Transition-Metal-Catalyzed C−S, C−Se, and C−Te Bond Formation via Cross-Coupling and Atom-Economic Addition Reactions

Indoles - A promising scaffold for drug development.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though that more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (rofecoxib, celecoxib, valdecoxib etc.) were developed as safer NSAIDs with improved gastric safety profile. However, the recent market removal of some COXIBs such as rofecoxib due to its adverse cardiovascular side effects clearly encourages the researchers to explore and evaluate alternative templates with COX-2 inhibitory activity. Recognition of new avenues for selective COX-2 inhibitors in cancer chemotherapy and neurological diseases such as Parkinson and Alzheimer’s diseases still continues to attract investigations on the development of COX-2 inhibitors. This review highlights the various structural classes of selective COX-2 inhibitors with special emphasis on their structure-activity relationships.

http://ijpr.sbmu.ac.ir/article_1047_48da80e362d9fbe2ee049a6f517f139c.pdf

Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships

Inside HDAC with HDAC inhibitors.

There are two branches in boron medicinal chemistry: the first focuses on single boron atom compounds, and the second utilizes boron clusters. Boron clusters and their heteroatom counterparts belong to the family of cage compounds. A subset of this extensive class of compounds includes dicarbadodecaboranes, which have the general formula C2B10H12, and their metal biscarboranyl complexes, metallacarboranes, with the formula [M(C2B10H12)2–2]. The unique properties of boron clusters have resulted in their utilization in applications such as in pharmacophores, as scaffolds in molecular construction, and as modulators of bioactive compounds. This Perspective presents an overview of the properties of boron clusters that are pertinent for drug discovery, recent applications in the design of various classes of drugs, and the potential use of boron clusters in the construction of new pharmaceuticals.

Challenges and Opportunities for the Application of Boron Clusters in Drug Design.

Synthesis and biological evaluation of substituted 2-sulfonyl-phenyl-3-phenyl-indoles: a new series of selective COX-2 inhibitors.

Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses

Discovery of 2-phenyl-3-sulfonylphenyl-indole derivatives as a new class of selective COX-2 inhibitors.

Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib.

AIM:
To investigate the inhibitory effect of imrecoxib, a synthetic compound of completely new structure, on cyclooxygenase 1 (COX-1) and 2 (COX-2) and its anti-inflammatory effect in vivo.
METHODS:
The inhibitory effects of imrecoxib on cyclooxygenase 1 and 2 were studied using whole cell assay with murine peritoneal macrophages induced by calcimycin and LPS. The inhibitory effects of imrecoxib on mRNA level of COX-1 and COX-2 in human macrophage cell line U937 were detected by reverse transcription polymerase chain reaction (RT-PCR) analysis. Effects of imrecoxib on acute and chronic inflammation were evaluated in rat carrageenan induced edema model and rat adjuvant-induced arthritis model, respectively.
RESULTS:
Imrecoxib was found to inhibit COX-1 and COX-2 with IC50 value of 115+/-28 nmol/L and 18+/-4 nmol/L, respectively. Imrecoxib was shown to selectively and dose-dependently inhibit COX-2 mRNA level. Imrecoxib effectively inhibited carrageenan-induced acute inflammation at the doses of 5, 10, and 20 mg/kg i.g. and adjuvant-induced chronic inflammation at the doses of 10 and 20 mg/kg/d i.g.
CONCLUSION:
Imrecoxib is a novel and moderately selective COX-2 inhibitor that possesses anti-inflammatory effect by inhibition of COX-2 mRNA expression.

Zongru Guo

Papers

Synthesis and biological evaluation of substituted 2-sulfonyl-phenyl-3-phenyl-indoles: a new series of selective COX-2 inhibitors.

Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses

Discovery of 2-phenyl-3-sulfonylphenyl-indole derivatives as a new class of selective COX-2 inhibitors.

Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib.

Imrecoxib: a novel and selective cyclooxygenase 2 inhibitor with anti-inflammatory effect.