Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers

Adam M Gilbert¹, Stephen Caltabiano, Frank E Koehn

¹Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965-1299, and Bone Metabolism and Osteoporosis Research, Wyeth Research, 145 King of Prussia Road, Radnor, Pennsylvania 19087-4588.

|May 17, 2002

Abstract:

A series of pyrazolo[4,3-d]pyrimidine sulfonamides and pyrazolo[3,4-d]pyrimidine sulfonamides have been synthesized. These compounds increase transcription of a calcitonin-luciferase promoter and production of cellular calcitonin in a calcitonin-secretion/RIA assay with minimized phosphodiesterase type 4 inhibitory activity at 30 microM as compared to structurally related xanthine methylene ketones such as denbufyllene. These two series are notable examples of small molecules that act as CT-inducers, a method to potentially treat bone loss diseases.

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Abstract:

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