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Synthesis of some acridine derivatives of possible pharmacological value

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MinnisJW_1943redux.pdf (11.06Mb)
Date
1943
Author
Minnis, J. W.
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Abstract
 
 
The German chemist Ehrlich may be regarded as the father of chemotherapy for, as early as 1904, he said, with true vision, "What we seek is 'specific chemotherapy.' That is, we are in search of a drug capable of destroying certain parasites without, at the same time, causing too much damage to the host" and his words still hold good to -day. His aim and that of all subsequent workers in this field has been expressed in other words by saying that "we seek a hidden key which can alone open a certain door." Although a considerable amount of work was accomplished in the field of chemotherapeutic agents during the intervening years modern research was given a great impetus following the publication in 1935 of the work of Domagk dealing with the clinical use of prontosil against diseases caused by haemolytic streptococci. The investigation of this branch of chemistry is, however, still in its infancy. At the present time, in spite. of the recent most intensive research, there are no general rules to guide the research work in chemotherapy and it is recognised that much experimental work has yet to be accomplished before any attempt can be made to formulate a satisfactory theory which would give a general correlation between chemical structure and chemotherapeutic action. "Meantime, it is possible to argue as to whether, in the search for new drugs, intuition is still of more value for guidance than the collected fruits of experience. One thing, however, is not arguable and that is that in either case one must still apply a great deal of patience to the search." In the course of these synthetical studies it became apparent that methoxy groups and methylenedioxy groups substituted in the 4:5 positions to a 2- carboxyl group in a diphenylamine -2- carboxylic acid in many cases led to inefficient ring closure with sulphuric acid or phosphorus oxychloride. On the other hand a chlorine substituted in the 5- position appears to lead to successful ring closure. A possible theoretical explanation is advanced for this effect and a suggestion made that further information on the influence of substituents on such ring closures is highly desirable.
 
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http://hdl.handle.net/1842/35351
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