Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist

  • Bioorg Med Chem Lett. 2005 Aug 1;15(15):3501-5. doi: 10.1016/j.bmcl.2005.05.109.
Zhixiong Ye  1 ,  Liangqin Guo ,  Khaled J Barakat ,  Patrick G Pollard ,  Brenda L Palucki ,  Iyassu K Sebhat ,  Raman K Bakshi ,  Rui Tang ,  Rubana N Kalyani ,  Aurawan Vongs ,  Airu S Chen ,  Howard Y Chen ,  Charles I Rosenblum ,  Tanya MacNeil ,  David H Weinberg ,  Qianping Peng ,  Constantin Tamvakopoulos ,  Randy R Miller ,  Ralph A Stearns ,  Doreen E Cashen ,  William J Martin ,  Joseph M Metzger ,  Alison M Strack ,  D Euan MacIntyre ,  Lex H T Van der Ploeg ,  Arthur A Patchett ,  Matthew J Wyvratt ,  Ravi P Nargund
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. [email protected]
PMID: 15982875 DOI: 10.1016/j.bmcl.2005.05.109
Abstract

A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist, 3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents.