BRPI0814818A2 - composto, uso de um composto, métodos para produzir um efeito anti-proliferativo e um efeito inibitório de mtor quinase em uma animal de sangue quente, método para tratar doenças, e, composição farmacêutica - Google Patents
composto, uso de um composto, métodos para produzir um efeito anti-proliferativo e um efeito inibitório de mtor quinase em uma animal de sangue quente, método para tratar doenças, e, composição farmacêutica Download PDFInfo
- Publication number
- BRPI0814818A2 BRPI0814818A2 BRPI0814818A BRPI0814818A BRPI0814818A2 BR PI0814818 A2 BRPI0814818 A2 BR PI0814818A2 BR PI0814818 A BRPI0814818 A BR PI0814818A BR PI0814818 A BRPI0814818 A BR PI0814818A BR PI0814818 A2 BRPI0814818 A2 BR PI0814818A2
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- BR
- Brazil
- Prior art keywords
- alkyl
- phenyl
- alkoxy
- amino
- bis
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 99
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 32
- 201000010099 disease Diseases 0.000 title claims abstract description 31
- 241001465754 Metazoa Species 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 230000001028 anti-proliverative effect Effects 0.000 title claims abstract description 6
- 108091000080 Phosphotransferase Proteins 0.000 title abstract description 22
- 102000020233 phosphotransferase Human genes 0.000 title abstract description 22
- 230000000694 effects Effects 0.000 title abstract description 15
- 239000003112 inhibitor Substances 0.000 title abstract description 5
- 101150097381 Mtor gene Proteins 0.000 title abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 20
- 230000002062 proliferating effect Effects 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 1515
- -1 nitro, hydroxy Chemical group 0.000 claims description 789
- 125000003545 alkoxy group Chemical group 0.000 claims description 500
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 324
- 125000005843 halogen group Chemical group 0.000 claims description 279
- 125000001424 substituent group Chemical group 0.000 claims description 222
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 218
- 229910052739 hydrogen Inorganic materials 0.000 claims description 202
- 239000001257 hydrogen Substances 0.000 claims description 202
- 125000000623 heterocyclic group Chemical group 0.000 claims description 193
- 125000003282 alkyl amino group Chemical group 0.000 claims description 179
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 155
- 229910052799 carbon Inorganic materials 0.000 claims description 136
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 129
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 127
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 108
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 107
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 79
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 70
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 69
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 64
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 125000004429 atom Chemical group 0.000 claims description 61
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 60
- 229910052717 sulfur Inorganic materials 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 57
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 55
- 125000001589 carboacyl group Chemical group 0.000 claims description 54
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 51
- 125000004076 pyridyl group Chemical group 0.000 claims description 51
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 50
- 125000002837 carbocyclic group Chemical group 0.000 claims description 45
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 31
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 31
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
- 125000005647 linker group Chemical group 0.000 claims description 29
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 28
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 24
