AU2013333938A1 - Pyrrolotriazinone derivatives as PI3K inhibitors - Google Patents

Info

Publication number

AU2013333938A1

AU2013333938A1 AU2013333938A AU2013333938A AU2013333938A1 AU 2013333938 A1 AU2013333938 A1 AU 2013333938A1 AU 2013333938 A AU2013333938 A AU 2013333938A AU 2013333938 A AU2013333938 A AU 2013333938A AU 2013333938 A1 AU2013333938 A1 AU 2013333938A1

Authority

AU

Australia

Prior art keywords

group

phenyl

amino

triazin

ethyl

Prior art date

2012-10-16

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• BEBRHYJBTAMGRW-UHFFFAOYSA-N pyrrolo[3,2-d]triazin-4-one Chemical class O=C1N=NN=C2C=CN=C12 BEBRHYJBTAMGRW-UHFFFAOYSA-N 0.000 title claims abstract description 7
• 239000012828 PI3K inhibitor Substances 0.000 title 1
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title 1
• 239000003112 inhibitor Substances 0.000 claims abstract description 23
• 102000038030 PI3Ks Human genes 0.000 claims abstract description 19
• 108091007960 PI3Ks Proteins 0.000 claims abstract description 19
• 238000000034 method Methods 0.000 claims abstract description 18
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims abstract description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims description 414
• 229910052757 nitrogen Inorganic materials 0.000 claims description 374
• 229910052717 sulfur Inorganic materials 0.000 claims description 367
• 125000005842 heteroatom Chemical group 0.000 claims description 364
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 347
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 313
• 125000002950 monocyclic group Chemical group 0.000 claims description 271
• 125000001424 substituent group Chemical group 0.000 claims description 247
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 245
• 125000005843 halogen group Chemical group 0.000 claims description 244
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 242
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 236
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 235
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 234
• 125000002619 bicyclic group Chemical group 0.000 claims description 234
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 219
• 150000001875 compounds Chemical class 0.000 claims description 176
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 114
• -1 R 13 R 1 4 R 1 5 Chemical compound 0.000 claims description 109
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 107
• 125000000217 alkyl group Chemical group 0.000 claims description 99
• 125000000623 heterocyclic group Chemical group 0.000 claims description 96
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 77
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 77
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 58
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 47
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 45
• 238000011282 treatment Methods 0.000 claims description 39
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 38
• 201000010099 disease Diseases 0.000 claims description 37
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 34
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 33
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 239000001257 hydrogen Substances 0.000 claims description 29
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 28
• 206010028980 Neoplasm Diseases 0.000 claims description 27
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 25
• 230000001575 pathological effect Effects 0.000 claims description 23
• 125000004076 pyridyl group Chemical group 0.000 claims description 22
