Dr. Parthasarathi Das

Dr. Parthasarathi Das
Medicinal Chemistry Division CSIR - Indian Institute of Integrative Medicine,Canal Road, Jammu – 180001 Email: partha@iiim.ac.in http://www.iiim.res.in/People/CV/cv_parthasarathi.php https://www.researchgate.net/profile/Parthasarathi_Das2 Indian Institute of Integrative Medicine Medicinal Chemistry Division (IIIM) Jammu, J&K, India CSIR-Indian Institute of Integrative Medicine (Council of Scientific & Industrial Research)
Positions Held
Position Held Date Organization Principal Scientist Since 2012 CSIR-IIIM Scientist Fellow 2011- 2012 CSIR-IIIM Research Investigator 2007-2011 Aurigene Discovery Technologies Ltd Principal Scientist 2004-2007 Dr. Reddy’s Laboratories Ltd Postdoctoral Fellow 2002-2003 Chemistry and Chemical Biology, Harvard University,  USA.   Researcher 2000-2002 Graduate School of Science, Tohoku University, Japan Postdoctoral Fellow 1999-2000 Inst. of Organische Chemie der RWTH Aachen, Germany.
Awards and Fellowships Harvard  University Postdoctoral Fellowship , USA. CREST-Japan Science  & Technology  Postdoctoral Fellowship, Japan Graduiertenkollegs- DFG Fellowship, Germany CSIR Research Fellowship, India . GATE-1993, India Membership
Chemical Research Society of India (CRSI), Bangalore, India Indian Society of Chemists and Biologist (ISCB), Lucknow, India.

Principal Scientist Dr. Parthasarathi Das, Department of Medicinal Chemistry CSIR-Indian Institute of Integrative Medicine-Jammu, who has given us interesting tips of his chemical life, and valuable advices to the future extraordinary chemists.

Dr. Parthasarathi Das
CSIR-Indian Institute of Integrative Medicine(IIIM) - Jammu

Research fields: Organic Synthesis, Medicinal Chemistry.

Current Area of Research: Medicinal Chemistry, developments of new synthetic methodology and synthesis of biologically active natural products.

Publications: (1) Copper-catalyzed sequential N-arylation of C-amino-NH-azoles. D. Nageswar Rao, Sk. Rasheed, Ram A Vishwakarma and Parthasarathi Das Chem. Commun 2014, 50, 12911; (2) Direct C-2 arylation of 7-azaindoles:Chemoselective access to multiarylated derivatives. Prakash Kannaboina, K. Anilkumar, S. Aravinda, Ram A. Vishwakarma and Parthasarathi Das. Org. Lett. 2013, 15, 5718.

* The most attractive part in the chemistry:
Common to both life and materials sciences

* How do you get inspiration for new research:
Exploring things that nobody previously achieved

* Why choose Chemistry as your career:
It is easiest way to bring something new to this world

* Advice for junior researchers:
Never give up and be confident in what you do 

Research Area

Catalysis

Our research is focused on the discovery of new catalytic, systems for organic synthesis that utilize the power of transition metal catalysts. Our goal is to enable greater efficiency and novel bond constructions in the synthesis of medicinally important heteroaromatics, with applications that extend to natural product synthesis, drug discovery and process chemistry. The development of these methods also provides a platform for mechanistic investigations, which will enable insight into questions of fundamental reactivity and catalyst design.

 

Total Synthesis

While complex architecture and dense functionality draw our attention to select natural products, with interesting biological activities. Pharmaceutical companies waning interest in natural products reflects the difficulties and costs associated with their synthesis and subsequent structure-activity relationship (SAR) studies. This offers academics the opportunity to develop novel chemical strategies in the context of various therapeutic areas.

Medicinal Chemistry

Infections caused by Gram negative bacteria constitute a major unmet medical need, particularly in the hospital setting, where Gram negative pathogens account for 61% of the infections. Gram-negative bacteria possess an additional outer membrane decorated with lipopolysaccharide (LPS). LPS is composed of three distinct units. The outermost unit is the O-antigen, which is a glycan polymer. This is linked to a sugar-containing core domain which is appended to the membrane anchoring group, lipid A (endotoxin). This outer membrane provides a substantial protective barrier, and Gram-negative bacteria lacking lipid A are either not viable or are highly susceptible to a range of anti-infective drugs, suggesting that enzymes involved in lipid A production could represent new drug targets. Nine unique enzymes catalyze the synthesis of lipid A and UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc−metalloamidase responsible for carrying out the second biosynthetic step. The essential role LpxC plays in the biosynthesis of lipid A, coupled with a lack of homology with mammalian proteins, has catalyzed efforts to identify small molecule LpxC inhibitors for the treatment of serious Gram-negative infections.

