860256-21-9Relevant articles and documents
Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for Metallo-β-Lactamases
Büttner, Dominik,Kramer, Jan S.,Klingler, Franca-M.,Wittmann, Sandra K.,Hartmann, Markus R.,Kurz, Christian G.,Kohnh?user, Daniel,Weizel, Lilia,Brüggerhoff, Astrid,Frank, Denia,Steinhilber, Dieter,Wichelhaus, Thomas A.,Pogoryelov, Denys,Proschak, Ewgenij
, p. 360 - 372 (2017/12/18)
Pathogens, expressing metallo-β-lactamases (MBLs), become resistant against most β-lactam antibiotics. Besides the dragging search for new antibiotics, development of MBL inhibitors would be an alternative weapon against resistant bacterial pathogens. Inhibition of resistance enzymes could restore the antibacterial activity of β-lactams. Various approaches to MBL inhibitors are described; among others, the promising motif of a zinc coordinating thiol moiety is very popular. Nevertheless, since the first report of a thiol-based MBL inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL inhibitors were reported that go beyond clinical isolate testing. In this study, we report on the synthesis and biochemical characterization of thiol-based MBL inhibitors and highlight the challenges behind the development of thiol-based compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs, selectivity against human off-targets, and reasonable activity against clinical isolates.
Rhodium(III)-catalyzed olefinic C-H alkynylation of acrylamides using tosyl-imide as directing group
Feng, Chao,Feng, Daming,Luo, Yang,Loh, Teck-Peng
, p. 5956 - 5959 (2015/01/08)
The Rh(III)-catalyzed C-H alkynylation of acrylamide derivative is realized using a hypervalent alkynyl iodine reagent. The use of a weakly coordinating directing group proved to be of critical importance. This reaction displays broad functional group tolerance and high efficiency, which opens a new synthetic pathway to access functionalized 1,3-enyne skeletons.
AMINOPHOSPHINIC DERIVATIVES THAT CAN BE USED IN THE TREATMENT OF PAIN
-
Page/Page column 12, (2011/06/19)
The present invention relates to a compound of the following general formula (I): R1—NH—CH(R2)—P(═O)(OR3)—CH2—C(R4)(R5)—CONH—CH(R6)—COOR7 (I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which R1 represents a —C(═O)—O—C(R8)(R9)—OC(═O)—R10 group; R2 represents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; R3 represents a hydrogen atom or a —C(R12)(R13)—OC(═O)—R14 group; R4 and R5 form, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or R4 represents a hydrogen atom and R5 represents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; R6 represents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substituted; and R7 represents a hydrogen atom or a benzyl, alkyl, heteroaryl, alkylheteroaryl, —CHMe—COOR18, —CHR19—OC(═O)OR20 and —CHR19—OC(═O)OR20 group. The present invention also relates to the use of these compounds as a medicinal product, and in particular for the treatment of pain, more advantageously neuropathic and neuroinflammatory pain, to their method of synthesis and also to the compositions containing them.
