6-arylamino-5-cyano-4-pyrimidinone as PDE9A-inhibitors

摘要

4-oxo-5-cyano-6-amino-dihydropyrimidine derivatives (I), their salts, solvates and solvate salts are new. 4-oxo-5-cyano-6-amino-dihydropyrimidine derivatives of formula (I), their salts, solvates and solvate salts are new. [Image] A : 1-8C alkyl, 3-8C cycloalkyl, tetrahydrofuryl or tetrahydropyranyl, all optionally substituted by 1-3 of 1-6C alkyl or alkoxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, amino, hydroxy, 1-6C alkylamino, halo, 1-6C alkylaminocarbonyl, 1-6C alkylcarbonyl, 1-6C alkylsulfonyl or 1-6C alkylthio, and all of these substituents that include a 1-6C alkyl residue may themselves be substituted by one or more of hydroxy, cyano, halo, carboxy or NR 3R 4; R 3 and R 4hydrogen or 1-6C alkyl or together they complete a 5-8 membered heterocycle; B 1phenyl or heteroaryl, optionally substituted by up to 3 of 1-6C alkyl or alkoxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, amino, nitro, hydroxy, 1-6C alkylamino, halo, 1-6C alkylaminocarbonyl, 1-6C alkoxycarbonyl, 1-6C alkylcarbonyl, 1-6C alkylsulfonyl or 1-6C alkylthio, where all substituents that include a 1-6C alkyl residue may themselves be substituted as above. An independent claim is also included for the preparation of (I). ACTIVITY : Nootropic; Tranquilizer; Neuroprotective. MECHANISM OF ACTION : Inhibition of phosphodiesterase (PDE) 9A. The compound 2-cyclopentylmethyl-4-[(4-fluorophenyl)amino]-6-oxo-1,6-dihydro-5-pyrimidine carbonitrile (Ia) had IC50 for inhibition of PDE 9A of 75 nM.