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Updated: May 21, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Design and synthesis of potent antagonists containing rigid spirocyclic privileged structures for the CGRP receptor
Prasad V Chaturvedula1, Sokhom Pin, George Tholady
1Department of Molecular Sciences, Bristol-Myers Squibb R&D, 5 Research Parkway, Wallingford, CT 06492, USA. prasad.chaturvedula@bms.com
Abstract:
We report the synthesis of rigid spirocyclic systems as conformationally constrained variants of the Ala-Phe-NH(2) 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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