76935-61-0Relevant academic research and scientific papers
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
Nguyen, Thuy,Gamage, Thomas F.,Finlay, David B.,Decker, Ann M.,Langston, Tiffany L.,Barrus, Daniel,Glass, Michelle,Li, Jun-Xu,Kenakin, Terry P.,Zhang, Yanan
, p. 257 - 270 (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.
Furoxan Incorporation into C-H Bonds Enabling Nitrogen-Containing Functional Group Installation into the Same
Dong, Chenlu,Zhao, Xufeng,Katsuragi, Yuki,Kim, Hojin,Hayashi, Masahiko,Matsubara, Ryosuke
, p. 15807 - 15817 (2021/11/01)
A C-C bond forming method was developed, whereby a furoxan ring is incorporated into various types of C-H bonds. The protocol not only offers a concise synthetic route to a variety of alkylated furoxan derivatives but also provides an efficient strategy for the insertion of various nitrogen-containing functional groups into C-H bonds via transformation of the resultant furoxan ring.
Convenient methods for the reduction of amides, nitriles, carboxylic esters, acids and hydroboration of alkenes using NaBH4/I2system
Bhanu Prasad,Bhaskar Kanth,Periasamy, Mariappan
, p. 4623 - 4628 (2007/10/02)
Reaction of amides with NaBH4-I2 system in THF gives the corresponding amines in 70-76% yields. Reduction of nitriles yields the corresponding amines in 70-75% yields. The I2/NaBH4 system is useful in the hydrocarboration of olefins and the corresponding alcohols are obtained in 78-92% yields after H2O2/OH- oxidation. The reagent system is also useful for the reduction of carboxylic esters and acids to the corresponding alcohols in 60-90% yields.
MOLECULAR CONFORMATION AND ELECTRONIC STRUCTURE OF AZOMETHINES. VIII. DIPOLE MOMENTS OF 3,4-DIHYDROISOQUINOLINES
Pitea, Demetrio,Beltrame, Pier Luigi,Ferrazza, Alberto,Todeschini, Roberto,Favini, Giorgio
, p. 35 - 40 (2007/10/02)
The dipole moments of some methyl derivatives of 3,4-dihydroisoquinoline have been measured in benzene at 25 deg C and the experimental directions determined.The correlation with the theoretical dipole moments of the corresponding benzaldimines supports the view that the 3,4-dihydroisoquinolines can be used as models for the Z conformation of N-benzylidenemethylamines.Moreover, the differences between the dipole moment of 3,4-dihydroisoquinolines and that of the corresponding benzaldimines can be ascribed to conjugation across the -CH2-CH2- bridge.Experimental and calculated values of the methyl replacement vectors are in good agreement.
