21226-36-8Relevant academic research and scientific papers
Effect of para substitution on dissociation of N-phenylbenzenesulfonamides
Mansfeld, Martin,Parik, Patrik,Ludwig, Miroslav
, p. 1479 - 1490 (2004)
The reaction of substituted anilines and benzenesulfonyl chlorides has been used to prepare 49 substituted N-phenylbenzenesulfonamides of general formula 4-X-C6H4SO2NHC6H4-Y- 4′. Their purity was checked by elemental analysis. The substituents X and Y include H, CH3, CH3O, Cl, Br, CN, and NO2. The dissociation constants of all compounds were determined by potentiometric titration in methanol, acetonitrile, N,N-dimethylformamide, and pyridine. The obtained dissociation constants, pKHA, were correlated with various sets of substituent constants. It was found that the effects of substituents X and Y on the dissociation are best described by using the Hammett equation with σp constants and the Yukawa-Tsuno equation with σp- and σp constants, respectively. This result confirms the direct conjugation of Y substituent with the reaction centre. The explained variability using the additive model was above 96% in all the solvents used. The data also provided information about the transmission effect of the SO2 group. The average dissociation constants were further processed by the latent variables methods, principal components and conjugated deviations analyses.
Design and synthesis of sulfonamide-substituted diphenylpyrimidines (SFA-DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B-cell lymphoblastic leukemia
Liu, He,Qu, Menghua,Xu, Lina,Han, Xu,Wang, Changyuan,Shu, Xiaohong,Yao, Jihong,Liu, Kexin,Peng, Jinyong,Li, Yanxia,Ma, Xiaodong
, p. 60 - 69 (2017/04/24)
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18?nM, 0.92?nM, 0.42?nM and 1.05?nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6.49?μM (Ramos cells) and 13.2?μM (Raji cells), and was stronger than the novel agent spebrutinib. In addition, the inhibitory potency toward the normal PBMC cells showed that inhibitor 10c possesses low cell cytotoxicity. All these explorations indicated that molecule 10c could serve as a valuable inhibitor for B-cell lymphoblastic leukemia treatment.
Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity
Qu, Menghua,Liu, Zhihao,Zhao, Dan,Wang, Changyuan,Zhang, Jianbin,Tang, Zeyao,Liu, Kexin,Shu, Xiaohong,Yuan, Hong,Ma, Xiaodong
, p. 3989 - 3996 (2017/07/05)
A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100?nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10?μM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10?μM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.
