LOW-MOLECULAR-WEIGHT NEUROKININ-NK(2) ANTAGONISTS

Authors
SMITH PW MCELROY AB PRITCHARD JM DEAL MJ EWAN GB HAGAN RM IRELAND SJ BALL D BERESFORD I SHELDRICK R JORDAN CC WARD P
Citation
Pw. Smith et al., LOW-MOLECULAR-WEIGHT NEUROKININ-NK(2) ANTAGONISTS, Bioorganic & medicinal chemistry letters, 3(5), 1993, pp. 931-936
Citations number
15
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
3
Issue
5
Year of publication
1993
Pages
931 - 936
Database
ISI
SICI code
0960-894X(1993)3:5<931:LNA>2.0.ZU;2-P
Abstract
A deletion - optimization strategy based on an initial heptapeptide le ad structure 1 led to potent and selective neurokinin NK2 antagonists 5 (pK(B)=9.3) and 9 (pK(B)=7.9) of substantially reduced molecular siz e. Tetrapeptide 5 (0.1 mumol/Kg i.v.) potently inhibits NK2 agonist-in duced bronchoconstriction in guinea-pigs. Whilst less potent than 5 in vivo, the dipeptoid 9 (5 mumol/Kg i.v.) had a significantly longer bi ological half-life (> 2 h), and provides a potential lead towards non- peptide analogues.