Subject: 97.04.28-29 Solid And Solution Phase Combinatorial Synthesis

From: Jan Labanowski <[email-masked]>
Date: Wed, 19 Feb 1997 14:45:45 -0500 (EST)

Solid And Solution Phase Combinatorial Synthesis

An In-Depth, Comparative Evaluation of Both Solid And Solution Phase Techniques

Small Molecule Synthesis Of Mixtures & Solid Compounds
Encoding & Deconvoluting & Screening Methods
Small Molecule Synthesis of Single Compounds
Compound Characterization & Analysis
Assaying Purity & Structural Identity
Automated Synthesis
Synthesis & Post-Synthesis Informatics
Automated Purification Methods
Reagent Preparation & Sample Processing
Sample Registration, Tracking & Structure Retrieval

April 28-29, 1997
The Crowne Plaza, New Orleans
New Orleans, LA

[Attend The Annual "Jazz in Heritage Festival", April 24-27 Register Early!]

Program
=======

Monday, April 28, 1997

7:45 Registration and Continental Breakfast

8:40 Chair's Opening Remarks
     Applications Of Solid And Solution Phase Combinatorial Synthesis
     In Drug Discovery
     David M. Floyd, Ph.D.
     Vice President of Discovery Chemistry
     BRISTOL MYERS SQUIBB

SMALL MOLECULE SYNTHESIS Of  MIXTURES

9:00 Heterocycles For Lead Generation
      -Novel structural elements
      -Variable ring size
      -Variable flexibility
      -Natural product-like with systematic synthesis
      -Solid phase synthesis; automated
     David Mendel, Ph.D.
     Senior Organic Chemist
     LILLY RESEARCH LABORATORIES

9:35  Solution Phase Combinatorial Chemistry: Discovery Of Linear And Cyclic
      Polyamines With Potent Antibacterial Activity By Solution Phase
      Simultaneous Addition Of Functionalities
       -Isis has invented a unique combinatorial chemistry composed
        of tertiary nitrogen and heterocyclic scaffolds
       -Isis builds its libraries by a proprietary "solution phase,
        simultaneous addition of functionalities (SPSAF)" approach
       -Libraries generated are of low molecular weight, diverse,
        information rich and present various levels of constraint
        (linear, cyclic, spherical shapes) 
       -Versatile synthetic methodologies allow a variety of scaffolds
        (footprints) to be rapidly prepared 
       -Extensive libraries from libraries methodologies have been developed
       -Libraries can be rapidly prepared (less than 5 days) in
        250-1000 mg. quantities
       -Methodologies to selectively target RNA motifs with cationic,
        constrained tertiary nitrogen scaffolds are in progress
       -Libraries are single compounds from linear and cyclic tertiary
        nitrogen scaffolds exhibit potent antibacterial activity 
      P. Dan Cook, Ph.D.
      Vice President of Chemistry
      ISIS PHARMACEUTICALS, INC.

10:10 Synthesis On Soluble Polymers: Liquid Phase Parallel Synthesis Of
      Chemical Libraries
       -The "Liquid Phase Parallel Synthesis" combines strategic features
        of both solid phase synthesis and solution phase synthesis
       -This method uses a supporting polymer (polyethylene glycol) that is
        soluble in the reaction media and the polymer can be precipitated
        selectively for isolation and purification purposes
       -Excess reagents and byproducts were removed by simple filtration
       -This technology allows reactions to be followed by NMR and TLC
       -The use of PEG resin as a soluble support for the synthesis of small
        organic molecules is demonstrated by the synthesis of several chemical
        libraries  
      Soan Cheng, Ph.D.
      Senior Research Chemist
      COMBICHEM, INC.

10:45 Coffee & Tea

ENCODING & DECONVOLUTION METHODS

11:10 Encoded Combinatorial Library Directed Toward The Discovery Of Aspartyl
      Protease Inhibitors
       -Design, synthesis and encoding
       -Screening against two aspartyl protease enzymes
       -Decoding of active components
      Theodore O. Johnson, Ph.D.
      Research Scientist
      PHARMACOPEIA, INC.

11:45 Synthesis And Deconvolution Methods For Mixture-Based Heterocyclic
      Combinatorial Libraries
       -The synthesis of many complex heterocycles has been achieved on
        solid phase
       -Synthesis of mixtures of these heterocycles by the "split and
        recombine" method greatly enhances the efficiency of the organic
        chemist
       -Screening libraries of heterocycles as organized mixtures is very
        efficient and does not necessitate a high-throughput assay
       -Active compounds are identified by iterative deconvolution or
        PositionalScan methods
      Michael C. Griffith, Ph.D.
      Senior Research Chemist
      HOUGHTON PHARMACEUTICALS, INC.

