MX2015004327A - Derivados de pirrolotriazinona como inhibidores de pi3k. - Google Patents
Derivados de pirrolotriazinona como inhibidores de pi3k.Info
- Publication number
- MX2015004327A MX2015004327A MX2015004327A MX2015004327A MX2015004327A MX 2015004327 A MX2015004327 A MX 2015004327A MX 2015004327 A MX2015004327 A MX 2015004327A MX 2015004327 A MX2015004327 A MX 2015004327A MX 2015004327 A MX2015004327 A MX 2015004327A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- phenyl
- amino
- methyl
- ethyl
- Prior art date
Links
- 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 6
- 239000012828 PI3K inhibitor Substances 0.000 title description 2
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title description 2
- 239000003112 inhibitor Substances 0.000 claims abstract description 21
- 108091007960 PI3Ks Proteins 0.000 claims abstract description 19
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 8
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 573
- 125000001072 heteroaryl group Chemical group 0.000 claims description 370
- 229910052757 nitrogen Inorganic materials 0.000 claims description 367
- 125000005842 heteroatom Chemical group 0.000 claims description 364
- 229910052760 oxygen Inorganic materials 0.000 claims description 363
- 229910052717 sulfur Inorganic materials 0.000 claims description 363
- 125000000217 alkyl group Chemical group 0.000 claims description 346
- -1 pip3erazinyl Chemical group 0.000 claims description 302
- 125000002950 monocyclic group Chemical group 0.000 claims description 248
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 247
- 125000001424 substituent group Chemical group 0.000 claims description 247
- 125000005843 halogen group Chemical group 0.000 claims description 243
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 241
- 125000002619 bicyclic group Chemical group 0.000 claims description 233
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 210
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 142
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 137
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 136
- 125000001188 haloalkyl group Chemical group 0.000 claims description 126
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 124
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 123
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 122
- 150000001875 compounds Chemical class 0.000 claims description 112
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 104
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 101
- 125000003545 alkoxy group Chemical group 0.000 claims description 91
- 125000000623 heterocyclic group Chemical group 0.000 claims description 85
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 73
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 71
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims description 65
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 50
- 201000010099 disease Diseases 0.000 claims description 45
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 40
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 37
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 25
- 125000003386 piperidinyl group Chemical group 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 19
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000005647 linker group Chemical group 0.000 claims description 17
- 229910052701 rubidium Inorganic materials 0.000 claims description 17
- 208000002193 Pain Diseases 0.000 claims description 16
- 208000009621 actinic keratosis Diseases 0.000 claims description 16
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 14
- 208000032839 leukemia Diseases 0.000 claims description 14
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 13
- 206010025323 Lymphomas Diseases 0.000 claims description 13
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 13
- 201000006417 multiple sclerosis Diseases 0.000 claims description 13
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 12
- 201000003883 Cystic fibrosis 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
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 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
- 201000004624 Dermatitis Diseases 0.000 claims description 11
- 150000001204 N-oxides Chemical class 0.000 claims description 11
- 208000010247 contact dermatitis Diseases 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 10
- 206010012442 Dermatitis contact Diseases 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 230000002757 inflammatory effect Effects 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
- 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
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 201000008937 atopic dermatitis Diseases 0.000 claims description 9
- 208000010668 atopic eczema Diseases 0.000 claims description 9
- 201000001981 dermatomyositis Diseases 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 201000000306 sarcoidosis Diseases 0.000 claims description 9
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 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
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 208000026935 allergic disease Diseases 0.000 claims description 8
- 201000010105 allergic rhinitis Diseases 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 208000030159 metabolic disease Diseases 0.000 claims description 8
- 230000002503 metabolic effect Effects 0.000 claims description 8
- 230000001575 pathological effect Effects 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 206010011686 Cutaneous vasculitis Diseases 0.000 claims description 7
- 208000017701 Endocrine disease Diseases 0.000 claims description 7
