PYRIDO (2, 3-D) PYRIMIDINONE COMPOUNDS AND THEIR USE AS PI3 INHIBITORS

• Main Authors: DILIP BHUMRALKAR, ROBERT STEVEN KANIA, MITCHELL DAVID NAMBU, MICHAEL BRUNO PLEWE, MARY CATHERINE JOHNSON, MASON ALAN PAIRISH, PHUONG THI QUY LE, KHANH TUAN TRAN, KLAUS RUPRECHT DRESS, JACQUI ELIZABET HOFFMAN, HENGMIAO CHENG
• Format: Patent
• Language: Croatian; English
• Published: 30.09.2011
• 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 Formule (I) ili njegova sol, naznačen time što: R1 je H ili (C1 do C8) alkil, izborno supstituiran s najmanje jednom skupinom R5;A je 3- do 10-eročlana cikloalkilna skupina; R2 je (C1 do C8) alkil, supstituiran s najmanje jednom skupinom R6, (C3 do C10) cikloalkil, (C2 do C8) cikloheteroalkil, (C8 do C14) aril, (C2 do C9) heteroaril, -NR7aR7b ili -N=CR8aR8b, gdje je svaki od navedenih (C3 do C10) cikloalkila, (C2 do C9) cikloheteroalkila, (C8 do C14) arila, te (C2 do C9) heteroarila izborno supstituiran s najmanje jednom skupinom R9;R3 je (C1 do C6) alkil, (C3 do C10) cikloalkil, (C2 do C9) cikloheteroalkil, (C2 do C8) alkenil, (C2 do C8) alkinil, halogen, cijano, -(CH2)nC(O)OR10, -(CH2)nC(O)N(R11aR11b), COR12, (C8 do C14) aril ili (C2 do C9) heteroaril, gdje su navedeni (C1 do C6) alkil, (C3 do C10) cikloalkil, (C2 do C9) cikloheteroalkil, (C2 do C8) alkenil, (C2 do C8) alkinil, (C8 do C14) aril i (C2 do C9) heteroaril izborno supstituirani s najmanje jednom skupinom R9;svaki R4 je neovisno -OH, halogen, CF3, -NR11aR11b, (C1 do C8) alkil, (C1 do C6) alkenil, (C1 do C8) alkinil, (C1 do C6) alkoksi, cijano, (C3 do C10) cikloalkil, (C2 do C9) cikloheteroalkil, (C8 do C14) aril, (C2 do C9) heteroaril, -C(O)R12-C(O)NR11aR11b, -S(O)mR12, -S(O)mNR11aR11b, -NR11aS(O)mR12-(CH2)nC(O)OR10, -(CH2)nC(O)N(R11aR11b), -OC(O)R12, -NR11aC(O)R12 ili -NR11aC(O)N(R11aR11b), gdje je svaki od navedenih (C1 do C6) alkila, (C1 do C6) alkenila, (C1 do C6) alkinila, (C1 do C6) alkoksi, (C3 do C10) cikloalkila, (C2 do C9) cikloheteroalkila, (C6 do C12) arila, te (C2 do C9) heteroarila izborno supstituiran s najmanje jednom skupinom R13;svaki R5 je neovisno -OH, halogen, CF3, -NR11aR11b, (C1 do C6) alkil, (C1 do C6) alkoksi, cijano, (C3 do C10) cikloalkil, (C2 do C9) cikloheteroalkil, (C6 do C14) aril, (C2 do C9) heteroaril, -S(O)mR12, -S(O)mR11aR11b, -C(O)R12 ili -C(O)NR11aR11b, gdje je svaki od navedenih (C1 do C6) alkila, (C1 do C6) alkoksi, (C3 do C10) cikloalkila, (C2 do C9) cikloheteroalkila, (C6 do C14) arila, te (C2 do C9) heteroarila izborno supstituiran s najmanje jednom skupinom R9;svaki R6 je neovisno -OH, (C1 do C6) alkinil, cijano, (C3 do C10) cikloalkil, (C2 do C9) cikloheteroalkil, (C8 do C14) aril, (C2 do C8) heteroaril, -C(O)R12 -C(O)NR11aR11b, -S(O)mR12, -S(O)mNR11aR11b, -NR11aS(O)mR12-(CH2)nC(O)OR10, -(CH2)nC(O)N(R11aR11b), -OC(O)R12, -NR11aC(O)R12 ili -NR11aC(O)N(R11aR11b), gdje je svaki od navedenih (C1 do C6) alkinila, (C3 do C10) cikloalkila, (C2 do C9) cikloheteroalkila, (C6 do C12) arila, te (C2 do C9) heteroarila izborno supstituiran s najmanje jednom skupinom R13;svaki od R7a i R7b je neovisno H, (C1 do C8) alkil, (C2 do C6)alkenil, (C2 do C6)alkinil, (C3 do C10) cikloalkil ili (C6 do C10)aril, gdje je svaki od navedenih (C1 do C6) alkila, (C2 do C6)alkenila, (C2 do C6)alkinila, (C3 do C10) cikloalkila, te (C6 do C10)arila izborno supstituiran s najmanje jednom skupinom R9; ili se R7a i R7b može uzeti zajedno s atomom dušika kako bi tvorili The present invention is directed to novel 4-methylpyridopyrimidinone compounds of Formula (I), and to salts thereof, their synthesis, and their use as inhibitors of phosphoinositide 3-kinase alpha (PI3-Kalpha).