CA2778291C - Akt inhibitors - Google Patents
Akt inhibitors Download PDFInfo
- Publication number
- CA2778291C CA2778291C CA2778291A CA2778291A CA2778291C CA 2778291 C CA2778291 C CA 2778291C CA 2778291 A CA2778291 A CA 2778291A CA 2778291 A CA2778291 A CA 2778291A CA 2778291 C CA2778291 C CA 2778291C
- Authority
- CA
- Canada
- Prior art keywords
- imidazol
- ethyl
- tert
- butyl
- piperidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003197 protein kinase B inhibitor Substances 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 364
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 95
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 85
- -1 tetrahydropyran-4-yl Chemical group 0.000 claims description 59
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 13
- 208000005017 glioblastoma Diseases 0.000 claims description 13
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 11
- 201000005202 lung cancer Diseases 0.000 claims description 11
- 208000020816 lung neoplasm Diseases 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- GCEGIRJJGSNKCZ-QGZVFWFLSA-N (5r)-4-[4-[4-ethyl-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidin-1-yl]-5-methyl-6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C1CN(C=2C=3[C@H](C)CC(=O)NC=3N=CN=2)CCC1C1=NC(CC)=CN1CCN1CCCC1 GCEGIRJJGSNKCZ-QGZVFWFLSA-N 0.000 claims 1
- QRULDXBXPXGMQS-QGZVFWFLSA-N (5r)-5-methyl-4-[4-[1-(2-pyrrolidin-1-ylethyl)-4-(3,3,3-trifluoropropyl)imidazol-2-yl]piperidin-1-yl]-6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C([C@H](C=12)C)C(=O)NC2=NC=NC=1N(CC1)CCC1C1=NC(CCC(F)(F)F)=CN1CCN1CCCC1 QRULDXBXPXGMQS-QGZVFWFLSA-N 0.000 claims 1
- WABHLXQVOYVYTI-UHFFFAOYSA-N 5-methyl-4-[4-[1-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)imidazol-2-yl]piperidin-1-yl]-6,8-dihydro-5h-pyrido[2,3-d]pyrimidin-7-one Chemical compound C=12C(C)CC(=O)NC2=NC=NC=1N(CC1)CCC1C1=NC(C(F)(F)F)=CN1CCN1CCCC1 WABHLXQVOYVYTI-UHFFFAOYSA-N 0.000 claims 1
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 77
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 73
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- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 21
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- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 14
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- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- LHTGBZMVHWJBQB-UHFFFAOYSA-N n,2-diethylaniline Chemical compound CCNC1=CC=CC=C1CC LHTGBZMVHWJBQB-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- OHEDMAIVEXQCOZ-UHFFFAOYSA-N piperidine;dihydrochloride Chemical compound Cl.Cl.C1CCNCC1 OHEDMAIVEXQCOZ-UHFFFAOYSA-N 0.000 description 1
- MDZVMZTXIHCNCQ-UHFFFAOYSA-N piperidine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CCNCC1 MDZVMZTXIHCNCQ-UHFFFAOYSA-N 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229960001302 ridaforolimus Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- JCOHXVDKRMWUQP-UHFFFAOYSA-M sodium;n-(5-bromothiophen-2-yl)sulfonyl-2,4-dichlorobenzenecarboximidate Chemical compound [Na+].ClC1=CC(Cl)=CC=C1C(=O)[N-]S(=O)(=O)C1=CC=C(Br)S1 JCOHXVDKRMWUQP-UHFFFAOYSA-M 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- SZVKVQUILFIMKD-UHFFFAOYSA-N tert-butyl 4-(5-cyano-1h-imidazol-2-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(C#N)=CN1 SZVKVQUILFIMKD-UHFFFAOYSA-N 0.000 description 1
- LXZPQDJRYRKCCL-UHFFFAOYSA-N tert-butyl 4-[1-(2-pyrrolidin-1-ylethyl)-4-(3,3,3-trifluoropropyl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(CCC(F)(F)F)=CN1CCN1CCCC1 LXZPQDJRYRKCCL-UHFFFAOYSA-N 0.000 description 1
- WDVJZCFXSHENLM-UHFFFAOYSA-N tert-butyl 4-[1-[2-(oxan-2-yloxy)ethyl]imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC=CN1CCOC1OCCCC1 WDVJZCFXSHENLM-UHFFFAOYSA-N 0.000 description 1
- BJQMFCXVEZFQAV-UHFFFAOYSA-N tert-butyl 4-[4-bromo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(Br)=CN1CCN1CCCC1 BJQMFCXVEZFQAV-UHFFFAOYSA-N 0.000 description 1
