AU2011242778B2 - Compounds and methods for kinase modulation, and indications therefor - Google Patents
Compounds and methods for kinase modulation, and indications therefor Download PDFInfo
- Publication number
- AU2011242778B2 AU2011242778B2 AU2011242778A AU2011242778A AU2011242778B2 AU 2011242778 B2 AU2011242778 B2 AU 2011242778B2 AU 2011242778 A AU2011242778 A AU 2011242778A AU 2011242778 A AU2011242778 A AU 2011242778A AU 2011242778 B2 AU2011242778 B2 AU 2011242778B2
- Authority
- AU
- Australia
- Prior art keywords
- fluoro
- pyridyl
- formula
- pyrrolo
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 859
- 238000000034 method Methods 0.000 title claims abstract description 36
- 108091000080 Phosphotransferase Proteins 0.000 title description 34
- 102000020233 phosphotransferase Human genes 0.000 title description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 122
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
- 208000002193 Pain Diseases 0.000 claims abstract description 6
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims abstract description 4
- 208000007569 Giant Cell Tumors Diseases 0.000 claims abstract description 4
- 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract description 4
- 208000005298 acute pain Diseases 0.000 claims abstract description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims abstract description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims abstract description 4
- 208000004296 neuralgia Diseases 0.000 claims abstract description 4
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims abstract description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims abstract description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims abstract description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 3
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 3
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims abstract description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 3
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 3
- 208000016192 Demyelinating disease Diseases 0.000 claims abstract description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims abstract description 3
- 208000028622 Immune thrombocytopenia Diseases 0.000 claims abstract description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 3
- 208000005777 Lupus Nephritis Diseases 0.000 claims abstract description 3
- 206010027452 Metastases to bone Diseases 0.000 claims abstract description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims abstract description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims abstract description 3
- 208000009905 Neurofibromatoses Diseases 0.000 claims abstract description 3
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 3
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 3
- 206010052306 Periprosthetic osteolysis Diseases 0.000 claims abstract description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims abstract description 3
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 3
- 206010038468 Renal hypertrophy Diseases 0.000 claims abstract description 3
- 206010038540 Renal tubular necrosis Diseases 0.000 claims abstract description 3
- 201000009594 Systemic Scleroderma Diseases 0.000 claims abstract description 3
- 206010042953 Systemic sclerosis Diseases 0.000 claims abstract description 3
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims abstract description 3
- 206010052779 Transplant rejections Diseases 0.000 claims abstract description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 3
- 208000005017 glioblastoma Diseases 0.000 claims abstract description 3
- 201000006334 interstitial nephritis Diseases 0.000 claims abstract description 3
- 208000028867 ischemia Diseases 0.000 claims abstract description 3
- 201000008627 kidney hypertrophy Diseases 0.000 claims abstract description 3
- 201000005202 lung cancer Diseases 0.000 claims abstract description 3
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 3
- 201000001441 melanoma Diseases 0.000 claims abstract description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 3
- 201000004931 neurofibromatosis Diseases 0.000 claims abstract description 3
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 3
- 238000002054 transplantation Methods 0.000 claims abstract description 3
- 206010018338 Glioma Diseases 0.000 claims abstract 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 1117
- 125000000217 alkyl group Chemical group 0.000 claims description 827
- 125000003545 alkoxy group Chemical group 0.000 claims description 635
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 405
- -1 2-hydroxy-2-methylpropyl Chemical group 0.000 claims description 356
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 322
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 267
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 196
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 118
- 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 101
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 94
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 89