Publications

Rao, D. N.; Rasheed, S.k.; Das, P. Palladium/ Silver Synergistic Catalysis in Direct Aerobic Carbonylation of C(sp2)−H Bonds Using DMF as a Carbon Source: Synthesis of Pyrido-Fused Quinazolinones and Phenanthridinones Org. Lett. (2016); (DOI: 10.1021/acs.orglett.6b01292). Kannaboina, P.; Kumar, K. A. ; Das, P. Site-Selective Intermolecular Oxidative C-3 Alkenylation of 7-Azaindoles at Room Temperature . Org. Lett.(2016) 18, 900-903 (DOI: 10.1021/ol4027478). Rao, D.N.; Rasheed, S.k.; Kumar, K. A.; Reddy, A. S.; Das,P. Copper-Catalyzed CNH2 Arylation of 2-Aminobenzimidazoles and Related C-Amino-NH-azoles. Adv. Synth. Catal. (2016). (DOI: 10.1002/adsc.201600035). Rasheed, Sk. ; Rao, D. N.; Das, P. Copper-Catalyzed Inter- and Intramolecular C−N Bond Formation: Synthesis of Benzimidazole-Fused Heterocycles. J. Org. Chem. (2015), 80, 9321−9327 (DOI: 10.1021/acs.joc.5b01396) Kumar, K.A .; Kannaboina, P.; Dhaked, D. K. ; Vishwakarma, R.A.; Bharatam, P.V. ; Das, P. Cu-catalyzed arylation of the amino group in the indazole ring: regioselective synthesis of pyrazolo-carbazoles. Org. Biomol. Chem. ( 2015), 13, 1481-1491 (DOI: 10.1039/c4ob02044h) K. Reddy, K. R.; Reddy, A. S.; Dhaked, D. K.; Rasheed, S. K.; Pathania, A.S.; Shankar, R. ; Malik, F.; Das,P. Palladium-catalyzed arylation of 2H-chromene: a new entry to pyrano[2,3-c]carbazoles. Org. Biomol. Chem.(2015), 13, 9285-9293 (DOI: 10.1039/c5ob01295c.). Reddy, K. R. ; Reddy, A. S.; Shankar, R.; Kant, R.; Das, P . Copper-Catalyzed Oxidative C-H Amination: Synthesis of Imidazo[1,2-a]-N-Heterocycles from N-Heteroaryl Enaminones. Asian J. Org. Chem. (2015), 4, 573-583 (DOI: 10.1002/ajoc.201500052). Khajuria, R.; Kannaboina, P.; Kapoor, K. K. ; Gupta, A.; Raina, G .; Jassal, A. K.; Rana, L. K.; Maninder , H. S.; Das, P. Divergent synthesis of 4, 6-diarylated pyridin-2(1H)-ones from chalcones: novel  access to 2,4,6-triaryl pyridines. Org. Biomol. Chem. (2015), 13, 5944-5954 (DOI: 10.1039/c5ob00545k). Rao, D. N.; Rasheed, S.k. ;Vishwakarma, R.A.; Das, P. Copper-catalyzed sequential N-arylation of C-amino-NH-azoles. Chem. Commun. (2014), 50, 12911-12914 (DOI: 10.1039/c4cc05628k). Kannaboina, P.; Kumar, K.A.; Aravinda, S.; Vishwakarma, Ram A. ; Das, P. Direct C‑2 Arylation of 7‑Azaindoles: Chemoselective Access to Multiarylated Derivatives. Org. Lett. (2013), 15, 5718-5721 (DOI: 10.1021/ol4027478).

Parthasarathi Das, Scientist, Indian Institute of Integrative Medicine (CSIR) Parthasarathi Das received his MSc degree from Burdwan university. He then moved to National Chemical laboratory, Pune to pursue his doctoral studies where he received his PhD in 1998 under the supervision of Dr. Ganesh Pandey. He did postdoctoral work at the RWTH-Aachen, Germany (Prof. H-J Gais), Tohoku University, Japan (Prof. Masahiro Hirama) and Harvard University, USA (Prof. Yoshito Kishi). In 2003 he moved to India to join Discovery Research of Dr. Reddy’s Laboratories Ltd. and worked in discovery chemistry with research focus in various therapeutic areas e.g. oncology, metabolic disorder and antibacterial. In 2011 he moved to Indian Institute of Integrative Medicine (CSIR), a premier research laboratory focused on drug discovery and natural products research. His current research interests include medicinal chemistry, development of new synthetic methodology and synthesis of biologically active natural products. He serves on the editorial board of the journals; The Scientific World Journal-Organic Chemistry and Journal of Pharmaceutics.

