HYDROXYLATED AND METHOXYLATED CYCLOPENTA [D] PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS

• Main Authors: STEPHEN T. SCHLACHTER, KEITH LEE SPENCER, DENGMING XIAO, BRIAN SAFINA, CHRISTINE CHABOT, JUN LIANG, STEVEN DO, IAN S. MITCHELL, NICHOLAS C. KALLAN, ELI W. WALLACE, JOSEF R. BENCSIK, RUI XU, BIRONG ZHANG, ANNA L. BANKA, JAMES F. BLAKE
• Format: Patent
• Language: Croatian; English
• Published: 29.02.2012
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Spoj, naznačen time, da ima formulu I: i rastvoreni enantiomeri, rastvoreni dijastereomeri i njegove soli, gdje: R1 je Me; R2 je H; R5 je H; A je,G je fenil opcijski supstituiran jednom do četiri R9 skupine ili 5-6-člani heteroaril opcijski supstituiran halogenom; R6 i R7 su neovisno H, OCH3, (C3-C6 cikloalkil)-(CH2), (C3-C6 cikloalkil)-(CH2CH2), V-(CH2)0-1 gdje V je 5-6-člani heteroaril, W-(CH2))1-2 gdje W je fenil opcijski supstituiran s F, Cl, Br, I, OMe, CF3 ili Me, C3-C6-cikloalkil opcijski supstituiran s C1-C3alkil ili O(C1-C3alkil), hidroksi-(C3-C6-cikloalkil), fluoro-(C3-C6-cikloalkil), CH(CH3)CH(OH)fenil, 4-6-člani heterocikl opcijski supstituiran sljedećima F, OH, C1-C3 alkil, ciklopropilmetil ili C(=O)(C1-C3 alkil), ili C1-C6-alkil opcijski supstituiran s jednom ili više skupina neovisno odabranih od sljedećih OH, okso, O(C1-C6-alkil), CN, F, NH2, NH(C1-C6-alkil), N (C1-C6-alkil)2, ciklopropil, fenil, imidazolil, piperidinil, pirolidinil, morfolinil, tetrahidrofuranil, oksetanil ili tetrahidropiranil, ili R6 i R7 zajedno s dušikom na koji su priključeni tvore 4-7-člani heterociklički prsten opcijski supstituiran s jednom ili više skupina neovisno odabranih od sljedećih OH, halogen, okso, CF3, CH2CF3, CH2CH2OH, O(C1-C3 alkil), C(=O)CH3, NH2, NHMe, N(Me)2, S(O)2CH3, ciklopropilmetil i C1-C3 alkil; Rc i Rd su H, R8 je H; svaki R9 je neovisno halogen, C1-C6-alkil, C3-C6-cikloalkil, O-(C1-C6-alkil), CF3, OCF3, S(C1-C6-alkil), CN,OCH2-fenil, CH2O-fenil, NH2, NH-(C1-C6-alkil), N-(C1-C6-alkil)2, piperidin, pirolidin, CH2F, CHF2, OCH2F, OCHF2, OH, SO2(C1-C6-alkil), C(O)NH2, C(O)NH(C1-C6-alkil) i C(O)N(C1-C6-alkil)2;R10 je H. Patent sadrži još 16 patentnih zahtjeva. The present invention provides compounds, including resolved enantiomers, resolved diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula I for use in oral dosage forms: Also provided are oral dosage forms comprising these compounds, methods of using the compounds and oral dosage forms of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer. Further provided are intermediate compounds from the synthesis of these compounds.