4759-58-4Relevant academic research and scientific papers
Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach
Armstrong, Roly J.,Akhtar, Wasim M.,Frost, James R.,Christensen, Kirsten E.,Stevenson, Neil G.,Donohoe, Timothy J.
supporting information, (2019/11/13)
A highly diastereoselective annulation strategy for the synthesis of alicyclic ketones from diols and pentamethylacetophenone is described. This process is mediated by a commercially available iridium(III) catalyst, and provides efficient access to a wide range of cyclopentane and cyclohexane products with high levels of stereoselectivity. The origins of diastereoselectivity in the annulation reaction have been explored by a series of control experiments, which provides an explanation for how each stereocentre around the newly forged ring is controlled.
Stereoselective Synthesis of Cyclohexanes via an Iridium Catalyzed (5 + 1) Annulation Strategy
Akhtar, Wasim M.,Armstrong, Roly J.,Frost, James R.,Stevenson, Neil G.,Donohoe, Timothy J.
supporting information, p. 11916 - 11920 (2018/09/27)
An iridium catalyzed method for the synthesis of functionalized cyclohexanes from methyl ketones and 1,5-diols is described. This process operates by two sequential hydrogen borrowing reactions, providing direct access to multisubstituted cyclic products with high levels of stereocontrol. This methodology represents a novel (5 + 1) strategy for the stereoselective construction of the cyclohexane core.
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
, 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.
Synthesis and biological evaluation of amide derivatives of (6-chloro-2,3-dihydro-1H-inden-1-yl)acetic acid as potential anti-inflammatory agents with lower gastrointestinal toxicity
Sharma, Meenakshi,Ray, Saumendra Mohan
, p. 626 - 635 (2008/12/21)
A variety of amide derivatives of (6-chloro-2,3-dihydro-1H-inden-1-yl) acetic acid were synthesized and screened for their anti-inflammatory and related biological activities. These compounds were found to be longer acting and showed residual activity exceeding that of standard indomethacin. The studies with SKF-525A, a standard hepatic microsomal enzyme inhibitor showed that probably the test compound per se is the active species. The compound 6y showed best activity profile with ED30 of 6.45 mg/kg however this compound was found to be toxic at 100 mg/kg p.o. Though these compounds exhibited appreciable analgesic and antipyretic activities but they failed to prevent the development of secondary inflammation in adjuvant induced arthritis assay. The compound 6x showed 94% inhibition of acetic acid induced writhing. Studies showed that antagonism of TNF-α is not possibly involved in the mechanism of action of these compounds. However these compounds were found to have only mild ulcerogenic potential at the tested dose level of 100 mg/kg p.o. in comparison to indomethacin.
