title: Comparison crystal structure conformations of two structurally related biphenyl analogues: 4,4'-bis-[3-(pyrrolidin-1-yl)prop-1-yn-1-yl]-1,1'-biphenyl and 4,4'-bis-{3-[(S)-2-methyl-pyrrolidin-1-yl]prop-1-yn-1-yl}-1,1'-biphen-yl.
abstract: The title compounds, C26H28N2, (I), and C28H32N2, (II), were designed based on the structure of the potent α9α10 nicotinic acetyl-choline receptor antagonist ZZ161C {1,1'-[[1,1'-biphen-yl]-4,4'-diylbis(prop-2-yne-3,1-di-yl)]bis-(3,4-di-methyl-pyridin-1-ium) bromide}. In order to improve the druglikeness properties of ZZ161C for potential oral administration, the title compounds (I) and (II) were prepared by coupling 4,4'-bis-(3-bromo-prop-1-yn-1-yl)-1,1'-biphenyl with pyrrol-idine, (I), and (S)-2-methyl-pyrrolidine, (II), respectively, in aceto-nitrile at room temperature. The asymmetric unit of (I) contains two half mol-ecules that each sit on sites of crystallographic inversion. As a result, the biphenyl ring systems in compound (I) are coplanar. The biphenyl ring system in compound (II), however, has a dihedral angle of 28.76 (11)°. In (I), the two independent mol-ecules differ in the orientation of the pyrrolidine ring (the nitro-gen lone pair points towards the biphenyl rings in one mol-ecule, but away from the rings in the other). The torsion angles about the ethynyl groups between the planes of the phenyl rings and the pyrrolidine ring N atoms are 84.15 (10) and -152.89 (10)°. In compound (II), the corresponding torsion angles are 122.0 (3) and 167.0 (3)°, with the nitro-gen lone pairs at both ends of the mol-ecule directed away from the central biphenyl rings.
authors.affiliation: Dept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Anqi
authors.initials: A
authors.lastname: Wan
authors.affiliation: Dept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Narsimha Reddy
authors.initials: NR
authors.lastname: Penthala
authors.affiliation: Dept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: E Kim
authors.initials: EK
authors.lastname: Fifer
authors.affiliation: Dept. of Chemistry, University of Kentucky, Lexington KY 40506, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Parkin
authors.affiliation: Dept. of Pharm. Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
keywords: biphenyl ring; bis-tertiary ammonium salt; crystal structure; pyrolidine ring