- 206010053177 Epidermolysis Diseases 0.000 claims description 7
- 201000011152 Pemphigus Diseases 0.000 claims description 7
- 208000036142 Viral infection Diseases 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 210000001185 bone marrow Anatomy 0.000 claims description 7
- 208000004921 cutaneous lupus erythematosus Diseases 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
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 230000006872 improvement Effects 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 claims description 6
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 6
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 5
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 5
- 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 5
- 239000004202 carbamide Substances 0.000 claims description 5
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 5
- 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 5
- OTOQBYWVJWOYKY-INIZCTEOSA-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]methanesulfonamide Chemical compound C1=C(NS(C)(=O)=O)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 OTOQBYWVJWOYKY-INIZCTEOSA-N 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 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 4
- IZHWRLKLKIUFPI-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-(3-fluoro-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=C(O)C(F)=C1 IZHWRLKLKIUFPI-HNNXBMFYSA-N 0.000 claims description 4
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 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
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- IMHBYKMAHXWHRP-UHFFFAOYSA-N anilazine Chemical compound ClC1=CC=CC=C1NC1=NC(Cl)=NC(Cl)=N1 IMHBYKMAHXWHRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003246 corticosteroid Substances 0.000 claims description 4
- 201000005787 hematologic cancer Diseases 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 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 description 3
- IDMJLBGEPARSNA-QHCPKHFHSA-N 2-[(1s)-1-[(6-amino-5-cyanopyrimidin-4-yl)amino]-3-phenylmethoxypropyl]-3-(3,5-difluorophenyl)-4-oxopyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile Chemical compound NC1=NC=NC(N[C@@H](CCOCC=2C=CC=CC=2)C=2N(C(=O)C3=C(C#N)C=CN3N=2)C=2C=C(F)C=C(F)C=2)=C1C#N IDMJLBGEPARSNA-QHCPKHFHSA-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
- 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 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
- 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
- SHTSEFLOAFHPDM-HNNXBMFYSA-N 2-[(1s)-1-[[5-(3-fluoro-5-hydroxyphenyl)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=C1C1=CC(O)=CC(F)=C1 SHTSEFLOAFHPDM-HNNXBMFYSA-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
- JDJVXWJMAGPGQT-KRWDZBQOSA-N 2-[(1s)-1-[[5-(6-methoxypyridin-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 COC1=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)=N1 JDJVXWJMAGPGQT-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
- RSVIKXZONRLYDM-KRWDZBQOSA-N 2-[(1s)-1-[[6-amino-5-(1h-indol-6-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=C3NC=CC3=CC=2)C)=NN2C=CC(C)=C2C(=O)N1C1=CC=CC=C1 RSVIKXZONRLYDM-KRWDZBQOSA-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
- YOURQHZNTIANMX-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-[3-hydroxy-5-(trifluoromethyl)phenyl]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(C(F)(F)F)=C1 YOURQHZNTIANMX-HNNXBMFYSA-N 0.000 claims description 3
- 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 3
- DRZXURUKFMUUSR-SFHVURJKSA-N FC=1C=C(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)NS(=O)(=O)CCO Chemical compound FC=1C=C(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)NS(=O)(=O)CCO DRZXURUKFMUUSR-SFHVURJKSA-N 0.000 claims description 3
- RVOXXQSFZGOPRO-NRFANRHFSA-N NC1=NC=NC(=C1C=1C=C(C=CC1)NS(=O)(=O)C1=CC(=C(C=C1)O)C)N[C@@H](C)C1=NN2C(C(N1C1=CC=CC=C1)=O)=C(C=C2)C Chemical compound NC1=NC=NC(=C1C=1C=C(C=CC1)NS(=O)(=O)C1=CC(=C(C=C1)O)C)N[C@@H](C)C1=NN2C(C(N1C1=CC=CC=C1)=O)=C(C=C2)C RVOXXQSFZGOPRO-NRFANRHFSA-N 0.000 claims description 3
- 230000001363 autoimmune Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
- 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 3
- 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 3
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 2
- IKSKQFXUEFMELC-FQEVSTJZSA-N 2-(dimethylamino)-n-[3-hydroxy-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]ethanesulfonamide 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(=O)(=O)CCN(C)C)=C1 IKSKQFXUEFMELC-FQEVSTJZSA-N 0.000 claims description 2
- VMJDKJFDKDLOOO-ZDUSSCGKSA-N 2-[(1S)-1-[[5-(5-amino-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 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 VMJDKJFDKDLOOO-ZDUSSCGKSA-N 0.000 claims description 2
- VWDICHXSRMTTAS-IBGZPJMESA-N 2-[(1S)-1-[[5-[1-(3-hydroxy-2,2-dimethylpropyl)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(CC(C)(C)CO)n3)c12)c1nn2ccc(C)c2c(=O)n1-c1ccccc1 VWDICHXSRMTTAS-IBGZPJMESA-N 0.000 claims description 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 description 2
- RQDDDXVFWVAHCJ-NRFANRHFSA-N 2-[(1S)-1-[[5-[1-[(2-methoxyphenyl)methyl]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 COc1ccccc1Cn1ccc(n1)-c1c[nH]c2ncnc(N[C@@H](C)c3nn4ccc(C)c4c(=O)n3-c3ccccc3)c12 RQDDDXVFWVAHCJ-NRFANRHFSA-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
- 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 2
- 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 description 2
- 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 2
- 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 description 2
