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
- Authority
- BR
- Brazil
- Prior art keywords
- alkyl
- phenyl
- alkoxy
- amino
- bis
- Prior art date
Links
- 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
- ZUOLJWMKBSNHMH-QHCPKHFHSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-ethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCCO)=CC=2)=N1 ZUOLJWMKBSNHMH-QHCPKHFHSA-N 0.000 claims 1
- UKMGZCCESJGQDR-QHCPKHFHSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-ethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-[(1-hydroxycyclopropyl)methyl]urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCC3(O)CC3)=CC=2)=N1 UKMGZCCESJGQDR-QHCPKHFHSA-N 0.000 claims 1
- GVGXIFVNHJJNBU-QHCPKHFHSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-ethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-cyclopropylurea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 GVGXIFVNHJJNBU-QHCPKHFHSA-N 0.000 claims 1
- HRFPKXLTEQFONU-SFHVURJKSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2,2-difluoroethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCC(F)F)=CC=2)=N1 HRFPKXLTEQFONU-SFHVURJKSA-N 0.000 claims 1
- WDWITOKODXBSEY-IBGZPJMESA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=N1 WDWITOKODXBSEY-IBGZPJMESA-N 0.000 claims 1
- SISSPCWSSLRIEP-IBGZPJMESA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-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=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 SISSPCWSSLRIEP-IBGZPJMESA-N 0.000 claims 1
- QQUCRBWPHRAIHZ-FQEVSTJZSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCCO)=CC=2)=N1 QQUCRBWPHRAIHZ-FQEVSTJZSA-N 0.000 claims 1
- PNRNJYMCLCZTMG-UXHICEINSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-[(2r)-1-hydroxypropan-2-yl]urea Chemical compound C1=CC(NC(=O)N[C@@H](CO)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=N1 PNRNJYMCLCZTMG-UXHICEINSA-N 0.000 claims 1
- PNRNJYMCLCZTMG-PMACEKPBSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-[(2s)-1-hydroxypropan-2-yl]urea Chemical compound C1=CC(NC(=O)N[C@H](CO)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=N1 PNRNJYMCLCZTMG-PMACEKPBSA-N 0.000 claims 1
- MOOQAPDBCQJTET-IBGZPJMESA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 MOOQAPDBCQJTET-IBGZPJMESA-N 0.000 claims 1
- ATXRDEYUAHGJHH-SFHVURJKSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-methylthiourea Chemical compound C1=CC(NC(=S)NC)=CC=C1C1=NC(N2[C@H](COCC2)C)=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=N1 ATXRDEYUAHGJHH-SFHVURJKSA-N 0.000 claims 1
- PYENJMDTDGSGCV-PMACEKPBSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s,5s)-3,5-dimethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound C[C@H]1COC[C@H](C)N1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=N1 PYENJMDTDGSGCV-PMACEKPBSA-N 0.000 claims 1
- LDSDKFOLECLJSQ-PMACEKPBSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-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)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=N1 LDSDKFOLECLJSQ-PMACEKPBSA-N 0.000 claims 1
- PADUHJGFBCCSJN-PMACEKPBSA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s,5s)-3,5-dimethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C[C@H]1COC[C@H](C)N1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 PADUHJGFBCCSJN-PMACEKPBSA-N 0.000 claims 1
- MGMYHZZLGCHORC-OALUTQOASA-N 1-[4-[4-[1-(benzenesulfonyl)cyclopropyl]-6-[(3s,5s)-3,5-dimethylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2[C@H](COC[C@@H]2C)C)=CC(C2(CC2)S(=O)(=O)C=2C=CC=CC=2)=N1 MGMYHZZLGCHORC-OALUTQOASA-N 0.000 claims 1
- KMAVNZVCOZUTRU-IBGZPJMESA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]urea Chemical compound CC[C@H]1COCCN1C1=CC(C2(CC2)S(C)(=O)=O)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 KMAVNZVCOZUTRU-IBGZPJMESA-N 0.000 claims 1
