Current Topics in Medicinal Chemistry - Volume 2, Issue 9, 2002

The worldwide population afflicted with diabetes is growing at an epidemic rate. There are almost five times the number of people suffering from this disease today as compared to 10 years ago and the worldwide diabetic population is expected to exceed 300 million by the year 2028. This trend appears to be driven by the world's adoption of a “western lifestyle” comprising a combination of unhealthy dietary habits and a s Read More

Over the past decade, protein kinases have emerged as a group of molecular targets with the potential to be “cancer-specific”, allowing the selective targeting of cancer cells versus normal cells. These selective anticancer drugs would eliminate the cytotoxic side effects that are associated with conventional cancer chemotherapy. This article will focus on two emerging and less-explored protein serine / threonine Read More

The Kinase insert Domain containing Receptor (KDR), alternatively referred to as VEGFR-2, is a receptor for Vascular Endothelial Growth Factors (VEGFs) and functions as a key regulator of angiogenesis, the process by which new capillaries are created from preexisting blood vessels. The induction of angiogenesis, or the “angiogenic switch,” is a critical step in tumor progression, and inhibitors of KDR have been demonstra Read More

This review covers literature describing research progress in erbB family tyrosine kinase inhibition over the last year. Excellent recent reviews are available, thus we have focussed on current developments of leading small molecule drug candidates as well as their erbB family inhibition profile. The most advanced erbB family tyrosine kinase (TK) inhibitors are demonstrating promising anti-cancer activity in clinical trials and are Read More

The p38 MAP kinase is thought to be involved in a variety of inflammatory and immunological disorders such as rheumatoid arthritis. The pyridinylimidazole class of compounds was the first to potently inhibit this kinase. Since the original reports of their efficacy, they have become the most widely studied series of inhibitors of this kinase. This framework has served as a starting point for further synthetic work and sever Read More

The p38 mitogen activated protein (MAP) kinase is an integral enzyme involved in the production of a wide variety of pro-inflammatory cytokines from various cell types. The identification of this kinase and of the diaryl imidazole containing inhibitor, SB203580, initiated an intense discovery effort in this field. Numerous inhibitors were subsequently produced containing replacements for the imidazole, as well as some of the p Read More

Protein kinases (Ser / Thr and Tyr) play a key role in signal transduction pathways. It has been shown that deregulation of the Cdk activity is linked to cell proliferation and cancer. Inhibition of cyclin-dependent kinases (Cdks) is an important target for potential new anti-cancer drugs. Following the discovery of Olomoucine, a wide range of tri-substituted purine derivatives have been synthesized, leading to potent Cdk inhibitors. Thes Read More

The first potent selective small molecule inhibitor of a protein kinase was reported in 1994 by Parke- Davis. PD-153035, 4-(3-bromoanilino)-6,7-dimethoxyquinazoline, is an ATP competitive inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFr), with no appreciable inhibitory activity against several other kinases. Subsequent structural elaboration of PD-153035 led to several 4-anilinoquinazolines that are curre Read More