Synthesis and biological activities of a new series of secosteroids: vitamin D phosphonate hybrids

Novel Alkynylphosphonate Analogue of Calcitriol with Potent Antiproliferative Effects in Cancer Cells and Lack of Calcemic Activity

“…KEYWORDS: 1R,25-(OH) 2 vitamin D 3 , alkynylphosphonate analogues, cancer, hypercalcemia, cellular proliferation ACS Medicinal Chemistry Letters LETTER phosphonate analogues have been shown to display a certain degree of dissociation between the vitamin D activity in vitro and undesired hypercalcemia in vivo. 8 The first reference to vitamin D analogues possessing phosphorus atoms in the side chain can be found in the work of Dauben et al 9 Since then, few of such derivatives have been described until Steinmeyer worked on vitamin D phosphonate hybrids. 8 We have now designed a convergent route for the synthesis of a novel vitamin D analogue 10 bearing an alkynylphosphonate moiety.…”

“…8 We have now designed a convergent route for the synthesis of a novel vitamin D analogue 10 bearing an alkynylphosphonate moiety. This analogue combines the low calcemic properties of phosphonates 8 with the decreased metabolic inactivation due to the presence of a triple bond in C-24. 10 The synthetic approach is also useful for the preparation of structurally related phosphonate analogues from the corresponding alkynylphosphonate precursor 5.…”

Bisphosphonate-Based Conjugates and Derivatives as Potential Therapeutic Agents in Osteoporosis, Bone Cancer and Metastatic Bone Cancer

“…Therefore, there is still a need to develop drugs that will be effective as anti-resorptive agents for treating osteoporosis. It is reported that vitamin D conjugates for effective for improving good bone health; hence, Steinmeyer et al synthesized a series of novel vitamin D conjugates by combining bisphosphonate moieties and vitamin D [33]. The in vitro evaluation of vitamin D conjugates (15, 16 and 18, 19) exhibited moderate activities, while 17 showed a highly moderate vitamin D-like activity in HL 60 and ROS 17/2.8 [33].…”

“…It is reported that vitamin D conjugates for effective for improving good bone health; hence, Steinmeyer et al synthesized a series of novel vitamin D conjugates by combining bisphosphonate moieties and vitamin D [33]. The in vitro evaluation of vitamin D conjugates (15, 16 and 18, 19) exhibited moderate activities, while 17 showed a highly moderate vitamin D-like activity in HL 60 and ROS 17/2.8 [33]. Tsushima et al synthesized and evaluated the effects of a new hybrid compound of estrogen-bisphosphonate, 20 [34].…”

Design and Synthesis of Novel Vitamin D–Coumarin Hybrids using Microwave Irradiation

“…6 Steinmeyer et al reported that the combination of phosphonate and bisphosphonate substructures with the vitamin D skeleton can produce biological activities. 7 In recent years, several esters linked to aromatic A-ring and CD-ring derivatives have been identified as improved and selective hedgehog inhibitors by Hadden and co-workers. 8,9 Coumarins are an important class of naturally occurring compounds that have attracted much attention in recent years due to a diverse range of biological and pharmacological properties.…”