Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist

Shuwen He; Zhixiong Ye; Peter H Dobbelaar; Iyassu K Sebhat; Liangqin Guo; Jian Liu; Tianying Jian; Yingjie Lai; Christopher L Franklin; Raman K Bakshi; James P Dellureficio; Qingmei Hong; Nancy N Tsou; Richard G Ball; Doreen E Cashen; William J Martin; David H Weinberg; Tanya Macneil; Rui Tang; Constantin Tamvakopoulos; Qianping Peng; Randy R Miller; Ralph A Stearns; Howard Y Chen; Airu S Chen; Alison M Strack; Tung M Fong; D Euan Macintyre; Matthew J Wyvratt Jr; Ravi P Nargund

doi:10.1016/j.bmcl.2010.02.058

Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist

Bioorg Med Chem Lett. 2010 Apr 1;20(7):2106-10. doi: 10.1016/j.bmcl.2010.02.058. Epub 2010 Feb 19.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. shuwen_he@merck.com

PMID: 20207541
DOI: 10.1016/j.bmcl.2010.02.058

Abstract

We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models.

MeSH terms

Animals
CHO Cells
Cricetinae
Cricetulus
Dogs
Erectile Dysfunction / drug therapy*
Haplorhini
Humans
Indans / chemistry*
Indans / pharmacokinetics
Indans / pharmacology
Indans / therapeutic use*
Male
Mice
Molecular Structure
Protein Binding
Rats
Receptor, Melanocortin, Type 4 / agonists*
Receptor, Melanocortin, Type 4 / metabolism*
Spiro Compounds / chemistry*
Spiro Compounds / pharmacokinetics
Spiro Compounds / pharmacology
Spiro Compounds / therapeutic use*
Structure-Activity Relationship

Substances

Indans
Receptor, Melanocortin, Type 4
Spiro Compounds