title: Exploration of ring size in a series of cyclic vicinal diamines with σ₁ receptor affinity.
abstract: Imidazolidine and 1,4-diazepane analogs of N-(2-benzofuranyl)methyl-N'-(4-alkoxybenzyl)piperazines were prepared to explore the effect of ring contraction and expansion on σ receptor affinity and subtype selectivity within a series of cyclic diamines. In vitro receptor binding assays revealed that all cyclic vicinal diamines possessed affinity and selectivity for σ(1) receptors. The imidazolidines possessed nanomolar σ(1) affinities (K(i)=6.45-53.5 nM), and relatively low levels of subtype selectivity (σ(2)/σ(1)=58-237). However, the piperazines and diazepanes achieved picomolar σ(1) interactions, with K(i) ranges of 0.05-10.28 and 0.10-0.194 nM, respectively. Moreover, the piperazines and diazepanes showed excellent discrimination over the σ(2) receptor, with σ(1) selectivities of 143-16140 and 220-11542, respectively.
authors: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
authors: Iman A
authors: IA
authors: Moussa
authors: Samuel D
authors: SD
authors: Banister
authors: Miral
authors: M
authors: Manoli
authors: Munikumar Reddy
authors: MR
authors: Doddareddy
authors: Jinquan
authors: J
authors: Cui
authors: Robert H
authors: RH
authors: Mach
authors: Michael
authors: M
authors: Kassiou
mesh_terms: D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D048288:Imidazolines / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C545228:1,4-diazepane; D001381:Azepines; D003959:Diamines; D048288:Imidazolines; D010879:Piperazines; D017480:Receptors, sigma