Vol. 24, No. 5
Chemistry in IUPAC
Accomplishments During the Past Decade and Relationships
chemistry is a key discipline vitally important to the pharmaceutical
industry. Medicinal chemists are involved in new drug discovery and
solving the problem of designing molecules to optimize their biological
properties. In the past decade the Medicinal Chemistry Section of IUPAC
has been very active, meeting twice yearly and providing a forum for
the exchange of knowledge and views among medicinal chemists from different
countries who are in academia and the pharmaceutical industry. This
cross fertilization of ideas has been stimulating and invaluable to
the chemists involved and has without doubt benefited the wider community
of medicinal chemists. For the industrially advanced countries these
meetings have provided useful information sources and improved understanding
of the subject. For the less industrialized countries they have helped
further the establishment of medicinal chemistry in their respective
output of the Medicinal Chemistry Section is seen in the publication
of books and articles, the organization of international meetings and
educational schools, the presentation of lectures, and in the formation
of the Asian Federation of Medicinal Chemistry (AFMC), as detailed below.
Training of Medicinal Chemists
Guidelines for Natural Product Collaborations
Formation of the Asian Federation of Medicinal
Future Representation of Medicinal Chemistry in IUPAC
important books have been published by the Medicinal Chemistry Section.
Medicinal Chemistry for the 21st Century,1 published
in 1992, forms part of the IUPAC series "Chemistry for the 21st
Century Monographs" and contains 24 chapters by eminent scientists
from industry and academia. It is organized into four parts: new lead
discovery, protein structure-function relationships, pharmacophore studies,
and bioavailability manipulations. It contains many thought-provoking
suggestions about the future of drug discovery.
recently, Drug Metabolism: Databases and High Throughput Testing During
Drug Design and Development was published.2 It deals
with the issue of predicting the likely metabolic transformations of
candidate drugs, a critical problem for pharmaceutical companies engaged
in the development of new medicines. Knowledge of likely metabolism
is valuable for prediction of the likely half-life of drug duration
and for assessing potential side effects that may have adverse toxicological
consequences. What then is predictable from structure-mechanism relationships?
Past experience has not been well publicized so that databases of compilations
of experimental information or predictive modelling would be very useful.
Current models are, however, of limited applicability and this book
identifies their potential uses and limitations. The book describes
how a joint project with the International Union of Pharmacology, IUPHAR,
is being conducted that aims to establish a human metabolism database
that can be accessed around the world for specific applications that
directly affect human welfare. The availability of such a searchable
database would be potentially very valuable in the design and development
of new therapeutic substances. The book also provides some case studies
by various practitioners from the pharmaceutical industry.
Section has also scored a real hit by producing this year the IUPAC
Handbook of Pharmaceutically Acceptable Salts.3 Because
many drug substances are acids or bases it is convenient to convert
them into salts to improve stability and increase water solubility.
Of course the counter ion must be suitable and non-toxic and must not
interfere with the desired biological action of the drug. This aspect
of drug presentation is of fundamental importance for drug development
and yet there is very little helpful literature for guidance. Preparation
of the optimal pharmaceutically acceptable salt form of a new drug substance
is a problem frequently faced by medicinal chemists who could greatly
benefit from a convenient, comprehensive, and authoritative source of
information concerning the full range of possibilities including the
more unusual salts. This book reviews the literature and generates a
critical compilation of information in this subject area. It is definitive
and will doubtless be the source book for the future.