- 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 2
- 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 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
- 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 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
- 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
- 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 description 2
- 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 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
- NFACPPYDVONKAK-SFHVURJKSA-N 2-[(1s)-1-[[6-amino-5-(3-fluoro-5-hydroxyphenyl)pyrimidin-4-yl]amino]ethyl]-3-phenyl-5-phenylsulfanylpyrrolo[2,1-f][1,2,4]triazin-4-one Chemical compound N([C@@H](C)C=1N(C(=O)C2=C(SC=3C=CC=CC=3)C=CN2N=1)C=1C=CC=CC=1)C1=NC=NC(N)=C1C1=CC(O)=CC(F)=C1 NFACPPYDVONKAK-SFHVURJKSA-N 0.000 claims description 2
- NGZQIEWQLIAQMG-INIZCTEOSA-N 2-[(1s)-1-[[6-amino-5-(3-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=CC(O)=C1 NGZQIEWQLIAQMG-INIZCTEOSA-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
- 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 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
- IGYUBUCZRDTDLP-HNNXBMFYSA-N 2-[(1s)-1-[[6-amino-5-[5-(difluoromethyl)pyridin-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(C(F)F)=C1 IGYUBUCZRDTDLP-HNNXBMFYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 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 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
- XTYIFCPPYJBJJL-NRFANRHFSA-N 4-amino-6-[[(1s)-1-(4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)-3-phenoxypropyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC=NC(N[C@@H](CCOC=2C=CC=CC=2)C=2N(C(=O)C3=CC=CN3N=2)C=2C=CC=CC=2)=C1C#N XTYIFCPPYJBJJL-NRFANRHFSA-N 0.000 claims description 2
- 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 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
- 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
- SFUUYMLUKMEUML-HNNXBMFYSA-N 4-amino-n-(3,5-dihydroxyphenyl)-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(O)=C1 SFUUYMLUKMEUML-HNNXBMFYSA-N 0.000 claims description 2
- JJYZCISHTCWIIV-NRFANRHFSA-N 4-hydroxy-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]benzenesulfonamide 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=CC=1NS(=O)(=O)C1=CC=C(O)C=C1 JJYZCISHTCWIIV-NRFANRHFSA-N 0.000 claims description 2
- ONYYLUFZDAZFHL-FQEVSTJZSA-N 4-hydroxy-n-[3-hydroxy-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]benzenesulfonamide 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=1NS(=O)(=O)C1=CC=C(O)C=C1 ONYYLUFZDAZFHL-FQEVSTJZSA-N 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 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 2
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Classifications
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12382399 | 2012-10-16 | ||
| US201261718782P | 2012-10-26 | 2012-10-26 | |
| PCT/EP2013/071551 WO2014060432A1 (en) | 2012-10-16 | 2013-10-15 | Pyrrolotriazinone derivatives as pi3k inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2015004327A true MX2015004327A (es) | 2015-06-10 |
Family
ID=47049114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2015004327A MX2015004327A (es) | 2012-10-16 | 2013-10-15 | Derivados de pirrolotriazinona como inhibidores de pi3k. |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US9388189B2 (https=) |
| EP (1) | EP2909207A1 (https=) |
| JP (1) | JP2015533181A (https=) |
| KR (1) | KR20150068953A (https=) |
| CN (1) | CN104854108A (https=) |
| AP (1) | AP2015008328A0 (https=) |
| AR (1) | AR093036A1 (https=) |
| AU (1) | AU2013333938A1 (https=) |
| BR (1) | BR112015007231A2 (https=) |
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- 2013-10-15 EA EA201500426A patent/EA027277B1/ru not_active IP Right Cessation
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- 2013-10-15 MX MX2015004327A patent/MX2015004327A/es unknown
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- 2013-10-15 CN CN201380065926.2A patent/CN104854108A/zh active Pending
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- 2013-10-15 BR BR112015007231A patent/BR112015007231A2/pt not_active IP Right Cessation
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2015
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- 2015-04-13 PH PH12015500813A patent/PH12015500813A1/en unknown
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- 2015-04-16 GT GT201500094A patent/GT201500094A/es unknown
- 2015-04-16 NI NI201500054AA patent/NI201500054A/es unknown
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| AU2013333938A1 (en) | 2015-04-09 |
| NI201500054A (es) | 2016-02-01 |
| CL2015000956A1 (es) | 2015-06-19 |
| IL237475A0 (en) | 2015-04-30 |
| GEP201706623B (en) | 2017-02-10 |
| GT201500094A (es) | 2017-08-01 |
| TW201429975A (zh) | 2014-08-01 |
| EA027277B1 (ru) | 2017-07-31 |
| PH12015500813B1 (en) | 2015-06-08 |
| SG11201502032VA (en) | 2015-05-28 |
| BR112015007231A2 (pt) | 2017-07-04 |
| KR20150068953A (ko) | 2015-06-22 |
| HK1211027A1 (en) | 2016-05-13 |
| AR093036A1 (es) | 2015-05-13 |
| UY35086A (es) | 2014-05-30 |
| CA2883426A1 (en) | 2014-04-24 |
| US9388189B2 (en) | 2016-07-12 |
| DOP2015000077A (es) | 2015-04-30 |
| WO2014060432A1 (en) | 2014-04-24 |
| PE20150637A1 (es) | 2015-05-08 |
| PH12015500813A1 (en) | 2015-06-08 |
| ZA201501220B (en) | 2017-04-26 |
| EP2909207A1 (en) | 2015-08-26 |
| JP2015533181A (ja) | 2015-11-19 |
| AP2015008328A0 (en) | 2015-03-31 |
| US20150291595A1 (en) | 2015-10-15 |
| TN2015000112A1 (en) | 2016-06-29 |
| EA201500426A1 (ru) | 2015-10-30 |
| CR20150175A (es) | 2015-05-11 |
| CN104854108A (zh) | 2015-08-19 |
| MD20150048A2 (ro) | 2015-10-31 |
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