- Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C C Triple Bond Cleavage
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Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.
- Sagadevan, Arunachalam,Charpe, Vaibhav Pramod,Ragupathi, Ayyakkannu,Hwang, Kuo Chu
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supporting information
p. 2896 - 2899
(2017/03/11)
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- Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L
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Upregulation of cathepsin L in a variety of tumors and its ability to promote cancer cell invasion and migration through degradation of the extracellular matrix suggest that cathepsin L is a promising biological target for the development of anti-metastatic agents. Based on encouraging results from studies on benzophenone thiosemicarbazone cathepsin inhibitors, a series of fourteen benzoylbenzophenone thiosemicarbazone analogues were designed, synthesized, and evaluated for their inhibitory activity against cathepsins L and B. Thiosemicarbazone inhibitors 3-benzoylbenzophenone thiosemicarbazone 1, 1,3-bis(4-fluorobenzoyl)benzene thiosemicarbazone 8, and 1,3-bis(2-fluorobenzoyl)-5-bromobenzene thiosemicarbazone 32 displayed the greatest potency against cathepsin L with low IC50 values of 9.9 nM, 14.4 nM, and 8.1 nM, respectively. The benzoylbenzophenone thiosemicarbazone analogues evaluated were selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10 μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5 μM. The most active cathepsin L inhibitors from this benzoylbenzophenone thiosemicarbazone series (1, 8, and 32) displayed low cytotoxicity toward normal primary cells [in this case human umbilical vein endothelial cells (HUVECs)]. In an initial in vivo study, 3-benzoylbenzophenone thiosemicarbazone (1) was well-tolerated in a CDF1 mouse model bearing an implanted C3H mammary carcinoma, and showed efficacy in tumor growth delay. Low cytotoxicity, inhibition of cell invasion, and in vivo tolerability are desirable characteristics for anti-metastatic agents functioning through an inhibition of cathepsin L. Active members of this structurally diverse group of benzoylbenzophenone thiosemicarbazone cathepsin L inhibitors show promise as potential anti-metastatic, pre-clinical drug candidates.
- Parker, Erica N.,Song, Jiangli,Kishore Kumar,Odutola, Samuel O.,Chavarria, Gustavo E.,Charlton-Sevcik, Amanda K.,Strecker, Tracy E.,Barnes, Ashleigh L.,Sudhan, Dhivya R.,Wittenborn, Thomas R.,Siemann, Dietmar W.,Horsman, Michael R.,Chaplin, David J.,Trawick, Mary Lynn,Pinney, Kevin G.
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p. 6974 - 6992
(2015/11/11)
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- COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS
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This invention is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin K or cathepsin L, will be therapeutically useful.
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- Production of hydroxy arylophenones
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Production of a hydroxy arylophenone by reacting an aromatic carboxylic acid Ar(--CO2 H)p where Ar is an aromatic radical, (--CO2 H) is an aromatic carboxylic acid group, and p is 1 or 2 with an aromatic compound H--Ar'--OH where Ar' is an aromatic radical and --H and --OH are aromatically bound para to each other in a benzenoid ring, in the presence of an alkyl sulphonic acid, particularly methane sulphonic acid, to produce a hydroxy arylophenone of formula Ar(--CO--Ar'--OH)p where the carbonyl and hydroxyl groups are para to each other in the hydroxyl-containing benzenoid ring of Ar'. The production of the hydroxy arylophenone proceeds through the intermediate ester (H--Ar'--O--CO--)p Ar and the production of the hydroxy arylophenone starting from the ester is also claimed.
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