin-4-amine-based compounds, compositions comprising them, and methods of their use to treat cancer |
| RU2009122670A (ru) | 2006-12-21 | 2011-01-27 | Плекссикон, Инк. (Us) | Соединения и способы для модуляции киназ и показания к их применению |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| PE20081581A1 (es) | 2006-12-21 | 2008-11-12 | Plexxikon Inc | COMPUESTOS PIRROLO[2,3-b]PIRIDINAS COMO MODULADORES DE QUINASA |
| BRPI0808196A2 (pt) | 2007-03-08 | 2014-07-08 | Plexxikon Inc | Compostos ativos de ppar |
| PE20090159A1 (es) | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| KR20090130345A (ko) | 2007-05-04 | 2009-12-22 | 아이알엠 엘엘씨 | Ｃ-ｋｉｔ 및 ｐｄｇｆｒ 키나제 억제제로서의 화합물 및 조성물 |
| SG183036A1 (en) | 2007-07-17 | 2012-08-30 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| JO3240B1 (ar) * | 2007-10-17 | 2018-03-08 | Janssen Pharmaceutica Nv | c-fms مثبطات كيناز |
| WO2009105712A1 (en) * | 2008-02-22 | 2009-08-27 | Irm Llc | Heterocyclic compounds and compositions as c-kit and pdgfr kinase inhibitors |
| WO2009115084A2 (de) | 2008-03-20 | 2009-09-24 | Schebo Biotech Ag | Neue pyrrolopyrimidin-derivate und deren verwendungen |
| US8865732B2 (en) | 2008-03-21 | 2014-10-21 | Novartis Ag | Heterocyclic compounds and uses thereof |
| PE20091846A1 (es) | 2008-05-19 | 2009-12-16 | Plexxikon Inc | DERIVADOS DE PIRROLO[2,3-d]-PIRIMIDINA COMO MODULADORES DE CINASAS |
| US8158636B2 (en) | 2008-05-19 | 2012-04-17 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP2313411A1 (en) | 2008-06-10 | 2011-04-27 | Plexxikon, Inc. | 5h-pyrr0l0 [2,3-b]pyrazine derivatives for kinase modulation, and indications therefor |
| WO2009152087A1 (en) | 2008-06-10 | 2009-12-17 | Plexxikon, Inc. | Bicyclic heteroaryl compounds and methods for kinase modulation, and indications therefor |
| BRPI0917459B1 (pt) | 2008-08-20 | 2017-09-12 | Zoetis Services Llc | N-methyl-1- [trans-4- [methyl (7h-pyrrol [2,3-d] pyridol [2,3-d] pyrimidine compounds, use of these in therapy and crystalline a form of n-methyl- pyrimidin-4-yl) amino] cyclohexyl} methanosulphonamide |
| KR101853026B1 (ko) | 2008-10-22 | 2018-04-27 | 어레이 바이오파마 인크. | ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５ａ］ 피리미딘 화합물 |
| AU2010224245B2 (en) | 2009-03-11 | 2016-07-21 | Plexxikon, Inc. | Pyrrolo [2, 3-b] pyridine derivatives for the inhibition of Raf kinases |
| TW201036972A (en) | 2009-03-11 | 2010-10-16 | Plexxikon Inc | Compounds and uses thereof |
| WO2010111527A1 (en) | 2009-03-26 | 2010-09-30 | Plexxikon, Inc. | Pyrazolo [ 3, 4 -b] pyridines as kinase inhibitors and their medical use |
| EA022924B1 (ru) | 2009-04-03 | 2016-03-31 | Ф.Хоффманн-Ля Рош Аг | ТВЁРДАЯ ФОРМА {3-[5-(4-ХЛОРФЕНИЛ)-1Н-ПИРРОЛО[2,3-b]ПИРИДИН-3-КАРБОНИЛ]-2,4-ДИФТОРФЕНИЛ}АМИДА ПРОПАН-1-СУЛЬФОНОВОЙ КИСЛОТЫ И ЕЁ ПРИМЕНЕНИЕ |
| MX2011011735A (es) | 2009-05-04 | 2011-11-29 | Plexxikon Inc | Compuestos y metodos para la inhibicion de renina, e indicaciones para ello. |
| TW201041888A (en) | 2009-05-06 | 2010-12-01 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
| MA33975B1 (fr) | 2009-11-06 | 2013-02-01 | Plexxikon Inc | Composés et méthodes de modulation des kinases et leurs indications d'emploi |
| CN105906631A (zh) | 2009-11-18 | 2016-08-31 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| RU2012131373A (ru) | 2009-12-23 | 2014-01-27 | Плексксикон, Инк. | Соединения и способы модулирования киназы, а также показания для такого модулирования |
| TWI510487B (zh) * | 2010-04-21 | 2015-12-01 | Plexxikon Inc | 用於激酶調節的化合物和方法及其適應症 |
| US8642606B2 (en) | 2010-09-29 | 2014-02-04 | Plexxikon Inc. | ZAP-70 active compounds |
| JP5941069B2 (ja) | 2011-02-07 | 2016-06-29 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | キナーゼ調節のための化合物および方法、ならびにそれに対する適応症 |
| AU2012255275B2 (en) | 2011-05-17 | 2016-01-28 | Plexxikon Inc. | Kinase modulation and indications therefor |
| US9358235B2 (en) | 2012-03-19 | 2016-06-07 | Plexxikon Inc. | Kinase modulation, and indications therefor |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| AU2013312477B2 (en) | 2012-09-06 | 2018-05-31 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP2935248B1 (en) | 2012-12-21 | 2018-02-28 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| KR102244719B1 (ko) | 2013-03-15 | 2021-04-26 | 플렉시콘 인코퍼레이티드 | 헤테로시클릭 화합물 및 그의 용도 |
| US20140303121A1 (en) | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| BR112015028845A2 (pt) | 2013-05-30 | 2017-07-25 | Plexxikon Inc | compostos para a modulação da quinase e indicações da mesma |