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 85
- 239000012453 solvate Substances 0.000 claims description 82
- 125000001246 bromo group Chemical group Br* 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 68
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
- 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 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 25
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- MCCFTLAQKWZOQM-UHFFFAOYSA-N n-(6-ethoxypyridin-3-yl)-6-fluoro-5-[[4-(2-methoxyethoxy)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methyl]pyridin-2-amine Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(OCCOC)=C12 MCCFTLAQKWZOQM-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 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
- 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 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[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
- 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
- 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
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005842 heteroatom Chemical group 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
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 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 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
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 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
- 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 12
- 241001024304 Mino Species 0.000 claims 11
- 102100024007 Neurofilament heavy polypeptide Human genes 0.000 claims 6
- 108010091047 neurofilament protein H Proteins 0.000 claims 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 3
- 229940127089 cytotoxic agent Drugs 0.000 claims 3
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 claims 2
- 241001293945 Pyla Species 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 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 1
- KHKJEQPWMFYWKH-UHFFFAOYSA-N 6-fluoro-n-(6-methoxypyridin-3-yl)-5-[(4-methyl-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(C)=C12 KHKJEQPWMFYWKH-UHFFFAOYSA-N 0.000 claims 1
- 208000010392 Bone Fractures Diseases 0.000 claims 1
- 206010006002 Bone pain Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 206010059282 Metastases to central nervous system Diseases 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- ORAFKLALYQRQIT-UHFFFAOYSA-N n-(6-ethoxypyridin-3-yl)-6-fluoro-5-[(4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]pyridin-2-amine Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(OC)=C12 ORAFKLALYQRQIT-UHFFFAOYSA-N 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 abstract description 20
- 101150111783 NTRK1 gene Proteins 0.000 abstract description 7
- 101150117329 NTRK3 gene Proteins 0.000 abstract description 7
- 101150056950 Ntrk2 gene Proteins 0.000 abstract description 7
- 238000009472 formulation Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 3
- 210000004556 brain Anatomy 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 622
- 239000001257 hydrogen Substances 0.000 description 622
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 444
- 150000002431 hydrogen Chemical class 0.000 description 169
- 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 99
- 229940002612 prodrug Drugs 0.000 description 73
- 239000000651 prodrug Substances 0.000 description 73
- LZTOGEVTAZHIFX-UHFFFAOYSA-N 5-chloro-3-iodo-1h-pyrrolo[2,3-b]pyridine Chemical compound ClC1=CN=C2NC=C(I)C2=C1 LZTOGEVTAZHIFX-UHFFFAOYSA-N 0.000 description 43
- 150000001721 carbon Chemical group 0.000 description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 32
- 102000001253 Protein Kinase Human genes 0.000 description 22
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 22
- 125000004414 alkyl thio 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
- 108060006633 protein kinase Proteins 0.000 description 22
- 239000003112 inhibitor Substances 0.000 description 17
- 230000009977 dual effect Effects 0.000 description 16
- IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 238000003674 kinase activity assay Methods 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
- SUTAZURMHGAKLC-UHFFFAOYSA-N 3-iodo-5-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound CC1=CN=C2NC=C(I)C2=C1 SUTAZURMHGAKLC-UHFFFAOYSA-N 0.000 description 5
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 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
- 102000003746 Insulin Receptor Human genes 0.000 description 5
- 108010001127 Insulin Receptor 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
- 108091008605 VEGF receptors Proteins 0.000 description 5
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 5
- 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 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 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 4
- BEUIXKFBVUPNKB-UHFFFAOYSA-N 5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-n-(6-ethoxypyridin-3-yl)-6-fluoropyridin-2-amine Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(C3CC3)=C12 BEUIXKFBVUPNKB-UHFFFAOYSA-N 0.000 description 4
