N-(Phosphonoacetyl)amino phosphonates. Phosphonate analogs of N-(phosphonoacetyl)-L-aspartic acid (PALA)

Abstract

Michaelis-Arbuzov reaction of N-(chloroacetyl)amino phosphonic acids or their esters, followed by acidolysis, gives moderate yields of N-(phosphonoacetyl) derivatives of a variety of (aminoalkyl)phosphonic acids, including analogues of the cytostatic agent PALA, in which the alpha- or beta-carboxylic groups in the aspartate moiety are replaced by a PO3H2 function. Assay of cytostatic activity with human KB cell lines indicates that the substitution of any of the COOH groups in PALA with PO3H2 results in total loss of cytostatic activity. No activity was observed also in the case of other [N-(phosphonoacetyl)amino]alkylphosphonic acids described in this report.

Complexes of aminophosphonates. Part 3. Copper(II) complexes of several monophosphono and diphosphono dipeptides

“…These are the protons of the -P 0 3 H 2 and the -NH,+ groups for the former ligands and the four protons of the two -PO,H, groups for the latter ligands. The first proton of PO,H, is very acidic, h ~w e v e r ' ~, ' ~ (pK z 1.0 for aminophosphonic acids), and thus it is fully deprotonated in the pH range studied (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). If the acidities of a -CO,H group in an amino acid and in a dipeptide molecule are compared a decrease in acidity (a 0 .…”

Novel Highlight in Malarial Drug Discovery: Aspartate Transcarbamoylase

“…Inspired by success of PALA as a potent inhibitor of ATCase, several groups tried to improve the inhibition ability of PALA for ATCase (Figure 2B and Table 1). Kafarski et al (Kafarski et al, 1985) designed a series of phosphate analogues of PALA, as well as the synthesis of other N-(phosphonoacetyl) amino phosphonic acids to evaluate their anticancer activity in human tumor cell lines. However, replacing the aor bcarboxylic groups in the aspartate moiety by a phosphate group resulted in the total loss of inhibition activity in human KB cell lines.…”

Palladium-Catalyzed Isomerization-Coupling Reactions of Allyl Chloride with Amines to Generate Functionalized Phosphorus Derivatives

“…For example, αand β-aminophosphonates are used as antibiotics, herbicides, antifungal agents, and enzyme inhibitors [1][2][3][4][5][6][7][8][9]. γ-Aminophosphonates and their analogues have been reported to show activity as receptor agonists and antagonists [10].…”