- BFNIIQIAMUFQTM-UHFFFAOYSA-N tert-butyl 4-[4-ethenyl-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(C=C)=CN1CCN1CCCC1 BFNIIQIAMUFQTM-UHFFFAOYSA-N 0.000 description 1
- XSIQQUMWCAEVQI-UHFFFAOYSA-N tert-butyl 4-[5-(2,2,2-trifluoroethyl)-1h-imidazol-2-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NC(CC(F)(F)F)=CN1 XSIQQUMWCAEVQI-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25430809P | 2009-10-23 | 2009-10-23 | |
| US61/254,308 | 2009-10-23 | ||
| PCT/US2010/053295 WO2011050016A1 (en) | 2009-10-23 | 2010-10-20 | Akt inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2778291A1 CA2778291A1 (en) | 2011-04-28 |
| CA2778291C true CA2778291C (en) | 2014-02-11 |
Family
ID=43467018
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2778291A Expired - Fee Related CA2778291C (en) | 2009-10-23 | 2010-10-20 | Akt inhibitors |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8436002B2 (enExample) |
| EP (1) | EP2491032B1 (enExample) |
| JP (1) | JP5581390B2 (enExample) |
| KR (1) | KR101398268B1 (enExample) |
| CN (1) | CN102574852B (enExample) |
| AU (1) | AU2010310786B2 (enExample) |
| BR (1) | BR112012011328A2 (enExample) |
| CA (1) | CA2778291C (enExample) |
| EA (1) | EA020151B1 (enExample) |
| ES (1) | ES2465094T3 (enExample) |
| MX (1) | MX2012004780A (enExample) |
| WO (1) | WO2011050016A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2582557T3 (es) * | 2012-05-17 | 2016-09-13 | Array Biopharma, Inc. | Proceso para la preparación de compuestos hidroxilados de ciclopentilpirimidina |
| BR112014028585B1 (pt) | 2012-05-17 | 2020-12-22 | Genentech , Inc | processo para fabricação de aminoácidos, e seus intermediários |
| LT2858989T (lt) | 2012-05-17 | 2020-08-10 | Genentech, Inc. | Akt inhibuojančio pirimidinil-ciklopentano junginio amorfinė forma, jo kompozicijos ir būdai |
| EP2850200A1 (en) | 2012-05-17 | 2015-03-25 | Genentech, Inc. | Process of making hydroxylated cyclopentapyrimidine compounds and salts thereof |
| ES2588878T3 (es) | 2012-05-17 | 2016-11-07 | Array Biopharma, Inc. | Proceso para preparar compuestos de ciclopentilpirimidina hidroxilada |
| AR093511A1 (es) | 2012-11-16 | 2015-06-10 | Merck Patent Gmbh | Derivados de imidazol-piperidinilo como moduladores de la actividad de cinasas |
| MX370448B (es) * | 2013-03-11 | 2019-12-13 | Merck Patent Gmbh | Derivados de 6- [4- (1h-imidazol-2-il) piperidin-1-il] pirimidin-4-amina como moduladores de la actividad de cinasa. |
| AU2014293013A1 (en) | 2013-07-26 | 2016-03-17 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| CA2922398C (en) | 2013-09-12 | 2023-08-29 | Dana-Farber Cancer Institute, Inc. | Methods for evaluating and treating waldenstrom's macroglobulinemia |
| GB201401198D0 (en) | 2014-01-24 | 2014-03-12 | Bial Portela & Ca Sa | Process for the syntheis of substituted urea compounds |
| US9925192B2 (en) | 2014-02-28 | 2018-03-27 | Merck Sharp & Dohme Corp. | Method for treating cancer |
| JP6576553B2 (ja) * | 2016-05-20 | 2019-09-18 | 大鵬薬品工業株式会社 | 新規５Ｈ−ピロロ［２，３−ｄ］ピリミジン−６（７Ｈ）−オン誘導体 |
| US12617784B2 (en) | 2019-01-29 | 2026-05-05 | Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. | AKT inhibitor |
| US20230295114A1 (en) * | 2020-05-08 | 2023-09-21 | Georgiamune Llc | Akt3 modulators |
| CN115485276B (zh) * | 2020-05-15 | 2024-05-31 | 南京正大天晴制药有限公司 | 氘代akt激酶抑制剂 |
| EP4186902A4 (en) * | 2020-07-22 | 2024-06-05 | Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. | DIHYDROPYRIDO[2,3-D]PYRIMIDINONE DERIVATIVE SALT, PREPARATION METHOD AND USE THEREOF |
| JP7472391B2 (ja) * | 2020-07-22 | 2024-04-22 | 南京正大天晴制薬有限公司 | ジヒドロピリド［２，３－ｄ］ピリミジノン誘導体の塩及び結晶形 |
| US12673061B2 (en) | 2020-07-22 | 2026-07-07 | Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. | Unit dosage composition of AKT inhibitor |
Family Cites Families (19)
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|---|---|---|---|---|
