Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors

  • Bioorg Med Chem Lett. 2003 Nov 17;13(22):3983-7. doi: 10.1016/j.bmcl.2003.08.056.
Scott D Edmondson  1 ,  Anthony Mastracchio ,  Jiafang He ,  Christine C Chung ,  Michael J Forrest ,  Scott Hofsess ,  Euan MacIntyre ,  Joseph Metzger ,  Naphtali O'Connor ,  Kajal Patel ,  Xinchun Tong ,  Michael R Tota ,  Lex H T Van der Ploeg ,  Jeff P Varnerin ,  Michael H Fisher ,  Matthew J Wyvratt ,  Ann E Weber ,  Emma R Parmee
Affiliations
  • 1. Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 14592490 DOI: 10.1016/j.bmcl.2003.08.056
Abstract

Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was selected for in vivo evaluation of lipolysis induction, metabolic rate increase, and cardiovascular effects.