Toward nonpeptidal substance P mimetic analogues: Design, synthesis, and biological activity

✍ Scribed by Michael Chorev; Eli Roubini; Chaim Gilon; Zvi Selincer

• Book ID: 102765867
• Publisher: Wiley (John Wiley & Sons)
• Year: 1991
• Tongue: English
• Weight: 663 KB
• Volume: 31
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360310617

✦ Synopsis

SYNOPSIS

1,4-Piperazine and 4-hydroxy proline, two small cyclic polyfunctional systems with defined stereochemistry, were introduced as "molecular scaffolds." We define a "bioactive topology," which is a derived putative low-energy conformation obtained through theoretical conformational analysis of substance P. Substitution of these molecular scaffolds by pharmacophors characteristic of the bioactive topology of the C-terminal hexapeptide of substance P resulted in active, partially nonpeptidal substance P mimetic agonists. The study discusses the concepts and tools used to achieve this structural transformation, and points out the need to address flexibility-rigidity issues in an attempt to maintain sufficient molecular plasticity.