• 229910052701 rubidium Inorganic materials 0.000 claims description 22
• IMHBYKMAHXWHRP-UHFFFAOYSA-N anilazine Chemical compound ClC1=CC=CC=C1NC1=NC(Cl)=NC(Cl)=N1 IMHBYKMAHXWHRP-UHFFFAOYSA-N 0.000 claims description 21
• 125000003386 piperidinyl group Chemical group 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 20
• ZUXFRUCHCPINRH-UHFFFAOYSA-N 2-phenyl-1h-pyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N1N2C=CC=C2C(=O)N=C1C1=CC=CC=C1 ZUXFRUCHCPINRH-UHFFFAOYSA-N 0.000 claims description 19
• 102220285342 rs777971423 Human genes 0.000 claims description 18
• 125000000304 alkynyl group Chemical group 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
• 206010004146 Basal cell carcinoma Diseases 0.000 claims description 16
• 208000002193 Pain Diseases 0.000 claims description 16
• 208000009621 actinic keratosis Diseases 0.000 claims description 16
• NBGSDBVODYCRCQ-UHFFFAOYSA-N 2-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound CC1=NN2C=CC=C2C(=O)N1C1=CC=CC=C1 NBGSDBVODYCRCQ-UHFFFAOYSA-N 0.000 claims description 14
• 206010025323 Lymphomas Diseases 0.000 claims description 14
• 208000014767 Myeloproliferative disease Diseases 0.000 claims description 14
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
• 208000032839 leukemia Diseases 0.000 claims description 14
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 12
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 12
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 12
• 201000004624 Dermatitis Diseases 0.000 claims description 12
• 208000012902 Nervous system disease Diseases 0.000 claims description 12
• 208000025966 Neurological disease Diseases 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 230000002757 inflammatory effect Effects 0.000 claims description 12
• 201000006417 multiple sclerosis Diseases 0.000 claims description 12
• QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 12
• 150000001204 N-oxides Chemical class 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 208000035475 disorder Diseases 0.000 claims description 11
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 10
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 10
• 208000010668 atopic eczema Diseases 0.000 claims description 10
• 201000011510 cancer Diseases 0.000 claims description 10
• 208000010247 contact dermatitis Diseases 0.000 claims description 10
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
• 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 9
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
• 208000011231 Crohn disease Diseases 0.000 claims description 9
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 9
• 206010012442 Dermatitis contact Diseases 0.000 claims description 9
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 9
• 206010034277 Pemphigoid Diseases 0.000 claims description 9
• 201000004681 Psoriasis Diseases 0.000 claims description 9
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
• 208000006673 asthma Diseases 0.000 claims description 9
• 201000008937 atopic dermatitis Diseases 0.000 claims description 9
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 9
• 208000002352 blister Diseases 0.000 claims description 9
• 208000000594 bullous pemphigoid Diseases 0.000 claims description 9
• 201000001981 dermatomyositis Diseases 0.000 claims description 9
• 201000000306 sarcoidosis Diseases 0.000 claims description 9
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 9
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 8
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 8
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 8
• 206010052779 Transplant rejections Diseases 0.000 claims description 8