of Terms Used in Medicinal Chemistry" was compiled with the aim
of providing concise definitions to those for whom the usage and meaning
may not always be clear.4a This is probably especially
helpful to chemists whose native language is not English. The glossary
was published in the Annual Report on Medicinal Chemistry,4b
which is distributed by the American Chemical Society to over 10 000
medicinal chemists, and also made available on the Web.4c
drug design is a continuously developing field which is now a very important
component in the discipline of medicinal chemistry. At the same time,
many medicinal chemists lack significant formal training in the field
and may not have a clear understanding of the terminology used. Furthermore,
there is the possibility that in different countries certain terms may
not have the same meaning, a fact that gives added value to the establishment
of a standard international definition. This led to production and publication
of a "Glossary of Terms Used in Computational Drug Design."5
chemistryinvolving the rapid synthetic assembly of structural
building blocks in various possible combinations to produce large libraries
of compounds for drug screening purposesis a rapidly expanding
field of medicinal chemistry. It is also generating a new vocabulary
to describe the various operations and components. To assist medicinal
chemists in their understanding of this field and to help with the acceptance
of a universally understood language, a "Glossary of Combinatorial
Chemistry Terms"6 was published in Pure and
Applied Chemistry and subsequently, in the Journal of Combinatorial
Chemistry. This ensures its use within the American Chemical Society
as a standard glossary of terms. Further work is focused on producing
an opinion document on the legal implications of patenting virtual libraries.
This is a very important issue which has profound implications for research
and development in the pharmaceutical industry.
glossaries of terms are being prepared, including a Glossary of Drug
Metabolism Terms, Glossary of Terms in Pharmaceutical Process Chemistry,
and Glossary of Terms in Pharmaceutical Technology.
project has been approved to publish as a book, a compilation of the
glossaries pertinent to chemistry and drug development that have been
published in Pure and Applied Chemistry during the past decade,
i.e., since 1992. See the Web site at <www.iupac.org/projects/2002/2002-001-1-700.html>.
of Medicinal Chemists
chemists are critical in the design, discovery, and synthesis of new
chemical entities in the pharmaceutical industry. Without them there
would be no successful research for new medicines. The path for chemists
to become medicinal chemists is, however, often indirect and training
is commonly "on the job." As a contribution to the discussion
about suitable formal training, the Medicinal Chemistry Section has
published between 1993 and 2001 a series of papers on this subject.
7-13 The series is based on the information received
in answers to questionnaires sent to leading pharmaceutical research
companies and universities that teach medicinal chemistry in Europe,
Japan, and the USA. The results have also been presented at international
symposia in the Netherlands (1993), Italy (1994), and Egypt (1998).
A syllabus for a short course on medicinal chemistry has also been published,14
and courses have been initiated in some Latin American countries.
for Natural Product Collaborations
in many countries throughout the world are interested in collaborating
with companies for the study and evaluation of natural products as potential
sources or leads to new medicinal agents. At the same time, there is
concernparticularly from scientists in developing countries who
typically have had little experience in this fieldregarding how
to proceed in such matters and how to handle related intellectual property
issues. The collaboration between pharmaceutical research companies
in the developed countries and natural products scientists in developing
countries is often hindered by suspicion on the part of the latter that
they are not being treated fairly. This can lead to protracted negotiations,
which may well founder because of the lack of understanding among all
concerned parties. To facilitate such collaborations, the Medicinal
Chemistry Section prepared a document of guidelines, which was published
in 1996 as IUPAC Recommendations entitled "Preservation and utilization
of natural biodiversity in context of the search for economically valuable
medicinal biota."15 This article is independent
from the Manila Declaration and Melaka Accord and describes general
topics and potential issues to be considered in a collaboration on natural
products. The Section also produced two other documents on the subject:
a technical report16 intended to help with drawing
up contracts and an article titled "Medicinal Chemistry in the
Development of Societies."17
of the Asian Federation of Medicinal Chemistry
the leadership of Dr. Naofumi Koga, the Section facilitated the formation
of the Asian Federation of Medicinal Chemistry (AFMC). An inaugural
meeting was held at the Pharmaceutical Society of Japans Nagai
Memorial Hall on 11 May 1992. The members include nine societies from
four countries: Australia (1), China (2), Japan (4) and Korea (2). The
AFMC has been very active in sponsoring symposia between countries (e.g.,
The Fourth Korea-Japan Joint Symposium on Drug Design and Development,
April 1994 in Tokushima, Japan and The First Australia-Japan Symposium
on Drug Design and Development, May 1994, Coolum, Australia). The first
AFMC Symposium on Medicinal Chemistry was held in Tokyo, September 1995
(AIMECS 95); subsequent meetings have been held in Seoul, Korea (1997),
Beijing, China (1999), and Brisbane, Australia (2001). The next meetings
will be in Kyoto in 2003 (AIMECS 03). The proceedings of the first meeting
were published in a book.18
Representation of Medicinal Chemistry in IUPAC
restructuring of the divisions in IUPAC, the Medicinal Chemistry Section
was combined in 1996 with the Division of Clinical Chemistry to form
Division VII, Chemistry and Human Health. The medicinal chemistry interest
is now represented by a Subcommittee on Drug Discovery and Development.
