ULHAS BHATT, Ph.D.

Phone: 408-***-****; Email: x4fest@r.postjobfree.com

web: http://www.linkedin.com/in/ulhasbhatt

Profile

An experienced team leader with more than 9 years of comprehensive, hands-on expertise in drug discovery and development. Executed high quality projects for external customers in the CRO domain. Proficient in hit-to-lead optimization and scale-up. Excellent communication and people skills. Permanent Resident of USA.

Employment and Education

2001 – current AMRI, Albany, NY, USA

1999 – 2001 Postdoc, University of Hannover, Hannover, GERMANY

1994 – 1999 Ph.D. McGill University, Montreal, CANADA

Accomplishments

Senior Research Scientist, Albany Molecular Research, Inc, Albany, NY,USA 2001-present

Skilled in planning and executing synthetic organic chemistry reactions

Synthesized target molecules for clients in medicinal and process chemistry projects

Conducted extensive SAR on lead compound – 2 compounds moved to preclinical stage

Evaluated targets for initiating new internal drug discovery programs

Expertise in chromatography, NMR, LCMS, microwave and analytical techniques

2 publications. 1 Chapter in a reference book

Group Leader at AMRI Hyderabad, India 2007-2010

3 year experience in Project Management at AMRI Hyderabad, India

43 projects worth >$2M successfully completed at AMRHRC- Med-Chem and Scale-Up

Supervised a team of 12-18 scientists in AMRI Hyderabad - both Ph.D. and M.Sc. level

Communicated project progress to AMRI Management

Engaged in Business Development – Attracted new clients to initiate their projects

Postdoc - Prof. Markus Kalesse, University of Hannover, Germany 1999-2001

Extensive experience in a variety of organic chemistry reactions

Completed the total synthesis of polyketide natural product ratjadone

Prepared 4 separate diastereoisomers to assign the absolute stereochemistry

Synthesized 5 ratjadone analogs in SAR study to determine key functional groups

Utilized chromatography, NMR, and analytical techniques to establish identity and purity

5 publications. 1 patent

Ph.D. - Prof. George Just, McGill University, Montreal, Canada 1994-1999

Synthesized oxopiperazine derivatives from amino acids as novel peptidomimetics

Prepared oxopiperazine analogs of a naturally occurring peptide TRH

Established protocols for solid phase synthesis of oxopiperazines

Extensive exposure to protection and deprotection techniques in peptide chemistry

3 publications.

Publications and Citations

2010 Tetrazoles in Modern Heterocyclic Chemistry Ed J. Barluenga; Wiley-VCH

2007 Synthetic Communications 37, 2793-2806 (Cited 2 times)

2005 British Journal of Pharmacology 146, 89-97 (Cited 5 times)

2004 Organic Letters 6, 3889-3892 (Cited 22 times)

2002 Patent DE 10106647 and WO 02064587

2001 ChemBioChem 2, 709-714 (Cited 13 times)

2001 Journal of Organic Chemistry 66, 1885-1893 (Cited 50 times)

2001 Tetrahedron Letters 42, 1269-1271 (Cited 18 times)

2000 Angewandte Chemie, Int. Ed. 39, 4364-4366 (Cited 47 times)

2000 Helvetica Chimica Acta, 83, 722-727 (Cited 10 times)

1998 Tetrahedron Letters 39, 8213-8216 (Cited 28 times)

1997 Tetrahedron Letters, 28, 2679-2682 (Cited 37 times)

Summary of research

Projects at Albany Molecular Research, Inc. Albany, NY

(Medicinal Chemistry Department Contract Research – Feb 2010 to current)

Project # 1: A client requested the synthesis of several scaffolds in 50 g amounts. I completed the synthesis of 1 target in 3 weeks and then worked on route-scouting for 3 other targets.

Project # 2: A client requested the synthesis of several targets in 100 mg quantities. I completed the synthesis of 8 out of the 10 targets assigned to me.

Project # 3: A client has requested the synthesis of 5 targets which is in progress.

Projects at AMRI Hyderabad Research Center, Hyderabad, India

(Chemical Development Group – Feb 2008 – Jan 2010)

FTE Medicinal Chemistry Project – 16 + months

A client initiated a FTE program that for the synthesis of scaffolds for their medicinal chemistry groups. It involved the preparation of small heterocyclic cores with varied substituents. I managed my group’s day-to-day work and aligned their activities with medium-term project goals. Our group shipped over 150 targets ranging from 10 mg to over 10 g. It involved extensive coordination with project managers from the customer’s end with continuous reporting to AMRI management.

