Matches in SemOpenAlex for { <https://semopenalex.org/work/W2797362218> ?p ?o ?g. }
- W2797362218 endingPage "477" @default.
- W2797362218 startingPage "472" @default.
- W2797362218 abstract "There is a significant unmet medical need for more efficacious and rapidly acting antidepressants. Toward this end, negative allosteric modulators of the N-methyl-d-aspartate receptor subtype GluN2B have demonstrated encouraging therapeutic potential. We report herein the discovery and preclinical profile of a water-soluble intravenous prodrug BMS-986163 (6) and its active parent molecule BMS-986169 (5), which demonstrated high binding affinity for the GluN2B allosteric site (Ki = 4.0 nM) and selective inhibition of GluN2B receptor function (IC50 = 24 nM) in cells. The conversion of prodrug 6 to parent 5 was rapid in vitro and in vivo across preclinical species. After intravenous administration, compounds 5 and 6 have exhibited robust levels of ex vivo GluN2B target engagement in rodents and antidepressant-like activity in mice. No significant off-target activity was observed for 5, 6, or the major circulating metabolites met-1 and met-2. The prodrug BMS-986163 (6) has demonstrated an acceptable safety and toxicology profile and was selected as a preclinical candidate for further evaluation in major depressive disorder." @default.
- W2797362218 created "2018-04-24" @default.
- W2797362218 creator A5002060265 @default.
- W2797362218 creator A5003355112 @default.
- W2797362218 creator A5008635272 @default.
- W2797362218 creator A5013900235 @default.
- W2797362218 creator A5016151028 @default.
- W2797362218 creator A5018503719 @default.
- W2797362218 creator A5020517616 @default.
- W2797362218 creator A5023546611 @default.
- W2797362218 creator A5023575873 @default.
- W2797362218 creator A5025602603 @default.
- W2797362218 creator A5025794528 @default.
- W2797362218 creator A5029365552 @default.
- W2797362218 creator A5030640333 @default.
- W2797362218 creator A5034887506 @default.
- W2797362218 creator A5036073512 @default.
- W2797362218 creator A5038743524 @default.
- W2797362218 creator A5041183323 @default.
- W2797362218 creator A5041985756 @default.
- W2797362218 creator A5045078701 @default.
- W2797362218 creator A5046345830 @default.
- W2797362218 creator A5046661488 @default.
- W2797362218 creator A5047723972 @default.
- W2797362218 creator A5048240991 @default.
- W2797362218 creator A5049256918 @default.
- W2797362218 creator A5053842134 @default.
- W2797362218 creator A5054752173 @default.
- W2797362218 creator A5057067211 @default.
- W2797362218 creator A5057334523 @default.
- W2797362218 creator A5065362371 @default.
- W2797362218 creator A5067968126 @default.
- W2797362218 creator A5068795523 @default.
- W2797362218 creator A5070008561 @default.
- W2797362218 creator A5070363563 @default.
- W2797362218 creator A5070894857 @default.
- W2797362218 creator A5071413501 @default.
- W2797362218 creator A5073212801 @default.
- W2797362218 creator A5074241358 @default.
- W2797362218 creator A5074354123 @default.
- W2797362218 creator A5079110291 @default.
- W2797362218 creator A5079862698 @default.
- W2797362218 creator A5080376326 @default.
- W2797362218 creator A5081280287 @default.
- W2797362218 creator A5081649221 @default.
- W2797362218 creator A5083960592 @default.
- W2797362218 creator A5087033381 @default.
- W2797362218 creator A5089945074 @default.
- W2797362218 creator A5090689955 @default.
- W2797362218 creator A5091601317 @default.
- W2797362218 date "2018-04-13" @default.
- W2797362218 modified "2023-10-10" @default.
- W2797362218 title "BMS-986163, a Negative Allosteric Modulator of GluN2B with Potential Utility in Major Depressive Disorder" @default.
- W2797362218 cites W1980203397 @default.
- W2797362218 cites W2017522371 @default.
- W2797362218 cites W2021685348 @default.
- W2797362218 cites W2024380057 @default.
- W2797362218 cites W2047397795 @default.
- W2797362218 cites W2054535395 @default.
- W2797362218 cites W2095159395 @default.
- W2797362218 cites W2095618681 @default.
- W2797362218 cites W2097540407 @default.
- W2797362218 cites W2111728433 @default.
- W2797362218 cites W2124134368 @default.
- W2797362218 cites W2132324173 @default.
- W2797362218 cites W2168927779 @default.
- W2797362218 cites W2171340584 @default.
- W2797362218 cites W2208668986 @default.
- W2797362218 cites W2236921590 @default.
- W2797362218 cites W2247074795 @default.
- W2797362218 cites W2337615202 @default.
- W2797362218 cites W2346390990 @default.
- W2797362218 cites W2588408561 @default.
- W2797362218 cites W2607263420 @default.
- W2797362218 cites W2757975929 @default.
- W2797362218 cites W2779386549 @default.
- W2797362218 doi "https://doi.org/10.1021/acsmedchemlett.8b00080" @default.
- W2797362218 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5949833" @default.
- W2797362218 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29795762" @default.
- W2797362218 hasPublicationYear "2018" @default.
- W2797362218 type Work @default.
- W2797362218 sameAs 2797362218 @default.
- W2797362218 citedByCount "12" @default.
- W2797362218 countsByYear W27973622182018 @default.
- W2797362218 countsByYear W27973622182019 @default.
- W2797362218 countsByYear W27973622182020 @default.
- W2797362218 countsByYear W27973622182021 @default.
- W2797362218 countsByYear W27973622182023 @default.
- W2797362218 crossrefType "journal-article" @default.
- W2797362218 hasAuthorship W2797362218A5002060265 @default.
- W2797362218 hasAuthorship W2797362218A5003355112 @default.
- W2797362218 hasAuthorship W2797362218A5008635272 @default.
- W2797362218 hasAuthorship W2797362218A5013900235 @default.
- W2797362218 hasAuthorship W2797362218A5016151028 @default.
- W2797362218 hasAuthorship W2797362218A5018503719 @default.
- W2797362218 hasAuthorship W2797362218A5020517616 @default.
- W2797362218 hasAuthorship W2797362218A5023546611 @default.
- W2797362218 hasAuthorship W2797362218A5023575873 @default.