Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2008

Abstract

This is the thirteenth installment of the comprehensive survey series in high throughput chemistry. 1 Biologically active libraries reported in 2009 are captured in Tables 1-5 under the headings of proteases, nonproteolytic enzymes, GPCRs, nonGPCRs, and oncolytics/ antiinfectives.

One‐Pot Synthesis of New (1,3‐Thiazolo[5,4‐b]pyridin‐2‐yl)benzenediols and Their Antiproliferative Activities against Human Cancer Cell Lines

“…-The thiazole and fused-thiazole heterocycles are important structural components of biologically active molecules, and, as a result, they serve as attractive targets for developing new, effective synthesis methods [1] [2]. Because of their pharmaceutical importance in the area of drug discovery, we have been interested in developing an efficient protocol to prepare fused-thiazole scaffolds of 1,3-thiazolo [5,4-b]pyridine that is relatively unexplored with regard to its biological activity.…”

“…For example, 3-cyclopentyl-N-(5-methoxythiazolo [5,4-b]pyridin-2-yl)-2-[4-(4-methylpiperazine-1-sulfonyl)phenyl]propionamide activates the GK enzyme in vitro at low nanomolar concentrations and significantly reduces glucose levels [17]. Thiazolo [5,4-b]pyridines with a MeO group at C(5) show potent inhibitory activities for Ab42 fibrillization at the micromolar level for Alzheimers disease treatment [15], whereas 5-chloro [1,3]thiazolo [5,4-b]pyridin-2-amines are H 3 receptor antagonists [4]. 2,6-Difluoro-3-methoxybenzamide derivatives are potent antistaphylococcal compounds with suboptimal drug-like properties [18].…”

Highlights in the solid-phase organic synthesis of natural products and analogues

“…79 While there are several ways to conduct high-throughput synthesis, combinatorial chemistry is by far the dominant activity leading to new diversity in compound libraries. 80 In a recent review, Dolle et al 81 described 505 libraries and 30 molecular probes extracted from 490 literature citations in 2008. Several technologies alongside the solid-phase organic synthesis (SPOS) has emerged in recent years aiming to facilitate the rapid generation of compound libraries, as for example microwave-assisted organic synthesis (MAOS) and continuous-flow organic synthesis.…”

Present status of quinoxaline motifs: Excellent pathfinders in therapeutic medicine

“…Targeted inhibition of protein kinases is an attractive therapeutic strategy because deregulation of protein kinases is implicated in a number of diseases, including cancer, diabetes and inflammation [168]. 4-Chlorotetrazolo[1,5-a] quinoxaline, 180 inhibited activation of syk kinase, thereby making it a useful agent in the treatment of mast cell-mediated allergic diseases [169], whereas potency of quinoxaline-6-carboxamide, 181 was exerted as 79.5% protein inhibitory efficiency at 50 µM [170].…”