106515-76-8Relevant articles and documents
Identification of small molecules blocking the pseudomonas aeruginosa type iii secretion system protein pcrv
Sundin, Charlotta,Saleeb, Michael,Spjut, Sara,Qin, Liena,Elofsson, Mikael
, p. 1 - 17 (2021/01/13)
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that employs its type III secretion system (T3SS) during the acute phase of infection to translocate cytotoxins into the host cell cytoplasm to evade the immune system. The PcrV protein is located at the tip of the T3SS, facilitates the integration of pore-forming proteins into the eukaryotic cell membrane, and is required for translocation of cytotoxins into the host cell. In this study, we used surface plasmon resonance screening to identify small molecule binders of PcrV. A follow-up structure-activity relationship analysis resulted in PcrV binders that protect macrophages in a P. aeruginosa cell-based infection assay. Treatment of P. aeruginosa infections is challenging due to acquired, intrinsic, and adaptive resistance in addition to a broad arsenal of virulence systems such as the T3SS. Virulence blocking molecules targeting PcrV constitute valuable starting points for development of next generation antibacterials to treat infections caused by P. aeruginosa.
γ-Lactone Synthesis via Palladium(II)-Catalyzed Lactonization of Unactivated Methylene C(sp3)-H Bonds
Liu, Bin,Shi, Bing-Feng
, p. 2396 - 2400 (2016/09/28)
A palladium(II)-catalyzed intramolecular lactonization of unactivated methylene C(sp3)-H bonds using PIP bidentate auxiliary is described. This method provides an efficient and concise pathway to synthesize functionalized γ-lactones.
Assessment of dopamine D1 receptor affinity and efficacy of three tetracyclic conformationally-restricted analogs of SKF38393
Clark, Alia H.,McCorvy, John D.,Watts, Val J.,Nichols, David E.
, p. 5420 - 5431 (2011/10/30)
To assess the effect of conformational mobility on receptor activity, the β-phenyl substituent of dopamine D1 agonist ligands of the phenylbenzazepine class, (±)-6,6a,7,8,9,13b-hexahydro-5H-benzo[d] naphtho[2,1-b]azepine-11,12-diol (8), and its oxygen and sulfur bioisosteres 9 and 10, respectively, were synthesized as conformationally-restricted analogs of SKF38393, a dopamine D1-selective partial agonist. Compounds trans-8b, 9, and 10 showed binding affinity comparable to that of SKF38393, but functionally, they displayed only very weak agonist activity. These results suggest that the conformationally-restricted structure of the analogs cannot adopt a binding orientation that is necessary for agonist activity.