- VDACHYLQEIVCET-HOTGVXAUSA-N 1-cyclopropyl-3-[4-[4-[(3s,5s)-3,5-dimethylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COC[C@H](C)N1C1=CC(C2(CC2)S(C)(=O)=O)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 VDACHYLQEIVCET-HOTGVXAUSA-N 0.000 claims 1
- ZINIPRIVILXKJX-KRWDZBQOSA-N 1-cyclopropyl-3-[4-[4-[1-(3-hydroxypropylsulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]thiourea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)CCCO)=NC(C=2C=CC(NC(=S)NC3CC3)=CC=2)=N1 ZINIPRIVILXKJX-KRWDZBQOSA-N 0.000 claims 1
- VCXQPNHGNFCRGA-SFHVURJKSA-N 1-cyclopropyl-3-[4-[4-[1-(4-fluorophenyl)sulfonylcyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]thiourea Chemical compound C[C@H]1COCCN1C1=CC(C2(CC2)S(=O)(=O)C=2C=CC(F)=CC=2)=NC(C=2C=CC(NC(=S)NC3CC3)=CC=2)=N1 VCXQPNHGNFCRGA-SFHVURJKSA-N 0.000 claims 1
- JYDYLIYPDHGUEZ-KRWDZBQOSA-N 1-ethyl-3-[4-[4-[1-(3-hydroxypropylsulfonyl)cyclopropyl]-6-[(3s)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]thiourea Chemical compound C1=CC(NC(=S)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=CC(C2(CC2)S(=O)(=O)CCCO)=N1 JYDYLIYPDHGUEZ-KRWDZBQOSA-N 0.000 claims 1
- 125000004463 2,4-dimethyl-thiazol-5-yl group Chemical group CC=1SC(=C(N1)C)* 0.000 claims 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical compound [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 abstract description 19
- 108090000790 Enzymes Proteins 0.000 abstract description 19
- 230000001404 mediated effect Effects 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 150000001721 carbon Chemical group 0.000 description 91
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 55
- 229910052727 yttrium Inorganic materials 0.000 description 50
- 150000001412 amines Chemical class 0.000 description 37
- 239000010949 copper Substances 0.000 description 36
- 230000006378 damage Effects 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
- 150000003905 phosphatidylinositols Chemical class 0.000 description 25
- 239000003513 alkali Substances 0.000 description 24
- 108091007960 PI3Ks Proteins 0.000 description 21
- 102000038030 PI3Ks Human genes 0.000 description 21
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 20
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 19
- 229940088598 enzyme Drugs 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 16
- 239000011737 fluorine Substances 0.000 description 16
- 125000000168 pyrrolyl group Chemical group 0.000 description 16
- 125000002541 furyl group Chemical group 0.000 description 15
- 125000005037 alkyl phenyl group Chemical group 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 125000002098 pyridazinyl group Chemical group 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 230000037361 pathway Effects 0.000 description 10
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 10
- 230000011664 signaling Effects 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 101100193519 Caenorhabditis elegans qui-1 gene Proteins 0.000 description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 125000006413 ring segment Chemical group 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 239000011593 sulfur Substances 0.000 description 8
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 7
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 7
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 125000003373 pyrazinyl group Chemical group 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 108091008611 Protein Kinase B Proteins 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 6
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 6
- 229960002930 sirolimus Drugs 0.000 description 6
- 208000005623 Carcinogenesis Diseases 0.000 description 5
- 241001024304 Mino Species 0.000 description 5
- 241001644525 Nastus productus Species 0.000 description 5
