Evaluation and Synthesis of Polar Aryl- and Heteroaryl Spiroazetidine-Piperidine Acetamides as Ghrelin Inverse Agonists
Year: 2014
Type: article
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.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml500414n
Authors: Suvi T. M. Orr, Ramsay Beveridge, Samit K. Bhattacharya, Kimberly O. Cameron, Steven Coffey, Dilinie Fernando, David Hepworth, Margaret V. Jackson, Vishal Khot, Rachel Kosa, Kimberly Lapham, Paula M. Loria, Kim F. McClure, Jigna Patel, Colin Rose, James Saenz, Ingrid A. Stock, Gregory Storer, Maria von Volkenburg, Derek Vrieze, Guoqiang Wang, Jun Xiao, Yingxin Zhang
Institution: Pfizer (United States)
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2067080330