Subject: bioavailability/summary of antivirals

From: [email-masked] (Marty Gallagher)
Date: Mon, 16 Oct 95 15:06:41 -0700

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Hello,

       I am interested in obtaining a list of pharmaceuticals that have an
especially low oral bioavailability.  Does anyone know where such a list
has been published?

        On an unrelated note, last week I asked the CCL subscribers for
pointers to good review articles that outline current questions concerning
the development of antivirals.  Since then, I received many excellent
responses.  Thanks to all those who replied!  I've summarized the responses
below for those who are interested.

                                        Thanks again,

                                        Marty Gallagher

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SUMMARY OF REVIEWS ON ANTIVIRAL DEVELOPMENT  --- Thanks to all those who
responded!

[email-masked] (Catherine Patterson):

There is a three volume set of books by Fields on _Virology_.  One of the
chapters is specifically titled "Antivirals".  I think it references
clincally used as well as drugs used in research.

From: [email-masked] Kent Stewart
Marty:  Every year the American Chemistry Society Division
of Medicinal Chemistry publishes a volume of  Annual Reports
in Medicinal Chemistry.  I would expect that any research library
would have the set of volumes.  The nice thing about the indexing
is that it is cummulative.  Thus you can easily pull off the
latest volume and search antiviral, antiinfective, antibacterial,
etc. and within minutes get a "cutting edge" review from
experts in the field.  This is always a good place to start
when starting a new field within medicinal chemistry.  In
your case, there are several nice reviews of anti-viral agents
in the last few years.

Saul Wolfe <[email-masked]>

Please take a look at Can. J. Chem. 66, 2687-2762 (1988) (5 papers),
Can. J. Chem. 72, 1014-1075 (1994) (5 papers) and JACS 117, 4240 (1995).
The JACS paper is the tip of an iceberg.

Ronald D Ferguson <[email-masked]>

Have you ever considered using a combinatorial chemical approach. You
could either use synthetic techniques or Phage CombiChem approaches.
Another news group which I review discusses these topics and
I'm sure that you would find some insight into your research topic. The
address is given below. If you want, in a few days I could scan my
literature articles for a viral application and return the results.
Unfortunately, I won't have time until the weekend.
Combinatorial Chemical News Group:  bionet.molecules.repertoires

[email-masked] (Adi Treasurywala)

        Some time ago I was involved with a project to do some structure based
 drug design on agents against the common cold virus (Rhinoviruses). I found
that to be an EXCELLENT challenge. Many questions remain unanswered about the
details of the reproductive cycle of these viruses although an ENORMOUS amount
(including several good X-ray structures of the intact virions) is known.
Behind each one of these unknowns IMHO lies a potential drug design target
and a potential for the greater understanding about these fascinating entities.
        I have published some papers in this area but the principles are Guy
Diana, and Michael Rossmann.

 Walter Hoeksma <[email-masked]>

Although somewhat dated you might try looking at the review
ANTIVIRAL THERAPY:CURRENT CONCEPTS AND PRACTICES by Bonnie Bean
This review is in CLINICAL MICROBIOLOGY REVIEWS April 1992 vol 5 no 2
pages146-182

Wayne Steinmetz <[email-masked]>

1) The following review article outlines the development of inhibitors to HIV
protease.  Leads from that project are in Phase II clinical trials.

J. Greer, J. W. Erickson, J. J. Baldwin, and M. D. Varney, "Application of the
Three-Dimensional Structures of Protein Target Molecules in Structure-Based
Drug Design", J. Med. Chem., Vol. 37, 1035-1054 (1994).

2) Vol. 203 in Methods of Enzymology is dedicated to molecular design and
modeling and has a number of useful articles.

Have you considered spending a postdoc in industry?  I spent my third
sabbatical leave at Abbott Labs and greatly benefited from the year there.

 [email-masked]

A supplement of the journal Antiviral Chemistry and Chemotherapy covered
most of
the current issues in antiviral chemotherapy. The issue is: #6, Supplement 1.
One of the papers was: In search of the perfect antiiral, by G. Darby (p54-63).

=========================================================================
Martin J. Gallagher             phone:  (617) 432-1729
Dept. of Neurobiology           fax:    (617) 734-7557
Harvard Medical School          E-mail: [email-masked]
220 Longwood Ave                http://ionchannel.med.harvard.edu/~marty
Boston, MA  02115

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