- 102000001253 Protein Kinase Human genes 0.000 description 5
- 230000036952 cancer formation Effects 0.000 description 5
- 231100000504 carcinogenesis Toxicity 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 108060006633 protein kinase Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 4
- 241000510609 Ferula Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 230000003831 deregulation Effects 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 125000002971 oxazolyl group Chemical group 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 3
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 150000008052 alkyl sulfonates Chemical class 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000004413 cardiac myocyte Anatomy 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 3
- 125000004212 difluorophenyl group Chemical group 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 239000002532 enzyme inhibitor Substances 0.000 description 3
- 125000001207 fluorophenyl group Chemical group 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- ORXTYTVXABMVJS-UHFFFAOYSA-N morpholine;pyrimidine Chemical class C1COCCN1.C1=CN=CN=C1 ORXTYTVXABMVJS-UHFFFAOYSA-N 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- AGQOIYCTCOEHGR-UHFFFAOYSA-N 5-methyl-1,2-oxazole Chemical compound CC1=CC=NO1 AGQOIYCTCOEHGR-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 101100219283 Amycolatopsis orientalis cyp165C4 gene Proteins 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 101100399480 Caenorhabditis elegans lmn-1 gene Proteins 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 241000320892 Clerodendrum phlomidis Species 0.000 description 2
- 102100031561 Hamartin Human genes 0.000 description 2
- 208000002927 Hamartoma Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 2
- 239000012828 PI3K inhibitor Substances 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- 206010034764 Peutz-Jeghers syndrome Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000000033 alkoxyamino group Chemical group 0.000 description 2
- 125000005055 alkyl alkoxy group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 208000026900 bile duct neoplasm Diseases 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000012660 pharmacological inhibitor Substances 0.000 description 2
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000007781 signaling event Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 239000000225 tumor suppressor protein Substances 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 210000003905 vulva Anatomy 0.000 description 2
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 description 1
- MTIRIKBRVALRPJ-NTMALXAHSA-N (Z)-[3-aminopropyl(propan-2-yl)amino]-hydroxyimino-oxidoazanium Chemical compound CC(C)N(CCCN)[N+](\[O-])=N\O MTIRIKBRVALRPJ-NTMALXAHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 description 1
- ZTVIKZXZYLEVOL-DGKWVBSXSA-N 2-hydroxy-2-phenylacetic acid [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] ester Chemical group C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-DGKWVBSXSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- GSSXLFACIJSBOM-UHFFFAOYSA-N 2h-pyran-2-ol Chemical compound OC1OC=CC=C1 GSSXLFACIJSBOM-UHFFFAOYSA-N 0.000 description 1
- 125000004011 3 membered carbocyclic group Chemical group 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1h-pyrazole Chemical compound CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 241001136782 Alca Species 0.000 description 1
- 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- 101001008973 Caenorhabditis elegans Casein kinase I isoform delta Proteins 0.000 description 1
- 101100367123 Caenorhabditis elegans sul-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091007958 Class I PI3Ks Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000012609 Cowden disease Diseases 0.000 description 1