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 21
- 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 21
- 125000002883 imidazolyl group Chemical group 0.000 claims description 21
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 21
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 20
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 20
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 19
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 17
- 125000000335 thiazolyl group Chemical group 0.000 claims description 17
- 125000001544 thienyl group Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 11
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 10
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 8
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 8
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 8
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 6
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 5
- 208000023504 respiratory system disease Diseases 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 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 4
- 208000026278 immune system disease Diseases 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 15
- 150000002431 hydrogen Chemical group 0.000 claims 10
- 239000004202 carbamide Substances 0.000 claims 7
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- JWGVUDPAMQEIJU-INIZCTEOSA-N 1-[4-[4-(1-cyclopropylsulfonylcyclopropyl)-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)thiourea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C2CC2)=NC(C=2C=CC(NC(=S)NCCO)=CC=2)=N1 JWGVUDPAMQEIJU-INIZCTEOSA-N 0.000 claims 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims 2
- HIEHQJOVJDWRSX-FQEVSTJZSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-[1-(2-methylphenyl)sulfonylcyclopropyl]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C(=CC=CC=2)C)=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=N1 HIEHQJOVJDWRSX-FQEVSTJZSA-N 0.000 claims 1
- JGBNGNTWBQKUHG-KRWDZBQOSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-[1-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]cyclopropyl]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2SC=C(C)N=2)=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=N1 JGBNGNTWBQKUHG-KRWDZBQOSA-N 0.000 claims 1
- PHWFBNWMJNYDGW-HNNXBMFYSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]thiourea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(C)(=O)=O)=NC(C=2C=CC(NC(=S)NCCO)=CC=2)=N1 PHWFBNWMJNYDGW-HNNXBMFYSA-N 0.000 claims 1
- SDARAZUEIRWPTB-SFHVURJKSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(1-pyridin-2-ylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2N=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 SDARAZUEIRWPTB-SFHVURJKSA-N 0.000 claims 1
- GWHGRDMKYYLJQZ-SFHVURJKSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(1-pyridin-4-ylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]thiourea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CN=CC=2)=NC(C=2C=CC(NC(=S)NCCO)=CC=2)=N1 GWHGRDMKYYLJQZ-SFHVURJKSA-N 0.000 claims 1
- TVSLEPMCGNSXKE-FQEVSTJZSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-[1-(2-methylphenyl)sulfonylcyclopropyl]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C(=CC=CC=2)C)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 TVSLEPMCGNSXKE-FQEVSTJZSA-N 0.000 claims 1
- QZAUFLOIQNLBCO-SFHVURJKSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-[1-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]cyclobutyl]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CCC2)S(=O)(=O)C=2SC=C(C)N=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 QZAUFLOIQNLBCO-SFHVURJKSA-N 0.000 claims 1
- RWHWLGUIESKCSW-KRWDZBQOSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-[1-[(4-methyl-1,3-thiazol-2-yl)sulfonyl]cyclopropyl]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2SC=C(C)N=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 RWHWLGUIESKCSW-KRWDZBQOSA-N 0.000 claims 1