| WO2015134536A1 (en) | 2014-03-04 | 2015-09-11 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
-
2011
- 2011-04-19 TW TW100113512A patent/TWI510487B/zh not_active IP Right Cessation
- 2011-04-19 TW TW104127657A patent/TWI619713B/zh not_active IP Right Cessation
- 2011-04-20 MY MYPI2012004649A patent/MY160780A/en unknown
- 2011-04-20 SG SG2012076584A patent/SG184874A1/en unknown
- 2011-04-20 BR BR112012026927A patent/BR112012026927A2/pt not_active IP Right Cessation
- 2011-04-20 EP EP11772612.5A patent/EP2560972B1/en active Active
- 2011-04-20 SI SI201131348T patent/SI2560972T1/sl unknown
- 2011-04-20 CA CA2796998A patent/CA2796998C/en active Active
- 2011-04-20 LT LTEP11772612.5T patent/LT2560972T/lt unknown
- 2011-04-20 ES ES11772612.5T patent/ES2641643T3/es active Active
- 2011-04-20 HU HUE11772612A patent/HUE036461T2/hu unknown
- 2011-04-20 NZ NZ703538A patent/NZ703538A/en not_active IP Right Cessation
- 2011-04-20 MX MX2012012197A patent/MX336056B/es unknown
- 2011-04-20 AR ARP110101385A patent/AR080940A1/es not_active Application Discontinuation
- 2011-04-20 HR HRP20171660TT patent/HRP20171660T1/hr unknown
- 2011-04-20 CN CN201180030925.5A patent/CN102947305B/zh active Active
- 2011-04-20 RS RS20171089A patent/RS56588B1/sr unknown
- 2011-04-20 EA EA201290973A patent/EA028105B1/ru not_active IP Right Cessation
- 2011-04-20 PL PL11772612T patent/PL2560972T3/pl unknown
- 2011-04-20 KR KR1020127030470A patent/KR101799126B1/ko not_active Expired - Fee Related
- 2011-04-20 AU AU2011242778A patent/AU2011242778B2/en active Active
- 2011-04-20 UA UAA201212061A patent/UA109128C2/ru unknown
- 2011-04-20 PH PH1/2012/502103A patent/PH12012502103A1/en unknown
- 2011-04-20 MA MA35365A patent/MA34229B1/fr unknown
- 2011-04-20 JP JP2013506264A patent/JP5808793B2/ja active Active
- 2011-04-20 NZ NZ603087A patent/NZ603087A/en not_active IP Right Cessation
- 2011-04-20 GE GEAP201112896A patent/GEP20156251B/en unknown
- 2011-04-20 SM SM20170458T patent/SMT201700458T1/it unknown
- 2011-04-20 US US13/090,969 patent/US8901118B2/en active Active
- 2011-04-20 SG SG10201505606QA patent/SG10201505606QA/en unknown
- 2011-04-20 PE PE2012002054A patent/PE20130240A1/es active IP Right Grant
- 2011-04-20 PT PT117726125T patent/PT2560972T/pt unknown
- 2011-04-20 WO PCT/US2011/033192 patent/WO2011133637A2/en not_active Ceased
- 2011-04-20 DK DK11772612.5T patent/DK2560972T3/da active
- 2011-04-25 UY UY0001033346A patent/UY33346A/es not_active Application Discontinuation
-
2012
- 2012-10-10 EC ECSP12012245 patent/ECSP12012245A/es unknown
- 2012-10-17 IL IL222498A patent/IL222498A/en active IP Right Grant
- 2012-10-19 ZA ZA2012/07898A patent/ZA201207898B/en unknown
- 2012-10-19 CR CR20120536A patent/CR20120536A/es unknown
- 2012-10-19 CL CL2012002937A patent/CL2012002937A1/es unknown
- 2012-10-22 CO CO12187143A patent/CO6620045A2/es not_active Application Discontinuation
-
2014
- 2014-12-01 US US14/556,709 patent/US9682981B2/en active Active
-
2015
- 2015-09-09 JP JP2015177852A patent/JP2016028073A/ja active Pending
-
2017
- 2017-06-19 US US15/627,223 patent/US20170283423A1/en not_active Abandoned
- 2017-12-19 CY CY20171101332T patent/CY1120554T1/el unknown
-
2019
- 2019-09-03 AR ARP190102503A patent/AR115233A2/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT2560972T (pt) | Compostos e métodos para a modulação da quinase, e suas indicações | |
| AU2010315126B2 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| ES2664985T3 (es) | Compuestos y métodos para modulación de quinasa, e indicaciones de los mismos | |
| EP2501236B1 (en) | N-[2-fluoro-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-phenyl]-4-benzenesulfonamide derivatives as Raf protein kinase modulators for the treatment of cancer | |
| EP2516438A2 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| SG192686A1 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| HK1182382A (en) | Compounds and methods for kinase modulation, and indications therefor | |
| HK1182382B (en) | Compounds and methods for kinase modulation, and indications therefor | |
| HK1176238A (en) | N-[2-fluoro-3-(4-amino-7h-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-phenyl]-4 benzenesulfonamid e derivatives as raf protein kinase modulators for the treatment of cancer | |
| HK1176238B (en) | N-[2-fluoro-3-(4-amino-7h-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-phenyl]-4 benzenesulfonamid e derivatives as raf protein kinase modulators for the treatment of cancer | |
| HK1193750A (en) | Compounds for kinase modulation |