- 201000002847 Cowden syndrome Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 101100061188 Drosophila melanogaster dila gene Proteins 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 101150036146 Fkbpl gene Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 description 1
- 101000795643 Homo sapiens Hamartin Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101000864057 Homo sapiens Serine/threonine-protein kinase SMG1 Proteins 0.000 description 1
- 101000795659 Homo sapiens Tuberin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 description 1
- CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010025102 Lung infiltration Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102100023421 Nuclear receptor ROR-gamma Human genes 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 240000004760 Pimpinella anisum Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 208000007531 Proteus syndrome Diseases 0.000 description 1
- 101710194805 Putative repressor Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 102100024908 Ribosomal protein S6 kinase beta-1 Human genes 0.000 description 1
- 101710108924 Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 102100029938 Serine/threonine-protein kinase SMG1 Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102100031638 Tuberin Human genes 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- XQRJFEVDQXEIAX-JFYQDRLCSA-M cobinamide Chemical compound [Co]N([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](O)C)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O XQRJFEVDQXEIAX-JFYQDRLCSA-M 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 229940069417 doxy Drugs 0.000 description 1
- HALQELOKLVRWRI-VDBOFHIQSA-N doxycycline hyclate Chemical group O.[Cl-].[Cl-].CCO.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O HALQELOKLVRWRI-VDBOFHIQSA-N 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000010200 folin Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940028332 halog Drugs 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004020 intracellular membrane Anatomy 0.000 description 1
- LNQCUTNLHUQZLR-OZJWLQQPSA-N iridin Chemical compound OC1=C(OC)C(OC)=CC(C=2C(C3=C(O)C(OC)=C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C=C3OC=2)=O)=C1 LNQCUTNLHUQZLR-OZJWLQQPSA-N 0.000 description 1
- 235000013847 iso-butane Nutrition 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- XOPUORAQCYGJPT-UHFFFAOYSA-N methanesulfonic acid;hydrochloride Chemical compound Cl.CS(O)(=O)=O XOPUORAQCYGJPT-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000004287 null lymphocyte Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 108090000629 orphan nuclear receptors Proteins 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003244 quercetin derivatives Chemical class 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 108700042226 ras Genes Proteins 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000009712 regulation of translation Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000007755 survival signaling Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 108010002164 tyrosine receptor Proteins 0.000 description 1
- 230000009750 upstream signaling Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94856607P | 2007-07-09 | 2007-07-09 | |
| 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)
| Publication Number | Publication Date |
|---|---|
| BRPI0814818A2 true BRPI0814818A2 (pt) | 2019-09-10 |
Family
ID=40010883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0814818A BRPI0814818A2 (pt) | 2007-07-09 | 2008-07-08 | 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 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US20090018134A1 (en:Method) |
| EP (1) | EP2074118A2 (en:Method) |
