55601-40-6Relevant articles and documents
Inverse acyl phosph(on)ates: Substrates or inhibitors of β-lactam-recognizing enzymes?
Morrison, Michael J.,Li, Naixin,Pratt
, p. 271 - 281 (2001)
Acyl phosph(on)ates represent a new class of inhibitors of β-lactam - recognizing enzymes. Previously described members of this class were aroyl phosph(on)ates. These compounds have been shown to acylate and/or phosphylate the active site serine residue, leading to either transient or essentially irreversible inhibition [Li, N., and Pratt, R. F. (1998) J. Am. Chem. Soc. 120, 4264-4268]. The present paper describes the synthesis and evaluation as inhibitors of an inverse pair of acyl phosph(on)ates that incorporate the amido side chain that represents a major substrate specificity determinant of these enzymes. Thus, N-(phenylacetyl)glycyl phenyl phosphate and benzoyl N-(benzyloxycarbonyl)aminomethyl phosphonate were prepared. The former of these compounds was found to be a substrate of typical class A and C β-lactamases and of the DD-peptidase of Streptomyces R61; it thus acylates the active site serine. In contrast, the latter compound was an irreversible inhibitor of the above enzymes, probably by phosphonylation of the active site serine. With each of these enzymes therefore, the amido side chain rather than the acyl group dictates the orientation of the bound phosph(on)ate and thus the mode of reaction.
Targeting ACE and ECE with dual acting inhibitors
Hanessian, Stephen,Guesne, Sebastien,Riber, Ludivine,Marin, Julien,Benoist, Alain,Mennecier, Philippe,Rupin, Alain,Verbeuren, Tony J.,Nanteuil, Guillaume De
, p. 1058 - 1062 (2008/12/20)
A series of urea analogues related to SA6817 and a GSK phosphonic acid with reported ACE inhibitory activity were prepared and tested for dual ACE and ECE activities. Although excellent ACE and NEP inhibition was achieved, only modest ECE inhibition was o
A mild and convenient oxidation of H-phosphinic acids
Berlicki,Mucha,Kafarski
, p. 1959 - 1962 (2008/09/19)
A new mild and convenient method of oxidation of H-phosphinic to the corresponding phosphonic acids was developed. Conversion of H-phosphinic acids into trivalent trimethylsilyl esters using hexamethyldisilazane, followed by their oxidation with air and subsequent methanolysis allowed obtaining the final compounds in good to excellent yields. The methodology was proved to be particularly useful for N-benzyloxycarbonyl-α-aminophosphinic acids. The scope and limitations of the reaction were additionally tested using a variety of both free and protected amino- and hydroxyphosphinates as substrates.
