Synthesis of IMD-0354 analogs and their inhibition on TNF-α induced NF-κB activation
碩士 === 東海大學 === 化學系 === 98 === Nuclear factor (NF)-κB is an important transcription factor. When a cell is stimulated by stress, over activated NF-κB would result in unexpected proliferation or death of the cell. Several studies demonstrated that IMD-0354 was a good inhibitor for NF-κB, we therefore...
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| Format: | Others |
| Language: | zh-TW |
| Published: |
2010
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| Online Access: | http://ndltd.ncl.edu.tw/handle/45682962830956367401 |
| Summary: | 碩士 === 東海大學 === 化學系 === 98 === Nuclear factor (NF)-κB is an important transcription factor. When a cell is stimulated by stress, over activated NF-κB would result in unexpected proliferation or death of the cell. Several studies demonstrated that IMD-0354 was a good inhibitor for NF-κB, we therefore synthesized three series of benzamide analogs and attempted to establish their structure-activity relationship. The benzamide analogs were synthesized by nucleophilic substitution and DCC coupling reaction while the stilbene analogs were synthesized by Horner-Wadsworth-Emmons reaction. Two methods were used to synthesize indole analogs. Some analogs were synthesized by Sonogashira coupling reaction followed by cyclization, and some were synthesized by tandem amidation-Suzuki reaction. The NF-κB inhibition of benzamide analogs showed that the trifluoromethyl group of IMD-0354 was essential for inhibition. Neither electronic nor steric effects imposed upon substitutions at third position of benzoyl group affected the NF-κB inhibition. The hydrogen on amide moiety seemed to influence NF-κB inhibition, which implied that hydrogen bond between NH of amide is critical for analog binding.
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