Vocational Training for Medicinal Chemists

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Eur J Med Chem (1996) 3 1,747-7600 Elsevier. Paris

747

Point of view

Vocational training for medicinal chemists: views from industry

WD Bussel, CR Ganellin**, LA Mitscher-’

iInternational Head of Research, Health Care Sector Pharma, Bayer AG, POB 10 17 09, D-42096, Wuppertal I, Germany;2Department of Chemistry, The Christopher lngold Laboratories, University College London,

20 Gordon Street, London WCIH OAJ, UK-<Department oj’Medicina1 Chemist ry, Kansas UnilBersity, Lawrence, KS 66045, USA

(Received 13 May 1996)

Summary - The Medicinal Chemistry Section of IUPAC sent a questionnaire regarding academic training for medicinal chemists tomajor research pharmaceutical companies in various countries in July 1992 and again in July 1993. A total of 102 replies were recei-ved from 65 companies, mainly from Germany, Italy, Japan, the UK and the USA, and these have been analysed and the results arepresented. Most companies (> 90%) indicated that they seek to hire organic chemists who may have received some additional educa-tion in medicinal chemistry, rather than hire specialists in medicinal chemistry. The subjects most often mentioned as beingdesirable fo r the additional education were biochemistry (or drug metabolism and pharmacokinetics), pharmacology and physiology,computer modelling and QSAR, and molecular biology.

postgraduate 1 curriculum i education I’ teaching i training i vocation i industry

Introduction

The education of medicinal chemists has been underdiscussion by the Medicinal Chemistry SectionCommittee [l] of IUPAC (International Union of Pure

and Applied Chemistry). One result has been to set upa Working Party to consider a medicinal chemistrycurriculum. It was decided to seek the viewpoint froman industrial perspective of what academic training(if any) should b e provided in medicinal chemistry.A questionnaire was devised [3] and was sent in July1992 to research directors or directors of medicinalchemistry in major research pharmaceutical compa-nies in Western Europe, Japan [4] and the USA,inviting them to complete the questionnaire and returnit (to WDB).

Replies were received from approximately 43 com-panies, the greatest numbers of which were inGermany, Japan and the UK. The companies were

also invited to photocopy the questionnaire and distri-bute it to their senior medicinal chemists in research.A total of 67 replies were received and these providedan initial set of data which was analysed [5] andreported in a conference proceedings [6].

Initially there were insufficient replies from certaincountries, and therefore the questionnaire was againsent in July 1993 to companies in France [7], Italy [7]

*Correspondence and reprints

and the USA [S]. The American companies returned atotal of 33 replies and these data have been publishedseparately [9]. The Italian replies were presented atthe 11th National Convention of Italian medicinalchemists, Bari, 1994 [lo]. There were also returns

from other countries but the numbers (in parentheses)were too fe w for analysis, thus: Belgium (l), France(l), Switzerland (2), Sweden (1) and unattributed (2).

The results have engendered considerable interestamong medicinal chemists and therefore the data fromthe main countries responding (a total of 95 replies)are presented in this article to permit a wider compari-son of the responses, according to country.

What is medicinal chemistry?

In the present context of the pharmaceutical industry‘medicinal chemistry’ is the design and synthesis of

compounds for biological evaluation as potential newdrug therapies, ie, the generation of new chemicalentities (NCEs) for medicinal purposes. In the phar-maceutical industry this is within the discovery phaseof research and development (R&D).

A more comprehensive definition formulated by theIUPAC Medicinal Chemistry Section [l l] is that“Medicinal chemistry is a chemistry-based discipline,also involving aspects of biological, medical andpharmaceutical sciences. It is concerned with the





determining the attitudes of the pharmaceutical com-panies as the ‘customer’ for the university ‘product’of trained chemists. Hence, as indicated in the

Introduction, a questionnaire was sent out. Becausethe replies were somewhat startling and provocativeand appear to cross national boundaries it is of interestto share the results with the international communityof active medicinal chemists and educators. Medicinalchemists, like other chemists, may take up variousjobs, but it is clear from the questionnaire replies thatthe industrial chemists focused their attention on thedesign and synthesis of new compounds for biologicaltesting. No doubt, this was assisted by the preamble ofthe questionnaire which stated: “Medicinal chemistsinvolved in new drug discovery have to be outstand-ingly good in synthetic organic chemistry and to under-stand modern approaches to structure-activity analysis.In addition they need to appreciate important concepts

at the interfaces with many other scientific disciplinesinvolved in the drug design process. In the past, mostmedicinal chemists were organic chemists who had toacquire the language and concepts needed to becomemedicinal chemists ‘on the job’. This takes a longtime, however, and, as is well known, not all organicchemists make a good transition. It should be possibleto greatly accelerate the learning process by intro-ducing appropriate training either whilst chemists arestill at university or shortly afterwards. We wouldvalue your opinion on this issue.”

Several answers indicated that there was no needfor medicinal chemistry to be taught in universities,because the subject could be taught adequately within

the company. On the other hand, this was more thancounterbalanced by the replies that wanted organicchemists foremost but also preferred them to have anawareness of biologically based subjects such as bio-chemistry, pharmacology, physiology and molecularbiology.

Results from analysis of the answers to the ques-

tionnaire

The questionnaire was comprised of seven mainquestions plus a request for information about the

749

respondent (position, responsibility, training andinvolvement in drug discovery). The numbers of com-panies polled and responding per country are given in

table I.In order to render the data between countries morereadily comparable the responses are given as percen-tages rather than as absolute numbers. The latter can,however, be easily derived from the indicated totalnumbers of responses. Because the total numbers ofreplies per country differ markedly, the minimumpercentage responses also differ substantially. Thus,for Italy the minimum response (1 out of 9 possible)appears as 1 %, whereas for Japan (1 out of 23 pos-sible) it is 4%, and for the USA (1 out of 33 possible)it is 3%.

Question I : When recruiting a new medicinal chemist,what do you look for in terms of knowledge, expertise,

qualification?

This is an open question and no guidance was pro-vided as to how to answer. Some misunderstanding wa sapparent from the answers in differentiating betweenknowledge, expertise, and qualification. These termswere not defined in the questionnaire since it wa sassumed that their meanings were self-evident. Someof the replies reflect the different national educationalcultures and systems. Thus experimental skills may betaken for granted when considering a PhD or postdoc-toral appointment but would be important for agraduate; this probably accounts for the high ratinggiven in the UK, where quite a number of graduates

(BS equivalent) are hired.A large majority of answers indicated (table II) that

they were seeking chemists with advanced knowledgein organic chemistry (over 80%) and expertise inorganic synthesis. Indeed, over half of the repliesfrom Germany and the USA suggested that theyrequired a PhD with postdoctoral experience in syn-thetic organic chemistry. Among the additional know-ledge and qualification required, biochemistry figuredquite highly, and pharmacology and molecular bio-logy had some mention. Surprisingly few answersmentioned molecular modelling or experience incomputing.

Table I. Numbersof companiesaskedand respondingper country.

Germany Italy Japan UK USA Total

No of companiesasked 12 16 44 14 33 119No of companies eplying 10

i12 12

Total number of repliesa 12 23 18 :; 5:

aThe number of replies s greater than the number of companiesbecause he latter were invited to make more than one return(see ntroduction).





rately in the Appendix (table IX). The priorities foreach subject have also been given a total score whichrepresents the sums of the number of answers timesthe priority value. The total score is also presentedas a percentage of the maximum possible. Thesepercentages are collected together in table IV to allowcomparison between the different countries. Bio-chemistry was not mentioned among the subjectslisted but was broken down into biological chemistry(which was identified as encompassing enzymemechanisms, nucleotides, proteins and peptides, carbo-hydrates, membranes), drug metabolism and pharmaco-kinetics. The results are also shown graphically infigures 1 and 2.