| JP (1) | JP2010533158A (en:Method) |
| KR (1) | KR20100031639A (en:Method) |
| CN (1) | CN101801962A (en:Method) |
| AR (1) | AR067478A1 (en:Method) |
| AU (1) | AU2008273889B2 (en:Method) |
| BR (1) | BRPI0814818A2 (en:Method) |
| CA (1) | CA2692945A1 (en:Method) |
| CL (1) | CL2008002006A1 (en:Method) |
| CO (1) | CO6390066A2 (en:Method) |
| CR (1) | CR11201A (en:Method) |
| DO (1) | DOP2010000011A (en:Method) |
| EA (1) | EA201000092A1 (en:Method) |
| NI (1) | NI201000004A (en:Method) |
| PE (1) | PE20090773A1 (en:Method) |
| TW (1) | TW200904813A (en:Method) |
| UY (1) | UY31215A1 (en:Method) |
| WO (1) | WO2009007748A2 (en:Method) |
| ZA (1) | ZA201000106B (en:Method) |
Families Citing this family (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2307400B1 (en) | 2008-05-30 | 2014-04-23 | Amgen, Inc | Inhibitors of pi3 kinase |
| TWI378933B (en) | 2008-10-14 | 2012-12-11 | Daiichi Sankyo Co Ltd | Morpholinopurine derivatives |
| TW201028410A (en) | 2008-12-22 | 2010-08-01 | Astrazeneca Ab | Chemical compounds 610 |
| CA2755061A1 (en) | 2009-03-13 | 2010-09-16 | 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 |
| NZ595759A (en) | 2009-05-07 | 2014-03-28 | Gruenenthal Chemie | Substituted phenylureas and phenylamides as vanilloid receptor ligands |
| US8946204B2 (en) | 2009-05-07 | 2015-02-03 | Gruenenthal Gmbh | Substituted phenylureas and phenylamides as vanilloid receptor ligands |
| KR20120106714A (ko) | 2009-07-02 | 2012-09-26 | 사노피 | 신규 (6-옥소-1,6-디히드로-피리미딘-2-일)아미드 유도체, 그의 제조법, 및 ａｋｔ(ｐｋｂ) 인산화 억제제로서의 그의 제약 용도 |
| 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) |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| US20120316137A1 (en) | 2009-10-30 | 2012-12-13 | Ariad Pharmaceuticals, Inc. | Methods and Compositions for Treating Cancer |
| JP6114554B2 (ja) | 2010-02-03 | 2017-04-12 | シグナル ファーマシューティカルズ，エルエルシー | Ｔｏｒキナーゼ阻害剤に対する感受性についての予測的なバイオマーカーとしてのｌｋｂ１変異の同定 |
| ES2535116T3 (es) | 2010-03-04 | 2015-05-05 | Cellzome Limited | Derivados de urea sustituida con morfolino como inhibidores de mtor |
| JP2013538808A (ja) * | 2010-09-03 | 2013-10-17 | ピラマル エンタープライジーズ リミテッド | Ｄｇａｔ１阻害剤としての複素環式化合物 |
| US8440662B2 (en) | 2010-10-31 | 2013-05-14 | Endo Pharmaceuticals, Inc. | Substituted quinazoline and pyrido-pyrimidine derivatives |
| EP2658844B1 (fr) | 2010-12-28 | 2016-10-26 | Sanofi | Nouveaux derives de pyrimidines, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| JP2014510122A (ja) | 2011-04-04 | 2014-04-24 | セルゾーム リミテッド | ｍＴＯＲ阻害剤としてのジヒドロピロロピリミジン誘導体 |
| AU2012290056B2 (en) | 2011-08-03 | 2015-03-19 | Signal Pharmaceuticals, Llc | Identification of gene expression profile as a predictive biomarker for LKB1 status |
| CA2849189A1 (en) | 2011-09-21 | 2013-03-28 | Cellzome Limited | Morpholino substituted urea or carbamate derivatives as mtor inhibitors |
| 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 |
| BR112014008241A2 (pt) | 2011-10-07 | 2017-04-18 | Cellzome Ltd | composto, composição farmacêutica, métodos para tratar, controlar, retardar ou prevenir doenças e distúrbios, e para preparar um composto, e, uso de um composto |
| 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 |
| MX355945B (es) | 2013-03-14 | 2018-05-07 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inhibidoras de idh mutante. |
| WO2014172431A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer |
| EP2986319A1 (en) | 2013-04-17 | 2016-02-24 | 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 |
| JP6382949B2 (ja) | 2013-04-17 | 2018-08-29 | シグナル ファーマシューティカルズ，エルエルシー | 癌を治療するためのｔｏｒキナーゼ阻害剤及び５−置換キナゾリノン化合物を含む組合せ療法 |
| 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 |
| SG11201508223YA (en) | 2013-04-17 | 2015-11-27 | Signal Pharm Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| EP3549940A1 (en) | 2013-04-17 | 2019-10-09 | Signal Pharmaceuticals, LLC | Pharmaceutical formulations, of 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 |
