ES2609606T3 - Derivados de urea y carbamato de 2-morfolino-1,3,5-triazina como inhibidores de mTOR para el tratamiento de enfermedades inmunológicas o proliferativas - Google Patents
Derivados de urea y carbamato de 2-morfolino-1,3,5-triazina como inhibidores de mTOR para el tratamiento de enfermedades inmunológicas o proliferativas Download PDFInfo
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- ES2609606T3 ES2609606T3 ES12761738.9T ES12761738T ES2609606T3 ES 2609606 T3 ES2609606 T3 ES 2609606T3 ES 12761738 T ES12761738 T ES 12761738T ES 2609606 T3 ES2609606 T3 ES 2609606T3
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- Prior art keywords
- phenyl
- triazin
- methylsulfonyl
- urea
- methylmorpholino
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 61
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims description 51
- 201000010099 disease Diseases 0.000 title claims description 44
- 238000011282 treatment Methods 0.000 title claims description 38
- 239000004202 carbamide Substances 0.000 title claims description 30
- 230000002062 proliferating effect Effects 0.000 title claims description 12
- 230000001900 immune effect Effects 0.000 title claims description 6
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title description 24
- 229940124302 mTOR inhibitor Drugs 0.000 title description 21
- 150000004657 carbamic acid derivatives Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- 150000002367 halogens Chemical class 0.000 claims abstract description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 32
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 76
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 76
- -1 8-oxa-3-azabicyclo [3.2.1] octan-3-yl Chemical group 0.000 claims description 66
- 238000000034 method Methods 0.000 claims description 57
- 239000003814 drug Substances 0.000 claims description 22
- 230000002265 prevention Effects 0.000 claims description 21
- 230000004900 autophagic degradation Effects 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 206010052779 Transplant rejections Diseases 0.000 claims description 10
- 230000004770 neurodegeneration Effects 0.000 claims description 10
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 10
- 230000002757 inflammatory effect Effects 0.000 claims description 9
- 208000030159 metabolic disease Diseases 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 230000001363 autoimmune Effects 0.000 claims description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 208000036142 Viral infection Diseases 0.000 claims description 6
- 208000016097 disease of metabolism Diseases 0.000 claims description 6
- 230000009385 viral infection Effects 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- JTWIUWYFTTUDAS-INIZCTEOSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 JTWIUWYFTTUDAS-INIZCTEOSA-N 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
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- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 208000024908 graft versus host disease Diseases 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- BTUQEGIDVUWXLY-SFHVURJKSA-N 1-(2,2-dimethylpropyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(C)(C)C)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 BTUQEGIDVUWXLY-SFHVURJKSA-N 0.000 claims description 3
- LGRSDZOSFNRFBX-INIZCTEOSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 LGRSDZOSFNRFBX-INIZCTEOSA-N 0.000 claims description 3
- SVVLFAXKYZRIEU-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SVVLFAXKYZRIEU-HNNXBMFYSA-N 0.000 claims description 3
- IQZVHHCWLJKABG-SFHVURJKSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(2-methylpropyl)urea Chemical compound C1=CC(NC(=O)NCC(C)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 IQZVHHCWLJKABG-SFHVURJKSA-N 0.000 claims description 3
- HJYVQAWXJMKHEL-INIZCTEOSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(3,3,3-trifluoropropyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCC(F)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 HJYVQAWXJMKHEL-INIZCTEOSA-N 0.000 claims description 3
- SNXHGDLEEWPMMH-KRWDZBQOSA-N 1-cyclobutyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SNXHGDLEEWPMMH-KRWDZBQOSA-N 0.000 claims description 3
- HGOXTLYZGOXGIM-IBGZPJMESA-N 1-cyclohexyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCCCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 HGOXTLYZGOXGIM-IBGZPJMESA-N 0.000 claims description 3
