Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE MEDICINAL CHEMISTRY OF N-HYDROXY-N'-AMINOGUANIDINES
Diss Abstr Int [B]; 52(4):2046 1991. Unique Identifier : AIDSLINE ICDB/92679163 Doubell PC; Univ. of Pretoria, South Africa
Abstract:
In this study the synthesis, structure elucidation and biological evaluation of a number of novel N-hydroxy-N'-aminoguanidines were performed. The derivatives were synthesized as Schiff bases by reacting 1-amino-3-hydroxyguanidine tosylate with various benzaldehydes. Benzaldehyde was used as the basic aldehyde in synthesizing the model compound (4). In addition to this a series of substituted benzaldehydes with different hydrophilic, lipophilic and electronic properties were prepared. This was done by using nitro, methyl, hydroxy and methoxy groups as well as halogens. Techniques such as nuclear magnetic resonance spectroscopy (1H and 13C NMR), infrared spectroscopy and mass spectrometry were employed to determine the structures of the derivatives. This series of compounds can exist as a mixture of tautomers with the double bond located in three possible positions as indicated in the diagram. The model compound (4) was studied further by means of 15N and two dimensional (Hetcor) NMR, single crystal X-ray diffraction and computer modelling techniques. The results indicate the double bond is primarily located in position 1 and is not present in position 3. The biological component of this study included an in vitro anti-HIV and an in vitro antineoplastic (leukemia) evaluation as well as an Irwin behavioral study. Four of the derivatives had anti-HIV activity (18 to 96% inhibition). Two of the compounds were tested against leukemia and showed promising inhibition of L1210 cell growth. The Irwin study indicated that the derivatives caused deviations in the behavior patterns of the test animals and that these compounds had various effects on the neurological and autonomic systems. A number of novel hydroxyguanidine derivatives were thus successfully synthesized and their molecular structure determined. Promising antiviral activity against the HIV-1 virus as well as antineoplastic activity were found for these newly synthesized hydroxyguanidines. These results confirm and extend the promise of potential therapeutic applications by compounds of this nature. (AFRIKAANS TEXT).
Keywords: Animal Antineoplastic Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY Guanidines/*CHEMICAL SYNTHESIS/PHARMACOLOGY HIV-1/*DRUG EFFECTS Mice THESIS
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