- IUFFUJSXZMPACZ-INIZCTEOSA-N 1-[4-[4-(1-cyclopropylsulfonylcyclopropyl)-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C2CC2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 IUFFUJSXZMPACZ-INIZCTEOSA-N 0.000 claims 1
- KCXPUAAWQBOQAV-IRXDYDNUSA-N 1-[4-[4-(1-cyclopropylsulfonylcyclopropyl)-6-[(3s,5s)-3,5-dimethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COC[C@H](C)N1C1=CC(C2(CC2)S(=O)(=O)C2CC2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 KCXPUAAWQBOQAV-IRXDYDNUSA-N 0.000 claims 1
- JIVMEOCATHYZDN-HNNXBMFYSA-N 1-[4-[4-(1-ethylsulfonylcyclopropyl)-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound C=1C(N2[C@H](COCC2)C)=NC(C=2C=CC(NC(=O)NC)=CC=2)=NC=1C1(S(=O)(=O)CC)CC1 JIVMEOCATHYZDN-HNNXBMFYSA-N 0.000 claims 1
- GMGAAJUMFDRDDP-SFHVURJKSA-N 1-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(C)(=O)=O)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 GMGAAJUMFDRDDP-SFHVURJKSA-N 0.000 claims 1
- JNYGNLVZELHTJV-HOTGVXAUSA-N 1-[4-[4-[(3s,5s)-3,5-dimethylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COC[C@H](C)N1C1=CC(C2(CC2)S(C)(=O)=O)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 JNYGNLVZELHTJV-HOTGVXAUSA-N 0.000 claims 1
- DYHHRFXAFJVSNH-HOTGVXAUSA-N 1-[4-[4-[(3s,5s)-3,5-dimethylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COC[C@@H]2C)C)=CC(C2(CC2)S(C)(=O)=O)=N1 DYHHRFXAFJVSNH-HOTGVXAUSA-N 0.000 claims 1
- DPZWLHXUFZVCQC-KRWDZBQOSA-N 1-[4-[4-[1-(2,4-difluorophenyl)sulfonylcyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C(=CC(F)=CC=2)F)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 DPZWLHXUFZVCQC-KRWDZBQOSA-N 0.000 claims 1
- LASWPFYHJKQHII-KRWDZBQOSA-N 1-[4-[4-[1-(2,6-difluorophenyl)sulfonylcyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C(=CC=CC=2F)F)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 LASWPFYHJKQHII-KRWDZBQOSA-N 0.000 claims 1
- LIAMMPWRLCODBB-SFHVURJKSA-N 1-[4-[4-[1-(3-fluorophenyl)sulfonylcyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=C(F)C=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 LIAMMPWRLCODBB-SFHVURJKSA-N 0.000 claims 1
- TZHFWCJOMAEYCX-SFHVURJKSA-N 1-[4-[4-[1-(4-chlorophenyl)sulfonylcyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 TZHFWCJOMAEYCX-SFHVURJKSA-N 0.000 claims 1
- SZYYCRZNFMZYIA-FQEVSTJZSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclobutyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CCC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 SZYYCRZNFMZYIA-FQEVSTJZSA-N 0.000 claims 1
- ZBKXTIXUBBIJJH-QFIPXVFZSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-ethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=N1 ZBKXTIXUBBIJJH-QFIPXVFZSA-N 0.000 claims 1
- OFXOHIFHOGGYQA-QFIPXVFZSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-ethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 OFXOHIFHOGGYQA-QFIPXVFZSA-N 0.000 claims 1
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
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| US3029708P | 2008-02-21 | 2008-02-21 | |
| PCT/GB2008/050546 WO2009007748A2 (en) | 2007-07-09 | 2008-07-08 | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
Publications (1)
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| BRPI0814818A2 true BRPI0814818A2 (pt) | 2019-09-10 |
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| EP (1) | EP2074118A2 (enExample) |
| JP (1) | JP2010533158A (enExample) |
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| WO2009155121A2 (en) | 2008-05-30 | 2009-12-23 | Amgen Inc. | Inhibitors of pi3 kinase |
| TWI378933B (en) | 2008-10-14 | 2012-12-11 | Daiichi Sankyo Co Ltd | Morpholinopurine derivatives |
| US20110053923A1 (en) | 2008-12-22 | 2011-03-03 | Astrazeneca | Chemical compounds 610 |
| EP2406258B1 (en) | 2009-03-13 | 2014-12-03 | Cellzome Limited | PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| UY32582A (es) | 2009-04-28 | 2010-11-30 | Amgen Inc | Inhibidores de fosfoinositida 3 cinasa y/u objetivo mamífero |
| WO2010127856A1 (en) | 2009-05-07 | 2010-11-11 | Grünenthal GmbH | Substituted phenyllureas and phenylamides as vanilloid receptor ligands |