For many subjects there is quite a wide diversity ofopinion as to priority rating and stage for learning,however, almost all replies identified synthetic method-ology (97%) and a mechanistic approach to synthetic

chemistry (93%) as having priorities (ratings 4 and 5)for additional education especially at the graduatestage. High priority (3-5) wa s also given to biologicalchemistry (at all stages), physical organic chemistry(undergraduate and graduate) and to a general know-ledge of drugs and drug action. Biological subjects,such as molecular biology, pharmacology and bio-assay had medium to low priorities as did drug metabo-lism and pharmacokinetics (mainly stage d). Compu-tational modelling and QSAR theories and correlationanalysis had medium priorities (rated 3-4 at all post-graduate stages). Specialist topics like analytical

751

chemistry, process development and pharmaceuticaltechnology received a medium to low rating (2-3).Specialist biological subjects like physiology and

toxicology had low priorities (rated l-3), and micro-biology was rated even lower (l-2).Some marked differences by country were apparent

in the suggested stages for learning various subjects.Thus the Japanese preferred that microbiology andtoxicology should be taught to undergraduates andthat metabolism, pharmacokinetics, knowledge of drugaction, and molecular biology should be taught tograduate students. In contrast the British andAmerican responses preferred on the whole that thesesubjects should only be tackled when in industry. Thisdoubtless reflects the national differences in theeducational process. In Japan, the undergraduates aretaught from faculties of pharmacy whereas in theUK and the US the preference is that undergraduates

and graduate students are taught undiluted chemistry.

Question 4: If additional courses in medicina l chemis-try were to be offered as options to chemistry students,

what should be their contents?

This is an open question. The possible courses werenot identified in the question but they were mentionedalready in Question 3. The question also does not dif-ferentiate between undergraduate or graduate students.Answers are listed in table V. Subjects cited by asubstantial proportion of respondents are molecular

Table IV. Answers to Question 3 per country expressed as percentages of total possible scores per subject (see Appendix forscores): If you were to employ a synthetic organic chemist who will join your company to become a medicina l chemist, stateyour priorities for addi tional education against the listed subjects (rated according to priority where I is low and 5 is highpriority).

No of replies to Q3 11

Synthetic methodologyMechanistic synthesisPhysical organic chemistryBiological chemistryQSARComputational modellingAnalytical chemistryProcess chemistry

General knowledge of drug actionDrug metabolismPharmacokineticsProdnlgsPrinciples of pharmacologyPhysiologyMolecular biologyToxicologyMicrobiologyPharmaceutics

10082

41477144

31

71584953

2:80494736

Germany Italy Japan UK

51315329

::

18

100977872

2:3832

26649

5:67474333



752

e Synthetic hlethodology rl

"....'.O.'...-.. hlechanistic Synthesis . . . * . . . .

----O---- Analytical Chemistry -mm. __..0

---- ----ti Process Chemistry ---- ----?! I

801

801

QSAR

Computational blodelling

Physical Organic Chemistry

Biological Chemistry

80

60

60-

0 1 2 3 4 5 0 1 2 3 4 5

PRIORrrY PNORIT\I

r-l

Y Metabolism

“.“‘..e,...... Pharmacokinetics

..-_ e.-. Prodrugs

e Principles of Pharmacology

........~ .,.._ _ Physooey

----o--- hIolecular Biology

60

__-- ____iI Toxicology -__- ---_ii80

hlicrobiolopy

0 1 2 3 4 5 0 1 2 3 4 5

PRIORI-l-Y PRIOFLITY

Fig 1. Priorities for addi tional education: tota l number of responses to Question 3 for each subject plotted against priorityrating. Data in Appendix (table IX).



753

80

1

Synthetic Mechanist. Analytical Process

Methodol. Synthesis Chemistry Chemistry

80,

60

Ep 40 2 4o

20 20

0 0

Q&R Com’putat. Physical

Modelling Organic

Chemistry

Biological

Chemistry

Metabolism Pharmaco- Prodrugs Toxicology Principles Physiology Molecular Micro-

kinetics Of Biology biology

Pharmacology

Fig 2. Stages when subjects should be taught: total number of respon to Question 3 for each subj plotted against stage.