- BNPDOVSUZOGACO-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(2-fluorophenyl)pyrimidin-2-amine Chemical compound FC1=CC=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 BNPDOVSUZOGACO-UHFFFAOYSA-N 0.000 description 4
- MJMRWGJDFKYTQB-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4,4-difluorocyclohexyl)pyrimidin-2-amine Chemical compound C1CC(F)(F)CCC1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 MJMRWGJDFKYTQB-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OTIQIXQAXLQVBB-UHFFFAOYSA-N [6-[(6-ethoxypyridin-3-yl)amino]-2-fluoropyridin-3-yl]-(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methanone Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=C(C)C=C12 OTIQIXQAXLQVBB-UHFFFAOYSA-N 0.000 description 4
- POFQRPQFAMZQJW-UHFFFAOYSA-N [6-[(6-ethylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methanone Chemical compound C1=NC(CC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=C(C)C=C12 POFQRPQFAMZQJW-UHFFFAOYSA-N 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 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 4
- 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 4
- 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 4
- 229910052727 yttrium Inorganic materials 0.000 description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- WOGKTRILIXDEDD-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-cycloheptylpyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1CCCCCC1 WOGKTRILIXDEDD-UHFFFAOYSA-N 0.000 description 3
- LDEYDWONANZBOT-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4-methylsulfanylphenyl)pyrimidin-2-amine Chemical compound C1=CC(SC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 LDEYDWONANZBOT-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229940124639 Selective inhibitor Drugs 0.000 description 3
- GENWKVGIZLQQTN-UHFFFAOYSA-N [2-fluoro-6-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methanone Chemical compound C1=NC(OC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=C(C)C=C12 GENWKVGIZLQQTN-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 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 3
- MWLPNUOHOUTGQJ-UHFFFAOYSA-N n-(4-tert-butylphenyl)-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)C)C=C1 MWLPNUOHOUTGQJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- LPXDZAOPZUIEQH-UHFFFAOYSA-N n-(6-ethoxypyridin-3-yl)-6-fluoro-5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyridin-2-amine Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=C(C)C=C12 LPXDZAOPZUIEQH-UHFFFAOYSA-N 0.000 description 3
- KJBNGJNDSKPULV-UHFFFAOYSA-N n-(6-ethylpyridin-3-yl)-6-fluoro-5-[[4-(2-methoxyethoxy)-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(OCCOC)=C12 KJBNGJNDSKPULV-UHFFFAOYSA-N 0.000 description 3
- LSMQPFBNHOXSHO-UHFFFAOYSA-N (4-cyclopropyl-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(C3CC3)=C12 LSMQPFBNHOXSHO-UHFFFAOYSA-N 0.000 description 2
- BCVMKRONCUNQIW-UHFFFAOYSA-N (4-cyclopropyl-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(C3CC3)=C12 BCVMKRONCUNQIW-UHFFFAOYSA-N 0.000 description 2
- MKVLVKPSKHTMNS-UHFFFAOYSA-N (4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[6-[(6-ethoxypyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(C3CC3)=C12 MKVLVKPSKHTMNS-UHFFFAOYSA-N 0.000 description 2
- LJBZLWOBKVYABU-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-[4-[[5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]pyrimidin-2-yl]amino]phenyl]propan-2-ol Chemical compound C12=CC(C)=CN=C2NC=C1CC(C=N1)=CN=C1NC1=CC=C(C(O)(C(F)(F)F)C(F)(F)F)C=C1 LJBZLWOBKVYABU-UHFFFAOYSA-N 0.000 description 2
- VFVXDLRMIQCASC-UHFFFAOYSA-N 1-cyclopropyl-4-[[5-[6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridine-3-carbonyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]pyrrolidin-2-one Chemical compound C=1C=C(C(=O)C=2C3=C(NC4CC(=O)N(C5CC5)C4)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 VFVXDLRMIQCASC-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
- QYRDNGSJFPWEFC-UHFFFAOYSA-N 5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-(6-methylpyridin-3-yl)pyridin-2-amine Chemical compound C1=NC(C)=CC=C1NC(N=C1F)=CC=C1CC1=CNC2=NC=NC(C3CC3)=C12 QYRDNGSJFPWEFC-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
- TVQAYSGMPHFGQH-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-cyclobutylpyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1CCC1 TVQAYSGMPHFGQH-UHFFFAOYSA-N 0.000 description 2
- NCORKKWHNDFVLA-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-cyclohexylpyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1CCCCC1 NCORKKWHNDFVLA-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
- XBNRADOMYLEETF-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-cyclopropylpyrimidin-2-amine Chemical compound C12=CC(Cl)=CN=C2NC=C1CC(C=N1)=CN=C1NC1CC1 XBNRADOMYLEETF-UHFFFAOYSA-N 0.000 description 2
