title: Synthesis and discovery of novel pyrazole carboxamide derivatives as potential osteogenesis inducers.
abstract: A series of novel N-aryl-3-aryl-1-arylmethyl-1H-pyrazole-5-carboxamide derivatives 4a-l was synthesized by the reaction of 3-aryl-1-arylmethyl-1H-pyrazole-5-carbonyl chloride with substituted aniline in good to excellent yields. Structures of the compounds were determined by IR, (1) H NMR, and HR-MS spectroscopy. The molecular structure was confirmed by the X-ray crystal analysis of one compound (4j) that was prone to crystallization. These compounds were used to induce mouse osteoblast precursors MC3T3-E1 into osteoblasts and the induction was assessed by alkaline phosphatase (ALP) activity and the gene expression of bone sialoprotein (BSP). The results showed that the compounds 4a-d, 4g, 4h, and 4k could increase the ALP activity in comparison with the negative control group and compound 4h was the most effective one which could induce osteogenesis. Furthermore, mRNA expression of BSP which is a marker of osteogenesis was up-regulated by the compound 4h.
authors: Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, PR China.
authors: Hong-Shui
authors: HS
authors: Lv
authors: Qian-Qian
authors: QQ
authors: Han
authors: Xiao-Ling
authors: XL
authors: Ding
authors: Ji-Liang
authors: JL
authors: Zhou
authors: Pi-Shan
authors: PS
authors: Yang
authors: Jun-Ying
authors: JY
authors: Miao
authors: Bao-Xiang
authors: BX
authors: Zhao
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003460:Crystallization; D018360:Crystallography, X-Ray; D058574:Integrin-Binding Sialoprotein / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D058574:Integrin-Binding Sialoprotein; D011720:Pyrazoles; D012333:RNA, Messenger; D000469:Alkaline Phosphatase