| 摘要 |
6-substituted methylpyrazolo[3,4-d]pyrimidin-4-one derivatives (I), their salts and/or solvates are new. 6-substituted methylpyrazolo[3,4-d]pyrimidin-4-one derivatives of formula (I), their salts and/or solvates are new. [Image] R 1> : 1-8C alkyl, 2-6C alkenyl or alkynyl, or 3-8C cycloalkyl, all optionally substituted by 1-3 of 1-6C alkyl or alkoxy, carboxy, cyano, trifluoromethyl, amino (optionally substituted by 1-6C alkyl, 6-10C arylcarbonyl,1-6C alkylcarbonyl, heteroarylcarbonyl or 1-6C alkylsulfonyl), nitro, hydroxy, halo, trifluoromethoxy, 1-6C alkylaminocarbonyl, 1-6C alkoxycarbonyl, 6-10C arylaminocarbonyl, heteroarylaminocarbonyl, 1-6C alkylsulfonyl or 1-6C alkylthio, where the alkyl, alkoxy, alkylamino, arylcarbonylamino, alkylcarbonylamino, alkylaminocarbonyl, alkoxycarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, heteroarylcarbonylamino, alkylsulfonyl(amino) and alkylthio are themselves optionally substituted by 1-3 hydroxy, cyano, halo, trifluoromethyl, trifluoromethoxy, carboxy or NR 3>R 4> ; R 2> : phenyl or heteroaryl, each optionally substituted by 1-3 of the substituents specified for R 1>; R 3> , R 4> : hydrogen or 1-6C alkyl or together complete a 5-8 membered heterocycle. An independent claim is also included for the preparation of (I). ACTIVITY : Nootropic; Neuroprotective. MECHANISM OF ACTION : Inhibition of phosphodiesterase (PDE) 9A. The compound 6-cyclopentylmethyl-1-(2-methylphenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (Ia) had IC 50 against recombinant PDE9A of 5 nM, when tested in an assay that measured hydrolysis of the substrate 8-tritiated guanosine-3',5'-cyclic phosphate. |
