Golomb G, Schlossman A, Eitan Y, Saadeh H, Van Gelder J M, Breuer E
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
J Pharm Sci. 1992 Oct;81(10):1004-7. doi: 10.1002/jps.2600811009.
Some geminal bisphosphonates are used clinically for a number of important bone- and/or calcium-related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bishydroxyiminophosphonates (e.g., adipoyl- and suberoylbisphosphonate dioximes). These compounds significantly inhibited hydroxyapatite formation and dissolution in vitro and the calcification of bioprosthetic tissue implanted subdermally in rats. The compounds reported in this paper are less active than the structurally related bisacylphosphonates. The results of this work indicate that the introduction of oxime groups adjacent to the phosphonic function in long-chain bisphosphonates confers calcium interaction capabilities and that complete ionizability of a bisphosphonate may enhance its biological activity.
一些双膦酸盐在临床上用于治疗多种重要的骨骼和/或钙相关疾病；然而，副作用和缺乏选择性阻碍了它们的广泛应用。本文报道了双羟基亚氨基膦酸盐（如己二酰双膦酸二肟和辛二酰双膦酸二肟）的合成与评价。这些化合物在体外显著抑制了羟基磷灰石的形成和溶解，以及大鼠皮下植入的生物假体组织的钙化。本文报道的化合物比结构相关的双酰基膦酸盐活性低。这项工作的结果表明，在长链双膦酸盐中膦酸官能团相邻位置引入肟基赋予了钙相互作用能力，并且双膦酸盐的完全离子化可能会增强其生物活性。