12:20 Luncheon For Speakers And Attendees

1:50  Radiofrequency Encoding As A Tool In The Synthesis Of Organic
      Compound Libraries: Combining The Advantages Of Parallel And
      Split-Pool Synthesis
       -Radiofrequency memory chip technology
       -Encoding orthogonal to chemical synthesis
       -Synthesis of 102-104 discrete compounds in 5-10 mg amounts
       -Automated microreactor handling using the AccusortTM split approach
      A. W. Czarnik, Ph.D.
      Senior Director, Chemistry
      IRORI QUANTUM MICROCHEMISTRY

2:25  Adventures In Screening: To Mix Or Not To Mix...Strategies And
      Experiences
       -Making and screening mixtures from single compound libraries
       -Synthesising non-encoded combinatorial mixtures for lead discovery
       -Deconvolution strategies
       -Single compound combinatorial synthesis for lead optimization
      Alex Harris, Ph.D.
      Director, Biochemical Pharmacology
      CHIRON CORPORATION
  
SMALL MOLECULE SYNTHESIS Of SINGLE COMPOUNDS

3:00  Manual And Automated Parallel Synthesis Of Individual Compounds At
      Affymax
       -Manual and automated parallel synthesis
       -Application for chemical library development
       -Drug discovery
       -Development of instrumentation for parallel synthesis
      Valery Antonenko, Ph.D.
      Senior Scientist and Group Leader, High-Throughput Parallel Organic
      Synthesis
      AFFYMAX RESEARCH INSTITUTE 

3:35  Coffee & Tea

3:55  Structure-Directed Parallel Unit Synthesis For Lead Generation &
      Optimization
      Joseph C. Hogan, Ph.D.
      Chairman and Chief Scientific Officer
      ARQULE, INC.

METHODS FOR COMPOUND CHARACTERIZATION & ANALYSIS

4:30  A Fully Automated Mass Spectrometry-Based System For The Rapid Analysis
      And Purification Of Combinatorial Libraries
       -Fast HPLC/MS analyses achieved in 5 minutes
       -Comparative performance of chromatographic supports for compound
        separations
       -Fully automated purity assessment (UV and TIC) and data processing
        using AppleScriptsTM
       -Purification based on "one-sample-one-tube" format, using mass
        spectrometer and AppleScriptingTM to trigger fraction collection 
       -Unattended "batch" purifications (i.e. 50 samples/instrument/night)
        at 10-50mg level
      Daniel B. Kassel, Ph.D.
      Director, Analytical Chemistry
      COMBICHEM, INC.

5:05  Chair's Closing Remarks Followed by Wine & Cheese Reception
 
7:30  Join your colleagues at New Orleans famous Antoine's for dinner tonight!
      The meal affords a great opportunity to unwind in a casual atmosphere
      after the first day's presentations and get to better know your fellow
      attendees.  Three courses will be offered and four wines tasted.  Price
      per person is $65, all inclusive.  Transportation will be provided to
      and from the Restaurant.  Please check the box on the back page
      registration form if you would like to join us!

Tuesday, April 29, 1997

7:45  Continental Breakfast

8:30  Chairs's Recap Of  Day One 
      David M. Floyd, Ph.D.
      BRISTOL-MYERS SQUIBB PRI

METHODS FOR COMPOUND CHARACTERIZATION & ANALYSIS (Continued)

8:40  Useful Methods To Monitor Solid Phase Reactions
       -Examples of common "wet chemical" tools
       -Analysis after cleavage from resin: pros and cons
       -Spectroscopic methods applied to compounds still attached to resin
        with a focus on IR and NMR
       -Examples and case histories of reaction monitoring
      James R. Wareing, Ph.D.
      Senior Fellow and Head of Combinatorial Chemistry
      SANDOZ, INC. 

9:15  Applications Of Capillary Electrophoresis To The Analysis Of
      Combinatorial Mixtures
       -Capillary Electrophoresis
       -Affinity capillary electrophoresis coupled to mass spectrometry
       -Electrospray ionization mass spectrometry
       -HPLC mass spectrometry
       -High resolution mass spectrometry
      Paul Vouros, Ph.D.
      Bradstreet Professor of Chemistry
      NORTHEASTERN UNIVERSITY

9:50  The Use Of Evaporative Light Scattering In Quality Control Of
      Combinatorial Libraries
      Cheryl Garr, Ph.D.
      Project Manager, Synthetic and Combinatorial Chemistry
      PANLABS, Inc.