• 208000026935 allergic disease Diseases 0.000 claims description 8
• 201000010105 allergic rhinitis Diseases 0.000 claims description 8
• 210000001185 bone marrow Anatomy 0.000 claims description 8
• 102220346868 c.35G>T Human genes 0.000 claims description 8
• 239000003795 chemical substances by application Substances 0.000 claims description 8
• 230000001404 mediated effect Effects 0.000 claims description 8
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 7
• 206010011686 Cutaneous vasculitis Diseases 0.000 claims description 7
• 206010014989 Epidermolysis bullosa Diseases 0.000 claims description 7
• 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 7
• 201000011152 Pemphigus Diseases 0.000 claims description 7
• 208000036142 Viral infection Diseases 0.000 claims description 7
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 claims description 7
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 7
• 230000006870 function Effects 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 210000000056 organ Anatomy 0.000 claims description 7
• 201000001976 pemphigus vulgaris Diseases 0.000 claims description 7
• 208000023504 respiratory system disease Diseases 0.000 claims description 7
• 230000009385 viral infection Effects 0.000 claims description 7
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 6
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
• 230000001363 autoimmune Effects 0.000 claims description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 6
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 6
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
• AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 claims description 6
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 5
• DQFBCPJYUUEXAD-SFHVURJKSA-N 2-[(1s)-1-[[5-(1h-indol-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C=3C(C=4C=5C=CNC=5C=CC=4)=CNC=3N=CN=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 DQFBCPJYUUEXAD-SFHVURJKSA-N 0.000 claims description 5
• YGKWLJOGDUVYOK-SFHVURJKSA-N 2-[(1s)-1-[[5-(2-hydroxy-5-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(C)=CC=C1O YGKWLJOGDUVYOK-SFHVURJKSA-N 0.000 claims description 5
• KZXXHEWNDFVNQB-QHCPKHFHSA-N 4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)-3-phenylmethoxypropyl]amino]pyrimidine-5-carbonitrile Chemical compound C([C@@H](C1=NN2C=CC(=C2C(=O)N1C=1C=CC=CC=1)C)NC=1C(=C(N)N=CN=1)C#N)COCC1=CC=CC=C1 KZXXHEWNDFVNQB-QHCPKHFHSA-N 0.000 claims description 5
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
• 230000007368 endocrine function Effects 0.000 claims description 5
• 230000007102 metabolic function Effects 0.000 claims description 5
• YQGHFKNCOZCKKN-SFHVURJKSA-N n-[3-[4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=CC(NS(C)(=O)=O)=C1 YQGHFKNCOZCKKN-SFHVURJKSA-N 0.000 claims description 5
• FGCZLXKOGNAMNO-SFHVURJKSA-N 2-[(1s)-1-[[5-[(3-hydroxyphenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1CC1=CC=CC(O)=C1 FGCZLXKOGNAMNO-SFHVURJKSA-N 0.000 claims description 4
• GHFFCMUNZNLRKQ-AWEZNQCLSA-N 2-[(1s)-1-[[6-amino-5-(3,4-difluoro-5-hydroxyphenyl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC(O)=C(F)C(F)=C1 GHFFCMUNZNLRKQ-AWEZNQCLSA-N 0.000 claims description 4
• WPVMCUDYRVHFCF-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-(3-chloro-5-hydroxyphenyl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC(O)=CC(Cl)=C1 WPVMCUDYRVHFCF-HNNXBMFYSA-N 0.000 claims description 4
• BMVNFWXGNXOBLY-KRWDZBQOSA-N 4-amino-6-[[(1s)-1-[5-[(3-methoxyphenyl)methyl]-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound COC1=CC=CC(CC2=C3C(=O)N(C=4C=CC=CC=4)C([C@H](C)NC=4C(=C(N)N=CN=4)C#N)=NN3C=C2)=C1 BMVNFWXGNXOBLY-KRWDZBQOSA-N 0.000 claims description 4