| US8946204B2 (en) | 2009-05-07 | 2015-02-03 | Gruenenthal Gmbh | Substituted phenylureas and phenylamides as vanilloid receptor ligands |
| EP2448932B1 (fr) | 2009-07-02 | 2014-03-05 | Sanofi | Nouveaux derives de 6-morpholin-4-yl-pyrimidin-4-(3h)-one, leur preparation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| CN102548970B (zh) | 2009-07-02 | 2015-11-25 | 赛诺菲 | 新型(6-氧代-1,6-二氢嘧啶-2-基)酰胺衍生物、其制备方法以及其作为akt(pkb)磷酸化抑制剂的医药用途 |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EA201290255A1 (ru) | 2009-10-30 | 2013-04-30 | Ариад Фармасьютикалз, Инк. | Способы и композиции для лечения рака |
| EP2992878A1 (en) | 2010-02-03 | 2016-03-09 | Signal Pharmaceuticals, LLC | Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors |
| US9249129B2 (en) | 2010-03-04 | 2016-02-02 | Cellzome Limited | Morpholino substituted urea derivatives as mTOR inhibitors |
| IN2013MN00581A (enExample) * | 2010-09-03 | 2015-06-05 | Piramal Entpr Ltd | |
| WO2012058671A1 (en) | 2010-10-31 | 2012-05-03 | Endo Pharmaceuticals Inc. | Substituted quinazoline and pyrido-pyrimidine derivatives |
| LT2658844T (lt) | 2010-12-28 | 2017-02-10 | Sanofi | Nauji pirimidino dariniai, jų gamyba ir jų farmacinis panaudojimas kaip akt (pkb) fosforilinimo slopiklių |
| US20140163023A1 (en) | 2011-04-04 | 2014-06-12 | Cellzome Limited | Dihydropyrrolo pyrimidine derivatives as mtor inhibitors |
| AU2012290056B2 (en) | 2011-08-03 | 2015-03-19 | Signal Pharmaceuticals, Llc | Identification of gene expression profile as a predictive biomarker for LKB1 status |
| KR20140070616A (ko) | 2011-09-21 | 2014-06-10 | 셀좀 리미티드 | Mtor 저해제로서의 모르폴리노 치환된 우레아 또는 카바메이트 유도체 |
| JP6026544B2 (ja) | 2011-09-27 | 2016-11-16 | ノバルティス アーゲー | 変異体ｉｄｈの阻害剤としての３−ピリミジン−４−イル−オキサゾリジン−２−オン類 |
| US9242993B2 (en) | 2011-10-07 | 2016-01-26 | Cellzome Limited | Morpholino substituted bicyclic pyrimidine urea or carbamate derivatives as mTOR inhibitors |
| UY34632A (es) | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
| KR20160027219A (ko) | 2012-05-23 | 2016-03-09 | 에프. 호프만-라 로슈 아게 | 내배엽 및 간세포를 수득하고 사용하는 조성물 및 방법 |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
| GEP201706699B (en) | 2013-03-14 | 2017-07-10 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
| SG11201508527VA (en) | 2013-04-17 | 2015-11-27 | Signal Pharm Llc | Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one |
| CA2909579A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and n-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide for treating cancer |
| MX364101B (es) | 2013-04-17 | 2019-04-12 | Signal Pharm Llc | Terapia de combinación que comprende un compuesto de dihidropirazino-pirazina y un antagonista de receptor de andrógenos para tratar cáncer de próstata. |
| HK1221150A1 (zh) | 2013-04-17 | 2017-05-26 | 西格诺药品有限公司 | 用二氢吡嗪并-吡嗪类对癌症的治疗 |
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- 2008-07-08 EP EP08776181A patent/EP2074118A2/en not_active Withdrawn
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- 2008-07-08 CA CA 2692945 patent/CA2692945A1/en not_active Abandoned
- 2008-07-08 AU AU2008273889A patent/AU2008273889B2/en not_active Expired - Fee Related
- 2008-07-08 BR BRPI0814818A patent/BRPI0814818A2/pt not_active IP Right Cessation
- 2008-07-08 WO PCT/GB2008/050546 patent/WO2009007748A2/en not_active Ceased
- 2008-07-08 KR KR1020107002969A patent/KR20100031639A/ko not_active Withdrawn
- 2008-07-08 CN CN200880106248A patent/CN101801962A/zh active Pending
- 2008-07-09 CL CL2008002006A patent/CL2008002006A1/es unknown
- 2008-07-09 PE PE2008001149A patent/PE20090773A1/es not_active Application Discontinuation
- 2008-07-09 US US12/170,128 patent/US20090018134A1/en not_active Abandoned
- 2008-07-09 TW TW097125962A patent/TW200904813A/zh unknown
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| WO2009007748A2 (en) | 2009-01-15 |
| CO6390066A2 (es) | 2012-02-29 |
| CN101801962A (zh) | 2010-08-11 |
| WO2009007748A3 (en) | 2009-04-23 |
| JP2010533158A (ja) | 2010-10-21 |
| NI201000004A (es) | 2010-10-12 |
| CR11201A (es) | 2010-06-17 |
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