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Anjali Pandey

Senior Vice President Medicinal Chemistry & Chemical Development, Portola Pharmaceuticals, Inc

ANJALI PANDEY, Ph.D.
Senior Vice President, Medicinal Chemistry and Chemical Development

Dr. Anjali Pandey joined Portola in November 2003 and has served as senior vice president of medicinal chemistry and chemical development since July 2015 and vice president chemistry since April 2006. Dr. Pandey is responsible for the overall leadership of medicinal chemistry, process research and development, manufacturing of active pharmaceutical ingredient and drug products for clinical candidates. Dr. Pandey is leading clinical and development efforts for Portola’s oral, dual Syk-JAK kinase inhibitor cerdulatinib, and development of Portola’s intellectual property portfolio. Prior to Portola, she held senior research positions at Millennium Pharmaceuticals and COR Therapeutics. Dr. Pandey has over 20 years of biotechnology experience with hands-on involvement in all stages of drug development, from initial lead identification to Phase 3 clinical trials. Dr. Pandey is the principal inventor of cerdulatinib, the Syk-selective inhibitor PRT2607, and the flt-3 receptor tyrosine kinase inhibitor tandutinib. She played a key role in the discovery and development of Portola’s Factor Xa inhibitor betrixaban and the P2Y12 receptor antagonist elinogrel. Dr. Pandey has published over 30 scientific publications and reviews and is co-inventor on 40 issued U.S. patents and 30 U.S. patent applications. She holds an M.S. from the Indian Institute of Technology in Kanpur, India, and a Ph.D. from Southern Illinois University. Dr. Pandey completed her postdoctoral fellowship in bioorganic chemistry at SRI International (formerly Stanford Research Institute).

Background*

Dr. Anjali Pandey, Ph.D. has been Senior Vice President of Medicinal Chemistry & Chemical Development at Portola Pharmaceuticals, Inc. since August 5, 2015. Dr. Pandey served as a Vice President of Chemistry at Portola Pharmaceuticals, Inc since April 2006 until August 5, 2015. Dr. Pandey served as Vice President of Medical Chemistry at Portola Pharmaceuticals, Inc. Ms. Pandey joined Portola in 2003. Ms. Pandey served as the Director of Chemistry at Millennium. She also served with COR, working in the area of oral GP IIb-IIIa antagonists, Receptor Tyrosine Kinase inhibitors and ADP receptor antagonists. She served as Director of Chemistry at COR Therapeutics. She served as Organic Chemist at Stanford Research Institute, where she was a Principal Investigator on grant funded from National Cancer Institute. Her efforts along with her team resulted in three drugs that are currently in clinical trials, one for leukemia and two for cardiovascular indications. Ms. Pandey has published over 20 scientific articles and reviews and is a named inventor on over 15 issued U.S. patents. Ms. Pandey holds an M.S. from Indian Institute of Technology, Kanpur, India and a Ph.D. from Southern Illinois University. She completed a Postdoctoral Fellowship in Organic Chemistry at the Stanford Research Institute.

links https://www.linkedin.com/in/anjali-pandey-587b9a

Experience

Senior Vice President, Medicinal Chemistry & Chemical Development

Portola Pharmaceuticals, Inc

July 2015 – Present (1 year 6 months)South San Francisco, CA

Twenty years of biopharmaceutical industry experience with in-depth involvement in all stages of drug discovery and development, from initial lead identification to Phase III clinical trials. Led multiple programs from initiation through first-in-man studies, made significant contributions to research activities related to lead identification, optimization, and selection of clinical candidates. Demonstrated strong scientific leadership, insights, know-how, and creativity in medicinal chemistry programs. Extensive experience in providing overall leadership to process research and development, outsourcing and discovery collaborations. Demonstrated ability to successfully deliver on discovery to manufacturing projects, partnering with global contract manufacturing organizations for API and Drug Product. Well versed in cGMP and CMC. Supervised the development and management of Portola’s intellectual property portfolio. Provided leadership role in IP due diligence analysis associated with S-1 filing for the IPO, subsequent offering and partnering discussions. As head of the department and member of the management team, have significant experience in in-house decision making and corporate partner interactions.

