1254035-83-0

Upstream product

• 123-08-0 4-hydroxy-benzaldehyde 
• 1254035-97-6 tert-butyl 3-[4-(2-oxa-6-azaspiro[3.3]hept-6-ylmethyl)phenoxy]azetidine-1-carboxylate 
• 1254035-94-3 4-(2-oxa-6-azaspiro[3.3]hept-6-ylmethyl)phenol 
• 174-78-7 2-oxa-6-azaspiro[3.3]heptane 
• 1254035-98-7 6-(4-(azetidin-3-yloxy)benzyl)-2-oxa-6-azaspiro[3.3]heptane 
• 16691-25-1 ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate 

Relevant academic research and scientific papers

Discovery of (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone (AZD1979), a Melanin Concentrating Hormone Receptor 1 (MCHr1) Antagonist with Favorable Physicochemical Properties

A novel series of melanin concentrating hormone receptor 1 (MCHr1) antagonists were the starting point for a drug discovery program that culminated in the discovery of 103 (AZD1979). The lead optimization program was conducted with a focus on reducing lipophilicity and understanding the physicochemical properties governing CNS exposure and undesired off-target pharmacology such as hERG interactions. An integrated approach was taken where the key assay was ex vivo receptor occupancy in mice. The candidate compound 103 displayed appropriate lipophilicity for a CNS indication and showed excellent permeability with no efflux. Preclinical GLP toxicology and safety pharmacology studies were without major findings and 103 was taken into clinical trials.

THERAPEUTIC AGENTS 713

Disclosed herein are compounds of Formula (I) in which R1, R2, R3, R4, R5, A, X, Y are as described in the specification, their use in pharmaceutical compositions and in methods of treatment or prophylaxis of a melanin-concentrating hormone related disease or condition.