The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives.

A series of new 6-substituted 3H-quinazolin-4-ones (3a-3d) were designed, synthesized and evaluated as the type I positive allosteric modulators (PAMs) of human α7 nAChR expressed in Xenopus ooctyes by two-electrode voltage clamp. However, no compound showed a better efficacious PAM than lead compound 2 in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis suggested that thiazolo[4,5-d]pyrimidin-7(6H)-one was the key biological skeleton. [ABSTRACT FROM AUTHOR]