- FZJLSYYBXRUXGH-SFHVURJKSA-N 1-cyclopentyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 FZJLSYYBXRUXGH-SFHVURJKSA-N 0.000 claims description 3
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- WLORGJWWSIEHGH-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3,3-dimethylmorpholin-4-yl)-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CC1(C)COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 WLORGJWWSIEHGH-UHFFFAOYSA-N 0.000 claims description 3
- RRBDAWQZDGPPKD-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3-ethylmorpholin-4-yl)-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CCC1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 RRBDAWQZDGPPKD-UHFFFAOYSA-N 0.000 claims description 3
- GWYWSNIEOOQQBY-HNNXBMFYSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylpyridin-3-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=NC=CC=2)S(C)(=O)=O)=N1 GWYWSNIEOOQQBY-HNNXBMFYSA-N 0.000 claims description 3
- DVBAKXMLTYRUSI-IBGZPJMESA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-pyrrolidin-1-ylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(=O)(=O)N2CCCC2)=N1 DVBAKXMLTYRUSI-IBGZPJMESA-N 0.000 claims description 3
- YKIWVDVZGHLPNJ-HNNXBMFYSA-N 1-methyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 YKIWVDVZGHLPNJ-HNNXBMFYSA-N 0.000 claims description 3
- MHPWJPNRJCISIB-AWEZNQCLSA-N 1-methyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylpyridin-3-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=NC=CC=2)S(C)(=O)=O)=N1 MHPWJPNRJCISIB-AWEZNQCLSA-N 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
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- VGGRTBRWWUFDQE-HNNXBMFYSA-N 1-(2,2-difluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 VGGRTBRWWUFDQE-HNNXBMFYSA-N 0.000 claims description 2
- WQSLRAHWQAGEEV-HNNXBMFYSA-N 1-(2-fluoroethyl)-3-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 WQSLRAHWQAGEEV-HNNXBMFYSA-N 0.000 claims description 2
- DWHLEZSBYLJWAP-INIZCTEOSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 DWHLEZSBYLJWAP-INIZCTEOSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| EP11182221 | 2011-09-21 | ||
| EP11182221 | 2011-09-21 | ||
| PCT/EP2012/068590 WO2013041652A1 (en) | 2011-09-21 | 2012-09-21 | Morpholino substituted urea or carbamate derivatives as mtor inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2609606T3 true ES2609606T3 (es) | 2017-04-21 |
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| EP (1) | EP2758379B1 (enExample) |
| JP (1) | JP5995975B2 (enExample) |
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| ES (1) | ES2609606T3 (enExample) |
| RU (1) | RU2616619C2 (enExample) |
| WO (1) | WO2013041652A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2011107585A1 (en) | 2010-03-04 | 2011-09-09 | Cellzome Limited | Morpholino substituted urea derivatives as mtor inhibitors |
| RU2609208C2 (ru) | 2011-10-07 | 2017-01-31 | Селлзоум Лимитед | МОРФОЛИНО-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ БИЦИКЛИЧЕСКИХ ПИРИМИДИНМОЧЕВИНЫ ИЛИ КАРБАМАТА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR |
| US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
| UY36294A (es) | 2014-09-12 | 2016-04-29 | Novartis Ag | Compuestos y composiciones como inhibidores de quinasa |
| EP3515446B1 (en) | 2016-09-19 | 2023-12-20 | Novartis AG | Therapeutic combinations comprising a raf inhibitor and a erk inhibitor |
| CA3057969A1 (en) | 2017-05-02 | 2018-11-08 | Novartis Ag | Combination therapy |
| CA3111980A1 (en) | 2018-09-10 | 2020-03-19 | Mirati Therapeutics, Inc. | Combination therapies |
| AU2020276695B2 (en) | 2019-05-13 | 2025-12-18 | Novartis Ag | New crystalline forms of N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2 (trifluoromethyl)isonicotinamide as RAF inhibitors for the treatment of cancer |
| US20220378754A1 (en) * | 2019-09-11 | 2022-12-01 | Yale University | Compositions and methods for treating slow-flow vascular malformations |
| CN115109049B (zh) * | 2022-08-12 | 2023-08-15 | 江西科技师范大学 | 含芳基脲结构的三嗪类化合物及其应用 |
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| ES2284200T3 (es) | 1997-02-12 | 2007-11-01 | Electrophoretics Limited | Marcadores proteicos para cancer de pulmon y uso de los mismos. |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| EP1054004B1 (en) | 1997-12-15 | 2008-07-16 | Astellas Pharma Inc. | Novel pyrimidine-5-carboxamide derivatives |
| EE05708B1 (et) | 1999-02-10 | 2014-04-15 | Astrazeneca Ab | Kinasoliini derivaat angiogeneesi inhibiitorina ja selle kasutamine |
| US7173038B1 (en) | 1999-11-05 | 2007-02-06 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