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 4
• 239000003246 corticosteroid Substances 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• UGPVIIQOJRQXIW-IBGZPJMESA-N n-[5-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-2-methoxypyridin-3-yl]-4-hydroxybenzenesulfonamide Chemical compound COC1=NC=C(C=2C(=NC=NC=2N)N[C@@H](C)C=2N(C(=O)C3=C(C)C=CN3N=2)C=2C=CC=CC=2)C=C1NS(=O)(=O)C1=CC=C(O)C=C1 UGPVIIQOJRQXIW-IBGZPJMESA-N 0.000 claims description 4
• VYEHSYWBLDTUHX-UHFFFAOYSA-N 1h-pyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound O=C1NC=NN2C=CC=C12 VYEHSYWBLDTUHX-UHFFFAOYSA-N 0.000 claims description 3
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims description 3
• DVZKUZHZHLIWQT-SFHVURJKSA-N 2-[(1s)-1-[(2-butyl-6-methylthieno[2,3-d]pyrimidin-4-yl)amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@H](C)NC=2N=C(N=C3SC(C)=CC3=2)CCCC)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 DVZKUZHZHLIWQT-SFHVURJKSA-N 0.000 claims description 3
• DBSWGWKKINIXNW-KRWDZBQOSA-N 2-[(1s)-1-[[5-(1h-indazol-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C=3C(C=4C=5C=NNC=5C=CC=4)=CNC=3N=CN=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 DBSWGWKKINIXNW-KRWDZBQOSA-N 0.000 claims description 3
• ZYJOHLFEJHFQGA-INIZCTEOSA-N 2-[(1s)-1-[[5-(2,4-dihydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=C(O)C=C1O ZYJOHLFEJHFQGA-INIZCTEOSA-N 0.000 claims description 3
• HBKHVUFZUQHJHY-INIZCTEOSA-N 2-[(1s)-1-[[5-(2-fluoro-6-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=C(O)C=CC=C1F HBKHVUFZUQHJHY-INIZCTEOSA-N 0.000 claims description 3
• KWOTXBDULSXYRD-KRWDZBQOSA-N 2-[(1s)-1-[[5-(2-fluorophenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=CC=C1F KWOTXBDULSXYRD-KRWDZBQOSA-N 0.000 claims description 3
• FTAOKGSTPLDORD-INIZCTEOSA-N 2-[(1s)-1-[[5-(3-fluoro-5-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(O)=CC(F)=C1 FTAOKGSTPLDORD-INIZCTEOSA-N 0.000 claims description 3
• UQIWWRMDAFMJFC-INIZCTEOSA-N 2-[(1s)-1-[[5-(3-fluoro-5-hydroxyphenyl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC=C1C1=CC(O)=CC(F)=C1 UQIWWRMDAFMJFC-INIZCTEOSA-N 0.000 claims description 3
• QEHPQGPRBITSKC-SFHVURJKSA-N 2-[(1s)-1-[[5-(3-methoxyphenyl)sulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound COC1=CC=CC(SC=2C3=C(N[C@@H](C)C=4N(C(=O)C5=C(C)C=CN5N=4)C=4C=CC=CC=4)N=CN=C3NC=2)=C1 QEHPQGPRBITSKC-SFHVURJKSA-N 0.000 claims description 3
• MTCAMWJUDYQEOR-KRWDZBQOSA-N 2-[(1s)-1-[[5-(4-fluoro-2-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound COC1=CC(F)=CC=C1C1=CNC2=NC=NC(N[C@@H](C)C=3N(C(=O)C4=C(C)C=CN4N=3)C=3C=CC=CC=3)=C12 MTCAMWJUDYQEOR-KRWDZBQOSA-N 0.000 claims description 3
• LAOPBSKJOXMHRY-KRWDZBQOSA-N 2-[(1s)-1-[[5-(4-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=C(O)C=C1 LAOPBSKJOXMHRY-KRWDZBQOSA-N 0.000 claims description 3
• FFYNCBSLSCNGOI-INIZCTEOSA-N 2-[(1s)-1-[[5-(5-amino-6-methoxypyridin-3-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1=C(N)C(OC)=NC=C1C1=CNC2=NC=NC(N[C@@H](C)C=3N(C(=O)C4=C(C)C=CN4N=3)C=3C=CC=CC=3)=C12 FFYNCBSLSCNGOI-INIZCTEOSA-N 0.000 claims description 3
• TTWFUORPZGJMAK-INIZCTEOSA-N 2-[(1s)-1-[[5-(5-fluoro-2-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(F)=CC=C1O TTWFUORPZGJMAK-INIZCTEOSA-N 0.000 claims description 3
• RBQLFHWLIBOWOZ-KRWDZBQOSA-N 2-[(1s)-1-[[5-[1-(2-hydroxyethyl)pyrazol-4-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C=1C=NN(CCO)C=1 RBQLFHWLIBOWOZ-KRWDZBQOSA-N 0.000 claims description 3
• BZMBGAXPBFDBTD-INIZCTEOSA-N 2-[(1s)-1-[[5-[2-hydroxy-5-(trifluoromethyl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(C(F)(F)F)=CC=C1O BZMBGAXPBFDBTD-INIZCTEOSA-N 0.000 claims description 3