| US9782427B2 (en) | 2013-04-17 | 2017-10-10 | Signal Pharmaceuticals, Llc | Methods for treating cancer using TOR kinase inhibitor combination therapy |
| US9604939B2 (en) | 2013-05-29 | 2017-03-28 | Signal Pharmaceuticals, Llc | Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-YL)pyridin-3-YL)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-B]pyrazin-2(1H)-one, a solid form thereof and methods of their use |
| JP2017511367A (ja) | 2014-04-16 | 2017-04-20 | シグナル ファーマシューティカルズ，エルエルシー | １−エチル−７−（２−メチル−６−（１Ｈ−１，２，４−トリアゾール−３−イル）ピリジン−３−イル）−３，４−ジヒドロピラジノ［２，３−ｂ］ピラジン−２（１Ｈ）−オン及び共形成物を含む固体形態、その組成物及び使用方法 |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 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, compositions thereof and methods of their use |
| AU2015264021B2 (en) * | 2014-05-21 | 2020-02-27 | Allergan, Inc. | Imidazole derivatives as formyl peptide receptor modulators |
| RS63190B1 (sr) | 2014-08-04 | 2022-06-30 | Nuevolution As | Opciono fuzionisani derivati pirimidina zamenjeni heterociklilom korisni za lečenje zapaljenskih, metaboličkih, onkoloških i autoimunskih bolesti |
| MX394386B (es) | 2014-08-28 | 2025-03-24 | Eisai R&D Man Co Ltd | Derivado de quinolina muy puro y metodo para su produccion. |
| US10227324B2 (en) | 2014-12-17 | 2019-03-12 | Shanghai Haiyan Pharmaceutical Technology Co., Ltd. | 2-morpholin-4,6-disubstituted pyrimidine derivative, and preparation method and pharmaceutical use thereof |
| WO2016127074A1 (en) | 2015-02-06 | 2016-08-11 | Blueprint Medicines Corporation | 2-(pyridin-3-yl)-pyrimidine derivatives as ret inhibitors |
| JP6816100B2 (ja) | 2015-07-16 | 2021-01-20 | アレイ バイオファーマ、インコーポレイテッド | ＲＥＴキナーゼ阻害物質としての置換ピラゾロ［１，５−ａ］ピリジン化合物 |
| TN2019000271A1 (en) | 2015-10-26 | 2021-01-07 | Univ Colorado Regents | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| WO2017079140A1 (en) | 2015-11-02 | 2017-05-11 | Blueprint Medicines Corporation | Inhibitors of ret |
| AR107912A1 (es) | 2016-03-17 | 2018-06-28 | Blueprint Medicines Corp | Inhibidores de ret |
| MX386416B (es) | 2016-04-04 | 2025-03-18 | Loxo Oncology Inc | Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida. |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| DK3439663T3 (da) | 2016-04-04 | 2024-08-26 | Loxo Oncology Inc | Fremgangsmåder til behandling af pædiatriske cancere |
| PE20190437A1 (es) | 2016-05-18 | 2019-03-27 | Loxo Oncology Inc | Procesos para la preparacion de (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidin-1-carboxamida y sales del mismo |
| US10227329B2 (en) | 2016-07-22 | 2019-03-12 | Blueprint Medicines Corporation | Compounds useful for treating disorders related to RET |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| CN110267960B (zh) | 2017-01-18 | 2022-04-26 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[1,5-a]吡嗪化合物 |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| WO2018218197A2 (en) | 2017-05-26 | 2018-11-29 | Board Of Regents, The University Of Texas System | Tetrahydropyrido[4,3-d]pyrimidine inhibitors of atr kinase |
| MY198676A (en) | 2017-06-22 | 2023-09-15 | Celgene Corp | Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection |
| WO2019014618A1 (en) | 2017-07-13 | 2019-01-17 | Board Of Regents, University Of Texas System | HETEROCYCLIC INHIBITORS OF KINASE ATR |
| WO2019036641A1 (en) | 2017-08-17 | 2019-02-21 | Board Of Regents, The University Of Texas System | HETEROCYCLIC INHIBITORS OF KINASE ATR |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| EP3740486A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| WO2019143977A1 (en) | 2018-01-18 | 2019-07-25 | Array Biopharma Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| WO2019178590A1 (en) | 2018-03-16 | 2019-09-19 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of atr kinase |
