Author/Authors :
Robin D. Clark، نويسنده , , Alam Jahangir، نويسنده , , Muzaffar Alam، نويسنده , , Cynthia Rocha، نويسنده , , Lin Lin، نويسنده , , Bodil Bjorner، نويسنده , , Van Khanh Nguyen، نويسنده , , Carole Grady، نويسنده , , Timothy J. Williams، نويسنده , , George Stepan، نويسنده , , Hai Ming Tang، نويسنده , , Anthony P.D.W. Ford، نويسنده ,
Abstract :
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.