Data in Appendix (table IX). q Undergraduate; q graduate student; postdoctoral appointment, only in industry .



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Table V. Answers to Question 4 per country: If add itional courses in medicinal chemistry would be offered as options tochemistry students, what should be their contents?

Subject

Germany

Percentage number o f responses

Italy Japan UK USA

Modelling or QSAR 50 33 35 40 36

Pharmacology or physiology 58 33 22 40olecular biology 25 11 263237

:zEnzymology 17 0 9 24Biochemistry or DMPKa 17 22 13 40 21Drug design 0 18Case histories of drug discoveryDrug action :

:: i 3:

22 9 40 :Biological chemistry 17 11Toxicology 25 0 E ii z

Microbiology i 11 4 0ell biology 0 13 13 ;No answer 33 b c 6

aDMPK = drug metabolism and pharmacokinetics; bother subjects mentioned were statistics, use of the biological literature,protein chemistry; cfour respondents (22%) indicated that medicinal chemistry courses should not be offered.

modelling or QSAR (33-50%), pharmacology or

physiology (22-58%), molecular biology (25-30%),biochemistry or drug metabolism and pharmacokine-tics (13-44%) and enzymology (9-33%).

Question 5: Should universities provide specificcourses for medicinal chemists already employed inindustry? If yes, please list topics in your priorityorder

or as a series of evening lectures. Answers are listedin table VI. It is noteworthy, and rather surprising, that13-20% of respondents in Japan, UK and USA fel tthat such curricula should not be offered at all! Exceptfor Japan, subjects cited by a substantial proportion ofrespondents are pharmacology or physiology (33-67%), QSAR or molecular modelling (27-50%),molecular biology (25-30%), biochemistry or drugmetabolism and pharmacokinetics (30-44%).

This is another question in which the possible subjectcourses were not iden tified, but they had, of course,already been mentioned in Question 3. The questiondoes not identify how the courses should be orga-nized, eg, for a short period (1 or 2 weeks), full time,

Question 6: Please list your suggestions for a medici-nal chemistry curriculum

This was not posed as a question, and nothing wasspecified as to when a medicinal chemistry curriculum

Table VI. Answers to Question 5 per country: Should universitiesprovide specific courses or medicinal chemists mployed inindustry? If yes, please ist topics.

Subject

Pharmacology or physiologyiochemistry or DMPKa

Modelling or QSARolecular biologyDrug designEnzymology

Toxicologyiological chemistryOrganic synthesisShould not be offeredNo answer

Germany

422

50508

420

Percentagenumber of responsesItaly Japan UK USA

44 13 334 13 40 z

33 3013 ;; iFi0 0 7 180 13 12

::

4”

73 7 :0 130 17 :; 2;

11 26 17 15

aDMPK = drug metabolismand pharmacokinetics.



should be taught. It is presumed that the respondentswere giving their views as to what subjects in generalconstitute the knowledge base for medicinal chemis-try. Answers are listed in table VII. No single subjectis mentioned by more than 40% of respondents.Apart from Japan, the most popular subjects werebiochemistry or pharmacokinetics and drug metabo-lism (1740%) pharmacology or physiology (1740%),synthetic organic chemistry (17-56%, but not fromthe UK) and molecular modelling or QSAR (7-21%).This last response rating is surprisingly low given thatmolecular modelling or QSAR received substantiallyhigher ratings in answers to Questions 3-5.

Question 7: Having regard to the present recruitmentsituation in your country, what suggestions do youhave for the future to better train chemists in medici-nal chemistry?

