Antonio Monge

Phenazine 5,10-Dioxide Derivatives as Hypoxic Selective Cytotoxins: Part II. Structure-Activity Relationship Studies

The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were developed as structural analogs of other bioreductive compounds and its in vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. To gain insight into its mechanism of action electrochemical behavior, interaction with DNA experiments and QSAR studies were performed.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics.

A series of new 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e] pyrimidin-5-ones 3-substituted and/or 8,9-hydrogenated was prepared and tested for their diuretic, natriuretic and kaliuretic activities on male Wistar rats at a dosage of 25 mg/kg or less. Diuretic and saliuretic activities were strongly influenced by substituents in 3-position. Quantitative structure-activity relationships show that electron withdrawn substituents in 3-position enhance both diuretic and saliuretic activities at 25 mg/kg. Global analysis of the variations introduced on pyridine, pyrimidine and thiazole rings of this tricyclic system showed an increases of diuretic and natriuretic activities when the formal charge on N9a and C9b increases. Potassium ion excretion also increases, although not as drastically a in the earlier cases. Regression equations were calculated by partial least squares method (PLS) and validated by the cross-validation (leave-one-out) technique.

Chemical Modifications of 1,2,5-Oxadiazole N-Oxide System Searching for Cytotoxic Selective Hypoxic Drugs

New analogues of 3-Formyl-4-phenyl-1,2,5-oxadiazole N-oxide (1) are prepared and evaluated as cytotoxic selective agents in hypoxia.

New Amide Derivatives as Melanin-concentrating Hormone Receptor 1 Antagonists for the Treatment of Obesity

Melanin-concentrating hormone (MCH) is a recently discovered central nervous system (CNS) target for treating obesity. Two novel series of amide derivatives were synthesized and evaluated biologically as MCH-R1 (melanin-concentrating hormone receptor 1) antagonists. The results showed that diphenyl substituents on the amide lead to better activity than biphenyl substituents.