Synthesis and In Vitro Biological Activity Evaluation of Novel Imidazo [2,1-B][1,3,4] Thiadiazole as Anti-Alzheimer Agents

被引：8
作者：
Azimi, Sara [1 ]
Firuzi, Omidreza [2 ]
Iraji, Aida [2 ]
Zonouzi, Afsaneh [1 ]
Khoshneviszadeh, Mahsima [2 ]
Mahdavi, Mohammad [3 ]
Edraki, Najmeh [2 ]
机构：
[1] Univ Tehran, Univ Coll Sci, Sch Chem, Tehran, Iran
[2] Shiraz Univ Med Sci, Med & Nat Prod Chem Res Ctr, Shiraz, Iran
[3] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran
来源：
LETTERS IN DRUG DESIGN & DISCOVERY | 2020年 / 17卷 / 05期
关键词：
Alzheimer's disease; BACE1; Imidazo[2,1-b][1,3,4] thiadiazol; AChE; BuChE; synthesize; SECRETASE INHIBITORS; DERIVATIVES; DESIGN; DISEASE; MEMANTINE; DEMENTIA; ANALOGS;
D O I：
10.2174/1570180816666181108115510
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Background: Considering that AD is multifactorial in nature, novel series of imidazo [2,1-b][1,3,4] thiadiazole derivatives were designed to address the basic factors responsible for the disease. Methods: These compounds were investigated as inhibitors of beta-site APP cleaving enzyme 1, acetylcholinesterase and butyryl cholinesterase. Results: The BACE1 inhibitory results indicated that nitro phenyl substituted derivatives of imidazo [2,1-b][1,3,4] thiadiazole scaffold (R-2 = m-NO2) demonstrated superior BACE1 inhibitory activity compared to other substituted moieties. In the BuChE assay, compounds 4h and 4l carrying meta NO2 at R-2 of phenyl ring turned out to be potent inhibitors. Conclusion: In conclusion, these novel synthesized derivatives seem to be promising anti-Alzheimer agents.
引用
收藏
页码：610 / 617
页数：8
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