Various suggestions were made in answer to this ques-tion and a representative selection is listed below.Some of the answers reflect the national character o fthe university training and so they are grouped bycountry. Some of the views expressed are distinctlycontradictory.Germany: ‘Medicinal chemistry courses should be

offered to graduate students in chemistry.’ ‘Requirestronger co-operation between industry and univer-sities.’ ‘ Encourage postdoctoral study abroad in anexcellent laboratory.’

Italy: ‘Italy has courses for chemistry and chemistrywith pharmaceutical technologies (CTF) but none

gives the right training for medicinal chemistry;they should be mutually reorganised.’ ‘It is not aproblem in Italy.’ ‘High level training centres areneeded in the universities.’ ‘Additional courses in

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universities for students and for industry resear-chers.’

Japan: ‘Drug discovery requires ‘what’ should be

synthesised and ‘how’. Japanese students are welltrained in ‘how’. University education must focusmore on the ‘what’ .’ ‘In Japan, the majority ofmedicinal chemists are hired with a Master’s degreefrom Faculties of Pharmacy. In future we willrequire some scientists with a PhD.’ ‘Establishmedicinal chemistry departments in universities forpostgraduate training.’

UK: ‘Introduce a four year Bachelor’s course (threeyears chemistry and one year medicinal chemis-try) .’ ‘Adapt undergraduate courses to substitutemedicinal chemistry topics for some inorganic orphysical chemistry topics.’ ‘Do not believe that amedicinal chemist can be produced at university.Organic chemistry is so vast that it should not be

diluted with other subjects.’USA: ‘Appoint more medicinal chemistry professors

from industry.’ ‘Provide additional courses tochemistry graduate students in topics related todrug design, eg, biochemistry, biological chemistry,molecular biology, pharmacology, computingskills.’ ‘Provide summer training in a medicinalchemistry laboratory during undergraduate orgraduate studies. ’ ‘Provide university short coursesin aspects of drug design to postdoctoral resear-chers who are working in industry.’ ‘Improve thecapability and desire to work in a team and theability to identify, prioritize and address commer-cial issues in addition to science.’ ‘Reverse the

trend in which the number of synthetic organicchemistry professors in the USA is declining due todecreased funding and the number of studentstaking this subject is also falling.’

Table VII. Answers to Question 6 per country: Suggestionstir a medicinal chemistry curriculum.

Subject Percentagenumber of responsesGermany Italya Japan UIP USA

Biochemistry or DMPKC 17 11 ?I 40 27Pharmacology or physiology 17 22 40 24Synthetic organic chemist ry 17 67 4 0 24Modelling or QSAR 17 11 17 7 21Drug design 0 0 0 7 18

Enzymology 0 0 0 0 15Biological chemistry 8 0Molecular biology

I!: 0”

?I7 15

20 15Toxicology 7Microbiology 8 I1 i :No answer 45 22 0

2;18

aOnly two responses from Italy identified specific topics; three replied in a general manner about the training required: eg, BSor MS in organic chemist ry plus PhD in organic or medicinal chemis try, followed by postdoctoral experience in medicinalchemistry or in a big pharmaceutical company. bThree replies indicated that medicinal chemistry should not be studied atuniversity at all. cDMPK = drug metabolism and pharmacokinetics.



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Additional remarks

Some interesting remarks were written on the formswhich illustrated a very wide spectrum of viewpoints,some very forcefully expressed. The view was indi-cated many times that a strong background in syntheticorganic chemistry is essential for success. It is a skillthat cannot be learned on the job. At one extreme wasthe statement ‘we do not ask for additional educationin medicinal chemistry since we find that this dilutesthe understanding of basic principles in chemistry.’Furthermore several answers indicated that medicinalchemistry and drug research is better taught in indus-try than in academic institutions. Indeed, as onerespondent indicated: ‘We only hire organic chemists.We have occasionally interviewed medicinal chemistsbut found their organic chemistry to be weak. We arenot set up to teach them organic chemistry but we

have much experience in teaching the principles ofmedicinal chemistry to organic chemists.’ In contrast,one respondent stated: ‘I want to emphasize that therole of a medicinal chemist is to solve biologicalproblems with an exact science in an interdisciplinaryenvironment. The chemists must not look at them-selves in isolation. If they do, they will end up beingtold what to do! This is one of the underlyingproblems as to why medicinal chemists are gettingshort shrift in many companies now. We collectivelyare to blame for this! ’ Another indicated: ‘most of ourPhD chemists have strong organic backgrounds andlook for similar chemists who can learn medicinalchemistry. It would be preferable to have a better

balance.’ It would be very difficult to reconcile suchdivergent views!

