1192217-75-6Relevant articles and documents
Structural Basis of Metallo-β-lactamase Inhibition by N-Sulfamoylpyrrole-2-carboxylates
Farley, Alistair J. M.,Ermolovich, Yuri,Calvopi?a, Karina,Rabe, Patrick,Panduwawala, Tharindi,Brem, Jürgen,Bj?rkling, Fredrik,Schofield, Christopher J.
, p. 1809 - 1817 (2021/06/21)
Metallo-β-lactamases (MBLs) can efficiently catalyze the hydrolysis of all classes of β-lactam antibiotics except monobactams. While serine-β-lactamase (SBL) inhibitors (e.g., clavulanic acid, avibactam) are established for clinical use, no such MBL inhibitors are available. We report on the synthesis and mechanism of inhibition of N-sulfamoylpyrrole-2-carboxylates (NSPCs) which are potent inhibitors of clinically relevant B1 subclass MBLs, including NDM-1. Crystallography reveals that the N-sulfamoyl NH2 group displaces the dizinc bridging hydroxide/water of the B1 MBLs. Comparison of crystal structures of an NSPC and taniborbactam (VRNX-5133), presently in Phase III clinical trials, shows similar binding modes for the NSPC and the cyclic boronate ring systems. The presence of an NSPC restores meropenem efficacy in clinically derived E. coli and K. pneumoniae blaNDM-1. The results support the potential of NSPCs and related compounds as efficient MBL inhibitors, though further optimization is required for their clinical development.
Discovery of N-arylpyrroles as agonists of GPR120 for the treatment of type II diabetes
Winters, Michael P.,Sui, Zhihua,Wall, Mark,Wang, Yuanping,Gunnet, Joseph,Leonard, James,Hua, Hong,Yan, Wen,Suckow, Arthur,Bell, Austin,Clapper, Wilmelenne,Jenkinson, Celia,Haug, Peter,Koudriakova, Tatiana,Huebert, Norman,Murray, William V.
supporting information, p. 841 - 846 (2018/02/21)
The discovery of a novel series of N-arylpyrroles as agonists of GPR120 (FFAR4) is discussed. One lead compound is a potent GPR120 agonist, has good selectivity for related receptor GPR40 (FFAR1), has acceptable PK properties, and is active in 2 models of Type 2 Diabetes in mice.
Design and synthesis of lamellarin D analogues targeting topoisomerase I
Ohta, Takeshi,Fukuda, Tsutomu,Ishibashi, Fumito,Iwao, Masatomo
experimental part, p. 8143 - 8153 (2010/02/17)
(Chemical Equation Presented) A general synthetic route to rationally designed lamellarinDanalogues, 1-dearyllamellarinD(1) and 1-substituted 1-dearyllamellarin D (2), has been developed. The key pentacyclic intermediate 22 was prepared by palladium-catalyzed direct arylation of 12, which in turn was synthesized via C-2-selective lithiation of 15 followed by palladium-catalyzed cross-coupling as the key reactions. Compound 22 was converted to a wide range of C-1-substituted analogues 2 via regioselective electrophilic substitution and palladium-catalyzed cross-coupling reactions.