| dc.description.abstract | STUDIES IN SULPHANILAMIDES AND SULPHONES
SECTION A: STUDIES ON SULPHANILAMIDES
Part I: Introduction
This part deals, in brief, with (i) the history and advance of chemotherapy, (ii) discovery and development of the modern sulphanilamide group of drugs, (iii) chemistry of some of the important sulpha-drugs, (iv) classification of sulphanilamides, (v) discussion on the correlation of structure with chemotherapeutic activity, (vi) discussion on the fundamental unit of activity, and (vii) discussion on the mechanism of sulphanilamide action and theory of relation of structure to activity of the sulpha-drugs.
II. Synthesis of N?-heterocyclic diacyl-sulphanilamides
Although N?-substituted derivatives of sulphanilamides are hailed to be therapeutically the most active, the activity of N-furoylsulphapyridine, N-nicotinylsulphanilamide, N?-quinolylsulphanilamide, N?-2-pyrrolidone-5-carboxy-4-aminobenzene sulphonamide and 3',3'-dibromobenzenesulphonamide warranted further work in this direction which may throw some light on the mode of action of these drugs.
This part deals with the synthesis of fourteen N?-heterocyclic diacyl-sulphanilamides obtained by the action of sulphanilamide on
(a) quinolinic acid,
(b) diethyl dihydrocollidine dicarboxylate,
(c) collidine dicarboxylic acid,
(d) chelidamic acid,
(e) furan-2,6-dicarboxylic acid,
(f) diethyl-3,4-dihydroxyfuran-2,6-dicarboxylate,
(g) methyl-3,4-dihydroxyfuran-2,6-dicarboxylate,
(h) 3,4-dioxane-5,5-dicarboxylate,
(i) cantharidin, and
(j) diethyl aceto-succinate.
III. Synthesis of N?-heterocyclic diacyl-sulphanilamides
The acidic dissociation theory of Fox and Rose and the theory of Bell and Roblin on the mechanism of action of sulphanilamides suggest the possibilities that if sulphanilamide could be rendered more acidic by suitable means, more potent chemotherapeuticals than those hitherto known could be obtained; they also raise a question whether by transformation of the sulphonamide part of the sulphanilamide, compounds of the same acidity and same degree of activity as the most powerful sulphanilamides now known, but having suitable physical and physico-chemical properties, cannot be prepared. With a view to exploring the possibilities of achieving these objects, seven N?-heterocyclic diacyl-sulphanilamides have been synthesised by the action of sulphanilamide, N-salt of acetyl sulphanilamide, or p-acetaminobenzenesulphochloride, as the case may be, on
(a) furan-2,6-dicarboxylic acid,
(b) chelidonic acid,
(c) quinolinic acid,
(d) dihydrocollidine dicarboxylate, and
(e) chelidamic acid.
IV. Synthesis of aliphatic and carbocyclic diacyl-sulphanilamides
In extension of the work detailed in Part III, twelve N?- and two N¹-diacylsulphanilamides have been prepared from
(a) monoethyl ester of malonic acid,
(b) succinic acid,
(c) glutaric acid,
(d) adipic acid,
(e) azelaic acid,
(f) sebacic acid, and
(g) phthalic acid.
A note on the preparation of quinoline and quinolinic acid
Quinoline and quinolinic acid are of industrial importance since the former is a base for very many dyes and drugs, and the latter on decarboxylation gives nicotinic acid, the anti-pellagra factor of great therapeutic value.
This part details the Skraup’s synthesis of quinoline by a new method using iodine as catalyst. This method has advantages over the methods generally used for the preparation of quinoline inasmuch as (i) it requires less time, (ii) avoids removal of nitrobenzene by steam distillation, and (iii) the glycerol required is moderate. It also details a method for preparing quinolinic acid in good yields.
SECTION B: STUDIES ON SULPHONES
Part I: Introduction
This part deals in brief with the discovery and development of the sulphone series of drugs, their chemistry, mode of action and relation of structure to chemotherapeutic activity.
Synthesis of Schiff’s bases from 4-nitro-4'-amino and 4,4'-diamino-diphenyl-sulphones
Although the anti-streptococcal activity of 4,4'-diamino-diphenylsulphone was known (approximately hundred times that of sulphanilamide), its toxicity prevented its application in chemotherapy. Recently, its anti-tubercular and anti-leprosy activity has aroused attention, and now efforts are being made towards rendering it less toxic by suitably masking the amino group(s) or otherwise, and obtaining substances similar in activity to 4,4'-diamino-diphenylsulphone having more suitable physical and physico-chemical properties, but less toxicity. Twenty-four Schiff’s bases of 4-nitro-4'-amino-diphenylsulphone and 4,4'-diamino-diphenylsulphone have been prepared and detailed in this part.
A note on the preparation of ‘Promin’ and ‘Diasone’
Experimental conditions for the preparation of the two modern anti-tubercular and anti-leprosy drugs — ‘Promin’ and ‘Diasone’ — have been established and are detailed in this part. | |
