Low-Calcemic, Highly Antiproliferative, 23-Oxa Ether Analogs of the Natural Hormone 1α,25-Dihydroxyvitamin D3:  Design, Synthesis, and Preliminary Biological Evaluation

Abstract

Eight new side-chain allylic, benzylic, and propargylic ether analogs of the natural hormone calcitriol have been rationally designed and easily synthesized. Three of these 23-oxa ether analogs lacking the typical side-chain OH group are more antiproliferative in vitro and desirably less calcemic in vivo than the natural hormone. One of these three 23-oxa analogs has transcriptional potency almost as high as that of calcitriol, even though it binds to the human vitamin D receptor only about 1% as well as calcitriol.

Synthesis of 24(28)-Methylene-1α-Hydroxyvitamin D3, a Novel Vitamin D3 Analogue

“…Vitamin D 2 was used as the raw material to synthesise the norvitamin D 2 aldehyde 14 following known literature methods. [15][16][17] Using literature procedures, 15,17 the crude intermediates (7)(8)(9)(10)(11) were taken forward without purification to bis-TBDMS ether 11, which was then separated on column chromatography and purified by recrystallisation. The preparation of aldehyde 14 is shown in Scheme 1.…”

“…6 For example, a series of vitamin D 3 analogues without 25-hydroxyl group have been reported for their high antiproliferative activity and low calcium activity. 7 Among these analogues, compound 2 and 3 which contain 24(28)-methylene groups displayed higher antiproliferative activity and had lower side effects of hypercalcemia than calcitriol. In recent years, several natural steroid products extracted from fish livers have been used as precursors of vitamin D. They have the same 2-isopropyl-1-butane side chain and better biological activity.…”

Identification of the Key Fields and Their Key Technical Points of Oncology by Patent Analysis

“…Therefore, it is very necessary to grasp the development direction of oncology, and discover new technological opportunities. The field of oncology develops rapidly and studies involving oncology is closely related to other subjects, including epidemiology, etiology and pathogenesis, drug discovery, diagnosis and treatment, surgery and so on [ 3 – 9 ]. In addition, studies related to oncology also involves scientometrics, such as publication quality [ 10 ], collaboration patterns [ 11 ], comparison of citation and usage indicators [ 12 ], and co-authorship network [ 13 ].…”