- SVNWYIKDFLUUJG-UHFFFAOYSA-N 6-fluoro-5-[[4-(2-methoxyethoxy)-7h-pyrrolo[2,3-d]pyrimidin-5-yl]methyl]-n-(6-methoxypyridin-3-yl)pyridin-2-amine Chemical compound C1=2C(OCCOC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(OC)N=C1 SVNWYIKDFLUUJG-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WPHJWOLPGQVPNJ-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-(1h-pyrrolo[2,3-b]pyridin-3-yl)methanone Chemical compound C=1C=C(C(=O)C=2C3=CC=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 WPHJWOLPGQVPNJ-UHFFFAOYSA-N 0.000 description 2
- MTFRNSCMCXYMRD-UHFFFAOYSA-N [6-[(6-ethoxypyridin-3-yl)amino]-2-fluoropyridin-3-yl]-(4-methyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methanone Chemical compound C1=NC(OCC)=CC=C1NC(N=C1F)=CC=C1C(=O)C1=CNC2=NC=NC(C)=C12 MTFRNSCMCXYMRD-UHFFFAOYSA-N 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 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 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
- 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
- MHVRZWMGUNQFDR-UHFFFAOYSA-N n-(6-bromopyridin-3-yl)-5-[(4-ethoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoropyridin-2-amine Chemical compound C1=2C(OCC)=NC=NC=2NC=C1CC(C(=N1)F)=CC=C1NC1=CC=C(Br)N=C1 MHVRZWMGUNQFDR-UHFFFAOYSA-N 0.000 description 2
- LQRBTQMLTQNZDC-UHFFFAOYSA-N n-(6-cyclopropylpyridin-3-yl)-5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoropyridin-2-amine Chemical compound C=1C=C(CC=2C3=C(C4CC4)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 LQRBTQMLTQNZDC-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
- MCAADPPLQIKSNB-UHFFFAOYSA-N (4-amino-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]methanone Chemical compound C1=2C(N)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 MCAADPPLQIKSNB-UHFFFAOYSA-N 0.000 description 1
- SIUOFTDYBMUWPQ-UHFFFAOYSA-N (4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)-[6-(6,7-dihydro-5h-cyclopenta[b]pyridin-3-ylamino)-2-fluoropyridin-3-yl]methanone Chemical compound FC1=NC(NC=2C=C3CCCC3=NC=2)=CC=C1C(=O)C(C=12)=CNC2=NC=NC=1C1CC1 SIUOFTDYBMUWPQ-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 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 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
- YMLRTBHSRMDLQP-UHFFFAOYSA-N 5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoro-n-(5-methylpyridin-3-yl)pyridin-2-amine Chemical compound CC1=CN=CC(NC=2N=C(F)C(CC=3C4=C(C5CC5)N=CN=C4NC=3)=CC=2)=C1 YMLRTBHSRMDLQP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- CAGKBZLKFIFJFW-UHFFFAOYSA-N 5-[(5-chloro-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4-methylcyclohexyl)pyrimidin-2-amine Chemical compound C1CC(C)CCC1NC(N=C1)=NC=C1CC1=CNC2=NC=C(Cl)C=C12 CAGKBZLKFIFJFW-UHFFFAOYSA-N 0.000 description 1
- IMNANFZYGBVODJ-UHFFFAOYSA-N 5-[(5-methyl-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-n-(4-propoxyphenyl)pyrimidin-2-amine Chemical compound C1=CC(OCCC)=CC=C1NC(N=C1)=NC=C1CC1=CNC2=NC=C(C)C=C12 IMNANFZYGBVODJ-UHFFFAOYSA-N 0.000 description 1
- 241000270722 Crocodylidae Species 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 101100438748 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cyt-2 gene Proteins 0.000 description 1
- 101150078855 RR33 gene Proteins 0.000 description 1
- ZVQNVYRKVWPYBM-UHFFFAOYSA-N [2-fluoro-6-[(5-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)F)=CC=C1NC1=CN=CC(OC)=C1 ZVQNVYRKVWPYBM-UHFFFAOYSA-N 0.000 description 1
- 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 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
- BMGUGRXFBFRZEV-UHFFFAOYSA-N [4-(cyclohexylamino)-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(NC3CCCCC3)=C12 BMGUGRXFBFRZEV-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
- XTLZUAAGYLGJEM-UHFFFAOYSA-N [4-(cyclopropylamino)-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(NC3CC3)=C12 XTLZUAAGYLGJEM-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- LICZZOHNIURVBP-LBPRGKRZSA-N [4-[[(1s)-1-cyclopropylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]-[6-[(4,4-difluorocyclohexyl)amino]-5-fluoropyridin-3-yl]methanone Chemical compound N([C@@H](C)C1CC1)C(C1=2)=NC=NC=2NC=C1C(=O)C(C=C1F)=CN=C1NC1CCC(F)(F)CC1 LICZZOHNIURVBP-LBPRGKRZSA-N 0.000 description 1
- 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 description 1
- FENZTOJYXRYVBZ-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)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=1NC1CCC(F)(F)CC1 FENZTOJYXRYVBZ-UHFFFAOYSA-N 0.000 description 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 description 1
- BLPGXVOGHTVVKM-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)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=1NC1CCC(F)(F)CC1 BLPGXVOGHTVVKM-UHFFFAOYSA-N 0.000 description 1
- LHRCGLXUDAFJTE-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-2-fluoropyridin-3-yl]-[4-[(1,1-dioxothian-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)CCC4)N=CN=C3NC=2)C(F)=NC=1NC1CCC(F)(F)CC1 LHRCGLXUDAFJTE-UHFFFAOYSA-N 0.000 description 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 description 1
- CGCPDJXUBBCKCK-UHFFFAOYSA-N [6-[(4,4-difluorocyclohexyl)amino]-5-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=C1F)=CN=C1NC1CCC(F)(F)CC1 CGCPDJXUBBCKCK-UHFFFAOYSA-N 0.000 description 1