Multi-KG synthesis of AMRI Catalog compound

A client requested 80 kg of one compound from AMRI Catalog. My team optimized the synthesis of the target at 1 kg scale and then scaled up the synthesis to run at 20 kg batches. The target was prepared in multiple batches and we ensured that appropriate quality controls were achieved.

Synthesis of marker compounds

A client requested the synthesis of 60 marker compounds in 20-100 mg quantities. The structural features present in these marker compounds varied greatly and most targets required individual synthesis. Managed a team of 10 scientists to ensure timely completion of the project.

Synthesis of metabolites of a drug candidate

A client requested the synthesis of the metabolites of a drug candidate in multi-gram quantities from the drug molecule. The oxidative metabolites were prepared synthetically and then underwent a difficult purification procedure. 1 target was prepared in >98% purity while the second was prepared in 95% purity.

Synthesis of novel molecules in multi gram scale

A client requested the synthesis of a compound with a unique structure with almost no literature precedent. My team came up with robust route to prepare the parent molecule and its analogs in multi gram scale.

Synthesis of known compounds

A client requested the synthesis of two known compounds from patent literature. My team prepared both these targets after ~ 15 steps in > 5g quantities. The final products were >99% pure.

A client requested the synthesis of 5 target molecules whose analogs were known in the patent literature. Using the same procedures, my team was able to prepare 4 out of these 5 targets in >20 g each with >97% purity.

Synthesis of AMRI Catalog Compounds

AMRI offers a large number of interesting compounds through its catalog. My team was involved in the synthesis of over 100 compounds over a 2 year period in amounts ranging from < 1 g to multi kg.

Overall, I handled 43 projects from 16 customers worth over $2M in 2 years.

Projects at AMRI, Albany, NY

(Chemical Development – Aug 2007 to Jan 2008)

Synthesis of a specific prostaglandin: Process Development and Scale Up

A client requested the synthesis of a specific prostaglandin in kg quantities. Literature syntheses were reported in mg quantities. As part of a group effort, various approaches were evaluated and the final product was prepared in gram quantities. I was involved in optimization of several key steps and then followed that up with scale up. Eventually, our team prepared 1.1 kg of the final product.

Projects at AMRI Hyderabad Research Center, Hyderabad, India

(Chemical Development Group – April to Aug 2007)

Fixed Fee preparation of both enantiomers of a target molecule

A client requested the synthesis both enantiomers of a target molecule. The procedure supplied by the customer involved a difficult separation of diastreoisomers. My group came up with a new and simplified 4-step asymmetric synthesis of both enantiomers and finished the project in 2 weeks to customer’s satisfaction.

Synthesis of new target compounds for the AMRI catalog

AMRI offers a large number of interesting and hard-to-get compounds through its commercial catalog. My team was given the task of coming up with new proposals for additional catalog compounds. In 2 months, we shipped 15 new targets.

Projects at AMRI, Albany, NY

(Internal Research & Development – Jan 2004 to April 2007)

Tetrahydroisoquinolines as novel reuptake inhibitors for treatment of depression

Depression is characterized by decreased levels of biogenic amines – serotonin, norepinephrine and dopamine in the synapse. The synaptic levels of these biogenic amines can be increased by blocking their reuptake by their respective transporters. Current therapies for treatment of depression rely on increasing the synaptic levels of serotonin and norepinephrine only. It is our belief that modulating dopamine levels in addition to serotonin and norepinephrine would result in a better antidepressant. At AMRI, functionalized tetrahydroisoquinolines were found to be novel reuptake inhibitors that modulated the levels of all three biogenic amines and a program was initiated to develop these compounds into a unique antidepressant.

Synthesized tetrahydroquinolines to establish basic binding affinity requirements.

Attached various aryl and heteroaryl groups to improve activity and overcome off-target interference.

Fine-tuned these structures to establish good pharmacokinetics in animal models.

Optimized and scaled up the synthesis of candidate to multiple hundred grams.

Learnt medicinal chemistry, data management, SAR analysis & compound selection.

Spirocyclic amine scaffolds and generation of small, focused compound libraries

Phenethyl amines are found to be pharmacologically useful in the treatment of various CNS disorders. In order to discover new compounds from this class of molecules, we designed several scaffolds that incorporated a spirocycle as a key structural feature to control spatial conformation. These scaffolds were then used to build small but focused libraries in screening for internal AMRI projects.

Designed and synthesized novel scaffold incorporating spirocyclic phenethylamine

Prepared small but focused libraries in collaboration with combinatorial chemistry.

