126090-33-3Relevant academic research and scientific papers
Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors
Kavanagh, Madeline E.,Gray, Janine L.,Gilbert, Sophie H.,Coyne, Anthony G.,McLean, Kirsty J.,Davis, Holly J.,Munro, Andrew W.,Abell, Chris
supporting information, p. 1924 - 1935 (2016/10/06)
The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.
HYDROXAMIC ACID DERIVATIVE AND AGE GENERATION INHIBITOR CONTAINING THE DERIVATIVE
-
Page/Page column 67, (2010/11/24)
To provide a novel compound which inhibits the generation of AGE and an AGE generation inhibitor containing the compound. A compound represented by the following formula or a pharmaceutically acceptable salt thereof, a medicinal composition containing the compound or such a salt thereof, and an additive composition containing the compound.
Compounds and inhibitors of phospholipases
-
, (2008/06/13)
The present invention relates generally to amino acid derivatives and to methods of making the same. In particular, the invention relates to compounds bearing a stereochemical identity, that is, the same stereochemistry, with the chiral α-carbon of D-α-amino acids and their use in methods of therapy, including the treatment of inflammatory diseases, and to compositions and enantiomeric mixtures containing them.
Synthesis and biological activities of phenyl piperazine- based peptidomimetic growth hormone secretagogues
Barakat, Khaled J.,Cheng, Kang,Chan, Wanda W.-S,Butler, Bridget S.,Jacks, Thomas M.,Schleim, Klaus D.,Hora Jr., Donald F.,Hickey, Gerard J.,Smith, Roy G.,Patchett, Arthur A.,Nargund, Ravi P.
, p. 1431 - 1436 (2007/10/03)
A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substitutent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.
An efficient preparation of the pseudopeptide endothelin-B receptor selective antagonist BQ-788
He,Cody,Doherty
, p. 8262 - 8266 (2007/10/03)
The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-γ-methylleucyl-D-1-(methoxyca rbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-γ-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.
