17207-57-7Relevant academic research and scientific papers
Kinetic resolution of oxazinones: Rational exploration of chemical space through the design of experiments
Renzi, Polyssena,Kronig, Christel,Carlone, Armando,Er?ksüz, Serap,Berkessel, Albrecht,Bella, Marco
, p. 11768 - 11775 (2014/10/15)
The organocatalytic kinetic resolution of 4-substituted oxazinones has been optimised (selectivity factor S up to 98, chiral oxazinone ee values up to 99.6% (1a-g) and product ee values up to 90% (3a-g)) in a rational way by applying the Design of Experiments (DoE) approach.
Synthesis, in vitro and in vivo biological evaluation, and comprehensive understanding of structure-activity relationships of dipeptidyl boronic acid proteasome inhibitors constructed from β-amino acids
Zhu, Yongqiang,Wu, Gang,Zhu, Xinrong,Ma, Yuheng,Zhao, Xin,Li, Yuejie,Yuan, Yunxia,Yang, Jie,Yu, Sen,Shao, Feng,Lei, Meng
, p. 8619 - 8626 (2011/03/20)
An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed fromβ -amino acids is reported. SAR analysis revealed that bicyclic groups at the R1 position, 3-F substituents at the Rsu
Synthesis, in vitro and in vivo biological evaluation, docking studies, and structure-activity relationship (SAR) discussion of dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids
Zhu, Yongqiang,Zhu, Xinrong,Wu, Gang,Ma, Yuheng,Li, Yuejie,Zhao, Xin,Yuan, Yunxia,Yang, Jie,Yu, Sen,Shao, Feng,Li, Runtao,Ke, Yanrong,Lu, Aijun,Liu, Zhenming,Zhang, Liangren
supporting information; experimental part, p. 1990 - 1999 (2010/08/03)
A series of novel dipeptidyl boronic acid proteasome inhibitors composed of β-amino acids were synthesized, in vitro and in vivo biologically evaluated, and theoretically modeled for the first time. From the screened racemic compounds in enzyme, 4i was the most active. The IC50 value of its pure enantiomer 4q was 9.6 nM, 36-fold more active than its isomer 4p and as active as the marketed bortezomib in inhibiting human 20S proteasome. This candidate also showed good activities with IC50 values nearly less than 5 μM against several human solid and hematologic tumor cell lines. Safety evaluation in vivo with zebrafish and Sprague-Dawley (SD) rats showed that the candidate 4q was less toxic than bortezomib. Pharmacokinetic profiles suggested candidate 4q showed a more plasma exposure and longer half-life than bortezomib. Docking results indicated that 4q nearly interacted with 20S proteasome in a similar way as bortezomib.
Kinetic resolution of oxazinones: An organocatalytic approach to enantiomerically pure β-amino acids
Berkessel, Albrecht,Cleemann, Felix,Mukherjee, Santanu
, p. 7466 - 7469 (2007/10/03)
(Chemical Equation Presented) A profitable split: An organocatalytic resolution converts readily available racemic oxazinones 1 into valuable enantiomerically pure β-amino acid derivatives 2 (> 99% ee of the remaining 1 at 53% conversion; 88% ee of the ester 2). This catalytic ring-opening reaction requires as little as 1 mol% of the modular and readily accessible thiourea organocatalyst 3.
A facile and stereocontrolled synthesis of syn-α-alkyl α-hydroxy β-amino acids
Nocioni, Alessandra Maria,Papa, Carmela,Tomasini, Claudia
, p. 8453 - 8456 (2007/10/03)
The diastereoselective synthesis of syn-α-alkyl α-hydroxy β-amino acids 4a-h was easily accomplished by reaction of the sodium dianion of the corresponding anti α-alkyl β-benzoylamino acid methyl esters with iodine. The intermediate α-iodo derivatives spontaneously afforded cis-oxazolines which, upon hydrolysis, provided the desired products, with diastereoselectivities up to 99:1.
β-substituted β-phenylpropionyl chymotrypsins. Structural and stereochemical features in stable acyl enzymes
Reed,Katzenellenbogen
, p. 1162 - 1176 (2007/10/02)
In order to develop effective alternate substrate inhibitors for serine proteases, we have prepared a series of β-substituted β-phenylpropionic acid esters related to some systems known to form stable acyl enzymes with α-chymotrypsin. Some of these compounds were prepared in enantiomerically pure form by asymmetric synthesis. Acyl enzyme species were generated from chymotrypsin by reaction with the active esters, and the progress of deacylation was monitored by the proflavin displacement assay. In some cases, it was possible to distinguish two different deacylation rates that correspond to the two enantiomers. β-Phenylpropionic acyl enzymes with β-substituents that are nonpolar were not especially stable, but a number of the polar derivatives and particularly the acylamino derivatives showed slow rates of deacylation (k(d) less than 0.005 min-1), with three systems showing deacylation enantioselectivities in the range of 500-1500. These results are consistent with a model in which additional stabilization of the acyl enzyme and enantioselectivity in the deacylation process derives from an additional hydrogen bond between the acyl enzyme species (as an acceptor) and the enzyme (as a donor). A number of active site residues that might be involved in this hydrogen bond are discussed.
Composition containing a penem or carbapenem antibiotic and the use of the same
-
, (2008/06/13)
Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially.
Composition containing a penem or carbapenem antibiotic
-
, (2008/06/13)
Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. The composition may be prepared by simple mixing.
