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Synthesis and Discovery of Novel Pyrazole Carboxamide Derivatives as Potential Osteogenesis Inducers
Author(s) -
Lv HongShui,
Han QianQian,
Ding XiaoLing,
Zhou JiLiang,
Yang PiShan,
Miao JunYing,
Zhao BaoXiang
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200180
Subject(s) - chemistry , carboxamide , aryl , pyrazole , alkaline phosphatase , bone sialoprotein , aniline , crystallization , osteoblast , nuclear magnetic resonance spectroscopy , stereochemistry , organic chemistry , enzyme , biochemistry , osteocalcin , in vitro , alkyl
Abstract A series of novel N ‐aryl‐3‐aryl‐1‐arylmethyl‐1 H ‐pyrazole‐5‐carboxamide derivatives 4a – l was synthesized by the reaction of 3‐aryl‐1‐arylmethyl‐1 H ‐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 .