| JP7422084B2 (ja) | 2018-04-03 | 2024-01-25 | ブループリント メディシンズ コーポレイション | Ｒｅｔ変化を有する癌の処置において使用するためのｒｅｔ阻害剤 |
| CA3224985C (en) | 2018-07-31 | 2025-11-18 | Loxo Oncology, Inc. | SPRAY-DRIED DISPERSIONS, FORMULATIONS AND POLYMORPHIES OF (S)-5-AMINO-3-(4-((5-FLUORO-2-METHOXYBENZAMIDO)METHYL)PHENYL)(1,1,1-TRIFLUOROPROPANE-2-YL)-1H-PYRAZOLE-4-CARBOXAMIDE |
| EP3849986B1 (en) | 2018-09-10 | 2022-06-08 | Array Biopharma, Inc. | Fused heterocyclic compounds as ret kinase inhibitors |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| JP2022515197A (ja) | 2018-12-19 | 2022-02-17 | アレイ バイオファーマ インコーポレイテッド | がんを治療するためのｆｇｆｒ阻害剤としての７－（（３，５－ジメトキシフェニル）アミノ）キノキサリン誘導体 |
| CN112047938B (zh) | 2019-06-06 | 2022-11-22 | 北京泰德制药股份有限公司 | 作为atr激酶抑制剂的2,4,6-三取代的嘧啶化合物 |
| WO2021113492A1 (en) | 2019-12-06 | 2021-06-10 | Schrödinger, Inc. | Cyclic compounds and methods of using same |
| US11685727B2 (en) | 2019-12-20 | 2023-06-27 | Nuevolution A/S | Compounds active towards nuclear receptors |
| AU2020405446A1 (en) | 2019-12-20 | 2022-05-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
| EP4081526A1 (en) | 2019-12-27 | 2022-11-02 | Schrödinger, Inc. | Cyclic compounds and methods of using same |
| MX2022012260A (es) | 2020-03-31 | 2022-11-30 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
| EP4126875A1 (en) | 2020-03-31 | 2023-02-08 | Nuevolution A/S | Compounds active towards nuclear receptors |
| WO2021243192A1 (en) | 2020-05-29 | 2021-12-02 | Blueprint Medicines Corporation | Solid forms of pralsetinib |
| CN111646985A (zh) * | 2020-06-01 | 2020-09-11 | 江苏集萃分子工程研究院有限公司 | 一种含嘧啶杂环抗肿瘤药物分子azd6738的合成方法 |
| CN116490507A (zh) | 2020-09-10 | 2023-07-25 | 薛定谔公司 | 用于治疗癌症的杂环包缩合cdc7激酶抑制剂 |
| EP4284804A1 (en) | 2021-01-26 | 2023-12-06 | Schrödinger, Inc. | Tricyclic compounds useful in the treatment of cancer, autoimmune and inflammatory disorders |
| TW202300150A (zh) | 2021-03-18 | 2023-01-01 | 美商薛定諤公司 | 環狀化合物及其使用方法 |
| AU2022401801A1 (en) * | 2021-12-02 | 2024-06-13 | Beigene, Ltd. | Methods of synthesis of chiral 3, 5-disubstituted morpholine compounds and intermediates useful therein |
| WO2025059027A1 (en) | 2023-09-11 | 2025-03-20 | Schrödinger, Inc. | Cyclopenta[e]pyrazolo[1,5-a]pyrimidine derivatives as malt1 inhibitors |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3922735A1 (de) * | 1989-07-11 | 1991-01-24 | Hoechst Ag | Aminopyrimidin-derivate, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
| JP2004524279A (ja) * | 2000-11-10 | 2004-08-12 | エフ．ホフマン−ラ ロシュ アーゲー | ピリミジン誘導体、及びニューロペプチドｙ受容体リガンドとしてのその使用 |
| DE602005001696T2 (de) * | 2004-03-02 | 2008-04-10 | F. Hoffmann-La Roche Ag | 4-(sulfanylpyrimidin-4-ylmethyl)morpholin-derivate und verwandte verbindungen als gaba-rezeptorliganden zur behandlung von angst, depression und epilepsie |
| US7772271B2 (en) * | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| KR20080052630A (ko) * | 2005-09-01 | 2008-06-11 | 어레이 바이오파마 인크. | Ｒａｆ 억제제 화합물 및 그의 사용 방법 |
| GB0520657D0 (en) * | 2005-10-11 | 2005-11-16 | Ludwig Inst Cancer Res | Pharmaceutical compounds |
| WO2008023159A1 (en) * | 2006-08-24 | 2008-02-28 | Astrazeneca Ab | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
| BRPI0814688A2 (pt) * | 2007-07-09 | 2017-06-06 | Astrazeneca Ab | composto, uso de um composto, métodos para produzir um efeito antiproliferativo em um animal de sangue quente, e para tratar doenças, e, composição farmacêutica |
| JP2010533159A (ja) * | 2007-07-09 | 2010-10-21 | アストラゼネカ アクチボラグ | 化合物９４７ |
-
2008
- 2008-07-08 WO PCT/GB2008/050546 patent/WO2009007748A2/en not_active Ceased
- 2008-07-08 CA CA 2692945 patent/CA2692945A1/en not_active Abandoned
- 2008-07-08 EP EP08776181A patent/EP2074118A2/en not_active Withdrawn