10:25 Coffee & Tea

AUTOMATION

10:45 Applications Of Automated Synthesis In Combinatorial Chemistry
       -Strategies for automated combinatorial chemistry
       -Automation of reagent delivery
       -Automated workstation approach to synthesis
       -Development and integration of automated quality control
       -Data management and compound tracking
      Martin A. Murphy, Ph.D.
      Research Scientist III
      AMGEN, INC.

11:20 Automated Technologies For The Handling And Preparation Of Reagents
      And Formulation Reactants For Combinatorial Synthesis
       -Setup and labeling of storage containers
       -Reagent preparation and formulation
       -Inert storage and container handling
       -Liquid transfer techniques of reagents and reactants
       -Data management and spatial address in an automated system
      Brian Lightbody
      Vice President Drug Discovery Business Development
      ZYMARK CORPORATION

12:00 Luncheon For Speakers And Attendees

AUTOMATION (Continued)

1:20  New Approaches For Solid And Liquid Material Handling At Glaxo-Wellcome
       -Customizing solid sample handling
       -Automating liquid handling
       -Barcoding
       -Solid and liquid inventory systems
       -Liquid storage
       -Future enhancements
      Brenda Johnson Ray
      Supervisor of Chemical Information Services
      GLAXO WELLCOME, INC.

SYNTHESIS & POST-SYNTHESIS INFORMATICS  

1:55  Computational Adventures In The Experimental World: Pre- And
      Post-Synthesis Instrument Interface
      Edward P. Jaeger, Ph.D.
      Senior Director
      3-DIMENSIONAL PHARMACEUTICALS, INC. 

2:30  Information Management And Combinatorial Chemistry: Reagent Tracking,
      Sample Registration And Structure Retrieval
      Maurizio Bronzetti, Ph.D.
      Senior Scientist, Chemistry Solutions
      MDL INFORMATION SYSTEMS, INC.

AUTOMATED PURIFICATION METHODS

3:05 Preparative HPLC In Automated Synthesis 
       -Rapid high-throughput preparative liquid chromatography
       -Column dimensions and particle size to optimize rapid analysis without
        loss of resolution
       -Autoinjection and multiple collectors for queuing capabilities
       -User-friendly interface to widen the user base
      Marion G. Young, Ph.D.
      Senior Research Scientist
      BRISTOL-MYERS SQUIBB PRI

3:40  Automated Parallel Purification Methods

      The generation of high quality products from combinatorial chemistry
      programs requires high-throughput methods for post-synthetic operations
      including workup, isolation, purification, and analysis.  The following
      tools have been integrated in our laboratories to provide methods for
      workup, isolation, and purification:
       -Parallel processing
       -Robotic automation
       -Phase separation technology for liquid-liquid extraction
       -Solid phase extraction for product purification
      Sheila H. DeWitt, Ph.D.
      Vice President, Technical Development
      DIVERSOMERR TECHNOLOGIES, INC. & PARKE-DAVIS PHARMACEUTICAL
      RESEARCH

4:15 Chair's Closing Remarks
 
WHO SHOULD ATTEND
Pharmaceutical, Biotech and Academic Research Chemists:

-Medicinal Chemists
-Organic Chemists
-Synthetic Chemists
-Structural Chemists
-Licensing

PAYMENTS:  The conference registration fee is $995.  This includes all
      breakfasts, lunches, refreshments, receptions and the conference
      documentation workbook.  Payments may be made by company check,
      American Express, Visa, MasterCard or Diner's Club.  Please make checks
      payable to Strategic Research Institute, L.P. and be sure to write the
      registrant's name on the face of the check along with the conference
      code CS110.  PAYMENTS MUST BE RECEIVED TEN (10) BUSINESS DAYS PRIOR TO
       THE CONFERENCE.

Discounts:

Advance Registration Drawing: Register by February 3 and your name will be
entered into a drawing for a complementary pass to attend the Conference

Academic Discount: The conference registration fee for full-time academic
and government is $695

Poster Session  We encourage attendees to display scientific work during
the conference;  please contact Mark Alexay at 800-599-4950, extention 251.
Poster board dimensions are 6' X 4'.  Registration fees are as stipulated
above.  You may submit an abstract for inclusion in the documentation book
until April 1, 1997.  The session will be limited to 10 posters. 

Hotel Accommodations:  We have reserved a limited block of rooms with the
hotel at a special discounted rate for our attendees.  To secure your
accommodations, please contact the hotel at least four weeks in advance
and specify that  you are a Strategic Research Institute conference
attendee.  The "rack" room rate at the Crown Plaza during the "Jazz
In Heritage Festival" is $226.95.   The SRI discounted rate is $135.
PLEASE BOOK YOUR ROOM BEFORE FEBRUARY 28 TO BE ASSURED OF ROOM AVAILABILITY
AT THIS RATE
   
Venue:
The Crowne Plaza, New Orleans
333 Powdras St.
New Orleans, LA 70130
ph: 504-525-9444
fax: 504-581-7179

Travel Discounts:  To take advantage of preferred airfares, please call the
Business Travel Buying Group reservations center at 1-800-327-8728 and
identify yourself as a Strategic Research Institute attendee/speaker.

Cancellations: All cancellations will be subject to a $227 administration fee.
n order to receive a prompt refund, your notice of cancellation must be
received in writing (by letter or fax) five (5) business days prior to the
conference.  We regret refunds will not be issued after this date. The
registration may be transferred to you or another member of your organization
for any Strategic Research Institute conference during the next twelve months.
If you plan to send a substitute in your place, please notify us as soon as
possible so that materials and preparations can be made. 
In the event of a conference cancellation, Strategic Research Institute
assumes no liability for non-refundable transportation costs, hotel
accommodations or additional costs incurred by registrants.

Dear Colleague:

I hope you will be able to join us for an exciting and informative conference
on Solid & Solution Phase Combinatorial Synthesis in New Orleans, LA
on April 28-29, 1997.

This is a "nuts & bolts", interdisciplinary meeting organized to provide
the pharmaceutical chemist an in-depth analysis of  both  solid and solution
phase methods and techniques for the synthesis, analysis and evaluation of
combinatorial libraries.  The conference is designed to enable you to do
a side-by-side comparison of a variety of combinatorial techniques currently
utlized for drug discovery and to explore some of the emerging techniques in
this rapidly evolving field.

Each section is carefully designed to take you through the steps involved
in automated high-throughput synthesis and to highlight the challenges 
that are yet to be overcome.  The meeting is set up to maximize your
opportunity to compare and contrast the relative merits of the  available
methods in terms of your own research needs. 

Some of the highlights include:

-Small Molecule Synthesis of Mixtures
-Encoding and Deconvolution Methods
-Small Molecule Synthesis of Single Compounds
-Methods for Compound Characterization And Analysis
-Automation
-Synthesis And Post-Synthesis Informatics
-Automated Purification Methods

You are also cordially invited to attend the optional wine-tasting dinner
at New Orleans famous Antoine's Restaurant  on April 28 after the first
day's presentations.  The dinner is organized to promote greater after
hours social interaction among participants in a casual atmosphere - it
should be a lot of fun!  Please register by March 21 as the private
dining room will have limited capacity.    

To reserve your place at the conference, please complete the registration
form on the back of the brochure and fax it to the sponsor, Strategic
Research Institute, at 212-302-9850.  You may also register by phone
at 800-599-4950 (212-302-1800 outside the USA), by E-mail at
[email-masked] or send the form to: SRI, 500 Fifth Ave., 11th floor,
New York, NY. 10110.

I look forward to meeting you, or seeing you again, on April 28.
 
Sincerely,
David M. Floyd, Ph.D.
Vice President of Discovery Chemistry
Bristol-Myers Squibb PRI

Conference Chairman

David M. Floyd, Ph.D.
Bristol-Myers Squibb PRI

Conference Faculty

Daniel B. Kassel, Ph.D.
CombiChem, Inc.

David Mendel, Ph.D.
Lilly Research Laboratories

Joseph C. Hogan, Jr.
ArQule, Inc.

Valery Antonenko, Ph.D.
Affymax Research Institute

Theodore O. Johnson, Ph.D.
Pharmacopeia, Inc.

Marian G. Young, Ph.D.
Bristol-Myers Squibb PRI

Cheryl Garr, Ph.D.
Panlabs, Inc.

A. W. Czarnik, Ph.D.
IRORI Quantum Microchemistry

Sheila H. DeWitt, Ph.D.
DIVERSOMERR & Parke-Davis Pharmaceutical Research

Martin A. Murphy, Ph.D.
Amgen, Inc.

Alex Harris, Ph.D.
Chiron Corporation

Brian G. Lightbody
Zymark Corporation

Brenda Johnson Ray
Glaxo Wellcome, Inc.

Edward P. Jaeger, Ph.D.
3-Dimensional Pharmaceuticals, Inc.

Paul Vouros, Ph.D.
Northeastern University

James Wareing, Ph.D.
Sandoz

Maurizio Bronzetti, Ph.D.
MDL Information Systems, Inc.

Michael C. Griffith, Ph.D.
Houghton Pharmaceuticals, Inc.

P. Dan Cook, Ph.D.
Isis Pharmaceuticals, Inc.

Soan Cheng, Ph.D.
CombiChem, Inc.