455957-73-0

Upstream product

• 455954-96-8 N-(methoxymethyl)-2-methyl-N-[(trimethylsilyl)methyl]propane-2-amine 
• 186758-21-4 methyl (2E)-3-(2,4-difluorophenyl)prop-2-enoate 
• 862283-30-5 PF-884918 
• 616-38-6 carbonic acid dimethyl ester 
• 455957-94-5 (3S,4R)-N-tert-butyl-4-(2,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid 
• 67-56-1 methanol 
• 79250-80-9 N-tert-butyl<(trimethylsilyl)metyl>amine 

Downstream Products

• 455957-94-5 (3S,4R)-N-tert-butyl-4-(2,4-difluoro-phenyl)-pyrrolidine-3-carboxylic acid 
• 923948-65-6 (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Pharmaceutical compositions (by machine translation)

[Problem] imidazole compound or its pharmacologically acceptable salt in the melanocortin receptor activity that operates as an active ingredient of a pharmaceutical composition comprising. "I" general formula [a]" Formula, the aryl group may be substituted A ring represents a; R1 Represents a hydrogen atom, or an alkyl group which may be substituted represented; R2 Represents a hydrogen atom, a halogen atom or represents a; R3 The alkyl group may be substituted " represented by the imidazole compound, its pharmacologically acceptable salt as an active ingredient in a pharmaceutical composition. [Drawing] no (by machine translation)

Discovery of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans

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.

Pharmaceutically active compounds

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

PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS

Certain novel piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

BICYCLIC PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS

Certain novel bicyclic N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or p

ACYLATED PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS

Certain novel 4-substituted N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.