58971-11-2Relevant articles and documents
Development of 3-(4-Chlorophenyl)-1-(phenethyl)urea Analogues as Allosteric Modulators of the Cannabinoid Type-1 Receptor: RTICBM-189 is Brain Penetrant and Attenuates Reinstatement of Cocaine-Seeking Behavior
Barrus, Daniel,Decker, Ann M.,Finlay, David B.,Gamage, Thomas F.,Glass, Michelle,Kenakin, Terry P.,Langston, Tiffany L.,Li, Jun-Xu,Nguyen, Thuy,Zhang, Yanan
, (2022/01/03)
We have shown that CB1 receptor negative allosteric modulators (NAMs) attenuated the reinstatement of cocaine-seeking behaviors in rats. In an effort to further define the structure-activity relationships and assess the druglike properties of the 3-(4-chlorophenyl)-1-(phenethyl)urea-based CB1 NAMs that we recently reported, we introduced substituents of different electronic properties and sizes to the phenethyl group and evaluated their potency in CB1 calcium mobilization, cAMP, and GTPγS assays. We found that 3-position substitutions such as Cl, F, and Me afforded enhanced CB1 potency, whereas 4-position analogues were generally less potent. The 3-chloro analogue (31, RTICBM-189) showed no activity at >50 protein targets and excellent brain permeation but relatively low metabolic stability in rat liver microsomes. Pharmacokinetic studies in rats confirmed the excellent brain exposure of 31 with a brain/plasma ratio Kp of 2.0. Importantly, intraperitoneal administration of 31 significantly and selectively attenuated the reinstatement of the cocaine-seeking behavior in rats without affecting locomotion.
DFT-Assisted Design and Evaluation of Bifunctional Amine/Pyridine-Oxazoline Metal Catalysts for Additions of Ketones to Unactivated Alkenes and Alkynes
Greve, Eric,Porter, Jacob D.,Dockendorff, Chris
, p. 450 - 462 (2019/01/10)
Bifunctional catalyst systems for the direct addition of ?-ketones to unactivated alkenes/alkynes were designed and modeled by density functional theory (DFT). The designed catalysts possess bidentate ligands suitable for binding of pi-acidic group 10 met
GPR40 receptor stimulant, and preparation method, pharmaceutical composition and application thereof
-
Paragraph 0163-0169, (2019/10/15)
The invention discloses a GPR40 receptor stimulant, and a preparation method, a pharmaceutical composition and application thereof. The invention particularly discloses a GPR40 receptor stimulant shown in general formula (I) and pharmacologically acceptable salt thereof, a preparation process of the compound, a pharmaceutical composition containing the compound of general formula (I), and application of the compound and the pharmaceutical composition in anti-diabetes.