344905-88-0Relevant articles and documents
Synthesis and pharmacological evaluation of novel γ-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors
Alstermark, Christer,Amin, Kosrat,Dinn, Sean R.,Elebring, Thomas,Fjellstr?m, Ola,Fitzpatrick, Kevin,Geiss, William B.,Gottfries, Johan,Guzzo, Peter R.,Harding, James P.,Holmén, Anders,Kothare, Mohit,Lehmann, Anders,Mattsson, Jan P.,Nilsson, Karolina,Sundén, Gunnel,Swanson, Marianne,Von Unge, Sverker,Woo, Alex M.,Wyle, Michael J.,Zheng, Xiaozhang
supporting information; experimental part, p. 4315 - 4320 (2009/05/30)
We have previously demonstrated that the prototypical GABAB receptor agonist baclofen inhibits transient lower esophageal sphincter relaxations (TLESRs), the most important mechanism for gastroesophageal reflux. Thus, GABAB agonists could be exploited for the treatment of gastroesophageal reflux disease. However, baclofen, which is used as an antispastic agent, and other previously known GABAB agonists can produce CNS side effects such as sedation, dizziness, nausea, and vomiting at higher doses. We now report the discovery of atypical GABAB agonists devoid of classical GABAB agonist related CNS side effects at therapeutic doses and the optimization of this type of compound for inhibition of TLESRs, which has resulted in a candidate drug (R)-7 (AZD3355) that is presently being evaluated in man.
