143656-69-3Relevant articles and documents
Transition State Analogue Inhibitors of 5′-Deoxyadenosine/5′-Methylthioadenosine Nucleosidase from Mycobacterium tuberculosis
Namanja-Magliano, Hilda A.,Evans, Gary B.,Harijan, Rajesh K.,Tyler, Peter C.,Schramm, Vern L.
, p. 5090 - 5098 (2017)
Mycobacterium tuberculosis 5′-deoxyadenosine/5′-methylthioadenosine nucleosidase (Rv0091) catalyzes the N-riboside hydrolysis of its substrates 5′-methylthioadenosine (MTA) and 5′-deoxyadenosine (5′-dAdo). 5′-dAdo is the preferred substrate, a product of radical S-adenosylmethionine-dependent enzyme reactions. Rv0091 is characterized by a ribocation-like transition state, with low N-ribosidic bond order, an N7-protonated adenine leaving group, and an activated but weakly bonded water nucleophile. DADMe-Immucillins incorporating 5′-substituents of the substrates 5′-dAdo and MTA were synthesized and characterized as inhibitors of Rv0091. 5′-Deoxy-DADMe-Immucillin-A was the most potent among the 5′-dAdo transition state analogues with a dissociation constant of 640 pM. Among the 5′-thio substituents, hexylthio-DADMe-Immucillin-A was the best inhibitor at 87 pM. The specificity of Rv0091 for the Immucillin transition state analogues differs from those of other bacterial homologues because of an altered hydrophobic tunnel accepting the 5′-substituents. Inhibitors of Rv0091 had weak cell growth effects on M. tuberculosis or Mycobacterium smegmatis but were lethal toward Helicobacter pylori, where the 5′-methylthioadenosine nucleosidase is essential in menaquinone biosynthesis. We propose that Rv0091 plays a role in 5′-deoxyadenosine recycling but is not essential for growth in these Mycobacteria.
PEPTIDE DEFORMYLASE INHIBITORS
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Page/Page column 153, (2009/06/27)
The present invention is directed to certain {2-(alkyl)-3-[2-(5-fluoro-4-pyrimidinyl)hydrazino]-3-oxopropyl}hydroxyformamide derivatives, compositions containing them, the use of such compounds in the inhibition of bacterial peptide deformylase (PDF) activity, and in the treatment of bacterial infections. Specifically, the invention is directed to compounds of formula (I), wherein R1, R2 and R3 are defined herein and to pharmaceutically acceptable salts thereof. The compounds of this invention are bacterial peptide deformylase inhibitors and can be useful in the treatment of bacterial infections.
Quinoline, naphthyridine and pyridobenzoxazine derivatives
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, (2008/06/13)
Novel antibacterial compounds are disclosed having the formula STR1 as well as pharmaceutically acceptable salts, esters, amide and prodrugs thereof, wherein R1 is selected from the group consisting of (a) lower alkyl, (b) halo(lower alkyl), (c
