Journal article
Synthesis and Activity of Substituted 2-Phenylquinolin-4-amines, Antagonists of Immunostimulatory CpG-Oligodeoxynucleotides
Journal of medicinal chemistry, Vol.46(7), pp.1242-1249
03/27/2003
DOI: 10.1021/jm020374y
PMID: 12646034
Abstract
Fifty-seven 2-phenylquinolines substituted at the phenyl group and C4 of the quinoline were synthesized and analyzed for inhibition of the immunostimulatory effect of oligodeoxynucleotides with a CpG-motif. The Fujita-Ban variant of the classical Free-Wilson analysis gave a highly significant correlation for a series of 48 relatively small molecules demonstrating that (i) the partial contributions of substituents to biological activity (EC50) are additive and (ii) assuming similar bioavailability for all quinolines studied, the larger molecules cannot be accommodated within a still unknown biological receptor. The results suggest interaction of a basic antagonist molecule with weakly acidic groups in the antagonist−receptor complex. N-[2-(Dimethylamino)ethyl]-2-[4-(4-methylpiperazino)phenyl]quinolin-4-amine (50) is the most effective antagonist found in this study (EC50 = 0.76 nM).
Details
- Title: Subtitle
- Synthesis and Activity of Substituted 2-Phenylquinolin-4-amines, Antagonists of Immunostimulatory CpG-Oligodeoxynucleotides
- Creators
- Lucjan STREKOWSKI - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandDonald E MACFARLANE - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandMartial SAY - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandMaged HENARY - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandPatricia RUIZ - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandLori MANZEL - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, PolandAndrzej J BOJARSKI - Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, Department of Medicine, Veterans Affairs MedicalCenter and University of Iowa, Iowa City, Iowa 52242, and Institute of Pharmacology, Polish Academy of Sciences,Smetna 12, Krakow, Poland
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.46(7), pp.1242-1249
- Publisher
- American Chemical Society
- DOI
- 10.1021/jm020374y
- PMID
- 12646034
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Language
- English
- Date published
- 03/27/2003
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094395202771
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