- FERDLOFWAJXPGK-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-(4-methyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methanone Chemical compound C1=2C(C)=NC=NC=2NC=C1C(=O)C(C(=N1)F)=CC=C1NC(C=N1)=CC=C1C1CC1 FERDLOFWAJXPGK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- VBHLKVYEPTYWMP-UHFFFAOYSA-N [6-[(6-cyclopropylpyridin-3-yl)amino]-2-fluoropyridin-3-yl]-[4-[(1,1-dioxothian-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)CCC4)N=CN=C3NC=2)C(F)=NC=1NC(C=N1)=CC=C1C1CC1 VBHLKVYEPTYWMP-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
- 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 description 1
- NXYJGRDGHPDSRT-CYBMUJFWSA-N [6-[(6-cyclopropylpyridin-3-yl)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=C1NC(C=N1)=CC=C1C1CC1 NXYJGRDGHPDSRT-CYBMUJFWSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940043355 kinase inhibitor Drugs 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
- WCMSRNKKCNJVLL-UHFFFAOYSA-N n-[5-[(4-cyclopropyl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]-6-fluoropyridin-2-yl]-6,7-dihydro-5h-cyclopenta[b]pyridin-3-amine Chemical compound FC1=NC(NC=2C=C3CCCC3=NC=2)=CC=C1CC(C=12)=CNC2=NC=NC=1C1CC1 WCMSRNKKCNJVLL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000011282 treatment Methods 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)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32662610P | 2010-04-21 | 2010-04-21 | |
| US61/326,626 | 2010-04-21 | ||
| PCT/US2011/033192 WO2011133637A2 (en) | 2010-04-21 | 2011-04-20 | Compounds and methods for kinase modulation, and indications therefor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2011242778A1 AU2011242778A1 (en) | 2012-11-22 |
| AU2011242778B2 true AU2011242778B2 (en) | 2015-09-03 |
Family
ID=44816304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011242778A Active AU2011242778B2 (en) | 2010-04-21 | 2011-04-20 | Compounds and methods for kinase modulation, and indications therefor |
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 |
| WO2009143018A2 (en) | 2008-05-19 | 2009-11-26 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| US8450322B2 (en) | 2008-09-22 | 2013-05-28 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as Trk kinase inhibitors |
| TR201807039T4 (tr) | 2008-10-22 | 2018-06-21 | Array Biopharma Inc | Trk kinaz inhibitörleri olarak sübstitüe edilmiş pirazolo[1,5-]pirimidin bileşikleri. |
| AU2010232670B2 (en) | 2009-04-03 | 2015-07-09 | F. Hoffmann-La Roche Ag | Propane- I-sulfonic acid {3- [5- (4 -chloro-phenyl) -1H-pyrrolo [2, 3-b] pyridine-3-carbonyl] -2, 4-difluoro-pheny l } -amide compositions and uses thereof |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| MX2012005284A (es) | 2009-11-06 | 2012-06-28 | Plexxikon Inc | Compuestos y metodos para la modulacion de cinasas. e indicaciones para ello. |
| CN102740698A (zh) | 2009-11-18 | 2012-10-17 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| BR112012015745A2 (pt) | 2009-12-23 | 2016-05-17 | Plexxikon Inc | compostos e métodos para a modulação de quinase, e indicações dos mesmos |
| TWI619713B (zh) | 2010-04-21 | 2018-04-01 | 普雷辛肯公司 | 用於激酶調節的化合物和方法及其適應症 |
| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| KR101911972B1 (ko) | 2011-02-07 | 2018-10-25 | 플렉시콘 인코퍼레이티드 | 키나제 조절을 위한 화합물 및 방법, 및 그에 대한 적응증 |
| AP2013007159A0 (en) | 2011-04-05 | 2013-10-31 | Pfizer Ltd | Pyrrolo [2,3-D] pyrimidine derivatives as inhibitors of tropomyosin-related kinase |
| SG194847A1 (en) | 2011-05-17 | 2013-12-30 | 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 |
| WO2014018888A1 (en) | 2012-07-26 | 2014-01-30 | Confluence Life Sciences Inc. | 4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as tak1 inhibitors in disease treatment |
| WO2014039714A2 (en) | 2012-09-06 | 2014-03-13 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2014053968A1 (en) | 2012-10-04 | 2014-04-10 | Pfizer Limited | Pyrrolo[3,2-c]pyridine tropomyosin-related kinase inhibitors |
| JP2015531393A (ja) | 2012-10-04 | 2015-11-02 | ファイザー・リミテッドＰｆｉｚｅｒ Ｌｉｍｉｔｅｄ | トロポミオシン関連キナーゼ阻害剤 |
| CA2885253A1 (en) | 2012-10-04 | 2014-04-10 | Pfizer Limited | Pyrrolo[2,3-d]pyrimidine tropomyosin-related kinase inhibitors |
| CA2895239C (en) | 2012-12-21 | 2020-10-27 | 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 |
| WO2014145051A1 (en) | 2013-03-15 | 2014-09-18 | Jiazhong Zhang | 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 |
| EP3628749A1 (en) | 2013-07-30 | 2020-04-01 | Blueprint Medicines Corporation | Ntrk2 fusions |
| JP2016540811A (ja) | 2013-12-20 | 2016-12-28 | ファイザー・リミテッドＰｆｉｚｅｒ Ｌｉｍｉｔｅｄ | Ｎ−アシルピペリジンエーテルトロポミオシン関連キナーゼ阻害剤 |
| CN114736305B (zh) * | 2014-01-10 | 2023-05-05 | 比奥贝拉蒂治疗公司 | 因子viii嵌合蛋白及其用途 |
| US9771369B2 (en) | 2014-03-04 | 2017-09-26 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2015159175A1 (en) | 2014-04-15 | 2015-10-22 | 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 |
| WO2016044067A1 (en) | 2014-09-15 | 2016-03-24 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| PT3699181T (pt) | 2014-11-16 | 2023-04-05 | Array Biopharma Inc | Forma cristalina de hidrogenossulfato de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| US20180263945A1 (en) * | 2014-12-19 | 2018-09-20 | Research Institute At Nationwide Children's Hospital | Pyruvate compounds for treatment of peripheral neuropathy |
