New imidazo (1,2-a) pyrimidin-5(1H)-one derivatives, useful as general anesthetics and sedatives having rapid action and short plasma half life

摘要

2-Phenyl or phenylalkyl imidazo (1,2-a) pyrimidin-5(1H)-one or 2,3-dihydro-imidazo (1,2-a) pyrimidin-5(1H)-one derivatives (I) are new. Imidazopyrimidinones of formula (I), including racemates and enantiomers in the case of 2,3-dihydro compounds, or their salts are new. Dotted line = optional bond; R1 = H; or alkyl, cycloalkyl, 2-6C alkenyl or 3-6C alkynyl (all optionally substituted by one or more of halo, OH, R, CONRR', COR, COOR or OCOR); R, R' = alkyl, cycloalkyl or aryl; R2 = H, alkyl or cycloalkyl, or is absent if the dotted line is a bond; R3 = -Y-Ph'; or R2 + R3 = (CH2)n; Y = direct bond or 1-6C alkylene (optionally interrupted by one or more of O, S and N); Ph' = phenyl (optionally substituted by one or more of halo, OH, NH2, NHR, NRR', CONH2, CONHR, CONRR', CHO, COR, COOH, COOR, OCHO, OCOR, NCOH (sic) or NCOR (sic)); n = 4-6; and R4 = H, halo or CHO; alkyl, cycloalkyl or 3-6C aryl (all optionally substituted by one or more of halo, OH, OR, CHO, COR, CONH2, OCOR, OCONRR' or OCONH2); or 5-12 membered saturated or unsaturated heterocyclyl containing one or more of O, S and N as heteroatom(s); unless specified otherwise alkyl moieties have 1-6C, cycloalkyl moieties 3-6C and aryl moieties 6-12C; the compound 7-methyl-2-phenyl-imidazo (1,2-a) pyrimidin-5(1H)-one (I') is excluded. Independent claims are included for: (i) (I) or (I') (including isomers as above and salts) as medicaments; (ii) the preparation of (I); (iii) the following new intermediates: the (R)-(+)- and (S)-(-)-isomers of 2-amino-5-phenyl-2-imidazoline (II'); 2-amino-5,5-pentamethylene-1-imidazoline derivatives of formula (II''); and acetoacetic acid esters of formula (III'); and (iv) the preparation of (R)-(+)-(II'). R'1 = as R1 but not H; and R5 = 1-6C alkyl.