Diphosphonates progress in drug research.docVIP

 PAGE \* MERGEFORMAT 17 Diphosphonates progress in drug research Of: Zhang Zhigang, Luting Li, Zhao Wen Tao [Keywords:] bisphosphonates; synthesis; derivatives Bisphosphonates (Bisphosphonates, BPs) drugs are 70s of last century developed an anti-metabolic bone disease medications, has been widely used in the treatment of osteoporosis, cancer-induced hypercalcemia, HE Burt’s disease, metastatic bone disease, metabolic bone disease [1]. current clinical use of bisphosphonates drugs according to their chronological and structural features are divided into three generations. drug development has brought relative intensity increased, but did not solve the clinical application of bisphosphonates in the number of defects [2]. bisphosphonates new synthesis and study of drug research focus in recent years. 1 Overview of bisphosphonates drugs Bisphosphonate drugs (Figure 1) the basic structure (Figure 2) is a two phosphonic acid groups connected to a central carbon atom to form a “PCP” structure, such structure is the first in the last century, 60 Fleisch inspired by the era of pyrophosphate obtained for the analogues of pyrophosphate [3]. with the pyrophosphate backbone “POP” different, BPs of the “PCP” structure on the stability of enzymes and many chemicals. It can and bone hydroxy phosphine in limestone (HA) showed high affinity to form chelates with calcium ions, adsorbed on the surface of bone mineral mass, and promote apoptosis of osteoclasts and inhibit bone resorption [4], but also stimulate osteoblasts proliferation, maturation [5]. Bisphosphonates drugs in accordance with the molecular mechanism [6] can be divided into two categories: the nitrogen and nitrogen-containing bisphosphonates bisphosphonates. The nitrogen bisphosphonates (such as acid chloride song sodium) in the formation of osteoclasts through the toxic metabolites or inhibit the activity of protein tyrosine phosphatases play a role. nitrogen-containing bisphosphonates (such as