• WYNOZPJNBIVVED-AWEZNQCLSA-N 2-[(1s)-1-[[6-amino-5-(3,5-difluoro-4-hydroxyphenyl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC(F)=C(O)C(F)=C1 WYNOZPJNBIVVED-AWEZNQCLSA-N 0.000 claims description 3
• DPJOTFSAEFHGTJ-KRWDZBQOSA-N 2-[(1s)-1-[[6-amino-5-[(3-hydroxyphenyl)methyl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1CC1=CC=CC(O)=C1 DPJOTFSAEFHGTJ-KRWDZBQOSA-N 0.000 claims description 3
• AHINZXAPARISBZ-HNNXBMFYSA-N 4-amino-6-[[(1s)-1-[5-(2-hydroxyphenyl)sulfanyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(SC=3C(=CC=CC=3)O)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C#N AHINZXAPARISBZ-HNNXBMFYSA-N 0.000 claims description 3
• CHYVFILMZHSKJD-HNNXBMFYSA-N 5-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-3h-1,3-benzoxazol-2-one Chemical compound C1([C@@H](NC=2C(=C(N)N=CN=2)C=2C=C3NC(=O)OC3=CC=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 CHYVFILMZHSKJD-HNNXBMFYSA-N 0.000 claims description 3
• QMNWZDQTMFMPIL-AWEZNQCLSA-N 5-methyl-2-[(1s)-1-[(2-methylthieno[2,3-d]pyrimidin-4-yl)amino]ethyl]-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C=3C=CSC=3N=C(C)N=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 QMNWZDQTMFMPIL-AWEZNQCLSA-N 0.000 claims description 3
• XAYGMFXAZIWYJY-HNNXBMFYSA-N 5-methyl-3-phenyl-2-[(1S)-1-[[5-(1H-pyrazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]pyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N1N=C(C=C1)C1=CNC=2N=CN=C(C21)N[C@@H](C)C2=NN1C(C(N2C2=CC=CC=C2)=O)=C(C=C1)C XAYGMFXAZIWYJY-HNNXBMFYSA-N 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
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• MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 claims description 3
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• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• LCVQUFNGYSNDJN-KRWDZBQOSA-N n-[3-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]phenyl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC=CC(NS(C)(=O)=O)=C1 LCVQUFNGYSNDJN-KRWDZBQOSA-N 0.000 claims description 3
• LASVPQPKADHGRS-FQEVSTJZSA-N n-[5-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-2-ethoxypyridin-3-yl]-4-hydroxybenzenesulfonamide Chemical compound CCOC1=NC=C(C=2C(=NC=NC=2N)N[C@@H](C)C=2N(C(=O)C3=C(C)C=CN3N=2)C=2C=CC=CC=2)C=C1NS(=O)(=O)C1=CC=C(O)C=C1 LASVPQPKADHGRS-FQEVSTJZSA-N 0.000 claims description 3
• KFARFOZSSYFILP-IBGZPJMESA-N n-[5-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-2-methoxypyridin-3-yl]-4-fluorobenzenesulfonamide Chemical compound COC1=NC=C(C=2C(=NC=NC=2N)N[C@@H](C)C=2N(C(=O)C3=C(C)C=CN3N=2)C=2C=CC=CC=2)C=C1NS(=O)(=O)C1=CC=C(F)C=C1 KFARFOZSSYFILP-IBGZPJMESA-N 0.000 claims description 3
• 102000020233 phosphotransferase Human genes 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 3
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 2
• WBXMKLUMWBPNFY-UHFFFAOYSA-N 2-(methanesulfonamido)benzamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1C(N)=O WBXMKLUMWBPNFY-UHFFFAOYSA-N 0.000 claims description 2
• HJLYXSLLJQWYKU-KRWDZBQOSA-N 2-[(1S)-1-[[5-[1-(2-hydroxyethyl)pyrazol-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C[C@H](Nc1ncnc2[nH]cc(-c3ccn(CCO)n3)c12)c1nn2ccc(C)c2c(=O)n1-c1ccccc1 HJLYXSLLJQWYKU-KRWDZBQOSA-N 0.000 claims description 2
• IZTHXJRGXWLWNN-HNNXBMFYSA-N 2-[(1S)-1-[[5-[5-(ethylamino)-1,3,4-thiadiazol-2-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C(C)NC1=NN=C(S1)C1=CNC=2N=CN=C(C21)N[C@@H](C)C2=NN1C(C(N2C2=CC=CC=C2)=O)=C(C=C1)C IZTHXJRGXWLWNN-HNNXBMFYSA-N 0.000 claims description 2
• MVRSNDOQMHCJQX-INIZCTEOSA-N 2-[(1s)-1-[[5-(3-chloro-2-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=CC(Cl)=C1O MVRSNDOQMHCJQX-INIZCTEOSA-N 0.000 claims description 2
