CGRP antagonists

Antinociceptive effect of the CGRP antagonist CGRP(8-37) in several pain models... 

In 1997 scientists from SmithKIine Beecham published a series of quinine analogs as CGRP antagonists (Daines et al.1997, W09709046). These compounds displayed only weak affinities for the human CGRP receptor in the micromolar range and were therefore not of great importance (Daines et al., 1997). 

CGRP antagonists from SmithKIine Beecham a) SB-(+)-273779, b) W09809630, c) W09856779. 

It is interesting to note that although several major pharmaceutical companies have tried to develop CGRP antagonists, only few compounds have been published. Together with the fact that most of them are bulky structures - like BIBN-4096BS or compound T... 

Doods, H., Hallermayer, G., Wu, D., Entzeroth, M., Rudolf, K., Engel, W., Eberlein, W. Pharmacological profile of BIBN-4096BS, the first selective small molecule CGRP antagonist, Br. J. Pharmacol. 

Doods, H. Development of CGRP antagonists for the treatment of migraine, Curr. Opin. Invest. Drugs... 

Hill, R.G., Patchett, A.A., Yang, L. (Merck Sharp and Dohme Limited, USA) Preparation of N-4-(oxobenzimidazolyl)piperidinocarbonyl]arylglycinamides as CGRP antagonists, W00018764 (2000). 

J.E. Macor, G.M. Dubowchik, Discovery of (R)-N- (3-(7-methyl-lH-indazol-5-yl)-l-(4-(l-methylpiperidin-4-yl)-l-oxopropan-2-yl)-4-(2- oxo-l,2-dihydroquinolin-3-yl)piperidine-l-carboxamide (BMS-742413) a potent human CGRP antagonist with superior safety profile for the treatment of migraine through intranasal delivery, Bioorg. Med. Chem. Lett. 23 (11) (2013) 3157-3161. 

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