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pubmed:abstractText |
Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence.
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pubmed:affiliation |
Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94303, USA. robin.clark5@verizon.net
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