Synthesis, anti-HIV and anti-Proliferative Activity of New Urea and Nitrosourea Derivatives of Amino Acids

Abstract

A series of N-methyl, N-(2-chloroethyl) and N-propargyl urea and nitrosourea derivatives of amino acids were synthesized and tested for anti-HIV and anti-proliferative activity. All the agents tested showed only a weak activity to counteract the cytopathic effects of the HIV-1 virus on a T4 lymphocyte cell line (CEM-IW). At high concentration, the N-methyl and N-propargyl ureas were cytotoxic. The nitrosoureas failed to suppress cell proliferation of uninfected CEM-IW cells. The lack of activity and cytotoxicity of the nitrosoureas in this model could be explained by their short chemical half-life.

O-Methyl-N-nitroisourea as a NCO Surrogate in Cu-Catalyzed Alkane C–H Amidination. A Masked Isocyanate Strategy

“…Carbamoylation of estrone was also efficiently performed, leading to 15d in excellent yield. Finally, urea 16a could also be prepared following this method …”

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…The compounds with n ) 4 were reported 1022 to have the greatest biological activity. In an extension of previous work 497 the synthesis and anti-HIV activity screening of a series of N1-substituted ureas and nitrosourea derivatives of diamino acids ornithine and lysine was reported. 1023 The structures of related compounds are shown in Chart 17.…”

“…A number of N -nitrosourea analogs of amino acid derivatives for which no anticancer activity could be obtained − are included in Chart . The series of N -methyl-, N -(2-chloroethyl)- and N -propargylnitrosoureas of amino acid benzyl esters (Chart ) were synthesized and tested for anti-HIV activity …”

“…Thus, for the R and β anomers 494 and 497 the %ILS values were 50 and 98, respectively. The L isomer (499) was more active and more toxic than the D isomer (497).…”

“…are included in Chart 17. The series of N-methyl-, N-(2-chloroethyl)-and N-propargylnitrosoureas of amino acid benzyl esters (Chart 17)were synthesized and tested for anti-HIV activity 497. …”