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buffer consisting of 0.02M Sodium phosphate and 0.01M Octane
sulfonic acid and pH adjusted to 4.2 with dilute phosphoric acid
solution. The analysis is performed on a gradient conditions with
mobile phase A , a mixture of buffer and acetonitrile (90:10,v/v)
and mobile phase B with a mixture of acetonitrile and buffer
(80:20,v/v). The mobile phase was filtered through a 0.45 µm
nylon membrane and degassed with helium for 5 min. The mobile
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column was maintained at 27 °C and the effluent was monitored at
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SUMMARY AND CONCLUSIONS
STUDIES TOWARDS PROCESS RESEARCH AND DEVELOPMENT OF
FEW BIOLOGICALLY ACTIVE COMPOUNDS CONTAINING
DIHYDROPYRIDINE AND PURINE NITROGEN HETEROCYCLES
Summary
Process research and development entails balancing the aspects of
chemistry, economy, safety, ecology, regulatory, intellectual property
robustness, and quality and yet speed. Coalescing the science,
technology, logic and business organically is the prime responsibility of a
process chemist. To a greater extent this analysis was applied and
demonstrated during the development of Lacidipine, Valacyclovir and
Ganciclovir during the research work.
Conclusions
In conclusion, the research studies presented in this thesis have
contributed to the existing knowledge of scientific community on nitrogen
heterocycles in the following aspects.
1. An improved, cost-viable, and plant-friendly process was developed for
the synthesis of Lacidipine, 1. Thorough understanding of the process
parameters coupled with integrated calorimetric approach ensured
successful design of improved process and well control of all process
related impurities. Investigation on five related substances
emphasizes the quality consciousness during process research.
277
2. The azide chemistry explored for Valacyclovir 49, opens up a new
pathway to prepare other commercially important purine derivatives.
More specifically to circumvent patent barricades so as to offer
affordable medicines to the needy patient population.
3. Explored the usage of chloromethylacetate to eradicate the prevailing
challenges in chloromethylation step and employed masked glycerol
protocol for the synthesis of Ganciclovir, 73. This synthetic strategy
can be extrapolated to other biologically and commercially important
analogues.
4. The frame work demonstrated for addressing GTIs rendered a frame of
reference to the process chemist to offer pharmaceutical products
devoid of GTIs.
Over the years, we at Dr. Reddy‟s with our experienced learning in the
same field, have identified some key areas and we believe that the
research work presented in this thesis would be imperative in the
direction to ensure availability of affordable medicines with highest
quality in the most economical, robust, safe, rapid, and environment
friendly way to the patient population.