923948-64-5Relevant academic research and scientific papers
Discovery of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans
Lansdell, Mark I.,Hepworth, David,Calabrese, Andrew,Brown, Alan D.,Blagg, Julian,Burring, Denise J.,Wilson, Peter,Fradet, David,Brown, T. Bruce,Quinton, Faye,Mistry, Neela,Tang, Kim,Mount, Natalie,Stacey, Peter,Edmunds, Nick,Adams, Cathryn,Gaboardi, Samantha,Neal-Morgan, Stevie,Wayman, Chris,Cole, Susan,Phipps, Joanne,Lewis, Mark,Verrier, Hugh,Gillon, Val,Feeder, Neil,Heatherington, Anne,Sultana, Stefan,Haughie, Scott,Martin, Steven W.,Sudworth, Maria,Tweedy, Sarah
supporting information; scheme or table, p. 3183 - 3197 (2010/09/15)
The relevance of the melanocortin system to sexual activity is well established, and nonselective peptide agonists of the melanocortin receptors have shown evidence of efficacy in human sexual dysfunction. The role of the MC4 receptor subtype has received particular scrutiny, but the sufficiency of its selective activation in potentiating sexual response has remained uncertain owing to conflicting data from studies in preclinical species. We describe here the discovery of a novel series of small-molecule MC4 receptor agonists derived from library hit 2. The addition of methyl substituents at C3 and C5 of the 4-phenylpiperidin-4-ol ring was found to be markedly potency-enhancing, enabling the combination of low nanomolar potencies with full rule-of-five compliance. In general, the series shows only micromolar activity at other melanocortin receptors. Our preferred compound 40a provided significant systemic exposure in humans on both sublingual and oral administration and was safe and well tolerated up to the maximum tested dose. In a pilot clinical study of male erectile dysfunction, the highest dose of 40a tested (200 mg) provided a similar level of efficacy to sildenafil.
Use of Mc4 Receptor Agonist Compounds
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Page/Page column 30, (2008/12/08)
This invention relates to the use of an MC4 receptor agonist compound for the manufacture of a medicament for the treatment of lower urinary tract dysfunction.
PIPERIDINOYL-PYRROLIDINE AND PIPERIDINOYL-PIPERIDINE COMPOUNDS
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Page/Page column 71-72, (2010/11/25)
The present invention relates to a class of compounds of general formula (I) and the salts, hydrates, solvates, polymorphs and prodrugs wherein n, R6, R7 and R10 are as defined herein and especially to MCR4 agonist compounds of formula (I), to their use in medicine, particularly in the treatment of sexual dysfunction and obesity, to intermediates useful in their synthesis and to compositions containing them.
Pharmaceutically active compounds
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Page/Page column 64, (2010/02/13)
The present invention relates to a class of melanocortin MCR4 agonists of general formula (I) wherein R1, R2, R3, R4 and R5 are as defined herein and especially to selective MCR4 agonist compounds, to