It is anticipated that it will continue to support the activities of
medicinal chemists in the future and contribute to the technical success
of the pharmaceutical industry. New members to the subcommittee are
Medicinal Chemistry for
the 21st Century. Ed. C. G. Wermuth, Blackwell, Oxford, 1992, ISBN
Drug Metabolism: Databases
and High Throughput Testing During Drug Design and Development.
Ed. P. W. Erhardt, Blackwell, Oxford, 1999. ISBN 0632054329.
Properties, Selection, and UseA Handbook, C.G. Wermuth and
P.H. Stahl, Wiley, 2002 ISBN 3-906390-26-8.
C. G. Wermuth et al., (a) Pure Appl. Chem. 1998, 70, 1129-1143;
(b) Ann. Rep. Med. Chem.1998, 33, 385-395; (c) <www.chem.qmul.ac.uk/iupac/medchem>
H. van de Waterbeemd et al., Pure
1997, 69, 1137-1152; Ann. Rep. Med. Chem. 1998, 33,
D. Maclean et al., Pure
1999, 71, 2349- 2365; J. Combinatorial Chem. 2000,
Views from industry on the medicinal chemistry curriculum: answers to
a questionnaire. Busse W. D., and Ganellin C. R., in Claasen V., (Ed),
Trends in Drug Research, Pharmacochemistry Library, vol 20, Elsevier,
Amsterdam 1993, pp. 305-315.
Educating medicinal chemists. Ganellin C. R., Mitscher L. A., Topliss
J. G., in Ann. Rep. Med. Chem., vol 30, Academic Press, New York,
1995, pp. 329-338.
Vocational training for medicinal chemists: views from industry. Busse
W. D., Ganellin C. R., Mitscher L. A., Eur. J. Med. Chem. 1996,
education of medicinal chemists: comparison of eight countries.
Ganellin C. R. et al., Eur. J. Med. Chem. 2000, 35, 163-174.
Education of medicinal chemists in department of medicinal chemistry
(USA). Ganellin C. R., Mitscher L. A., Topliss J. G., Med. Res. Rev.
1998, 18, 121-137.
Medicinal chemistry graduate school curriculum and contribution to pharmaceutical
industry in Japan. Kobayashi T.-H. and Ganellin C. R., Medchem. News
1998, 8, 21-28; Chem.
Int. 1999, 21,
Two routes to becoming a medicinal chemist. Ganellin C.R., Chem.
Int. 2001, 23, 43-45.
Syllabus for a short postgraduate course in medicinal chemistry. Ganellin
C. R., Chem. Int.1995, 17, 212-214.
Preservation and utilization of natural biodiversity in context of search
for economically valuable medicinal biota by P. R. Andrews et al., Pure
1996, 68, 2325-2332.
P. R. Andrews et al., Pure
1996, 68, 2333- 2337.
Monge et al., Eur. J. Med. Chem. 2000, 35, 1121-1125;
2001, 23, 39-43; and journals of various Latin American countries.
Medicinal Chemistry: Today
and Tomorrow. Ed. M. Yamazaki, Blackwell Science Ltd., Oxford 1996.
Ganellin was the last president of the Medicinal Chemistry Section
and is now chairman of the Subcommittee on Drug Discovery and Development.
He is a professor of medicinal chemistry at University College London,