An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Abstract

This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. 2265

An Easy Procedure for Synthesis of 1,3,4-Oxadiazines: A Potential Antimicrobial Agents

“…1. The synthetic strategy involves the preparation of hydrazones (3a-f) by the reaction of substituted phenylhydrazine hydrochloride (2a-f) with 2-chlorophenyl chloroformate (1). Then, the reaction of hydrazones (3a-f) in the presence of triethylamine to leading to the formation of 1,3,4-oxadiazines (4a-f The synthesized new compounds were characterized by spectral analysis and evaluated for their in vitro antimicrobial activities.…”

Benzo[ b ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase

“…Assessment of the origin of their toxicity is necessary to find ways to decrease their cytotoxic properties. At the same time, the bioavailability of the compounds may be increased by introducing appropriate functional groups (76,77) or by using host guest-based drug delivery systems such as lipids, cyclodextrins, or liposomes (78,79).…”

Application of tris(trimethylsilyl) phosphite as convenient phosphorus nucleophile in the direct synthesis of tetrasubstituted α-aminophosphonic acids from ketimines

“…It is well known that heterocyclic derivatives are a prevalent motif in natural compounds and are well known to play a pivotal role in the design of scaffolds and probes for pharmaceutical applications. [6][7][8] As a part of our continuing interest in organophosphorus chemistry [9][10][11][12] and particularly in the synthesis of new α-functionalized phosphonates and corresponding phosphonic acids [13][14][15][16][17][18] we decided to embark on a project aiming at development of an effective and mild protocol for the synthesis of tetrasubstituted α-aminophosphonic acids. We report herein the addition of tris(trimethylsilyl) phosphite to various N-benzyl ketimines as a very useful direct method, which affords desired α-aminophosphonic acids with good overall yields and under mild reaction conditions.…”

“…Pyridine and thiophene derived ketones were chosen as starting materials since small and simple heteroaromatics often have surprisingly complex biological properties and belong to one of the most important classes of compounds in medicinal chemistry. [6][7][8] In turn, to demonstrate the versatility of the method we also applied it to ketimines derived from aliphatic ketones. Importantly, the use of benzylamine for the synthesis of ketimines allowed us to easily deprotect the amine function by hydrogenolysis, yielding the tetrasubstituted α-aminophosphonic acids with a free amine group ready for use in e.g.…”