22884-10-2Relevant articles and documents
Pharmacological evaluation of imidazole-derived bisphosphonates on receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation and function
Lin, Jianguo,Peng, Ying,Liu, Qingzhu,Li, Ke,Lv, Gaochao,Seimbille, Yann,Huang, Gang,Gao, Feng,Qiu, Ling
, p. 121 - 133 (2020/08/10)
Bisphosphonates (BPs) have been commonly used in the treatment of osteolytic bone lesions, such as osteoporosis and osteogenesis imperfecta. However, serious side-effects can occur during the therapy. To search for novel potent BPs with lower side-effects, a series of imidazole-containing BPs (zoledronic acid [ZOL]; ZOL derivatives by substitution of the hydrogen at the 2-position on the imidazole ring with a methyl [MIDP], ethyl [EIDP], n-propyl [PIDP], or n-butyl group [BIDP]) were developed and the effects on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation were investigated using the murine macrophage RAW 264.7 cells at the protein, gene, and morphological and functional levels. Influences of these BPs on the cell growth and proliferation of RAW 264.7 were also studied in order to determine cytotoxicity. The results showed that PIDP significantly inhibited the RANKL-induced osteoclast formation in a dose-dependent fashion without inducing cytotoxicity under the concentration of 12.5?μM. It exerted remarkable suppressive effects on the development of actin rings, the bone resorption, and the expressions of osteoclastogenesis-related gene and protein markers. The down-regulation of c-Jun N-terminal kinase (JNK), protein kinase B (Akt), and inhibitor of nuclear factor kappa-B (IκB) phosphorylation in the early signaling event and subsequent inhibition of the expression of c-Fos and nuclear factor of activated T cells (NFATc1) might be involved in these effects. All these results indicated that PIDP might be a promising drug to treat bone-related disorders.
Imidazole heterocyclic diphosphonic acid compound as well as preparation method and application thereof
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Paragraph 0074; 0075, (2017/07/20)
The invention belongs to the field of pharmaceutical chemistry, and in particular relates to an imidazole heterocyclic diphosphonic acid compound as well as a preparation method and application thereof. The imidazole heterocyclic diphosphonic acid compound has a larger non-toxic concentration range for an osteoclast precursor, and can significantly inhibit the formation of osteoclasts at the same time; the imidazole heterocyclic diphosphonic acid compound can damage actin ring to the utmost extent, thus having an obvious inhibiting effect on the osteoclasts and further being used as an osteoclast inhibitor; the imidazole heterocyclic diphosphonic acid compound solves the problems that diphosphonate in the prior art is low in inhibiting effect on the osteoclasts, high in toxicity and large in side effects.
Process for making zoledronic acid
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Page/Page column 7, (2010/06/17)
The invention relates to a process a process, which comprises: reacting in a solvent/diluent a compound of formula (2) or a salt or ester thereof with a phosphonation agent to form phosphonated intermediates; and subsequently hydrolyzing said intermediates to form a compound of formula (1) or a salt or hydrate thereof wherein said solvent/diluent comprises a mixture of (i) a polyalkylene glycol and (ii) a cyclic carbonate of the formula (3) wherein n is an integer from 2 to 4, and R1 and R2 each independently represent a hydrogen or a C1-C4 alkyl group and to the use of intermediates therein.
