کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1369627 981784 2012 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of potent antagonists containing rigid spirocyclic privileged structures for the CGRP receptor
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of potent antagonists containing rigid spirocyclic privileged structures for the CGRP receptor
چکیده انگلیسی

We report the synthesis of rigid spirocyclic systems as conformationally constrained variants of the Ala-Phe-NH2 dipeptide amide C-terminus of the calcitonin gene-related peptide (CGRP). CGRP receptor antagonists containing these moieties displayed potent affinity, functional antagonism and excellent oxidative stability. Structure–activity relationship studies demonstrated the relative importance of hydrogen bond donor/acceptor functionalities and the preferred orientation of an aromatic ring. Antagonists showed potent and full reversal of CGRP-induced dilation of ex vivo human intracranial arteries.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 14, 15 July 2012, Pages 4719–4722
نویسندگان
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