Evaluation and synthesis of polar aryl- and heteroaryl spiroazetidine-piperidine acetamides as ghrelin inverse agonists.
Basic Information
ID: ALA3393021
Journal: ACS Med Chem Lett
Title: Evaluation and synthesis of polar aryl- and heteroaryl spiroazetidine-piperidine acetamides as ghrelin inverse agonists.
Authors: Orr ST, Beveridge R, Bhattacharya SK, Cameron KO, Coffey S, Fernando D, Hepworth D, Jackson MV, Khot V, Kosa R, Lapham K, Loria PM, McClure KF, Patel J, Rose C, Saenz J, Stock IA, Storer G, von Volkenburg M, Vrieze D, Wang G, Xiao J, Zhang Y.
Abstract: Several polar heteroaromatic acetic acids and their piperidine amides were synthesized and evaluated as ghrelin or type 1a growth hormone secretagogue receptor (GHS-R1a) inverse agonists. Efforts to improve pharmacokinetic and safety profile was achieved by modulating physicochemical properties and, more specifically, emphasizing increased polarity of our chemical series. ortho-Carboxamide containing compounds provided optimal physicochemical, pharmacologic, and safety profile. pH-dependent chemical stability was also assessed with our series.
CiteXplore: 25699143
DOI: 10.1021/ml500414n
Patent ID: ┄