-
Title
-
Synthesis and characterization of biologically active phenanthrolines, quinolines and related materials.
-
Identifier
-
AAI3127842
-
identifier
-
3127842
-
Creator
-
Abeywickrama, Chandima.
-
Contributor
-
Adviser: Arthur David Baker
-
Date
-
2004
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Chemistry, Organic
-
Abstract
-
Derivatives of 1,4,5,12-tetraazatriphenylenes and analogues of dequalinium diiodide were synthesized and investigated.;In the first project, efficient preparations of 1,4,5,12-tetraazatriphenylene, also known as 4',7'-phenanthrolino-5,6:5 '6'-pyrazine 1 (ppz) and a number of its substituted derivatives were developed. The condensation of 5,6-diamino-4,7-phenanthroline 6 with glyoxal provides a quantitative yield of ppz itself. This synthetic strategy avoids the disproportionation reaction and resulting minimum 50% loss of possible ppz product that occurs in the previously used preparation which involved the condensation of 4,7-phenanthroline-5,6-dione 2 with ethylenediamine. Use of dicarbonyl compounds other than glyoxal forms ppz derivatives including 2,3-diphenyl-1,4,5,12-tetraazatriphenylene 7, 2,3-dimethyl-1,4,5,12-tetraazatriphenylene 8, 2,3-dipyridin-2-yl-1,4,5,12-tetraazatriphenylene 9, 1,8,9,10,17,18-hexaazaphenanthro[9,10-b]triphenylene 10. Other ppz derivatives have been prepared via the condensation of diaminomaleonitrile with 4,7-phenanthroline-5,6-dione 2 and subsequent functional group transformations on the two cyano groups of the resulting 1,4,5,12-tetraazatriphenylene-2,3-dicarbonitrile 14.;In the second project, protein kinase C (PKC) inhibitors related in structure to dequalinium salts were investigated. Structural changes were made with the ultimate goal of developing better therapeutic agents. The parent compound Dequalinium diiodide (C10-DECA) 20c gave the optimum potency in this series. However Dequalinium diiodide analogues based on 4-aminoquinoline and 4-N,N-dimethylaminoquinoline show similar potency to that of the parent compound. The methyl group at the second position does not contribute significantly to inhibitory activity. Substituted pyridine rings (rather than quinoline rings) reduce the potency. Unsubstituted quinoline rings are relatively inactive towards PKC. The quarternized exocyclic ring nitrogens of DECA analogues are less potent than that of quarternized ring nitrogens of DECA analogues. Other potent compounds were also discovered, e.g. the triphenylphosphine based DECA type analogues.;Gauss view 3.0/Restricted Hartree-Fock, 6-31G Level calculations were performed on free bases and on quarternized model compounds with the goal of obtaining a structure-activity relationship.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
