Design, synthesis, and evaluation of a novel 4-aminomethyl-4-fluoropiperidine as a T-type Ca2+ channel antagonist

  • J Med Chem. 2008 Jul 10;51(13):3692-5. doi: 10.1021/jm800419w.
William D Shipe  1 ,  James C Barrow ,  Zhi-Qiang Yang ,  Craig W Lindsley ,  F Vivien Yang ,  Kelly-Ann S Schlegel ,  Youheng Shu ,  Kenneth E Rittle ,  Mark G Bock ,  George D Hartman ,  Cuyue Tang ,  Jeanine E Ballard ,  Yuhsin Kuo ,  Emily D Adarayan ,  Thomayant Prueksaritanont ,  Matthew M Zrada ,  Victor N Uebele ,  Cindy E Nuss ,  Thomas M Connolly ,  Scott M Doran ,  Steven V Fox ,  Richard L Kraus ,  Michael J Marino ,  Valerie Kuzmick Graufelds ,  Hugo M Vargas ,  Patricia B Bunting ,  Martha Hasbun-Manning ,  Rose M Evans ,  Kenneth S Koblan ,  John J Renger
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, WP14-1, P.O. Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, USA. [email protected]
PMID: 18540666 DOI: 10.1021/jm800419w
Abstract

The novel T-type antagonist ( S)- 5 has been prepared and evaluated in in vitro and in vivo assays for T-type calcium ion channel activity. Structural modification of the piperidine leads 1 and 2 afforded the fluorinated piperidine ( S)- 5, a potent and selective antagonist that displayed in vivo CNS efficacy without adverse cardiovascular effects.

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