1048983-27-2Relevant academic research and scientific papers
Identification of a dual δ or antagonist/μ or agonist as a potential therapeutic for diarrhea-predominant Irritable Bowel Syndrome (IBS-d)
Breslin, Henry J.,Diamond, Craig J.,Kavash, Robert W.,Cai, Chaozhong,Dyatkin, Alexey B.,Miskowski, Tamara A.,Zhang, Sui-Po,Wade, Paul R.,Hornby, Pamela J.,He, Wei
, p. 4869 - 4872 (2012/08/13)
A small set of acyclic analogs 5 were prepared to explore their structure-activity relationships (SARs) relative to heterocyclic core, opioid receptor (OR) agonists 4. Compound 5l was found to have very favorable OR binding affinities at the δ and μ ORs (r Ki δ = 1.3 nM; r Ki μ = 0.9 nM; h Ki μ = 1.7 nM), with less affinity for the κ OR (gp Ki κ = 55 nM). The OR functional profile for 5l varied from the previously described dual δ/μ OR agonists 4, with 5l being a potent, mixed dual δ OR antagonist/μ OR agonist [δ IC50 = 89 nM (HVD); μ EC50 = 1 nM (GPI); κ EC50 = 1.6 μM (GPC)]. Compound 5l has progressed through a clinical Phase II Proof of Concept study on 800 patients suffering from diarrhea-predominant Irritable Bowel Syndrome (IBS-d). This Phase II study was recently completed successfully, with 5l demonstrating statistically significant efficacy over placebo.
Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase
Kumar, Sanjeev,Jaller, Daniel,Patel, Bhumika,LaLonde, Judith M.,DuHadaway, James B.,Malachowski, William P.,Prendergast, George C.,Muller, Alexander J.
experimental part, p. 4968 - 4977 (2009/07/11)
Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. With the goal of developing more potent IDO in
