67293-68-9Relevant articles and documents
α-Methylation enhances the potency of isoprenoid triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors
Matthiesen, Robert A.,Varney, Michelle L.,Xu, Pauline C.,Rier, Alex S.,Wiemer, David F.,Holstein, Sarah A.
, p. 376 - 385 (2018)
Disruption of protein geranylgeranylation via inhibition of geranylgeranyl diphosphate synthase (GGDPS) represents a novel therapeutic strategy for a variety of malignancies, especially those characterized by excessive protein secretion such as multiple myeloma. Our work has demonstrated that some isoprenoid triazole bisphosphonates are potent and selective inhibitors of GGDPS. Here we present the synthesis and biological evaluation of a new series of isoprenoid triazoles modified by incorporation of a methyl group at the α-carbon. These studies reveal that incorporation of an α-methyl substituent enhances the potency of these compounds as GGDPS inhibitors, and, in the case of the homogeranyl/homoneryl series, abrogates the effects of olefin stereochemistry on inhibitory activity. The incorporation of the methyl group allowed preparation of a POM-prodrug, which displayed a 10-fold increase in cellular activity compared to the corresponding salt. These studies form the basis for future preclinical studies investigating the anti-myeloma activity of these novel α-methyl triazole bisphosphonates.
Challenging synthesis of bisphosphonate derivatives with reduced steric hindrance
Chiminazzo, Andrea,Sperni, Laura,Fabris, Fabrizio,Scarso, Alessandro
supporting information, (2021/04/12)
An alternative approach is reported for the synthesis of methyl ester protected bisphosphonate building blocks, such as methylene bisphosphonate, vinylidenebisphosphonate and aryl substituted prochiral vinylidenebisphosphonates, that cannot be obtained directly from dimethyl phosphite and dichloromethane.
Synthesis of novel bisphosphonate polyamine conjugates and their affinity to hydroxyapatite
Sankala, Elina,Weisell, Janne M.,Huhtala, Tuulia,Naervaenen, Ale T. O.,Vepsaelaeinen, Jouko J.
, p. 233 - 241 (2013/09/24)
Bisphosphonates are negatively charged molecules, widely used as bone drugs since they have high affinity to bone surface. Polyamines are small organic bases that are positively charged under the physiological conditions and they participate in the regulation of important cellular functions. In this study, we report a general synthesis strategy for bisphosphonate-polyamine conjugates starting from ethenylidene bisphosphonates and N-Boc protected polyamines. Four novel conjugates were prepared and characterized with spectroscopic methods. The affinity of these novel compounds to hydroxyapatite was also determined by using 99mTc procedure. ARKAT-USA, Inc.
