Cyclic amidines as benzamide bioisosteres: EPC synthesis and SAR studies leading to the selective dopamine D4 receptor agonist FAUC 312

  • Bioorg Med Chem Lett. 2003 Mar 10;13(5):851-4. doi: 10.1016/s0960-894x(03)00004-0.
Jürgen Einsiedel  1 ,  Harald Hübner ,  Peter Gmeiner
Affiliations
  • 1. Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
PMID: 12617906 DOI: 10.1016/s0960-894x(03)00004-0
Abstract

Investigation of conformationally restricted benzamide bioisosteres led to the chiral phenyltetrahydropyrimidine derivative ent2a (FAUC 312) displaying strong and highly selective dopamine D4 receptor binding (K(i(high))=1.5 nM). Mitogenesis experiments indicated 83% ligand efficacy when compared to the unselective agonist quinpirole. The target compounds of type 2 and 3 were synthesized in enantiopure form starting from asparagine.

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