Spiro-isobenzofuranones 1a and 1b were discovered as potent, selective, and brain- penetrable non-imidazole H3 receptor inverse agonists. Our corporate sample collection was screened to identify 2a as a lead. Recognizing the right-hand portion of 2a as an essential pharmacophore, an extensive screen of the left-hand piperidine portion was carried out to yield the potent spiro-derivatives 2t− x. Spiro-isobenzofuranone 2x, the most ...
