title: Long-chain triazolyl acids as inhibitors of osteoclastogenesis.
abstract: Saturated fatty acids (e.g., palmitic acid) are known to moderately inhibit the development of osteoclasts in vitro. In pursuit of more effective inhibitors of osteoclastogenesis we explored two new classes of palmitic acid analogues containing either an ether or triazolyl group at various positions along the chain. The compounds were evaluated for their ability to inhibit the formation of osteoclasts in primary mouse bone marrow cultures. The oxyacids were generally prepared by condensation of the appropriate alkyl halides and diols, followed by Jones oxidation. The triazolyl acids were prepared by copper-catalysed click chemistry between alkyl azides and acetylenic acids, or with the appropriately-protected azides and alkynes, followed by deprotection and oxidation. The oxyacids were little more effective than palmitic acid, but the triazolyl analogues were much more effective osteoclastogenesis inhibitors, especially when the triazole was distant from the acid unit.
authors.affiliation: Auckland Cancer Society Research Centre, School of Medical Sciences, New Zealand.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Marshall
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Grey
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D014230:Triazoles