| AU2016209046A1 (en) | 2015-01-23 | 2017-07-20 | Aclaris Therapeutics, 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 |
| BR112017023540B1 (pt) | 2015-05-06 | 2023-04-04 | Plexxikon, Inc. | Processos de preparação de derivados de 1h-pirrolo[2,3-b]piridina que modulam quinases |
| HRP20201383T1 (hr) | 2015-05-06 | 2020-11-27 | Plexxikon Inc. | Kruti oblici spoja za moduliranje kinaza |
| US10316032B2 (en) | 2015-05-22 | 2019-06-11 | Plexxikon Inc. | Solid forms of a compound for modulating kinases |
| TN2017000502A1 (en) | 2015-06-01 | 2019-04-12 | Loxo Oncology Inc | Methods of diagnosing and treating cancer |
| RS61485B1 (sr) | 2015-07-16 | 2021-03-31 | Array Biopharma Inc | Supstituisana pirazolo [1,5-a] piridinska jedinjenja kao inhibitori ret kinaze |
| WO2017019804A2 (en) | 2015-07-28 | 2017-02-02 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| EP3353179B1 (en) | 2015-09-21 | 2022-02-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| TN2018000138A1 (en) | 2015-10-26 | 2019-10-04 | Array Biopharma Inc | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| WO2017100201A1 (en) | 2015-12-07 | 2017-06-15 | 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 |
| ES2904615T3 (es) | 2016-03-16 | 2022-04-05 | Plexxikon Inc | Compuestos y métodos para la modulación de quinasas e indicaciones al respecto |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| CN109414442B (zh) | 2016-04-04 | 2024-03-29 | 洛克索肿瘤学股份有限公司 | 一种化合物的液体制剂 |
| RS65988B1 (sr) | 2016-04-04 | 2024-10-31 | Loxo Oncology Inc | Postupak lečenja pedijatrijskih karcinoma |
| EP3454860B1 (en) * | 2016-05-11 | 2025-09-17 | Beta Pharma, Inc. | 2-anilinopyrimidine derivatives as therapeutic agents for treatment of brain cancers |
| DK3800189T3 (da) | 2016-05-18 | 2023-07-31 | Loxo Oncology Inc | Fremstilling af (s)-n-(5-((r)-2-(2,5-difluorphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid |
| SG11201901197PA (en) * | 2016-08-24 | 2019-03-28 | Arqule Inc | Amino-pyrrolopyrimidinone compounds and methods of use thereof |
| 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 |
| IL308416B2 (en) | 2016-12-02 | 2025-08-01 | 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 |
| WO2018136202A2 (en) | 2016-12-23 | 2018-07-26 | Plexxikon Inc. | Compounds and methods for cdk8 modulation and indications therefor |
| EP3571203B1 (en) | 2017-01-18 | 2023-06-07 | Array BioPharma Inc. | Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| 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 |
| 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 |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CA3056777A1 (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 |
| WO2018226846A1 (en) | 2017-06-07 | 2018-12-13 | Plexxikon Inc. | Compounds and methods for kinase modulation |
| TWI805599B (zh) | 2017-07-25 | 2023-06-21 | 美商第一三共公司 | 激酶調節化合物之調配物 |
| 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 |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 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 |
| US10717735B2 (en) | 2017-10-13 | 2020-07-21 | Plexxikon Inc. | 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 |
| TWI803530B (zh) | 2017-10-27 | 2023-06-01 | 美商普雷辛肯公司 | 調節激酶之化合物之調配物 |
| CN111615514B (zh) | 2018-01-18 | 2022-10-11 | 奥瑞生物药品公司 | 作为ret激酶抑制剂的取代的吡唑并[4,3-c]吡啶化合物 |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds 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 |
| MA52630B1 (fr) | 2018-05-18 | 2025-07-31 | Bioverativ Therapeutics Inc. | Procédés de traitement de l'hémophilie a |
| 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 |
| CA3224945C (en) | 2018-07-31 | 2025-11-18 | Loxo Oncology, Inc. | SPRAY DRIED DISPERSIONS, FORMULATIONS AND POLYMORPHIES OF (S)-5-AMINO-3-(4-((5-FLUORO-2-METHOXYBENZAMIDO)METHYL)PHENYL)(1,1,1-TRIFLUOROPROPAN-2-YL)-1H-PYRAZOLE-4-CARBOXAMIDE |
| 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 |
| US11969472B2 (en) | 2018-08-22 | 2024-04-30 | Cullgen (Shanghai), Inc. | Tropomyosin receptor kinase (TRK) degradation compounds and methods of use |
| EP3841098A4 (en) | 2018-08-22 | 2022-05-04 | Cullgen (Shanghai), Inc. | TROPOMYOSIN RECEPTOR KINASE (TRK) DEGRADATION COMPOUNDS AND METHOD OF USE |
| JP2022500383A (ja) | 2018-09-10 | 2022-01-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての縮合複素環式化合物 |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| CN113474337A (zh) | 2018-12-19 | 2021-10-01 | 奥瑞生物药品公司 | 作为fgfr抑制剂用于治疗癌症的7-((3，5-二甲氧基苯基)氨基)喹喔啉衍生物 |
| AU2020271836B2 (en) | 2019-04-09 | 2025-11-13 | Opna Bio SA | 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 |
| CN115697989B (zh) | 2020-02-26 | 2025-03-18 | 上海睿跃生物科技有限公司 | 原肌球蛋白受体激酶(trk)降解化合物和使用方法 |
| AU2021261383A1 (en) | 2020-04-23 | 2022-11-17 | Opna Bio SA | Compounds and methods for CD73 modulation and indications therefor |
| EP4143168A1 (en) | 2020-04-29 | 2023-03-08 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| WO2022040180A1 (en) | 2020-08-18 | 2022-02-24 | Incyte Corporation | Process and intermediates for preparing a jak inhibitor |
