- (2Z)-2,3,4,5,5-Pentachloropenta-2,4-dienic acid as a minor product in the synthesis of 5,5-dimetoxytetrachlorocyclopentadiene from hexachlorocyclopentadiene
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Pentachloropentadienic acid was isolated, apart from the expected 5,5-dimetoxytetrachlorocyclopentadiene, in the reaction of hexachlorocyclopentadiene with potassium hydroxide in methanol. The structure of this minor product was established by X-ray crystallography. The plausible mechanism of its formation is discussed.
- Egorov,Khalilov,Gimalova,Miftakhov
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Read Online
- INHIBITORS OF MTOR-DEPTOR INTERACTIONS AND METHODS OF USE THEREOF
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Provided herein are substituted hydrazone compounds useful as inhibitors of DEPTOR. The invention further provides pharmaceutical compositions of the compounds of the invention. The invention also provides medical uses of substituted hydrazone compounds.
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Page/Page column 42
(2018/05/24)
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- Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction
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DEPTOR is a 48 kDa protein that binds to mTOR and inhibits this kinase within mTORC1 and mTORC2 complexes. Over-expression of DEPTOR specifically occurs in the multiple myeloma (MM) tumor model and DEPTOR knockdown is cytotoxic to MM cells, suggesting it is a potential therapeutic target. Since mTORC1 paralysis protects MM cells against DEPTOR knockdown, it indicates that the protein–protein interaction between DEPTOR and mTOR is key to MM viability vs death. In a previous study, we used a yeast two-hybrid screen of a small inhibitor library to identify a compound that inhibited DEPTOR/mTOR binding in yeast. This therapeutic (compound B) also prevented DEPTOR/mTOR binding in MM cells and was selectively cytotoxic to MM cells. We now present a structure–activity relationship (SAR) study around this compound as a follow-up report of this previous work. This study has led to the discovery of five new leads – namely compounds 3g, 3k, 4d, 4e and 4g – all of which have anti-myeloma cytotoxic properties superior to compound B. Due to their targeting of DEPTOR, these compounds activate mTORC1 and selectively induce MM cell apoptosis and cell cycle arrest.
- Lee, Jihye,Shi, Yijiang,Vega, Mario,Yang, Yonghui,Gera, Joseph,Jung, Michael E.,Lichtenstein, Alan
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p. 4714 - 4724
(2017/09/29)
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- Catalytic Enantioselective Desymmetrization of Norbornenoquinones via C(sp2)-H Alkylation
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The enantioselective Diels-Alder (DA) reaction with monosubstituted p-benzoquinones is an unmet challenge. A new approach for the enantioselective synthesis of monosubstituted quinone-DA adducts is presented based on C(sp2)-H alkylative desymmetrization of meso-DA adducts. Catalyzed by a tertiary amino-thiourea derivative, this reaction utilizes nitroalkanes as the alkylating agents and generates densely functionalized products bearing at least four contiguous stereogenic centers remote from the reaction site with excellent enantioselectivities.
- Sarkar, Rahul,Mukherjee, Santanu
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supporting information
p. 6160 - 6163
(2016/12/09)
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- Synthetic studies on CP-225,917 and CP-263,114: Access to advanced tetracyclic systems by intramolecular conjugate displacement and [2,3]-wittig rearrangement
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An advanced intermediate related to the structures of CP-225,917 and CP-263,114 was constructed by a sequence based on the use of Grob-like fragmentation, intramolecular conjugate displacement, and [2,3]-Wittig rearrangement. A variant of the [2,3]-Wittig rearrangement was developed.
- Malihi, Farzad,Clive, Derrick L. J.,Chang, Che-Chien,Minaruzzaman
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p. 996 - 1013
(2013/04/10)
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