876-05-1Relevant articles and documents
TREK Channel Family Activator with a Well-Defined Structure-Activation Relationship for Pain and Neurogenic Inflammation
Qiu, Yunguang,Huang, Lu,Fu, Jie,Han, Chenxia,Fang, Jing,Liao, Ping,Chen, Zhuo,Mo, Yiqing,Sun, Peihua,Liao, Daqing,Yang, Linghui,Wang, Jing,Zhang, Qiansen,Liu, Jin,Liu, Feng,Liu, Tingting,Huang, Wei,Yang, Huaiyu,Jiang, Ruotian
, p. 3665 - 3677 (2020/04/30)
TWIK-related K+ (TREK) channels are potential analgesic targets. However, selective activators for TREK with both defined action mechanism and analgesic ability for chronic pain have been lacking. Here, we report (1S,3R)-3-((4-(6-methylbenzo[d]
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists
Geyer, Roland,Nordemann, Uwe,Strasser, Andrea,Wittmann, Hans-Joachim,Buschauer, Armin
supporting information, p. 3452 - 3470 (2016/05/19)
2-Cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[2-(phenylsulfanyl)ethyl]guanidine (UR-PI376, 1) is a potent and selective agonist of the human histamine H4 receptor (hH4R). To gain information on the active conformation, we synthesized analogues of 1 with a cyclopentane-1,3-diyl linker. Affinities and functional activities were determined at recombinant hHxR (x: 1-4) subtypes on Sf9 cell membranes (radioligand binding, [35S]GTPγS, or GTPase assays) and in part in luciferase assays on human or mouse H4R (HEK-293 cells). The most potent H4R agonists among 14 racemates were separated by chiral HPLC, yielding eight enantiomerically pure compounds. Configurations were assigned based on X-ray structures of intermediates and a stereocontrolled synthetic pathway. (+)-2-Cyano-1-{[trans-(1S,3S)-3-(1H-imidazol-4-yl)cyclopentyl]methyl}-3-[2-(phenylsulfanyl)ethyl]guanidine ((1S,3S)-UR-RG98, 39a) was the most potent H4R agonist in this series (EC50 11 nM; H4R vs H3R, >100-fold selectivity; H1R, H2R, negligible activities), whereas the optical antipode proved to be an H4R antagonist ([35S]GTPγS assay). MD simulations confirmed differential stabilization of the active and inactive H4R state by the enantiomers.
Tetrapropylammonium perruthenate catalyzed glycol cleavage to carboxylic (Di)acids
Schmidt, Andrea-Katharina C.,Stark, Christian B. W.
supporting information; experimental part, p. 5788 - 5791 (2011/12/05)
A new method to accomplish glycol cleavage to carboxylic (di)acids in one step using catalytic amounts of tetrapropylammonium perruthenate (TPAP) together with N-methylmorpholine N-Oxide (NMO) as the stoichiometric oxidant is presented. In addition to regenerating the active catalyst, the N-oxide stabilizes intermediary carbonyl hydrates and thereby shifts a crucial equilibrium. The mild oxidation protocol is applicable to a broad range of substrates providing the respective acids, diacids, or keto acids in high yields.
