654682-76-5Relevant academic research and scientific papers
Synthesis, characterization and biological activities of 2-[(methyl sulfonyl)]amino benzoic acid derivatives and their metal complexes
Bokhari, Tanveer Hussain,Ashraf, Naveeda,Shafiq, Muhammad,Ahmed, Matloob,Rasool, Nasir,Shad, Hazoor Ahmad,Ashraf, Nabeela,Arshad, Nadeem,Tahir, Muhammad Nawaz
, p. 1326 - 1330 (2015/02/19)
Sulfonamide derivatives and their metal complexes are acknowledged pharmaceutical moieties because this group has been played the key role as a functional part of the most of the drug structures due to constancy and for bearance in human beings. Sulfonamides have endowed great biological potential such as antibacterial, insulin releasing, carbonic anhydrase inhibitory, anti-inflammatory, antifungal and antitumor activities. In the present work, 2-[(methyl sulfonyl)] amino benzoic acid was N-alkylated using alkylating agent such as methyl. Due to the presence of electron donating groups like, -COOH, -SO2, N-, the above mentioned molecules act as an excellent chelating agent. These substituted N-alkylated sulfonamide ligands were treated with a number of outer and inner transition metals such as Co(II), Cu(II), Ce(II), Pr(II), Dy(II) and Nd(II) to form coordinate complexes. These newly synthesized sulfonamides and their metal complexes were characterized by melting points, solubility, colour, FTIR analysis and XRD. These products were subjected for antimicrobial activities as well as other accessible applications.
Discovery and characterization of novel allosteric FAK inhibitors
Iwatani, Misa,Iwata, Hidehisa,Okabe, Atsutoshi,Skene, Robert J.,Tomita, Naoki,Hayashi, Yoko,Aramaki, Yoshio,Hosfield, David J.,Hori, Akira,Baba, Atsuo,Miki, Hiroshi
, p. 49 - 60 (2013/04/23)
Focal adhesion kinase (FAK) regulates cell survival and proliferation pathways. Here we report the discovery of a highly selective series of 1,5-dihydropyrazolo[4,3-c][2,1]benzothiazines that demonstrate a novel mode of allosteric inhibition of FAK. These compounds showed slow dissociation from unphosphorylated FAK and were noncompetitive with ATP after long preincubation. Co-crystal structural analysis revealed that the compounds target a novel allosteric site within the C-lobe of the kinase domain, which induces disruption of ATP pocket formation leading to the inhibition of kinase activity. The potency of allosteric inhibition was reduced by phosphorylation of FAK. Coupled SAR analysis revealed that N-substitution of the fused pyrazole is critical to achieve allosteric binding and high selectivity among kinases.
Structure-based discovery of cellular-active allosteric inhibitors of FAK
Tomita, Naoki,Hayashi, Yoko,Suzuki, Shinkichi,Oomori, Yoshimasa,Aramaki, Yoshio,Matsushita, Yoshihiro,Iwatani, Misa,Iwata, Hidehisa,Okabe, Atsutoshi,Awazu, Yoshiko,Isono, Osamu,Skene, Robert J.,Hosfield, David J.,Miki, Hiroshi,Kawamoto, Tomohiro,Hori, Akira,Baba, Atsuo
, p. 1779 - 1785 (2013/04/10)
In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5- dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5- dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0.64 μM) and in cellular assays (IC50 = 7.1 μM). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents.
