《基於阻斷突變SOD1與p38MAPK相互作用設計合成和評價治療ALS藥物》是劉俊義為項目負責人，北京大學為依託單位的面上項目。
基本介紹
- 中文名：基於阻斷突變SOD1與p38MAPK相互作用設計合成和評價治療ALS藥物
- 項目類別 ：面上項目
- 項目負責人：劉俊義
- 依託單位 ：北京大學
科研成果,項目摘要,
科研成果
序號 | 標題 | 類型 | 作者 |
|---|---|---|---|
1 | Rapid access to multi-substituted pyrimido[4,5-b][1,4]diazepine-2,4,6-trione and pyrimido[4,5-b][1,4]diazepine-2,4-dione as novel and versatile scaffolds for drug discovery | 期刊論文 | Tian, Chao|Zhang, Tongbo|Zhang, Zhili|Liu, Junyi| |
2 | Design, Synthesis, and Biological Evaluation of (E)-3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents | 期刊論文 | Du, Yansheng|Ma, Zhizhong|Zhang, Zhili|Liu, Junyi| |
3 | An approach to synthesis of pyrimido[b]azepines via Ruthenium-catalyzed ring-closing metathesis. | 期刊論文 | 劉俊義| |
4 | 1-Ethoxymethyl-5-methyl-9-phenyl-6,7,8,9-tetrahydro-1Hpyrimido[ 4,5-b ][1,4]diazepine-2,4(3H,5H)-dione | 期刊論文 | 劉俊義|李功| |
5 | Rapid Access to 10-(Cyclohexylimino)-7,9-diazaspiro[4.5]decane-6,8-dione Derivatives for HIV-1 Reverse Transcriptase Inhibition via Ruthenium-Catalyzed Ring-Closing Metathesis | 期刊論文 | Zhang, Zhili|Tian, Chao|Wang, Xiaowei|Liu, Junyi| |
6 | Design, synthesis, and biological evaluation of (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides as novel multifunctional neuroprotective agents | 期刊論文 | Du Y.|Ma Z.|Zhang Z.|Liu J.| |
7 | Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury | 期刊論文 | Zhang, Zhili|Wang, Xiaowei|Ma, Zhizhong|Liu, Junyi| |
8 | Synthesis and Biological Evaluation of Novel 2-Arylalkylthio-5-iodine-6-substituted-benzyl-pyrimidine-4(3H)-ones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors | 期刊論文 | Tian, Chao|Zhang, Zhili|Liu, Junyi|Wang, Xiaowei| |
9 | Design, Synthesis, and Biological Evaluation of 1-[(2-Benzyloxyl/alkoxyl)methyl]-5-halo-6-aryluracils as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors with an Improved Drug Resistance Profile | 期刊論文 | 劉俊義|王孝偉| |
10 | Synthesis and neuroprotective effect of E-3,4-dihydroxy styryl aralkyl ketones derivatives against oxidative stress and inflammation | 期刊論文 | Wang, Xiaowei|Ma, Zhizhong|Zhang, Zhili|Liu, Junyi| |
11 | Synthesis and biological evaluation of pyridinone analogues as novel potent HIV-1 NNRTIs. | 期刊論文 | Yuanyuan Cao, Yu Zhang, Shaotong Wu, Quanzhi Yang| |
12 | Novel Pyridinone Derivatives As Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with High Potency against NNRTI-Resistant HIV-1 Strains | 期刊論文 | Du, Yansheng|Ma, Liying|Wang, Xiaowei|Liu, Junyi| |
13 | Rapid access to multi-substituted pyrimido[4,5-b][1,4]diazepine-2,4,6-trione and pyrimido[4,5-b][1,4]diazepine-2,4-dione as novel and versatile scaffolds for drug discovery | 期刊論文 | 劉俊義|李功| |
14 | Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury | 期刊論文 | 劉俊義| |
15 | Neuroprotective effects of (E)-3,4-diacetoxystyryl sulfone andsulfoxide derivatives in vitro models of Parkinson's disease | 期刊論文 | 劉俊義| |
項目摘要
肌萎縮側索硬化症（ALS）是一種致死性神經變性疾病，發病機制未完全清楚，也沒有有效的治療藥物和方法。目前只有一個藥物力如太被FDA批准用於ALS治療。因此研究治療和預防ALS藥物具有現實和重大的科學意義。以超氧歧化酶（SOD1）突變體SOD1ox激活神經細胞內p38 MAPK而導致ALS發病，是2010新發現的ALS發病機制。本申請以這個發病新機制的啟動因子SOD1ox為靶點，設計了三個系列化合物作為其抑制劑，研究其合成方法、評價活性，探究結構與活性關係，尋找新的治療ALS藥物並以此為探針進一步研究ALS發病機制。因此本研究有三個特色：一是緊跟ALS國際研究前沿，從發病源頭阻止病變的發生；二是避免了直接干預SOD1和p38 MAPK帶來的副作用；三是所設計的化合物結構新穎。可見該研究具有原始創新性，將開闢一條ALS藥物研究的新思路，其結果對ALS的分子病理機制和新藥研究均有創新性的推動作用