Senior Director, Medicinal Chemistry

Portola Pharmaceuticals, Inc

November 2003 – March 2006 (2 years 5 months)

-Played a leading role in discovery and development of an orally bioavailable, reversible and potent P2Y12 receptor antagonist, Elinogrel (Phase II Clinical Trial completed, Partnered with Novartis)
-Responsible and supported the development of Factor Xa inhibitor.betrixaban (Phase II SPAF trial completed)
•Managed and directed the medicinal chemistry efforts towards identification and characterization of structurally distinct orally bioavailable and once a day backup Factor Xa inhibitor.
•Principal inventor and key contributor in the discovery and preclinical development of a once a day, orally bioavailable and potent Flt-3 (receptor tyrosine kinase inhibitor), Tandutinib (MLN518) in Phase II for Acute Myelogenous Leukemia (AML).
•Key inventor of orally bioavailable platelet derived growth factor receptor antagonist, MLN608 (Preclinical).
•Played a key role in discovery and development of 2nd Generation Oral GPIIb-IIIa antagonist clinical candidate CT51464 (on hold) with better pharmacokinetics properties (F% & T1/2) than other inhibitors in clinical trials.

Director, Chemistry

COR Therapeutics/Millennium Pharm

2001 – 2003 (2 years)

Director, Chemistry

Millennium Pharmaceuticals/COR Therapeutics, Inc

2000 – 2003 (3 years)

Director, Chemistry

COR Therapeutics, Inc/Millenium Pharmaceuticals

2000 – 2003 (3 years)

Director, Chemistry

Millennium Pharmaceuticals

1999 – 2003 (4 years)

Director

Cor Therapeutics

1994 – 2002 (8 years)

Director

COR Therapeutics/Millenium SF

1994 – 2001 (7 years)

Chemist

SRI International

1989 – 1994 (5 years)

Organic Chemist

SRI Internatinal (Formerly Stanford Research Institute)

1990 – 1993 (3 years)

Masters in Chemistry

IIT Kanpur

1980 – 1984 (4 years)

Education

Southern Illinois University, Carbondale

Ph.D., Synthetic Organic Chemistry

1984 – 1989

Indian Institute of Technology, Kanpur

Master of Science, Chemistry

a clip

AML FIGHTERPandey, shown in her lab at Millennium, helped develop an acute myelogenous leukemia agent.MILLENNIUM PHARMACEUTICALS PHOTO

Anjali Pandey, director of cardiovascular chemistry at Millennium Pharmaceuticals, South San Francisco, reported on CT53518 (also known as MLN518), a potent, orally available inhibitor of the enzyme FLT-3. The drug is a potential therapy for acute myelogenous leukemia (AML), a form of cancer in which abnormal white blood cells accumulate in the blood and bone marrow, resulting in hemorrhage, fatigue, and other symptoms.

FLT-3 is a receptor tyrosine kinase (a tyrosine kinase found in cell membranes) and a member of the platelet-derived growth factor receptor (PDGFR) family of enzymes. These cell-signaling enzymes have been implicated in a variety of cancers and other diseases and are a major focus of current drug discovery efforts.

"Kinase inhibition represents a novel mechanism-based approach to selectively block cell-signaling pathways," Pandey said. "This strategy has been validated recently by the introduction of the Bcr-Abl kinase inhibitor Gleevec for chronic myeloid leukemia" (CML). Gleevec is a Novartis drug that prevents activation of Bcr-Abl, the abnormal nonreceptor tyrosine kinase that causes CML.

More than one-quarter of AML patients have internal duplications in FLT-3 that cause the enzyme to be activated inappropriately and that are associated with significant increases in relapse and mortality rates. Inhibiting FLT-3 could help ameliorate AML symptoms in such patients.

Pandey and coworkers at Millennium began their project by identifying a quinazoline class of compounds as leads for FLT-3 inhibitors in a high-throughput screening procedure. Pandey noted that, in the past, the quinazolines have been a prolific source of tyrosine kinase inhibitors, such as ZD1839 (Iressa) and OSI-774 (Tarceva), which are in Phase III and Phase II clinical trials for cancer, respectively. ZD1839 is an AstraZeneca drug; OSI-774 is being codeveloped by OSI Pharmaceuticals, Genentech, and Roche.

The original quinazolines identified by Pandey and coworkers had instability, potency, and aqueous solubility problems. So the researchers synthesized a range of variants, analyzed SAR data on these compounds, and further modified their structures to zero in on agents with optimal in vitro potency and physicochemical properties. They narrowed the field to four compounds, tested them in animals, and chose CT53518 (MLN518) as a clinical candidate for further characterization.

The group found that the drug delayed disease progression in a mouse model of FLT-3-associated AML and caused apoptosis (cell death) in a human AML cell line. "We have done 28-day toxicological tests in rat and dog, and it looks pretty good," Pandey said--except for some slight suppression of bone marrow, which she and her coworkers had expected. "Phase I clinical trials in AML patients have been initiated," she said, "and we are very hopeful" that results will continue to be favorable.