| CN1329390C (zh) | 2000-02-15 | 2007-08-01 | 苏根公司 | 吡咯取代的2－二氢吲哚酮蛋白激酶抑制剂 |
| US7135298B2 (en) | 2003-03-26 | 2006-11-14 | The Burnham Institute For Medical Research | Screening assay for agents that alter target of Rapamycin activity |
| JP2008540391A (ja) | 2005-05-05 | 2008-11-20 | アストラゼネカ アクチボラグ | ピラゾリルアミノ置換ピリミジン、および癌の処置におけるそれらの使用 |
| EP1891446B1 (en) | 2005-06-14 | 2013-04-10 | Cellzome GmbH | Process for the identification of novel enzyme interacting compounds |
| GB0616747D0 (en) * | 2006-08-24 | 2006-10-04 | Astrazeneca Ab | Novel compounds |
| ATE414281T1 (de) | 2006-08-03 | 2008-11-15 | Cellzome Ag | Verfahren zur identifizierung von molekülen die mit pi3k interagieren und verfahren zur reinigung von pi3k |
| EP2057140B1 (en) | 2006-08-24 | 2012-08-08 | AstraZeneca AB | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
| US20080233127A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| US8012986B2 (en) * | 2007-04-02 | 2011-09-06 | Hoffmann-La Roche Inc. | Pyridine and pyrimidine derivatives as MGLUR2 antagonists |
| JP4782239B2 (ja) | 2007-04-18 | 2011-09-28 | ファイザー・プロダクツ・インク | 異常細胞増殖治療のためのスルホニルアミド誘導体 |
| EP2178563A2 (en) | 2007-07-06 | 2010-04-28 | OSI Pharmaceuticals, Inc. | Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mtorc2 |
| CA2692945A1 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Compounds - 945 |
| US20100261723A1 (en) | 2007-07-09 | 2010-10-14 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| US20100227858A1 (en) | 2007-07-09 | 2010-09-09 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| EA018708B1 (ru) | 2007-07-09 | 2013-10-30 | Астразенека Аб | ПРОИЗВОДНЫЕ МОРФОЛИНОПИРИМИДИНА, ИСПОЛЬЗУЕМЫЕ ПРИ ЗАБОЛЕВАНИЯХ, СВЯЗАННЫХ С mTOR КИНАЗОЙ И/ИЛИ PI3K |
| CN101224207A (zh) | 2007-10-12 | 2008-07-23 | 中国科学院上海有机化学研究所 | 具有诱导自吞噬治疗错误折叠蛋白聚集所致疾病的药物及其筛选方法 |
| WO2009093981A1 (en) * | 2008-01-23 | 2009-07-30 | S Bio Pte Ltd | Triazine compounds as kinase inhibitors |
| DK2245181T3 (da) | 2008-02-04 | 2012-02-06 | Cellzome Ag | Selektivitetsprofilering af PI3K-interagerende molekyler med multiple mål |
| KR101331341B1 (ko) * | 2008-05-23 | 2013-11-19 | 와이어쓰 엘엘씨 | Ｐｉ３ 키나제 및 ｍｔｏｒ 억제제로서의 트리아진 화합물 |
| KR20110046514A (ko) | 2008-07-31 | 2011-05-04 | 제넨테크, 인크. | 피리미딘 화합물, 조성물 및 사용 방법 |
| GB2465405A (en) | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| WO2010096619A1 (en) | 2009-02-23 | 2010-08-26 | Wyeth Llc | Process, purification and crystallization of 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea |
| CA2755061A1 (en) * | 2009-03-13 | 2010-09-16 | Cellzome Limited | Pyrimidine derivatives as mtor inhibitors |
| WO2010120994A2 (en) | 2009-04-17 | 2010-10-21 | Wyeth Llc | Ureidoaryl-and carbamoylaryl-morpholino- pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their synthesis |
| ES2439793T3 (es) | 2009-04-17 | 2014-01-24 | Wyeth Llc | Compuestos de pirimidina, su uso como inhibidores de la mTOR quinasa y de la PI3 quinasa, y su síntesis |
| EP2456869A4 (en) | 2009-07-23 | 2013-11-27 | Trustees Of The University Of Princeton | MTOR KINASE HEMMER AS ANTIVIRUS AGENT |
| WO2011107585A1 (en) | 2010-03-04 | 2011-09-09 | Cellzome Limited | Morpholino substituted urea derivatives as mtor inhibitors |
| WO2012136622A1 (en) | 2011-04-04 | 2012-10-11 | Cellzome Limited | Dihydropyrrolo pyrimidine derivatives as mtor inhibitors |
| RU2609208C2 (ru) | 2011-10-07 | 2017-01-31 | Селлзоум Лимитед | МОРФОЛИНО-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ БИЦИКЛИЧЕСКИХ ПИРИМИДИНМОЧЕВИНЫ ИЛИ КАРБАМАТА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR |
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2012
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- 2012-09-21 CA CA2849189A patent/CA2849189A1/en not_active Abandoned
Also Published As
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| CA2849189A1 (en) | 2013-03-28 |
| EP2758379A1 (en) | 2014-07-30 |
| RU2014109747A (ru) | 2015-10-27 |
| RU2616619C2 (ru) | 2017-04-18 |
| EP2758379B1 (en) | 2016-10-19 |
| US9175011B2 (en) | 2015-11-03 |
| BR112014006743A2 (pt) | 2017-04-11 |
| US20140378438A1 (en) | 2014-12-25 |
| BR112014006743A8 (pt) | 2018-01-09 |
| JP2014530197A (ja) | 2014-11-17 |
| AU2012311458A1 (en) | 2014-04-10 |
| AU2012311458B2 (en) | 2016-02-04 |
| KR20140070616A (ko) | 2014-06-10 |
| WO2013041652A1 (en) | 2013-03-28 |
| CN103917530B (zh) | 2016-08-24 |
| JP5995975B2 (ja) | 2016-09-21 |
| CN103917530A (zh) | 2014-07-09 |
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