Design and synthesis of piperazinylpyrimidinones as novel selective 5-HT(2C) agonists.
This Letter reports the design and synthesis of several novel series of piperazinyl pyrimidinones as 5-HT(2C) agonists. Several of the compounds presented exhibit good in vitro potency and selectivity over the closely related 5-HT(2A) and 5-HT(2B) receptors. Compound 11 was active in in vivo models of stress urinary incontinence.
Andrews
Mark D
MD
Department of Medicinal Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, UK. mark.d.andrews@pfizer.com
Green
Martin P
MP
Allerton
Charlotte M N
CM
Batchelor
David V
DV
Blagg
Julian
J
Brown
Alan D
AD
Gordon
David W
DW
McMurray
Gordon
G
Millns
Daniel J
DJ
Nichols
Carly L
CL
Watson
Lesa
L
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D006801:Humans; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D044403:Receptor, Serotonin, 5-HT2B / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014521:Urethra / Q000187:drug effects; D014549:Urinary Incontinence / Q000188:drug therapy
D011744:Pyrimidinones; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists