ULHAS BHATT, Ph.D.

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

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 SAR and

hit-to-lead optimization. Excellent communication and people skills.

Permanent Resident of USA.

Employment and Education

2001 - current AMRI (Albany, NY, USA & Hyderabad, INDIA)

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

. Synthesized target molecules for clients in medicinal chemistry

projects

. Developed new lead and conducted extensive SAR in internal project

. Expanded the scope of existing lead compound to advance to ECN

status

. Evaluated targets for initiating new internal drug discovery

programs

. Designed & synthesized new scaffolds for internal focused libraries

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

techniques

. 2 publications. 1 Chapter in a reference book

Group Leader, AMRI - Hyderabad Research Center, Hyderabad, INDIA

2007-2010

. 3 years' experience in Project Management at AMRI Hyderabad, INDIA

. 43 projects worth >$2M successfully completed - Med-Chem and Scale-

Up

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

. In charge for lab safety policies and implementation

. Recruited over 30 scientists - MS level to Group Leaders

. Purchased laboratory instrumentation for a new lab - 50 hoods

. Key member of Business Development Team

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

1999-2001

Completed the total synthesis of polyketide natural product ratjadone.

Prepared 4 separate diastereoisomers to assign the absolute

stereochemistry. Synthesized 5 ratjadone analogs in SAR studies to find

functional groups essential for biological activity. 5 publications and 1

patent.

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

1994-1999

Synthesized oxopiperazine derivatives from amino acids as novel

peptidomimetics. Optimized the process to prepare oxopiperazines on solid

support. Prepared oxopiperazine analogs of a naturally occurring peptide

Thyrotropin Releasing Hormone. 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 AMRI Hyderabad Research Center, Hyderabad, India

(Chemical Development Group - 2007 - 2010)

FTE Medicinal Chemistry Project - 16 + months

A client initiated a FTE program 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.

Overall, my group prepared over 200 targets in 100 mg - 20 g quantities.

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 the final shipped material met their analytical

specifications.

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 > 5 g

quantities. The final products were >99% pure.

A client requested the synthesis of 5 target molecules (20 g each) 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.

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 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 3 year

period in amounts ranging from < 1 g to multi kg.

Overall, I managed 43 projects from 16 customers worth over $2M in 3

years.

Projects at AMRI, Albany, NY

(Chemical Development - 2007)

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.

. Studied various approaches to the synthesis of the final product.

. Optimized 2 key procedures in its synthesis.

. Involved in scale up of the final product

.

(Internal Research & Development - 2004 to 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 tetrahydroisoquinolines 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 - 2001 to 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 phosphonic

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 was

carried out.

. Vinylogous Mukaiyama and Evan's aldol reactions, Wittig, Heck and

Diels-Alder reactions.

. Small library of ratjadone diastereoisomers prepared

. Key structural requirement for biological activity and initial SAR

established.

. Manuscripts published in Angew Chemie, J. Org. Chem., Tetrahedron

Letters 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 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.

. 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 achieved.

. Manuscripts published in Tetrahedron Letters and Helvetica Chimica

Acta.

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