Azaindole therapeutic agents.

Azaindole structural framework is an integral part of several biologically active natural and synthetic organic molecules; and several FDA approved drugs for various diseases. In the last decade, quite a number of literature reports appeared describing the pharmacology, biological activity and therapeutic applications of a variety of azaindole molecules. This prompted the organic and medicinal chemistry community to develop novel synthetic methods for various azaindoles and test them for a bioactivity against a variety of biological targets.

Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist for Use in Central Nervous System Disease Models.

Activation of prostanoid EP2 receptor exacerbates neuroinflammatory and neurodegenerative pathology in central nervous system diseases such as epilepsy, Alzheimer's disease, and cerebral aneurysms. A selective and brain-permeable EP2 antagonist will be useful to attenuate the inflammatory consequences of EP2 activation and to reduce the severity of these chronic diseases. We recently developed a brain-permeable EP2 antagonist (TG6-10-1), which displayed anti-inflammatory and neuroprotective actions in rodent models of status epilepticus.

The Discovery and Development of Oxalamide and Pyrrole Small Molecule Inhibitors of gp120 and HIV Entry - A Review.

Human immunodeficiency virus type-1 (HIV-1) is the causative agent responsible for the acquired immunodeficiency syndrome (AIDS) pandemic. More than 60 million infections and 25 million deaths have occurred since AIDS was first identified in the early 1980s. Advances in available therapeutics, in particular combination antiretroviral therapy, have significantly improved the treatment of HIV infection and have facilitated the shift from high mortality and morbidity to that of a manageable chronic disease.

A simple, tandem approach to the construction of pyridine derivatives under metal-free conditions: a one-step synthesis of the monoterpene natural product, (-)-actinidine.

A simple and modular one-step synthesis of diversely substituted pyridines from readily available α,β-unsaturated carbonyl compounds and propargylic amines has been developed. The present protocol has a broad substrate scope and allows access to multi-substituted pyridines with select control of the substitution pattern under mild and metal-free conditions. The reaction involves imine formation followed by concomitant cyclization through an allenyl intermediate to afford pyridines in excellent yields, with water as the sole by-product.

A Unified Strategy for the Synthesis of β-Carbolines, γ-Carbolines, and Other Fused Azaheteroaromatics under Mild, Metal-Free Conditions.

An efficient, unified approach for the synthesis of β-carbolines, γ-carbolines, and other fused azaheteroaromatics has been realized under metal-free conditions, from propargylic amines and (hetero)aromatic aldehydes. This unified strategy provides β- and γ-carbolines as well as a range of fused azaheteroaromatics with a broad substrate scope and excellent functional group compatibility. The formal synthesis of oxopropalines D and G has been achieved on gram scale (3a), in a one-pot reaction from commercially available materials (previous shortest reported route to 3a was 5 steps).

Stereocontrolled Total Synthesis of Nonenolide.

Nonenolide (1) was first isolated from the entomopathogenic fungus Cordyceps militaries BCC2816 and exhibited good antimalarial activity against Plasmodium falciparum K1. Structurally, it features a decanolide with a trans-double bond attached to two chiral hydroxy groups, making the total synthesis of the exclusive isomer of 1 more difficult. Herein, we report the successful synthesis of 1 by employing a MacMillan α-hydroxylation to generate three chiral centers in both the key fragments, starting from 1,6-hexanediol and 1,4-butanediol, followed by Steglich esterification of compounds 2 and 3.

A general method for the metal-free, regioselective, remote C-H halogenation of 8-substituted quinolines.

An operationally simple and metal-free protocol for geometrically inaccessible C5-H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv.