Synthetic Medicinal Chemistry Research Articles

Book Review: New Trends in Synthetic Medicinal Chemistry. (Series: Methods and Principles in Medicinal Chemistry, Vol. 7.) Edited by Fulvio Gualtieri

Book Review: New Trends in Synthetic Medicinal Chemistry. (Series: Methods and Principles in Medicinal Chemistry, Vol. 7.) Edited by Fulvio Gualtieri

NMR spectroscopy in drug discovery: tools for combinatorial chemistry, natural products, and metabolism research.

NMR spectroscopy has enjoyed many advances recently, and the pace of development shows no signs of slowing. This article focuses on advances that have affected solution-state NMR. These advances fall into three general categories: new experimental techniques (new pulse sequence tools), improved hardware and more powerful software. These advances are allowing NMR to help solve important problems in the field of drug discovery. Their impact is widespread. NMR spectroscopy is now being used to determine protein structures, to monitor ligand-receptor binding, to study diffusion, to analyze mixtures using LC-NMR, to analyze solid-phase synthesis resins and to determine the structures of organic small molecules. NMR spectroscopy can provide both qualitative and quantitative information, and can be used in both routine analytical applications and demanding research applications. The applications described here can benefit numerous disciplines in drug discovery, including natural products research, synthetic medicinal chemistry, metabolism studies, drug production, quality control, rational drug design and combinatorial chemistry.

Identification and SAR for a selective, nonpeptidyl thrombin inhibitor.

A novel, nonpeptidyl thrombin inhibitor, L-636,619 (1), was identified via topological similarity searching over the Merck Corporate Sample Database. X-ray crystallographic studies determined the geometry for ligand binding to the enzyme. Chemical modification of the P1 and P3 segments of the ligand resulted in enhanced potency and improvement in the chemical stability of the lead. Analog 9 proved to be the most interesting lead from this structurally novel series.

4-Aryldihydropyrimidines via the Biginelli Condensation: Aza-Analogs of Nifedipine-Type Calcium Channel Modulators

Recent results from the author's laboratory in the area of dihydropyrimidine chemistry are summarized.

Organic chemistry: the past 100 years

This account will be built around some of the leading figures in organic chemistry in this country during the past 100 years. The choice necessarily will be somewhat arbitrary, and many outstanding figures and some important developments will be omitted. Nevertheless, I hope to present a reasonably comprehensive picture of the development of a major science that has played a basic role in the growth of related fields, such as both naturally occurring and synthetic polymers, biochemistry, molecular biology, medicinal chemistry, organic photochemistry, and several areas of spectroscopy—mass, ultraviolet, infrared, nuclear magnetic resonance (NMR), and electron spin resonance (ESR). The year 1876 is a natural starting point for an account of organic chemistry in this country. The American Chemical Society was founded in 1876; Johns Hopkins University, with its graduate program in chemistry under Ira Remsen, opened in 1876 also; the Journal of the American Chemical Society and the American Chemical Journal we...