| AU4128089A (en) | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| NL1004346C2 (nl) | 1996-10-23 | 1998-04-24 | Dsm Nv | Werkwijze voor het scheiden van een mengsel van enantiomeren in een geschikt oplosmiddel. |
| EP1478648B1 (en) | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| US7563748B2 (en) | 2003-06-23 | 2009-07-21 | Cognis Ip Management Gmbh | Alcohol alkoxylate carriers for pesticide active ingredients |
| WO2005117909A2 (en) | 2004-04-23 | 2005-12-15 | Exelixis, Inc. | Kinase modulators and methods of use |
| EP1769092A4 (en) | 2004-06-29 | 2008-08-06 | Europ Nickel Plc | IMPROVED LIXIVIATION OF BASE METALS |
| MY179032A (en) | 2004-10-25 | 2020-10-26 | Cancer Research Tech Ltd | Ortho-condensed pyridine and pyrimidine derivatives (e.g.purines) as protein kinase inhibitors |
| US7767687B2 (en) * | 2004-12-13 | 2010-08-03 | Biogen Idec Ma Inc. | Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors |
| AU2005322085B2 (en) | 2004-12-28 | 2012-07-19 | Exelixis, Inc. | [1H-pyrazolo[3, 4-d]pyrimidin-4-yl]-piperidine or -piperazine compounds as serine-threonine kinase modulators (p70S6K, Atk1 and Atk2) for the treatment of immunological, inflammatory and proliferative diseases |
| ATE498358T1 (de) | 2005-06-29 | 2011-03-15 | Compumedics Ltd | Sensoranordnung mit leitfähiger brücke |
| WO2007125321A2 (en) | 2006-04-25 | 2007-11-08 | Astex Therapeutics Limited | Purine and deazapurine derivatives as pharmaceutical compounds |
| JP2009534456A (ja) * | 2006-04-25 | 2009-09-24 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| TW200801513A (en) | 2006-06-29 | 2008-01-01 | Fermiscan Australia Pty Ltd | Improved process |
| AR064416A1 (es) * | 2006-12-21 | 2009-04-01 | Cancer Rec Tech Ltd | Derivados de purina, piridina y pirimidina condensadas con heterociclos, moduladores de pka y/o pkb, composiciones farmaceuticas que los contienen, y usos para el tratamiento de enfermedades hiperproliferativas. |
| UA99284C2 (ru) | 2007-05-11 | 2012-08-10 | Елі Ліллі Енд Компані | ИНГИБИТОРЫ р70 S6-КИНАЗЫ |
| AR074072A1 (es) | 2008-11-11 | 2010-12-22 | Lilly Co Eli | Compuesto de imidazol -piperidin -pirrol-pirimidin-6-ona, composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para tratar el glioblastoma multiforme |
-
2010
- 2010-10-20 BR BR112012011328A patent/BR112012011328A2/pt not_active IP Right Cessation
- 2010-10-20 CN CN201080046941.9A patent/CN102574852B/zh not_active Expired - Fee Related
- 2010-10-20 ES ES10774072.2T patent/ES2465094T3/es active Active
- 2010-10-20 EA EA201270590A patent/EA020151B1/ru not_active IP Right Cessation
- 2010-10-20 CA CA2778291A patent/CA2778291C/en not_active Expired - Fee Related
- 2010-10-20 US US13/391,895 patent/US8436002B2/en not_active Expired - Fee Related
- 2010-10-20 EP EP10774072.2A patent/EP2491032B1/en not_active Not-in-force
- 2010-10-20 WO PCT/US2010/053295 patent/WO2011050016A1/en not_active Ceased
- 2010-10-20 JP JP2012535319A patent/JP5581390B2/ja not_active Expired - Fee Related
- 2010-10-20 MX MX2012004780A patent/MX2012004780A/es active IP Right Grant
- 2010-10-20 KR KR1020127010282A patent/KR101398268B1/ko not_active Expired - Fee Related
- 2010-10-20 AU AU2010310786A patent/AU2010310786B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010310786A1 (en) | 2012-04-19 |
| AU2010310786B2 (en) | 2014-03-27 |
| US8436002B2 (en) | 2013-05-07 |
| ES2465094T3 (es) | 2014-06-05 |
| EP2491032A1 (en) | 2012-08-29 |
| EP2491032B1 (en) | 2014-04-16 |
| JP2013508382A (ja) | 2013-03-07 |
| MX2012004780A (es) | 2012-08-23 |
| BR112012011328A2 (pt) | 2016-11-22 |
| KR101398268B1 (ko) | 2014-05-23 |
| CN102574852A (zh) | 2012-07-11 |
| EA201270590A1 (ru) | 2012-09-28 |
| EA020151B1 (ru) | 2014-09-30 |
| US20120149684A1 (en) | 2012-06-14 |
| JP5581390B2 (ja) | 2014-08-27 |
| KR20120068941A (ko) | 2012-06-27 |
| CN102574852B (zh) | 2014-06-25 |
| CA2778291A1 (en) | 2011-04-28 |
| WO2011050016A1 (en) | 2011-04-28 |
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