42596-58-7Relevant academic research and scientific papers
Reinvestigation of the structure-activity relationships of isoniazid
Hegde, Pooja,Boshoff, Helena I.M.,Rusman, Yudi,Aragaw, Wassihun Wedajo,Salomon, Christine E.,Dick, Thomas,Aldrich, Courtney C.
, (2021/06/14)
Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of the pyridyl nitrogen atom, isomerization of the pyridine nitrogen to other positions, replacement of the pyridine ring with isosteric heterocycles, and modification of the hydrazide moiety of INH abolishes antitubercular activity. Similarly, substitution of the pyridine ring at the 3-position is not tolerated while substitution at the 2-position is permitted with 2-methyl-INH 9 displaying antimycobacterial activity comparable to INH. To assess the specific activity of this series of INH analogs against mycobacteria, we assayed them against a panel of gram-positive and gram-negative bacteria, as well as a few fungi. As expected INH and its analogs display a narrow spectrum of activity and are inactive against all non-mycobacterial strains evaluated, except for 4, which has modest inhibitory activity against Cryptococcus neoformans. Our findings provide an updated analysis of the structure-activity relationship of INH that we hope will serve as useful resource for the community.
Dynamic Combinatorial Chemistry to Identify Binders of ThiT, an S-Component of the Energy-Coupling Factor Transporter for Thiamine
Monjas, Leticia,Swier, Lotteke J. Y. M.,Setyawati, Inda,Slotboom, Dirk J.,Hirsch, Anna K. H.
supporting information, p. 1693 - 1696 (2017/10/27)
We applied dynamic combinatorial chemistry (DCC) to identify ligands of ThiT, the S-component of the energy-coupling factor (ECF) transporter for thiamine in Lactococcus lactis. We used a pre-equilibrated dynamic combinatorial library (DCL) and saturation-transfer difference (STD) NMR spectroscopy to identify ligands of ThiT. This is the first report in which DCC is used for fragment growing to an ill-defined pocket, and one of the first reports for its application with an integral membrane protein as target.
Acylhydrazone derivative used for treating heart failure
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Paragraph 0048; 0049; 0050, (2016/10/08)
The invention belongs to the technical field of medicines, and relates to design and preparation method for acylhydrazone derivatives shown as a general formula I, and the acylhydrazone derivatives can be used for treating systolic heart failure comprising congestive heart failure.
Facile Reduction of Pyridines with Nickel-Aluminum Alloy
Lunn, George,Sansone, Eric B.
, p. 513 - 517 (2007/10/02)
Nickel-aluminum alloy in dilute base can be used to reduce a variety of pyridines, quinolines, and isoquinoline to the corresponding piperidines, 1,2,3,4-tetrahydroquinolines, and 1,2,3,4-tetrahydroisoquinoline in good yield.The reaction is simple to perform, and high temperatures, high pressures, or hydrogen atmospheres are not required.The reaction is accelerated by substituents in the 2-position and by electron-withdrawing groups in the 3- and 4-positions while electron-supplying groups in the 3- and 4-positions retard the reaction.The major product isolated from the reduction of 2-phenylpyridine was 2-cyclohexylpiperidine hydrochloride.With isoniazid (1) and iproniazid (4) the pyridine ring is hydrogenated before the hydrazine is cleaved.