• PXUMMGKMGNAKQB-KRWDZBQOSA-N 2-[(1s)-1-[[5-(3-hydroxyphenyl)sulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1SC1=CC=CC(O)=C1 PXUMMGKMGNAKQB-KRWDZBQOSA-N 0.000 claims description 2
• RXZWDJAMFHLGND-KRWDZBQOSA-N 2-[(1s)-1-[[5-(4-hydroxy-3-methoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1=C(O)C(OC)=CC(C=2C3=C(N[C@@H](C)C=4N(C(=O)C5=C(C)C=CN5N=4)C=4C=CC=CC=4)N=CN=C3NC=2)=C1 RXZWDJAMFHLGND-KRWDZBQOSA-N 0.000 claims description 2
• UUEWWWDEGOIACD-KRWDZBQOSA-N 2-[(1s)-1-[[5-(4-hydroxyphenyl)sulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1SC1=CC=C(O)C=C1 UUEWWWDEGOIACD-KRWDZBQOSA-N 0.000 claims description 2
• QHMFFSYPBHCCHA-INIZCTEOSA-N 2-[(1s)-1-[[5-(5-fluoro-2-hydroxyphenyl)sulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1SC1=CC(F)=CC=C1O QHMFFSYPBHCCHA-INIZCTEOSA-N 0.000 claims description 2
• FWEBWFLXVYOWOP-KRWDZBQOSA-N 2-[(1s)-1-[[5-[(3-fluoro-5-hydroxyphenyl)methyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1CC1=CC(O)=CC(F)=C1 FWEBWFLXVYOWOP-KRWDZBQOSA-N 0.000 claims description 2
• OVTIXRVAVAGQJZ-SFHVURJKSA-N 2-[(1s)-1-[[5-[1-(3-hydroxypropyl)pyrazol-4-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C=1C=NN(CCCO)C=1 OVTIXRVAVAGQJZ-SFHVURJKSA-N 0.000 claims description 2
• FSXBPLVRNPPEMD-IBGZPJMESA-N 2-[(1s)-1-[[5-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C=1C=NN(CCN(C)C)C=1 FSXBPLVRNPPEMD-IBGZPJMESA-N 0.000 claims description 2
• QYCHGSGPOZYLQP-ZDUSSCGKSA-N 2-[(1s)-1-[[6-amino-5-(1,3-thiazol-2-yl)pyrimidin-4-yl]amino]ethyl]-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=CC=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=NC=CS1 QYCHGSGPOZYLQP-ZDUSSCGKSA-N 0.000 claims description 2
• BMTHPBSYALEHLY-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-(3-fluoro-4-hydroxyphenyl)sulfanylpyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1SC1=CC=C(O)C(F)=C1 BMTHPBSYALEHLY-HNNXBMFYSA-N 0.000 claims description 2
• CKVHCRPEVCJGQW-FQEVSTJZSA-N 2-[(1s)-1-[[6-amino-5-(3-morpholin-4-ylsulfonylphenyl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(C=1)=CC=CC=1S(=O)(=O)N1CCOCC1 CKVHCRPEVCJGQW-FQEVSTJZSA-N 0.000 claims description 2
• UWPFAJYIVJXHBL-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-(5-hydroxypyridin-3-yl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CN=CC(O)=C1 UWPFAJYIVJXHBL-HNNXBMFYSA-N 0.000 claims description 2
• IPQOZTKCGDRACV-INIZCTEOSA-N 2-[(1s)-1-[[6-amino-5-[1-(2-hydroxyethyl)pyrazol-4-yl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C=1C=NN(CCO)C=1 IPQOZTKCGDRACV-INIZCTEOSA-N 0.000 claims description 2
• FGUSTAJPWOXHJW-NRFANRHFSA-N 2-[(1s)-1-[[6-amino-5-[1-(4-hydroxyphenyl)sulfonylindol-6-yl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(C=C12)=CC=C1C=CN2S(=O)(=O)C1=CC=C(O)C=C1 FGUSTAJPWOXHJW-NRFANRHFSA-N 0.000 claims description 2
• VJWIJZCRRWBIQC-QFIPXVFZSA-N 2-[(1s)-1-[[6-amino-5-[1-(4-methoxyphenyl)sulfonylindol-6-yl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC(C=3C(=NC=NC=3N)N[C@@H](C)C=3N(C(=O)C4=C(C)C=CN4N=3)C=3C=CC=CC=3)=CC=C2C=C1 VJWIJZCRRWBIQC-QFIPXVFZSA-N 0.000 claims description 2
• FVTLXRJYQTWYRF-AWEZNQCLSA-N 2-[(1s)-1-[[6-amino-5-[2-oxo-6-(trifluoromethyl)-1h-pyridin-4-yl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C=1C=C(C(F)(F)F)NC(=O)C=1 FVTLXRJYQTWYRF-AWEZNQCLSA-N 0.000 claims description 2
• XSBQOGLHVAKLAL-QHCPKHFHSA-N 4-amino-6-[[(1S)-1-[4-oxo-5-[6-oxo-6-(4-propan-2-ylpiperazin-1-yl)hex-1-ynyl]-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC=NC(=C1C#N)N[C@@H](C)C1=NN2C(C(N1C1=CC=CC=C1)=O)=C(C=C2)C#CCCCC(=O)N2CCN(CC2)C(C)C XSBQOGLHVAKLAL-QHCPKHFHSA-N 0.000 claims description 2
