1424621-40-8Relevant articles and documents
The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 2
Han, Xiaojun,Civiello, Rita L.,Conway, Charles M.,Cook, Deborah A.,Davis, Carl D.,Degnan, Andrew P.,Jiang, Xiang-Jun,MacCi, Robert,Mathias, Neil R.,Moench, Paul,Pin, Sokhom S.,Schartman, Richard,Signor, Laura J.,Thalody, George,Tora, George,Whiterock, Valerie,Xu, Cen,MacOr, John E.,Dubowchik, Gene M.
, p. 1870 - 1873 (2013)
Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03 mg/kg SC, compound 2 (a racemic mixture of 3 and its (S)-enantiomer) demonstrated robust inhibition of CGRP-induced increases in mamoset facial blood flow up to 105 min. The compound possesses a favorable predictive in vitro toxicology profile, and good aqueous solubility. When dosed as a nasal spray in rabbits, 3 was rapidly absorbed and showed good intranasal bioavailability (42%).
