97801-48-4Relevant articles and documents
Furoxans (1,2,5-Oxadiazole- N -oxides) as novel no mimetic neuroprotective and procognitive agents
Schiefer, Isaac T.,Vandevrede, Lawren,Fa', Mauro,Arancio, Ottavio,Thatcher, Gregory R.J.
supporting information; experimental part, p. 3076 - 3087 (2012/06/01)
Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied
An improved large scale procedure for the preparation of N-Cbz amino acids
Pehere, Ashok D.,Abell, Andrew D.
experimental part, p. 1493 - 1494 (2011/05/16)
A simple and scalable method for the preparation of N-Cbz protected amino acids is presented which uses a mixture of aqueous sodium carbonate and sodium bicarbonate to maintain the appropriate pH during the addition of benzyl chloroformate. The method has been extended to other N-protections and is amenable to large scale preparation of an intermediate toward Zofenopril, an ACE inhibitor.
Peptidic aldehydes based on α- and β-amino acids: Synthesis, inhibition of m-Calpain, and anti-cataract properties
Payne, Richard J.,Brown, Karina M.,Coxon, James M.,Morton, James D.,Lee, Hannah Yun-Young,Abell, Andrew D.
, p. 877 - 884 (2007/10/03)
We present a new synthesis of SJA6017 (a potent m-calpain inhibitor) and its adaptation in order to prepare analogues in which the constituent Leu and Val residues are systematically replaced with their corresponding β-amino acids and/or the N-terminal fl
Exploration of cornea permeable calpain inhibitors as anticataract agents
Nakamura, Masayuki,Yamaguchi, Masazumi,Sakai, Osamu,Inoue, Jun
, p. 1371 - 1379 (2007/10/03)
To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an α-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-insoluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hemiacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model.
Structure-activity relationship study and drug profile of N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (SJA6017) as a potent calpain inhibitor
Inoue, Jun,Nakamura, Masayuki,Cui, Ying-She,Sakai, Yusuke,Sakai, Osamu,Hill, Jeanette R.,Wang, Kevin K. W.,Yuen, Po-Wai
, p. 868 - 871 (2007/10/03)
Novel N-arylsulfonyldipeptidyl aldehyde derivatives were prepared by DMSO oxidation from the corresponding dipeptide alcohol, and their potencies as calpain inhibitors were evaluated in vitro. Among them, N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (8,
Protease inhibitors. Part 7: Inhibition of Clostridium histolyticum collagenase with sulfonylated derivatives of L-valine hydroxamate
Supuran, Claudiu T.,Scozzafava, Andrea
, p. 67 - 76 (2007/10/03)
Sulfonylated L-valine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl halides with the title amino acid, followed by treatment with benzyl chloride, and conversion of the COOH moiety to the CONHOH group. Other derivatives were obtained by reaction of N-benzyl-L- valine with arylisocyanates, arylsulfonylisocyanates or benzoylisothiocyanate, followed by the similar conversion of the COOH into the CONHOH moiety, with hydroxylamine in the presence of carbodiimides. The obtained compounds were assayed as inhibitors of the Clostridium histolyticum collagenase, ChC (EC 3.4.24.3), a zinc enzyme which degrades triple helical collagen. The hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series of synthesized derivatives, substitution patterns leading to best ChC inhibitors were those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl; 3- and 4-protected-aminophenylsulfonyl-; 3- and 4-carboxyphenylsulfonyl-; 3-trifluoromethylphenylsulfonyl; or 1- and 2- naphthyl among others. Similarly to the matrix metalloproteinase hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate hydrophobic moieties at the P(2') and P(3') subsites, in order to achieve tight binding to the enzyme. Such compounds might lead to drugs useful in the treatment corneal bacterial keratitis. (C) 2000 Elsevier Science B.V.
