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.
