title: Fancy bioisosteres: synthesis and dopaminergic properties of the endiyne FAUC 88 as a novel non-aromatic D3 agonist.
abstract: Enlargement of the pi-electronic system of the non-aromatic D3 agonist FAUC 73 led to dopaminergic endiynes of type 1 being synthesized via the bromovinyl triflate 7a as a key intermediate when palladium catalyzed coupling reactions were exploited for the introduction of the (aza)alkyne substituents. As the first neuroreceptor active endiyne, FAUC 88 (1c) displayed high and selective dopamine D3 receptor affinity (K(ihigh) = 3.2 nM) and substantial ligand efficacy (72%, EC(50) = 2.5 nM). Similarities between molecular electrostatic potentials induced by the catechol subunit of the genuine neurotransmitter and those of its non-aromatic endiyne bioisostere are discussed.
authors.affiliation: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Lenz
authors.forename: Christian
authors.initials: C
authors.lastname: Haubmann
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.forename: Frank
authors.initials: F
authors.lastname: Boeckler
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D000480:Alkynes; D003514:Cyclohexylamines; C493593:DRD3 protein, human; D018491:Dopamine Agonists; C500408:FAUC 88; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3