| BR112023002939A2 (pt) | 2020-08-18 | 2023-04-25 | Incyte Corp | Processo e intermediários para preparar um inibidor de jak1 |
| JP2023542473A (ja) | 2020-08-21 | 2023-10-10 | プレキシコン インコーポレーテッド | 併用薬抗がん治療 |
| KR20230058134A (ko) * | 2020-09-25 | 2023-05-02 | 점보 드러그 뱅크 컴퍼니 리미티드 | 1H-피롤로[2,3-c]피리딘계 화합물 및 이의 용도 |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007013896A2 (en) * | 2005-05-17 | 2007-02-01 | Plexxikon, Inc. | Pyrrol (2,3-b) pyridine derivatives protein kinase inhibitors |
| US20090076046A1 (en) * | 2006-11-22 | 2009-03-19 | Plexxikon Inc | Compounds modulating c-fms and/or c-kit activity and uses therefor |
Family Cites Families (73)
| 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 |
| SK17342002A3 (sk) | 2000-06-26 | 2004-06-08 | Pfizer Products Inc. | Derivát pyrolo[2,3-d]pyrimidínu ako činidlo potlačujúce imunitu |
| GB0107368D0 (en) * | 2001-03-23 | 2001-05-16 | Novartis Ag | Organic compounds |
| WO2002092087A1 (en) | 2001-05-11 | 2002-11-21 | Vertex Pharmaceuticals Incorporated | 2,5-disubstituted pyridine, pyrimidine, pyridazine and 1, 2, 4-triazine derivatives for use as p38 inhibitors |
| CN101001857B (zh) | 2002-01-22 | 2011-06-22 | 沃尼尔·朗伯有限责任公司 | 2-(吡啶-2-基氨基)-吡啶并[2,3-d]嘧啶-7-酮 |
| US20040171062A1 (en) | 2002-02-28 | 2004-09-02 | Plexxikon, Inc. | Methods for the design of molecular scaffolds and ligands |
| EP1558751A4 (en) | 2002-09-16 | 2007-08-22 | Plexxikon Inc | CRYSTALLINE STRUCTURE OF PROTEIN KINASE PIM-1 |
| 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 |
| DK1648889T3 (da) | 2003-07-11 | 2009-01-05 | Warner Lambert Co | Isethionatsalt af en selektiv CDK4-inhibitor |
| US7348338B2 (en) | 2003-07-17 | 2008-03-25 | Plexxikon, Inc. | PPAR active compounds |
| WO2005009958A1 (en) | 2003-07-17 | 2005-02-03 | Plexxikon, Inc. | Ppar active compounds |
| US20050164300A1 (en) | 2003-09-15 | 2005-07-28 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
| US7517970B2 (en) | 2003-12-19 | 2009-04-14 | Plexxikon, Inc. | Nucleic acids encoding kinase and phosphatase enzymes, expression vectors and cells containing same |
| US20070066641A1 (en) | 2003-12-19 | 2007-03-22 | Prabha Ibrahim | Compounds and methods for development of RET modulators |
| US7504509B2 (en) | 2003-12-19 | 2009-03-17 | Plexxikon, Inc. | Compounds and methods for development of Ret modulators |
| ES2424642T3 (es) * | 2004-02-14 | 2013-10-07 | Irm Llc | Compuestos y composiciones como inhibidores de la proteína quinasa |
| 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 |
| CA2565965A1 (en) | 2004-05-06 | 2006-07-27 | Plexxikon, Inc. | Pde4b inhibitors and uses therefor |
| WO2005116035A1 (en) | 2004-05-27 | 2005-12-08 | Pfizer Products Inc. | Pyrrolopyrimidine derivatives useful in cancer treatment |
| US20060058339A1 (en) | 2004-06-17 | 2006-03-16 | Ibrahim Prabha N | Compounds modulating c-kit activity and uses therefor |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| CA2583428A1 (en) | 2004-09-03 | 2006-03-09 | Plexxikon, Inc. | Bicyclic heteroaryl pde4b inhibitors |
| CA2589896A1 (en) | 2004-11-30 | 2006-06-08 | Plexxikon, Inc. | Indole derivatives for use as ppar active compounds |
| AU2005311925A1 (en) | 2004-11-30 | 2006-06-08 | Plexxikon, Inc. | Indole derivatives for use as PPAR 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 |
| TWI473808B (zh) | 2005-06-22 | 2015-02-21 | Plexxikon Inc | 用於激酶調節的化合物及方法及其適應症 |
| CN101304992A (zh) | 2005-09-07 | 2008-11-12 | 普莱希科公司 | 用作ppar调节剂的1,3-二取代吲哚衍生物 |
| JP2009507846A (ja) | 2005-09-07 | 2009-02-26 | プレキシコン，インコーポレーテッド | Ｐｐａｒ活性化合物 |
| US20080234349A1 (en) | 2005-09-07 | 2008-09-25 | Jack Lin | PPAR active compounds |
| 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 |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| JP2010514695A (ja) | 2006-12-21 | 2010-05-06 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物および方法およびそのための適応症 |
| PE20121126A1 (es) | 2006-12-21 | 2012-08-24 | Plexxikon Inc | Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa |
| PE20090159A1 (es) | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| JP2010520303A (ja) | 2007-03-08 | 2010-06-10 | プレキシコン，インコーポレーテッド | Ｐｐａｒ活性化合物 |
| EP2148875A1 (en) * | 2007-05-04 | 2010-02-03 | Irm Llc | Compounds and compositions as c-kit and pdgfr kinase inhibitors |
| 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 |
| CL2009000400A1 (es) * | 2008-02-22 | 2010-09-10 | Irm Llc | Compuestos heterociclicos derivados de 3-fenil-1,6- naftiridin-2-ona; moduladores de la actividad cinasa; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como trastornos alergicos, trastornos autoinmunes, neoplasias, rechazo en trasplante de organos, entre otras. |
| 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 |
| WO2009143018A2 (en) | 2008-05-19 | 2009-11-26 | Plexxikon, Inc. | Compounds and methods 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 |
| CN104530052A (zh) | 2008-06-10 | 2015-04-22 | 普莱希科公司 | 用于激酶调节的5h-吡咯[2,3-b]吡嗪衍生物和其适应症 |
| 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 |
| TR201807039T4 (tr) | 2008-10-22 | 2018-06-21 | Array Biopharma Inc | Trk kinaz inhibitörleri olarak sübstitüe edilmiş pirazolo[1,5-]pirimidin bileşikleri. |
