Search

Pyrimidines have become an increasingly important core structure in many drug molecules over the past 60 years. This article surveys recent areas in which pyrimidines have had a major impact in drug discovery therapeutics, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article presents the synthesis of the medicinal agents and highlights the role of the biological target with respect to the disease model. Additionally, the biological potency, ADME properties and pharmacokinetics/pharmacodynamics (if available) are discussed. This survey attempts to demonstrate the versatility of pyrimidine-based drugs, not only for their potency and affinity but also for the improved medicinal chemistry properties of pyrimidine as a bioisostere for phenyl and other aromatic π systems. It is hoped that this article will provide insight to researchers considering the pyrimidine scaffold as a chemotype in future drug candidates in order to counteract medical conditions previously deemed untreatable. [ABSTRACT FROM AUTHOR]

A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. These syntheses involve: (1) reduction or oxidation followed by cyclization; (2) SNAr-terminated sequences; (3) acid-catalyzed ring closures or rearrangements; (4) high temperature cyclizations and (5) metal-promoted processes as well as several less thoroughly studied reactions. Each domino method is presented with a brief discussion of mechanism, scope, yields, simplicity and potential utility. [ABSTRACT FROM AUTHOR]

A tandem Michael-S(N)Ar annulation reaction has been developed for the synthesis of 1-alkyl and (±)-1,2-dialkyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones. Treatment of 1-(2-chloropyridin-3-yl)prop-2-en-1-one (R = H) or (E or Z)-1-(2-chloropyridin-3-yl)but-2-en-1-one (R = CH3) with R'NH2 in DMF at 50 °C for 24 h provides 2,3-dihydro-1,8-naphthyridin-4(1H)-ones in 65-85% yields. Mechanistic studies suggest that the reaction sequence is initiated by Michael addition to the side chain enone.