Design, Synthesis, and Structure-Activity Relationship Studies of Himbacine Derived Muscarinic Receptor Antagonists

Bioorg Med Chem Lett. 1999 Mar 22;9(6):901-6. doi: 10.1016/s0960-894x(99)00101-8.

Abstract

A parallel synthesis of racemic himbacine analogs was carried out by N-alkylation of various commercially available cyclic amine derivatives with the alkylating agent 4 which bears the tricyclic unit of himbacine. Several of these analogs have potency comparable to that of himbacine, albeit lacking the desired selectivity. Structure-activity relationship studies support the existence of a hydrophobic pocket in the receptor where the piperidine ring of dihydrohimbacine binds.

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / pharmacology
  • Furans
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Muscarinic Antagonists / chemical synthesis*
  • Muscarinic Antagonists / chemistry*
  • Naphthalenes
  • Piperidines
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Furans
  • Muscarinic Antagonists
  • Naphthalenes
  • Piperidines
  • himbacine