| KR101663339B1 (ko) | 2009-03-11 | 2016-10-06 | 플렉시콘 인코퍼레이티드 | Ｒａｆ 키나제의 억제를 위한 피롤로［２,３-ｂ］피리딘 유도체 |
| CN102421775A (zh) | 2009-03-11 | 2012-04-18 | 普莱希科公司 | 抑制Raf激酶的吡咯并[2，3-b]吡啶衍生物 |
| WO2010111527A1 (en) | 2009-03-26 | 2010-09-30 | Plexxikon, Inc. | Pyrazolo [ 3, 4 -b] pyridines as kinase inhibitors and their medical use |
| AU2010232670B2 (en) | 2009-04-03 | 2015-07-09 | F. Hoffmann-La Roche Ag | Propane- I-sulfonic acid {3- [5- (4 -chloro-phenyl) -1H-pyrrolo [2, 3-b] pyridine-3-carbonyl] -2, 4-difluoro-pheny l } -amide compositions and uses thereof |
| 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 |
| MX2012005284A (es) | 2009-11-06 | 2012-06-28 | Plexxikon Inc | Compuestos y metodos para la modulacion de cinasas. e indicaciones para ello. |
| CN102740698A (zh) | 2009-11-18 | 2012-10-17 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| BR112012015745A2 (pt) | 2009-12-23 | 2016-05-17 | Plexxikon Inc | compostos e métodos para a modulação de quinase, e indicações dos mesmos |
| TWI619713B (zh) * | 2010-04-21 | 2018-04-01 | 普雷辛肯公司 | 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 |
| KR101911972B1 (ko) | 2011-02-07 | 2018-10-25 | 플렉시콘 인코퍼레이티드 | 키나제 조절을 위한 화합물 및 방법, 및 그에 대한 적응증 |
| SG194847A1 (en) | 2011-05-17 | 2013-12-30 | 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 |
| WO2014039714A2 (en) | 2012-09-06 | 2014-03-13 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CA2895239C (en) | 2012-12-21 | 2020-10-27 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| WO2014145051A1 (en) | 2013-03-15 | 2014-09-18 | Jiazhong Zhang | Heterocyclic compounds and uses thereof |
| 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 |
| US9771369B2 (en) | 2014-03-04 | 2017-09-26 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
-
2011
- 2011-04-19 TW TW104127657A patent/TWI619713B/zh not_active IP Right Cessation
- 2011-04-19 TW TW100113512A patent/TWI510487B/zh not_active IP Right Cessation
- 2011-04-20 HU HUE11772612A patent/HUE036461T2/hu unknown
- 2011-04-20 PH PH1/2012/502103A patent/PH12012502103A1/en unknown
- 2011-04-20 WO PCT/US2011/033192 patent/WO2011133637A2/en not_active Ceased
- 2011-04-20 ES ES11772612.5T patent/ES2641643T3/es active Active
- 2011-04-20 PE PE2012002054A patent/PE20130240A1/es active IP Right Grant
- 2011-04-20 CN CN201180030925.5A patent/CN102947305B/zh active Active
- 2011-04-20 MY MYPI2012004649A patent/MY160780A/en unknown
- 2011-04-20 SM SM20170458T patent/SMT201700458T1/it unknown
- 2011-04-20 JP JP2013506264A patent/JP5808793B2/ja active Active
- 2011-04-20 SG SG10201505606QA patent/SG10201505606QA/en unknown
- 2011-04-20 NZ NZ603087A patent/NZ603087A/en not_active IP Right Cessation
- 2011-04-20 BR BR112012026927A patent/BR112012026927A2/pt not_active IP Right Cessation
- 2011-04-20 SI SI201131348T patent/SI2560972T1/sl unknown
- 2011-04-20 US US13/090,969 patent/US8901118B2/en active Active
- 2011-04-20 MA MA35365A patent/MA34229B1/fr unknown
- 2011-04-20 MX MX2012012197A patent/MX336056B/es unknown
- 2011-04-20 EA EA201290973A patent/EA028105B1/ru not_active IP Right Cessation
- 2011-04-20 HR HRP20171660TT patent/HRP20171660T1/hr unknown
- 2011-04-20 AU AU2011242778A patent/AU2011242778B2/en active Active
- 2011-04-20 EP EP11772612.5A patent/EP2560972B1/en active Active
- 2011-04-20 GE GEAP201112896A patent/GEP20156251B/en unknown
- 2011-04-20 CA CA2796998A patent/CA2796998C/en active Active
- 2011-04-20 LT LTEP11772612.5T patent/LT2560972T/lt unknown
- 2011-04-20 PT PT117726125T patent/PT2560972T/pt unknown
- 2011-04-20 RS RS20171089A patent/RS56588B1/sr unknown
- 2011-04-20 UA UAA201212061A patent/UA109128C2/ru unknown
- 2011-04-20 AR ARP110101385A patent/AR080940A1/es not_active Application Discontinuation
- 2011-04-20 DK DK11772612.5T patent/DK2560972T3/da active
- 2011-04-20 NZ NZ703538A patent/NZ703538A/en not_active IP Right Cessation
- 2011-04-20 SG SG2012076584A patent/SG184874A1/en unknown
- 2011-04-20 PL PL11772612T patent/PL2560972T3/pl unknown
- 2011-04-20 KR KR1020127030470A patent/KR101799126B1/ko not_active Expired - Fee Related
- 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 CR CR20120536A patent/CR20120536A/es unknown
- 2012-10-19 ZA ZA2012/07898A patent/ZA201207898B/en 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
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007013896A2 (en) * | 2005-05-17 | 2007-02-01 | Plexxikon, Inc. | Pyrrol (2,3-b) pyridine derivatives protein kinase inhibitors |
| US20090076046A1 (en) * | 2006-11-22 | 2009-03-19 | Plexxikon Inc | Compounds modulating c-fms and/or c-kit activity and uses therefor |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011242778B2 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| AU2010315126B2 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| 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 | |
| SG192686A1 (en) | Compounds and methods for kinase modulation, and indications therefor | |
| CA2784393A1 (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 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| PC | Assignment registered |
Owner name: OPNA IMMUNO ONCOLOGY, SA Free format text: FORMER OWNER(S): PLEXXIKON, INC. |