67852-96-4Relevant academic research and scientific papers
Development of 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors
Shang, Erchang,Liu, Ying,Wu, Yiran,Zhu, Wei,He, Chong,Lai, Luhua
, p. 2396 - 2402 (2014/05/06)
Human 5-lipoxygenase (5-LOX) is a well-validated target for anti-inflammatory therapy. Development of novel 5-LOX inhibitors with higher activities is highly demanded. In previous study, we have built a model for the active conformation of human 5-LOX, and identified naphthalen-1-yl 3,5-dinitrobenzoate (JMC-4) as a 5-LOX inhibitor by virtual screening. In the present work, 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors were developed. Twenty aryl 3,5-dinitrobenzoates, N-aryl 3,5-dinitrobenzamides and analogues were designed and synthesized. Several of them were found with significantly increased activities according to cell-free assay and human whole blood assay. The structure-activity relationship study may provide useful insights for designing effective 5-LOX inhibitors.
IMIDAZO(1,2-a)PYRIDINE DERIVATIVE
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Page 112, (2010/02/09)
A compound reprsented by the following formula (I), its salts or nsolvates thereof capable of specifically or selectively expressig an antifungal activity in a broad spectrum based on the novel mechanism thereof of 1,6-β-glucan synthesis inhibition, and an antifungal agent containing any of them.
Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen
Adlington,Baldwin,Becker,Chen,Cheng,Cooper,Hermann,Howe,McCoull,McNulty,Neubauer,Pritchard
, p. 1491 - 1508 (2007/10/03)
A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 ± 0.90 μM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 ± 0.92 μM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 ± 0.19 μM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 ± 0.05 μM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1.59 ± 0.15 μM), 11 IC50 = 3.08 ± 0.41 μM) and 13 (IC50 = 2.19 ± 0.36 Mμ) which were perceived to bind to PSA by a rotation of 180° relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 IC50 = 348 ± 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 ± 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.
Reactive immunization elicits catalytic antibodies for polyester hydrolysis
Chen,Kubiak,Ashley,Janda
, p. 2796 - 2803 (2007/10/03)
In the search for biocatalysts for degradation of nonnatural polymers, reactive immunization with haptens 7 and 11 was used to prepare catalytic antibodies capable of cleaving short oligomeric esters, as well as the insoluble polyester 25. These antibodies were found to be highly specific and efficient esterases for oligomers. Triester 24 was preferentially hydrolyzed by an endo-cleavage pathway, however, with a higher molecular weight polymer 25 no site specificity could be observed. Catalytic efficiency of the antibodies towards the insoluble polymer 25 was limited due to physical constraints.
AN EFFICIENT SUBSTITUTE FOR THE α-AMINODIPOYL MOIETY OF δ-(L-α-AMINOADIPOYL)-L-CYSTEINYL-D-VALINE IN THE ENZYMATIC SYNTHESIS OF PENICILLINS
Baldwin, Jack E.,Adlington, Robert M.,Crabbe, M. James C.,Nomoto, Takashi,Schofield, Christopher J.
, p. 4217 - 4220 (2007/10/02)
meta-Carboxyphenylacetyl-L-cysteinyl-D-valine was shown to be a highly efficient substrate for Isopenicillin N Synthetase, with similar Michaelis constant and maximum velocity parameters to the natural substrate δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine.
