Matches in SemOpenAlex for { <https://semopenalex.org/work/W2617106989> ?p ?o ?g. }
- W2617106989 endingPage "1080" @default.
- W2617106989 startingPage "1070" @default.
- W2617106989 abstract "Spirocyclic thiophene derivatives represent promising σ1 ligands with high σ1 affinity and selectivity over the σ2 subtype. To increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring, and the pyran ring was opened. Late-stage diversification by regioselective C−H arylation of thiazoles 9 a–c resulted in a set of 53 compounds with high diversity. This set of compounds was analyzed with respect to σ1 affinity, σ1/σ2 selectivity, lipophilicity (logD7.4), lipophilicity-corrected ligand efficiency (LELP), and molecular target interactions. The most promising candidates were pyridyl-substituted thiazole derivatives 33 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-3-yl)thiazole) and 34 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-4-yl)thiazole), possessing low-nanomolar σ1 affinity (Ki=1.3 and 1.9 nm), high σ1/σ2 selectivity (>1500-fold), low lipophilicity (logD7.4=1.8) and very good ligand efficiency (LELP=5.5), indicating promising pharmacodynamics and pharmacokinetics. Molecular simulation studies, including docking and deconvolution of the free binding energy into its major components, led to decreased hydrophobic stabilization of pyridyl derivatives 33 c and 34 c, which was compensated by lower desolvation energy." @default.
- W2617106989 created "2017-06-05" @default.
- W2617106989 creator A5003544522 @default.
- W2617106989 creator A5003802897 @default.
- W2617106989 creator A5015679062 @default.
- W2617106989 creator A5037395594 @default.
- W2617106989 creator A5040260186 @default.
- W2617106989 creator A5040867141 @default.
- W2617106989 creator A5060965882 @default.
- W2617106989 creator A5081568695 @default.
- W2617106989 date "2017-06-22" @default.
- W2617106989 modified "2023-09-27" @default.
- W2617106989 title "Thiazole-Based σ<sub>1</sub>Receptor Ligands: Diversity by Late-Stage C−H Arylation of Thiazoles, Structure-Affinity and Selectivity Relationships, and Molecular Interactions" @default.
- W2617106989 cites W1549357029 @default.
- W2617106989 cites W1606372320 @default.
- W2617106989 cites W1969752694 @default.
- W2617106989 cites W1970503530 @default.
- W2617106989 cites W1975777081 @default.
- W2617106989 cites W1978009405 @default.
- W2617106989 cites W1980523891 @default.
- W2617106989 cites W1981373150 @default.
- W2617106989 cites W1981907642 @default.
- W2617106989 cites W1988587884 @default.
- W2617106989 cites W1992768650 @default.
- W2617106989 cites W2000516637 @default.
- W2617106989 cites W2000941955 @default.
- W2617106989 cites W2001369831 @default.
- W2617106989 cites W2002332690 @default.
- W2617106989 cites W2008525757 @default.
- W2617106989 cites W2009149581 @default.
- W2617106989 cites W2010919671 @default.
- W2617106989 cites W2014997914 @default.
- W2617106989 cites W2019079031 @default.
- W2617106989 cites W2020278286 @default.
- W2617106989 cites W2021298759 @default.
- W2617106989 cites W2026692772 @default.
- W2617106989 cites W2027600077 @default.
- W2617106989 cites W2031798888 @default.
- W2617106989 cites W2033854365 @default.
- W2617106989 cites W2040526588 @default.
- W2617106989 cites W2041389478 @default.
- W2617106989 cites W2045254485 @default.
- W2617106989 cites W2050666972 @default.
- W2617106989 cites W2050750242 @default.
- W2617106989 cites W2052002840 @default.
- W2617106989 cites W2053659951 @default.
- W2617106989 cites W2055862612 @default.
- W2617106989 cites W2055897353 @default.
- W2617106989 cites W2062458432 @default.
- W2617106989 cites W2062709038 @default.
- W2617106989 cites W2067120735 @default.
- W2617106989 cites W2083494854 @default.
- W2617106989 cites W2084477006 @default.
- W2617106989 cites W2088799477 @default.
- W2617106989 cites W2088846288 @default.
- W2617106989 cites W2088872562 @default.
- W2617106989 cites W2091897182 @default.
- W2617106989 cites W2093330856 @default.
- W2617106989 cites W2104346865 @default.
- W2617106989 cites W2105668062 @default.
- W2617106989 cites W2111117466 @default.
- W2617106989 cites W2122203261 @default.
- W2617106989 cites W2125368083 @default.
- W2617106989 cites W2125816654 @default.
- W2617106989 cites W2126283488 @default.
- W2617106989 cites W2127137755 @default.
- W2617106989 cites W2131087015 @default.
- W2617106989 cites W2132629607 @default.
- W2617106989 cites W2137893487 @default.
- W2617106989 cites W2140546989 @default.
- W2617106989 cites W2145594744 @default.
- W2617106989 cites W2157697844 @default.
- W2617106989 cites W2157764621 @default.
- W2617106989 cites W2158988264 @default.
- W2617106989 cites W2161482481 @default.
- W2617106989 cites W2168779153 @default.
- W2617106989 cites W2185095623 @default.
- W2617106989 cites W2216036820 @default.
- W2617106989 cites W2318554523 @default.
- W2617106989 cites W2326124692 @default.
- W2617106989 cites W2338034663 @default.
- W2617106989 cites W2411859496 @default.
- W2617106989 cites W2747324333 @default.
- W2617106989 cites W2953233103 @default.
- W2617106989 cites W4255564749 @default.
- W2617106989 doi "https://doi.org/10.1002/cmdc.201700166" @default.
- W2617106989 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28544475" @default.
- W2617106989 hasPublicationYear "2017" @default.
- W2617106989 type Work @default.
- W2617106989 sameAs 2617106989 @default.
- W2617106989 citedByCount "7" @default.
- W2617106989 countsByYear W26171069892018 @default.
- W2617106989 countsByYear W26171069892019 @default.
- W2617106989 countsByYear W26171069892020 @default.
- W2617106989 countsByYear W26171069892021 @default.
- W2617106989 countsByYear W26171069892023 @default.
- W2617106989 crossrefType "journal-article" @default.
- W2617106989 hasAuthorship W2617106989A5003544522 @default.