• DBHYJFRSKVCSJY-INIZCTEOSA-N 4-amino-6-[[(1s)-1-[5-[(3-hydroxyphenyl)methyl]-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(CC=3C=C(O)C=CC=3)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C#N DBHYJFRSKVCSJY-INIZCTEOSA-N 0.000 claims description 2
• UKBMYOSMHIUOEZ-IBGZPJMESA-N 4-amino-6-[[(1s)-1-[5-[2-[2-(dimethylamino)ethylamino]phenyl]sulfanyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(SC=3C(=CC=CC=3)NCCN(C)C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C#N UKBMYOSMHIUOEZ-IBGZPJMESA-N 0.000 claims description 2
• WKMGMSXBESZLKJ-INIZCTEOSA-N 4-amino-n-(2-hydroxyphenyl)-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidine-5-carboxamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(=O)NC1=CC=CC=C1O WKMGMSXBESZLKJ-INIZCTEOSA-N 0.000 claims description 2
• BORKDQVFESVPLD-HNNXBMFYSA-N 4-amino-n-(3-fluoro-5-hydroxyphenyl)-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidine-5-carboxamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(=O)NC1=CC(O)=CC(F)=C1 BORKDQVFESVPLD-HNNXBMFYSA-N 0.000 claims description 2
• OYVUFLBFGYRMBX-HNNXBMFYSA-N 4-amino-n-(5-carbamoyl-2-hydroxyphenyl)-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidine-5-carboxamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(=O)NC1=CC(C(N)=O)=CC=C1O OYVUFLBFGYRMBX-HNNXBMFYSA-N 0.000 claims description 2
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• HDVAYLPTZDWOMH-INIZCTEOSA-N n-[3-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-5-hydroxyphenyl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC(O)=CC(NS(C)(=O)=O)=C1 HDVAYLPTZDWOMH-INIZCTEOSA-N 0.000 claims description 2
• FDFFUXNSAJHTBQ-INIZCTEOSA-N n-[3-hydroxy-5-[4-[[(1s)-1-(4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=CC=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(O)=CC(NS(C)(=O)=O)=C1 FDFFUXNSAJHTBQ-INIZCTEOSA-N 0.000 claims description 2
• JAZZPHQRSUKEKV-SFHVURJKSA-N n-[3-methoxy-5-[4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]methanesulfonamide Chemical compound COC1=CC(NS(C)(=O)=O)=CC(C=2C3=C(N[C@@H](C)C=4N(C(=O)C5=C(C)C=CN5N=4)C=4C=CC=CC=4)N=CN=C3NC=2)=C1 JAZZPHQRSUKEKV-SFHVURJKSA-N 0.000 claims description 2
• PTUVJUXELJCXHW-SFHVURJKSA-N n-[4-[4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=C(NS(C)(=O)=O)C=C1 PTUVJUXELJCXHW-SFHVURJKSA-N 0.000 claims description 2
• QTBPSVXBOXFUMY-KRWDZBQOSA-N n-[5-[4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-3-yl]methanesulfonamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CN=CC(NS(C)(=O)=O)=C1 QTBPSVXBOXFUMY-KRWDZBQOSA-N 0.000 claims description 2
• RNPUOBPNALKXQK-HNNXBMFYSA-N n-[5-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-2-methoxypyridin-3-yl]-1,1,1-trifluoromethanesulfonamide Chemical compound C1=C(NS(=O)(=O)C(F)(F)F)C(OC)=NC=C1C1=C(N)N=CN=C1N[C@@H](C)C(N(C1=O)C=2C=CC=CC=2)=NN2C1=C(C)C=C2 RNPUOBPNALKXQK-HNNXBMFYSA-N 0.000 claims description 2
• JSBLYAIAVQWTSH-IBGZPJMESA-N n-benzyl-4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidine-5-carboxamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C(=O)NCC1=CC=CC=C1 JSBLYAIAVQWTSH-IBGZPJMESA-N 0.000 claims description 2
• BZWBVJMBRDVINC-SFHVURJKSA-N n-methyl-3-[4-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-5-yl]benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC(C=2C3=C(N[C@@H](C)C=4N(C(=O)C5=C(C)C=CN5N=4)C=4C=CC=CC=4)N=CN=C3NC=2)=C1 BZWBVJMBRDVINC-SFHVURJKSA-N 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• HIAWBBYDNBTXCP-QHCPKHFHSA-N tert-butyl 4-[4-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]phenyl]piperazine-1-carboxylate Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(C=C1)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 HIAWBBYDNBTXCP-QHCPKHFHSA-N 0.000 claims description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 12
