4759-55-1Relevant academic research and scientific papers
4-benzimidazolyl-3-phenylbutanoic acids as novel pif-pocket-targeting allosteric inhibitors of protein kinase PKCΧ
Fr?hner, Wolfgang,Lopez-Garcia, Laura A.,Neimanis, Sonja,Weber, Nadja,Navratil, Jeanette,Maurer, Frauke,Stroba, Adriana,Zhang, Hua,Biondi, Ricardo M.,Engel, Matthias
supporting information; experimental part, p. 6714 - 6723 (2011/12/02)
Protein kinase inhibitors with an allosteric mode of action are expected to reach, in many cases, higher selectivity for the target enzyme than ATP-competitive compounds. Therefore, basic research is aiming at identifying and establishing novel sites on the catalytic domain of protein kinases which might be targeted by allosteric inhibitors. We previously published the first structure-activity relationships (SARs) for allosteric activators of protein kinase PDK1. Here, we present the design, synthesis, and SAR data on a series of novel compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical protein kinace C (PKC) Χ via binding to the PIF-pocket. Key positions were identified in the compounds that can be modified to increase potency and selectivity. Some congeners showed a high selectivity toward PKCΧ, lacking inhibition of the most closely related isoform, PKC1, and of further AGC kinases. Furthermore, evidence is provided that these compounds are also active toward cellular PKCΧ without loss of potency compared to the cell-free assay.
A facile synthesis of 4-aryl-5-alkoxycarbonyl-6-hydroxy-6-methyl-4,5,6,7-tetrahydro-3-hydroxy-2-(pyridin-2-yl)-indazoles and their nmr characterizations
Amirthaganesan, Shanmugasundaram,Aridoss, Gopalakrishnan,Park, Young Hwan,Kim, Jong Su,Son, Se Mo,Jeong, Yeon Tae
, p. 537 - 554 (2008/09/20)
A series of N-pyridinyl tetrahydroindazoles have been synthesized by a convenient and regioseletive method by taking cyclic 2-ketoesters as scaffolds. An optimum reaction condition was achieved by monitoring the reaction in different reaction c
