Mikami, Satoshi; Kawasaki, Masanori; Ikeda, Shuhei; Negoro, Nobuyuki; Nakamura, Shinji; Nomura, Izumi; Ashizawa, Tomoko; Kokubo, Hironori; Hoffman, Isaac Dylan; Zou, Hua; Oki, Hideyuki; Uchiyama, Noriko; Hiura, Yuuto; Miyamoto, Maki; Itou, Yuuki; Nakashima, Masato; Iwashita, Hiroki; Taniguchi, Takahiko published the artcile< Discovery of a novel series of pyrazolo[1,5-a]pyrimidine-based phosphodiesterase 2A inhibitors structurally different from N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), for the treatment of cognitive disorders>, Electric Literature of 660867-80-1, the main research area is pyrazolopyrimidine preparation phosphodiesterase inhibitor SAR; intramolecular hydrogen bond; phospodiesterase 2A; phototoxicity; pyrazolo[1,5-a]pyrimidine; schizophrenia; structure-based drug design.
This article described a drug design strategy for a new series of lead compounds structurally distinct from the clin. candidate TAK-915, and subsequent medicinal chem. efforts to optimize potency, selectivity over other PDE families, and other preclin. properties including in-vitro phototoxicity and in-vivo rat plasma clearance. These efforts resulted in the discovery of N-((1S)-2-hydroxy-2-methyl-1-(4-(trifluoromethoxy)phenyl)propyl)-6-methyl-5-(3-methyl-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, which robustly increased 3′,5′-cyclic guanosine monophosphate (cGMP) levels in the rat brain following an oral dose, and moreover, attenuated MK-801-induced episodic memory deficits in a passive avoidance task in rats. These data provide further support to the potential therapeutic utility of PDE2A inhibitors in enhancing cognitive performance.
Chemical & Pharmaceutical Bulletin published new progress about Bioavailability. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Electric Literature of 660867-80-1.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts