کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1361117 | 981457 | 2008 | 11 صفحه PDF | دانلود رایگان |

In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1–5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3-dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1–5 show an excellent neuroprotective profile, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca2+] elevation elicited by K+ depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer’s disease.
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Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 16, 15 August 2008, Pages 7759–7769