title: The effect of bromine scanning around the phenyl group of 4-phenylquinolone derivatives.
abstract: Three quinolone compounds were synthesized and crystallized in an effort to study the structure-activity relationship of these calcium-channel antagonists. In all three quinolones, viz. ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, (I), ethyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, (II), and ethyl 4-(2-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, (III), all C21H24BrNO3, common structural features such as a flat boat conformation of the 1,4-dihydropyridine (1,4-DHP) ring, an envelope conformation of the fused cyclohexanone ring and a bromophenyl ring at the pseudo-axial position and orthogonal to the 1,4-DHP ring are retained. However, due to the different packing interactions in each compound, halogen bonds are observed in (I) and (III). Compound (III) crystallizes with two molecules in the asymmetric unit. All of the prepared derivatives satisfy the basic structural requirements to possess moderate activity as calcium-channel antagonists.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Missoula, MT 59812, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Steiger
authors.affiliation: Department of Chemistry, Ithaca College, 953 Danby Road, Ithaca, NY 14850, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Monacelli
authors.affiliation: Department of Chemistry, Ithaca College, 953 Danby Road, Ithaca, NY 14850, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemistry, Ithaca College, 953 Danby Road, Ithaca, NY 14850, USA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Hunting
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Missoula, MT 59812, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Natale
mesh_terms: D001966:Bromine / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D011804:Quinolines / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry*
chemical_list: C094410:4-phenylquinolone; D011804:Quinolines; D015363:Quinolones; C000592712:ethyl 4-(2-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate; C000592711:ethyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylat; C000592710:ethyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate; D001966:Bromine
keywords: 1,4-dihydropyridine rings; bromine scanning; calcium-channel antagonists; crystal structure; halogen bonding; hydrogen bonding; quinolone compounds; structure–activity relationships
references.citation: Med Res Rev. 1989 Apr-Jun;9(2):123-80
references.pmid: 2654521
references.citation: J Med Chem. 1992 Jun 12;35(12):2238-43
references.pmid: 1319494
references.citation: Acta Crystallogr D Biol Crystallogr. 2009 Feb;65(Pt 2):148-55
references.pmid: 19171970
references.citation: J Med Chem. 2013 Feb 28;56(4):1363-88
references.pmid: 23145854
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16789-94
references.pmid: 15557000
references.citation: Acta Crystallogr C. 2002 Jul;58(Pt 7):o436-8
references.pmid: 12094070
references.citation: Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
references.pmid: 18156677
references.citation: J Med Chem. 1986 Feb;29(2):305-7
references.pmid: 3005572
references.citation: Acta Crystallogr C. 2004 Oct;60(Pt 10):o711-3
references.pmid: 15467138
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D668-72
references.pmid: 16381955
references.citation: J Med Chem. 2013 Apr 25;56(8):3121-47
references.pmid: 23458846
references.citation: Cell Mol Neurobiol. 2003 Jun;23(3):293-303
references.pmid: 12825828
references.citation: Arch Pharm (Weinheim). 1990 May;323(5):281-6
references.pmid: 2166493
references.citation: Acta Crystallogr C. 2005 Dec;61(Pt 12):o731-4
references.pmid: 16330861
references.citation: Biol Pharm Bull. 2008 Mar;31(3):473-9
references.pmid: 18310913