76618-89-8Relevant academic research and scientific papers
Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor
Meng, Kaicheng,Shim, Paul,Wang, Qingtin,Zhao, Shuai,Gu, Ting,Kahsai, Alem W.,Ahn, Seungkirl,Chen, Xin
, p. 2320 - 2330 (2018/03/29)
The β2-adrenergic receptor (β2AR), a G protein-coupled receptor, is an important therapeutic target. We recently described Cmpd-15, the first small molecule negative allosteric modulator (NAM) for the β2AR. Herein we report in details the design, synthesis and structure-activity relationships (SAR) of seven Cmpd-15 derivatives. Furthermore, we provide in a dose-response paradigm, the details of the effects of these derivatives in modulating agonist-induced β2AR activities (G-protein-mediated cAMP production and β-arrestin recruitment to the receptor) as well as the binding affinity of an orthosteric agonist in radio-ligand competition binding assay. Our results show that some modifications, including removal of the formamide group in the para-formamido phenylalanine region and bromine in the meta-bromobenzyl methylbenzamide region caused dramatic reduction in the functional activity of Cmpd-15. These SAR results provide valuable insights into the mechanism of action of the NAM Cmpd-15 as well as the basis for future development of more potent and selective modulators for the β2AR based on the chemical scaffold of Cmpd-15.
Discovery of new C3aR ligands. Part 2: Amino-piperidine derivatives
Denonne, Frederic,Binet, Sophie,Burton, Maggi,Collart, Philippe,Defays, Sabine,Dipesa, Alan,Eckert, Maria,Giannaras, Alexander,Kumar, Seema,Levine, Beth,Nicolas, Jean-Marie,Pasau, Patrick,Pegurier, Cecile,Preda, Dorin,Van houtvin, Nathalie,Volosov, Andrew,Zou, Dong
, p. 3262 - 3265 (2008/02/08)
The synthesis and structure-activity relationships against the C3a receptor of a series of substituted aminopiperidine derivatives are reported. DMPK properties and functional activities of selected compounds are described. The compounds obtained are the first non-arginine ligands of C3aR.
Solvolysis of 2-Cyclohexyl-2-phenylethyl Tosylates Substituted at the Phenyl Ring
Krstic, Vera,Muskatirovic, Milan
, p. 1637 - 1650 (2007/10/02)
The solvolysis of 2-cyclohexyl-2-phenylethyl tosylates substituted at the phenyl ring by X= p-H (1), p-NO2, p-IO2, p-CN, p-COCH3, m-Cl, m-F, p-Cl, p-Br, p-CH3, and p-OCH3 (2a-k) in ethanol, acetic acid, and formic acid has been investigated.The total rate constants kt were determined and the obtained values together with corresponding Hammett ? constants were used to calculate the rate constants kΔ (for aryl-assisted reactions) and ks (for non-assisted reactions).The acetolysis values FkΔ and ks of 2-cyclohexyl-2-phenylethyl tosylate (1) at 100 deg C are in good agreement with those formerly obtained on the basis of product analysis.
