Heterocyclization Reactions of Pyruvic Acids and Aminoazoles with Controlled Chemoselectivity

The present review includes the analysis of known literature data concerning linear and multicomponent heterocyclizations involving pyruvic acids and aminoazoles. In particular, the review demonstrates the approaches to control regio- and chemoselectivity of these types of treatments and their application to solve the matters of Diversity Oriented Synthesis

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

The comprehensive review contains the analysis of literature data concerning reactions of heterocyclization of aminoazoles and demonstrates the application of these types of transformations in diversity-oriented synthesis. The review is oriented to wide range of chemists working in the field of organic synthesis and both experimental and theoretical studies of nitrogen-containing heterocycles

Temperature Controlled Diastereoselective Doebner / Ugi Tandem Reaction

Novel peptidomimetics containing a pyrrolone fragment were synthesized by a tandem combination of Doebner and Ugi-type multicomponent reactions with controlled diastereoselectivity. This approach represents a convenient synthesis in the temperature range from 25 °C to 45 °C. In most cases, the new method allowed each diastereomer to be isolated separately

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

Substituted 1H-pyrazolo[3,4-b]pyridine-4- and 1H-pyrazolo[3,4-b]pyridine-6-carboxamides have been synthetized through a Doebner-Ugi multicomponent reaction sequence in a convergent and versatile manner using diversity generation strategies: combination of two multicomponent reactions and conditions-based divergence strategy. The target products contain as pharmacophores pyrazolopyridine and peptidomimetic moieties with four points of diversity introduced from readily available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity.status: publishe

Study of the chemoselectivity of multicomponent heterocyclizations involving 3-amino-1,2,4-triazole and pyruvic acids as key reagents, and biological activity of the reaction products

Three-component reactions involving 3-amino-1,2,4-triazole, aldehydes, including salicylic aldehydes, and pyruvic acids were studied in detail. The reaction pathway and products of the heterocyclizations could be changed by variation of the reaction parameters. The broad antimicrobial activity of the products was also studied. Compound 9d showed specific anti-influenza virus (A/H1N1) activity, with an IC50 of 0.57 mu M and a CC50 of >100 mu M

Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate profiles. The prodrug is completely independent of biotransformations and animal-independent because it becomes an active compound via a pH-triggered intramolecular cyclization-elimination reaction. As a proof-of-concept, the utility of this novel amino AOCOM ether prodrug approach was demonstrated on an antimalarial compound series representing a variety of antimalarial 4(