64297-93-4Relevant articles and documents
SAR and identification of 2-(quinolin-4-yloxy)acetamides as Mycobacterium tuberculosis cytochrome bc 1 inhibitors
Phummarin, Narisa,Boshoff, Helena I.,Tsang, Patricia S.,Dalton, James,Wiles, Siouxsie,Barry, Clifton E.,Copp, Brent R.
, p. 2122 - 2127 (2016)
A previous phenotypic screen by GSK identified 2-(quinolin-4-yloxy)acetamides as potent growth inhibitors of Mycobacterium tuberculosis (Mtb). We report the results of a preliminary structure-activity relationship (SAR) study of the compound class which has yielded more potent inhibitors. An Mtb cytochrome bd oxidase deletion mutant (cydKO) was found to be hypersensitive to most members of the compound library, while strains carrying single-nucleotide polymorphisms of the qcrB gene, which encodes a subunit of the menaquinol cytochrome c oxidoreductase (bc1) complex, were resistant to the library. These results identify that the 2-(quinolin-4-yloxy)acetamide class of Mtb growth inhibitors can be added to the growing number of scaffolds that target the M. tuberculosis bc1 complex.
Functionalizing glycine derivatives by direct C-C bond formation
Zhao, Liang,Li, Chao-Jun
supporting information; experimental part, p. 7075 - 7078 (2009/04/07)
(Chemical Equation Presented) Come on glycine: Two different types of glycine derivatives are α-functionalized using cross-dehydrogenative- coupling (CDC) reactions. The method allows the efficient attachment of a malonate or aromatic alkyne group on the α-position of the glycine derivatives under very mild conditions.
Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
, p. 4898 - 4908 (2008/03/11)
The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