Elaborated the initial hit from these scaffolds into a new series in BAM project.

Identified key structural features in spirocyclic scaffold for BAM reuptake inhibition.

Target evaluation for new internal projects at AMRI

The R&D division of AMRI initiated a program to identify biological targets for which future medicinal chemistry projects. These covered metabolic diseases and CNS disorders. The evaluation criterion included medical need, basic biological validity, in vitro and in vivo assays, confirmatory animal models, intellectual property restrictions and competitive landscape.

Evaluated ghrelin antagonism for obesity, melanocortin hormone for obesity, glucagons-like-peptide modulation for diabetes, and glycine transport inhibition for schizophrenia.

Two targets carried forward to pre-project levels. Involved in preliminary project initiation.

One full-fledged project in progress with 3 full time chemists.

Scale-up of existing AMRI anti-cancer compounds

Scale-up synthesis of AMRI anti-cancer compounds to gram quantities.

(Medicinal Chemistry Department Contract Research – Nov 2001 to Dec 2003)

Novel pyrrole-derived heterocyclics as cannaboid receptor antagonists

A customer initiated a project at AMRI where pyrroles-derived heterocyclic compounds were required for evaluation as cannaboid receptor antagonists. Several known CB1 antagonists were also prepared in the project.

New route of synthesis of pyrroles developed to encompass the structural diversity requested by the customer.

One new scaffold suggested to customer and then prepared upon their acceptance.

Manuscript detailing novel chemistry efforts published in Synth. Commun.

Novel fluorine and phosphorus containing amino acids

A customer project required the synthesis of amino acids with phosponic acid and fluorine atom attachments. Several such small molecules were prepared, one of which made it to animal toxicity studies.

Synthesis of fluorinated phosphonic amino acids carried out.

Scale up of selected candidate molecule carried out to multiple grams.

Manuscript describing detailed animal studies published by the customer in Brit. J. Pharmacology.

Projects at University of Hannover, Germany (Postdoctoral research Sept 1999 to Oct 2001)

Chemistry and biology of ratjadone

Ratjadone is a natural product that exhibited interesting anti-cancer and anti-fungal properties. Its interesting structural features and low availability from natural sources led us to embark on its total synthesis. Our group initiated the total synthesis of ratjadone with a goal of not only establishing the correct absolute stereochemistry of the 7 chiral centers of ratjadone, but also provide samples for additional biological evaluation. Our research went beyond just the synthesis of the natural product – we wanted to synthesize a variety of ratjadone analogs that would enable us to critically evaluate the various subgroups and functionalities responsible for its biological activities.

A highly divergent, efficient and elegant synthesis of ratjadone carried out.

Vinylogous Mukaiyama and Evan’s aldol reactions, Wittig, Heck and Diels-Alder reactions key steps.

Small library of ratjadone diastereoisomers prepared

Biological profiling of ratjadone and its analogs carried out.

Key structural requirement for biological activity and initial SAR established.

Manuscripts published in Angew Chemie Int Ed, J. Org. Chem., Tetrahedron Lett. and ChemBioChem.

Towards the total synthesis of hexacyclinic acid

Hexacyclinc acid is a novel polyketide derived natural product with a unique structure that exhibits promising anti-cancer activities comparable to that shown by Taxol. Its structural complexity and potential medical applications led us to undertake the total synthesis.

Retrosynthetic analysis and initial synthetic route established for this complex natural product.

Prepared model substrate to demonstrate feasibility of intramolecular Diels-Alder reaction.

Synthesized the AB ring system with correct stereochemistry.

Manuscript published in Organic Letters.

Projects at McGill University, Canada (Doctoral research Fall 1994 to Summer 1999)

Functionalized 2-oxopiperazines from amino acids

The goal of our research was the synthesis of functionalized 2-oxopiperazines from amino acids. Our studies included the synthesis of these peptidomimetic compounds in both solution and solid phase in order to unravel the biological activities of this class of compounds. We developed four synthetic routes starting from amino acids to generate these ethylene-bridged compounds.

4 synthetic routes from amino acids developed for ethylene-bridged dipeptides.

N-allylation, alkene oxidation, sulfonamide alkylation, Mitsunobu key steps.

Solid phase synthesis of 2-oxopiperazine derivatives carried out.

Synthesis of two new analogs of Thyrotropin Releasing Hormone (TRH) incorporating the 2-oxopiperazine-ring-system also achieved.

Manuscripts published in Tetrahedron Letters and Helvetica Chimica Acta.

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