• NRVASKBOAIJOKI-UHFFFAOYSA-N 5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound O=C1C2=C(C)C=CN2N=CN1C1=CC=CC=C1 NRVASKBOAIJOKI-UHFFFAOYSA-N 0.000 claims 2
• 102000015617 Janus Kinases Human genes 0.000 claims 2
• 108010024121 Janus Kinases Proteins 0.000 claims 2
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• 239000000556 agonist Substances 0.000 claims 2
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims 2
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
• OIWXDNWAXGASFE-IBGZPJMESA-N 2-[(1S)-1-[[5-[1-(3-hydroxyphenyl)pyrazol-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C[C@H](Nc1ncnc2[nH]cc(-c3ccn(n3)-c3cccc(O)c3)c12)c1nn2ccc(C)c2c(=O)n1-c1ccccc1 OIWXDNWAXGASFE-IBGZPJMESA-N 0.000 claims 1
• COAPTOHOYMSMFA-IBGZPJMESA-N 2-[(1S)-1-[[5-[1-(3-hydroxyphenyl)sulfonylpyrazol-3-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound OC=1C=C(C=CC1)S(=O)(=O)N1N=C(C=C1)C1=CNC=2N=CN=C(C21)N[C@@H](C)C2=NN1C(C(N2C2=CC=CC=C2)=O)=C(C=C1)C COAPTOHOYMSMFA-IBGZPJMESA-N 0.000 claims 1
• UEEGDIJYKXUKFK-HNNXBMFYSA-N 2-[(1s)-1-[(2,6-dimethylthieno[2,3-d]pyrimidin-4-yl)amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C=3C=C(C)SC=3N=C(C)N=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 UEEGDIJYKXUKFK-HNNXBMFYSA-N 0.000 claims 1
• PSUGETYGEXPIBR-SFHVURJKSA-N 2-[(1s)-1-[[5-(1h-indol-7-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C=3C(C=4C=5NC=CC=5C=CC=4)=CNC=3N=CN=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 PSUGETYGEXPIBR-SFHVURJKSA-N 0.000 claims 1
• TWLUUMHXOOFHTJ-KRWDZBQOSA-N 2-[(1s)-1-[[5-(2-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC=CC=C1O TWLUUMHXOOFHTJ-KRWDZBQOSA-N 0.000 claims 1
• QIKXZKYZSJTRJM-KRWDZBQOSA-N 2-[(1s)-1-[[5-(2-hydroxyphenyl)sulfanyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1SC1=CC=CC=C1O QIKXZKYZSJTRJM-KRWDZBQOSA-N 0.000 claims 1
• WMDHOHMRHUBOIH-INIZCTEOSA-N 2-[(1s)-1-[[5-(3-amino-5-hydroxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(N)=CC(O)=C1 WMDHOHMRHUBOIH-INIZCTEOSA-N 0.000 claims 1
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• ZXMIESGAANTVQM-KRWDZBQOSA-N 2-[(1s)-1-[[5-[3-hydroxy-5-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C(C=1)=CC(O)=CC=1C1=NN=C(C)O1 ZXMIESGAANTVQM-KRWDZBQOSA-N 0.000 claims 1
• LJDRFZAZXHNIRD-INIZCTEOSA-N 2-[(1s)-1-[[5-[3-hydroxy-5-(sulfamoylamino)phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazine Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C(C1=2)=NC=NC=2NC=C1C1=CC(O)=CC(NS(N)(=O)=O)=C1 LJDRFZAZXHNIRD-INIZCTEOSA-N 0.000 claims 1
• PUSTUILQGTZJGP-KRWDZBQOSA-N 2-[(1s)-1-[[6-amino-5-(1h-indol-4-yl)pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound C1([C@@H](NC=2C(=C(N)N=CN=2)C=2C=3C=CNC=3C=CC=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 PUSTUILQGTZJGP-KRWDZBQOSA-N 0.000 claims 1
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• MEJMWWBLGVSIBK-IBGZPJMESA-N 2-[(1s)-1-[[6-amino-5-[1-(2-fluoro-4-hydroxyphenyl)sulfonyl-4-hydroxyindol-6-yl]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(C=C12)=CC(O)=C1C=CN2S(=O)(=O)C1=CC=C(O)C=C1F MEJMWWBLGVSIBK-IBGZPJMESA-N 0.000 claims 1
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• GZRHGQYLZOQAEA-FQEVSTJZSA-N 3-[4-amino-6-[[(1s)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-n-(3-hydroxyphenyl)benzamide Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(C)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C(C=1)=CC=CC=1C(=O)NC1=CC=CC(O)=C1 GZRHGQYLZOQAEA-FQEVSTJZSA-N 0.000 claims 1
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