870816-58-3Relevant academic research and scientific papers
Discovery of agonists of cannabinoid receptor 1 with restricted central nervous system penetration aimed for treatment of gastroesophageal reflux disease
Plowright, Alleyn T.,Nilsson, Karolina,Antonsson, Madeleine,Amin, Kosrat,Broddefalk, Johan,Jensen, J?rgen,Lehmann, Anders,Jin, Shujuan,St-Onge, Stephane,Tomaszewski, Miros?aw J.,Tremblay, Maxime,Walpole, Christopher,Wei, Zhongyong,Yang, Hua,Ulander, Johan
, p. 220 - 240 (2013)
Agonists of the cannabinoid receptor 1 (CB1) have been suggested as possible treatments for a range of medical disorders including gastroesophageal reflux disease (GERD). While centrally acting cannabinoid agonists are known to produce psychotropic effects, it has been suggested that the CB1 receptors in the periphery could play a significant role in reducing reflux. A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries. Development of this series focused on improving potency and efficacy at the CB1 receptor, reducing lipophilicity and limiting the central nervous system (CNS) exposure while maintaining good oral absorption. Improvement of the series led to compounds having excellent potency at the CB1 receptor and high levels of agonism, good physical and pharmacokinetic properties, and low penetration into the CNS. A range of compounds demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.
THERAPEUTIC COMPOUNDS
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Page/Page column 64-65, (2008/06/13)
Compounds of formula I or pharmaceutically acceptable salts thereof: (I) wherein R1, R2, R3, R4, m and n are as defined in the specification as well as salts and pharmaceutical compositions including the compoun
