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 Citations (Scopus)

Abstract

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
Volume17
Issue number9
DOIs
StatePublished - May 1 2007

Fingerprint

Scaffolds
Melanocortin Receptors
Ligands
human MC3R protein
4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one
SHU 9119
ACTH (6-9)

Keywords

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

ASJC Scopus subject areas

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

Cite this

Novel selective human melanocortin-3 receptor ligands : Use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold. / Ballet, Steven; Mayorov, Alexander V.; Cai, Minying; Tymecka, Dagmara; Chandler, Kevin B.; Palmer, Erin S.; Rompaey, Karolien Van; Misicka, Aleksandra; Tourwé, Dirk; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 9, 01.05.2007, p. 2492-2498.

Research output: Contribution to journalArticle

Ballet, Steven ; Mayorov, Alexander V. ; Cai, Minying ; Tymecka, Dagmara ; Chandler, Kevin B. ; Palmer, Erin S. ; Rompaey, Karolien Van ; Misicka, Aleksandra ; Tourwé, Dirk ; Hruby, Victor J. / Novel selective human melanocortin-3 receptor ligands : Use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 9. pp. 2492-2498.
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