Novel selective human melanocortin-3 receptor ligands: Use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold

Steven Ballet, Alexander V. Mayorov, Minying Cai, Dagmara Tymecka, Kevin B. Chandler, Erin S. Palmer, Karolien Van Rompaey, Aleksandra Misicka, Dirk Tourwé, Victor J. Hruby

Research output: Contribution to journalArticle

20 Scopus citations


In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-NH2) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-His-d-Nal(2′)-Arg-Trp-Lys]-NH2) by replacing the His-d-Phe and His-d-Nal(2′) fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx = d-Phe/pCl-d-Phe/d-Nal(2′)). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists.

Original languageEnglish (US)
Pages (from-to)2492-2498
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Issue number9
StatePublished - May 1 2007



  • 4-Amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones
  • Conformational restrictions
  • Cyclic lactam analogues
  • Human melanocortin receptors
  • hMC3R/hMC5R antagonists

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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