- 2008-07-08 BR BRPI0814818A patent/BRPI0814818A2/pt not_active IP Right Cessation
- 2008-07-08 KR KR1020107002969A patent/KR20100031639A/ko not_active Withdrawn
- 2008-07-08 JP JP2010515600A patent/JP2010533158A/ja active Pending
- 2008-07-08 CN CN200880106248A patent/CN101801962A/zh active Pending
- 2008-07-08 EA EA201000092A patent/EA201000092A1/ru unknown
- 2008-07-08 AR ARP080102944A patent/AR067478A1/es unknown
- 2008-07-08 AU AU2008273889A patent/AU2008273889B2/en not_active Expired - Fee Related
- 2008-07-09 PE PE2008001149A patent/PE20090773A1/es not_active Application Discontinuation
- 2008-07-09 TW TW097125962A patent/TW200904813A/zh unknown
- 2008-07-09 UY UY31215A patent/UY31215A1/es unknown
- 2008-07-09 US US12/170,128 patent/US20090018134A1/en not_active Abandoned
- 2008-07-09 CL CL2008002006A patent/CL2008002006A1/es unknown
-
2010
- 2010-01-06 ZA ZA2010/00106A patent/ZA201000106B/en unknown
- 2010-01-08 DO DO2010000011A patent/DOP2010000011A/es unknown
- 2010-01-08 NI NI201000004A patent/NI201000004A/es unknown
- 2010-01-08 CR CR11201A patent/CR11201A/es not_active Application Discontinuation
- 2010-02-09 CO CO10014104A patent/CO6390066A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AR067478A1 (es) | 2009-10-14 |
| JP2010533158A (ja) | 2010-10-21 |
| WO2009007748A3 (en) | 2009-04-23 |
| CR11201A (es) | 2010-06-17 |
| KR20100031639A (ko) | 2010-03-23 |
| TW200904813A (en) | 2009-02-01 |
| EA201000092A1 (ru) | 2010-06-30 |
| DOP2010000011A (es) | 2010-03-31 |
| AU2008273889B2 (en) | 2012-03-08 |
| EP2074118A2 (en) | 2009-07-01 |
| PE20090773A1 (es) | 2009-07-23 |
| CA2692945A1 (en) | 2009-01-15 |
| CO6390066A2 (es) | 2012-02-29 |
| US20090018134A1 (en) | 2009-01-15 |
| NI201000004A (es) | 2010-10-12 |
| WO2009007748A2 (en) | 2009-01-15 |
| CN101801962A (zh) | 2010-08-11 |
| CL2008002006A1 (es) | 2009-06-26 |
| AU2008273889A1 (en) | 2009-01-15 |
| ZA201000106B (en) | 2011-06-29 |
| UY31215A1 (es) | 2009-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0814818A2 (pt) | 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 | |
| CA3128155C (en) | 3-carbonylamino-5-cyclopentyl-1h-pyrazole compounds having inhibitory activity on cdk2 | |
| JP7089061B2 (ja) | サイクリン依存性キナーゼ阻害剤としての２－アミノ－ピリジンまたは２－アミノ－ピリミジン誘導体 | |
| AU2019290197B2 (en) | Protein tyrosine phosphatase inhibitors and methods of use thereof | |
| EP2601185B1 (en) | Derivatives of pyrazolophenyl-benzenesulfonamide compounds and use thereof as antitumor agents | |
| BR112021008991A2 (pt) | derivados de 2,3-di-hidro-1h-pirrolo [3,4c]piridin-1-ona como inibidores de hpk1 para o tratamento de câncer | |
| EP3710456B1 (en) | Macrocyclic indole derivatives | |
| CN109803968A (zh) | 吡啶并嘧啶酮cdk2/4/6抑制剂 | |
| TWI810220B (zh) | 經取代之巨環吲哚衍生物 | |
| ES2425068T3 (es) | Compuestos de pirido[2,3-d]pirimidin-7-ona como inhibidores de PI3K-alfa para el tratamiento del cáncer | |
| BR112016008276B1 (pt) | derivados bicíclicos de piridila fundidos ao anel, seus usos e seu intermediário, e composição farmacêutica | |
| SA517380830B1 (ar) | 2-(مورفولين-4- يل)-7،1- نفثيريدينات | |
| UA123010C2 (uk) | Модулятори сот та способи їх застосування | |
| CN107849013A (zh) | 作为dub抑制剂用于治疗癌症的氰基吡咯烷类 | |
| AU2022271290A1 (en) | Cdk2 degraders and uses thereof | |
| MXPA04008807A (es) | Derivados de 4-(imidazol-5-il)-2-(4-sulfonilanilino)pirimidina con actividad inhibidora de cdk. | |
| JP7384536B2 (ja) | キナゾリン化合物並びにその調製方法、使用及び医薬組成物 | |
| TW200846344A (en) | Chemical compounds | |
| CA3187514A1 (en) | Fused bicyclic raf inhibitors and methods for use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE AS 7A, 8A, 9A, 10A E 11A ANUIDADES. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2541 DE 17-09-2019 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |
|
| B350 | Update of information on the portal [chapter 15.35 patent gazette] |