Antagonists of luteinising hormone-releasing hormone (LHRH). Progress towards non-peptide leads

• Published in: Bioorganic & medicinal chemistry letters Vol. 3; no. 5; pp. 943 - 948
• Main Authors: Dutta, A.S., Gormley, J.J., Woodburn, J.R., Paul, P.K.C., Osguthorpe, D.J., Campbell, M.M.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1993
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)80697-6

In an attempt to generate information leading to non-peptide antagonists of LHRH, conformationally restricted analogues of LHRH antagonists have been synthesised. Information on the design, molecular modelling studies and biological activity of several analogues including a bicyclic antagonist c[D-Phe(p-Cl)-D-Phe(p-Cl)-D-Trp- Ser-G lu-D-Arg-Leu-Lys -Pro-D-MeAla], obtained by forming bonds between N- and C-terminal ends and the side chains of Glu and Lys residues, are reported here. In an attempt to generate information leading to non-peptide antagonists of LHRH, conformationally restricted analogues of LHRH antagonists have been synthesised. Information onn the design, molecular modelling studies and biological activity of several analogues including a bicyclic antagonist c[D-Phe(p-Cl)-D-Phe(p-Cl)-D-Trp-Ser-Glu-D-Arg-Leu-Lys-Pro-D-MeAla], obtained by forming amide bonds between N- and C-terminal ends and the side chains of Glu and Lys residues, are reported here.