- Synthesis and biological evaluation of C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors
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Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure–activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80. It also inhibited in vitro hypoxia-mediated angiogenic processes in human retinal microvascular endothelial cells (HRMEC). The docking study of 5 showed a similar binding mode as L-80: it occupied the C-terminal ATP-binding pocket of HSP90, indicating that the anticancer and antiangiogenic activities of 5 were derived from HIF-1α destabilization by inhibiting the C-terminal ATP-binding site of hHSP90.
- Kim, Ho Shin,Hong, Mannkyu,Ann, Jihyae,Yoon, Suyoung,Nguyen, Cong-Truong,Lee, Su-Chan,Lee, Ho-Young,Suh, Young-Ger,Seo, Ji Hae,Choi, Hoon,Kim, Jun Yong,Kim, Kyu-Won,Kim, Joohwan,Kim, Young-Myeong,Park, So-Jung,Park, Hyun-Ju,Lee, Jeewoo
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- A deuterium generation of card abundantly for nepal derivatives, preparation method thereof, and wherein the intermediate application
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The invention belongs to the technical field of pharmaceutical chemistry, and discloses a deuterated cabozantinib derivative, a preparation method and an application thereof, and an intermediate of the deuterated cabozantinib derivative. The deuterated ca
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Paragraph 0136; 0137
(2018/03/26)
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- Process for piperidine intermediates for quinine, quinidine and analogs thereof
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Quinine, quinidine and analogs thereof, are prepared by reacting a 4-quinolyllithium compound with a 4,5-erythro-5-ethyl(or vinyl)-quinuclidine-2ε -carboxaldehyde or the corresponding quinuclidine-2-carboxylic acid alkyl ester. Also described, inter alia, is the preparation of a 4,5-erythro-5-ethyl(or vinyl)-quinuclidine-2ε-carboxaldehyde, and a 4,5-crythro-5-ethyl(or vinyl)-quinuclidine-2ε -carboxylic acid and esters thereof. The end products are useful as antimalarial and antiarrhythmic agents.
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