New dihydro-1H-imidazo(1,2-a)pyrimidin-5-one compounds are Vps34 inhibitors useful for treating e.g. fibrotic disorders, mesangial cell proliferation disorders, metabolic disorders, allergies, asthma, thrombosis, retinopathy and psoriasis
ARIGON JEROME,JEROME ARIGON,BROLLO MAURICE,MAURICE BROLLO,CLEMENT JACQUES,JACQUES CLEMENT,EL AHMAD YOUSSEF,YOUSSEF EL AHMAD,LABROSSE JEAN ROBERT,JEAN ROBERT LABROSSE,RONAN BAPTISTE,BAPTISTE RONAN
申请号：
FR1061194
公开号：
FR2969612A1
申请日:
2010.12.23
申请国别(地区):
FR
年份:
2012
代理人:
摘要：
Dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound (I) and their racemic forms, enantiomers, diastereoisomers, and addition salts with mineral and organic acids or with bases are new. Dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound of formula (I) and their racemic forms, enantiomers, diastereoisomers, and addition salts with mineral and organic acids or with bases are new. R1 : alkyl, alkenyl, alkynyl or 1-7C (hetero)cycloalkyl group (all optionally substituted by one or more halo, R7, -S(O) x-R7, -SO 2NR5R7, -CN, -OR5, -NR5R6, -NR5-COR7, -NR5-CO 2-R7, -NR5-SO 2-R7-NHCONR5R6, -COR7, -CO 2R5 or CONR5R6)； x : 0-2； either R2 : H, alkyl or cycloalkyl group； and R3 : alkyl, cycloalkyl or phenyl group (optionally substituted by one or more -OR5 or NR5R6)； or R2R3 : 3-10 membered cyclic ring containing one or more heteroatoms of O, S or NR5 and optionally substituted by halo, oxo, R5, -OR5 or -NR5R6； R4 : H, alkyl, halo or CN； R5, R6 : H, alkyl, cycloalkyl or heterocycloalkyl group； and R7 : alkyl, cycloalkyl or heterocycloalkyl group. Independent claims are included for: (1) the preparation of (I)； and (2) intermediates comprising 7-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound of formula (D), 7-chloro-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound of formula (E), 7-chloro-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound of formula (J) and 7-morpholin-4-yl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one compound of formula (F). [Image] [Image] ACTIVITY : Cytostatic； Vasotropic； Antiinflammatory； Metabolic； Antiasthmatic； Antiallergic； Anticoagulant； Thrombolytic； Ophthalmological； Antipsoriatic； Antiarthritic； Antirheumatic； Antidiabetic； Muscular-Gen. MECHANISM OF ACTION : Vps34 inhibitor. The ability of (I) to inhibit Vps34 was tested in vitro. The result showed that (2S)-1-(2-ethylbutyl)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one exhibited an IC 5 0value of less than 10 nM.L'invention concerne
