Current Topics in Medicinal Chemistry - Volume 14, Issue 21, 2014

The vitamin D nuclear receptor (VDR) and its ligand, 1α, 25-dihydroxyvitamin D3 (1,25(OH)2D3, or calcitriol) regulate numerous biological functions. Therefore, VDR represents an important therapeutic target in the treatment of various diseases such as cancers, psoriasis, rickets, renal osteodystrophy, and autoimmune dysfunctions. Despite the number of newly synthesized 1,25(OH)2D3 analogues, the need for highly p Read More

The first determination of the X-ray crystal structure of the ligand binding domain (LBD) of the vitamin D receptor (VDR) complexed with 1α,25-dihydroxyvitamin D3 was reported in 2000. Since then several dozen crystal structures of VDR accommodating various ligands have been presented. Almost all of these complexes display the canonical active conformation observed in the VDR-LBD/1α,25- dihydroxyvitamin D Read More

The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. T Read More

The development of non-microbial methods for the selective functionalization of non-activated C-H bonds has constituted a challenge, with important economical and environmental implications, for chemists for over a century. The present review provides a comprehensive and current compendium that illustrates the power of C-H functionalization and, namely, of remote functionalization strategies, to expeditiously acce Read More

The active metabolite of vitamin D, 1α, 25 dihydroxyvitamin D3 (calcitriol) is classically known to regulate calcium and phosphate homeostasis and bone mineralization. In addition, calcitriol has also been documented to act as a potent anticancer agent in multiple cell culture and animal models of cancer. However, major side effects, such as hypercalcemia, hinder broad-spectrum therapeutic uses of calcitriol in cancer chemothe Read More

Vitamin D, through its hormonally active form 1α,25-dihydroxyvitamin D3 [1α,25- (OH)2-D3], exhibits a much broader spectrum of bio logical activities than expected in the endocrine system. However, 1α,25-(OH)2-D3 causes hypercalcemia a t pharmacologically r elevant doses wh ich forms a major obstacle in the clinical development of this compound. As a result, considerable effort has been made toward the synthes Read More

The hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1a), has a wide variety of biological activities and its major molecular target is considered to be the vitamin D receptor (VDR). The A-ring stereoisomers of 1a as well as its C2-modified analogues, which have different stereochemistry at the C1 and/or C3 hydroxy groups, are of interest since recent metabolic studies have shown that catabolism could oc Read More

As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson’s catalyst regioselectively to obtain 2α- and 2β-methyl analogs after separation; therefore, five new 14-epi-19- nortachysterols Read More