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Organic and Biomolecular Chemistry

History

It was established in 1985 by Dr. AV Rama Rao, FNA. The then Director of CSIR-IICT. As Organic Chemistry Division-III. The division was ably developed by Dr A. V. Rama Rao, which was later nurtured by Dr. M. K. Gurjar, Dr. A. K. Singh and Dr. T. K. Chakraborty. Since 2009, the division is headed by Dr. G. V. Madhava Sharma.

The 30 years young division, since its inception has been doing excellent in the area of Organic Synthesis both in basic and applied research. The division has undertaken challenging synthetic chemistry assignments that include the synthesis of vancomycin, fredericamycin, rhizoxin and several macrodiolides and macrotriolidses, besides depsipeptides, peptides and peptidomimetics. Additionally, development of diverse asymmetric synthetic methods is one of the focused areas of research of the division. Likewise, the division has been actively engaged on the projects of importance to the Pharma and fragrance Industry, both from India and overseas. The technologies developed include timolol (chiral technology), AZT, etc.; new routes to lead molecules such as CMI-977 (USA) and SB-214857 (UK), which were transferred to the clients. The contributions of the division towards the new drug discovery include the leads such as IICT-189719 (anti-HIV), IICT-TA67 (asthma-PDE-4) and others to name a few. It is worth mentioning that, IICT-TA67 is into Phase-I clinical trials.

The Division developed process chemistry for the first chiral drug, '(S)-timolol maleate', widely used for the treatment of glaucoma, from D-mannitol. The process development for 'AZT', one of the most expensive drugs for the treatment of AIDS, was developed indigenously for the first time, bringing down the costs in the world market. A new and highly cost-effective route for azido thymidine, a crucial intermediate for AZT, was also developed from D- xylose. Likewise, process know-how for the anti-cancer agents etoposide and mitoxantorne; ^-blockers, such as metoprolol, nadolol; gemfibrozile (cholesterol reducing drug) and others, using innovative and economical routes, was developed. Bench scale processes were developed for norfloxacin, ciprofloxacin, omeprazole, astemizole, naltrexone (DuPont, USA) and others, for several clients both from India and abroad This Division has the distinction of attracting the overseas client/ CytoMed, USA, for Contract Research, for the first time.

An innovative new route for a multi KG preparation of CMI-977, their lead molecule, was developed, solving the problems associated with the discovery route. The work paved way for the synthesis of its stereoisomers and related molecules like CMI-983 and others. Likewise, a new route for the process development for SB-213584 was achieved and transferred to SmithKline Beechem, UK. New routes developed for Georgywood / amberketal, two fragrance chemicals,and were transferred to Givaudan, Switzerland. Translation of chemical reactions in solution into the Solid Phase produced small libraries for SmithKline Beechem, UK. Similarly, validation studies were carried out for the solution phase reactions for the library generation, for ArQule, USA, besides generating libraries for DuPont, USA, as potential agro products. A new route was developed for eptifibatide, a cyclic peptide, for Biocon, India.

The Division has been extensively engaged on the synthesis of NCEs for anti-HIV; anti-asthma (COX-2, 5-LO, PDE-4, ICAM-1); anti-TB; anti-malaria and anti-cancer. The first product patent was filed on IICT-187919, an anti-HIV (NNRTI agent). Similarly, the efforts in the area of asthma resulted in several hit molecules, while, IICT-TA67, as a lead molecule, completed pre-clinical studies and entered into Phase-I clinical trials, for the first time from IICT. Several PDE-4 / ICAM-1 dual inhibitory molecules identified are under investigation. Several other NCEs evaluated against TB under the OSDD (Open Source Drug Discovery) programme, cancer and malaria, led to few hit molecules, which are evaluated for the lead generation.

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