Perhaps these viewpoints arise out of the currenthighly specialised and sophisticated organisation ofresearch in the big companies. This wa s succinctlyexpressed by a respondent who stated: ‘Increasinglydrug discovery is dependent on the application ofmany skills and disciplines at the state-of-the-art level.This is best achieved by the efficient functioning of agroup of experts, each highly skilled in the requisitediscipline. This dictates the training of such specialistsand they only need to be sufficiently knowledgeable inthe other disciplines to allow effective team inter-action.’

Information about the respondents

The respondents vary in industrial medicinal chemis-try experience with 10-25 years being representative(table VIII). In the USA, 50% had > 20 years exper-ience whereas in Germany, Japan and the UK thepercentage having such extensive experience wassubstantially lower (28-33%). There was a wide range

in their levels of responsibility, all the way fromresearcher, through manager to head or director ofmedicinal chemistry, to vice president. The numbersof PhD or equivalent chemists reporting to them(managerially) ranged mainly from 5 to 25. Not sur-prisingly, a very high proportion received their formaltraining in synthetic organic chemistry: a significantminority (20%) had combined their chemistry withbiochemistry, pharmacology, pharmacy, or medicinalchemistry. The companies represented are mainly bigand multinational.

Discussion

In the research-based pharmaceutical companies mostmedicinal chemists are employed in the design andsynthesis of new compounds for biological testing as

part of the new drug discovery process. It was obviousthat this was the basis for the replies received. Theoverwhelming response was clear. The companieswish to recruit first-rate synthetic organic chemists.Since synthetic organic chemistry is a more basicscience it must be made secure; medicinal chemistryis viewed as being capable of being grafted on, but thepoints at issue are when and how. There are manydiverse opinions. One extreme view expressed severaltimes was that medicinal chemistry can be learned byexperience and that there is no need to teach it inuniversity. If it is taught it must not be at the expenseof specialist organic chemistry. Most responses wereless extreme. Senior chemists responsible for hiring

new medicinal chemists looked favourably on additio-nal courses, such as biochemistry, biological chemis-try, pharmacology, physiology, molecular biology,QSAR and molecular modelling.

One issue that was posed by a substantial numberof the respondents was whether one can ‘teach medi-cinal chemistry’ at university or has it to be learned onthe job since drug design is an applied subject. Thisseems to be a misunderstanding by some respondentsabout the aim of the questionnaire and, indeed, aboutthe process of education. It takes many years to gainsufficient experience ‘on the job’ for drug .design!One answer indicated 15 years! The point o f teachingsome ideas and methods is not to replace experience

but to enhance it. By introducing new ideas andconcepts early in the education process studentsbecome imprinted and this removes barriers to futurelearning and modifies the way they think. This isespecially true where other scientific disciplines areconcerned and this is very important for effectivecommunication across the disciplines. The purpose ofteaching is to shorten the time it takes to achieveperceptive understanding and to get the scientist to thecreative cutting edge much faster. Nowadays, the



757

Table VIII. Information about the respondents; numbers of replies per country.

Experience (number of years)45-910-20>20

Germany Italy

0 00 28 34 4

Japan UK USA

1 0 06 3 48 10 127 5 16a

PositionVP or Research Director 2 6 4Director or Head of Medicina l Chemistry 10 8 i 13 22Senior researcher 1 4Manager 6 3Researcher 2 1No information 1 2

Responsibility (number of PhDs or equivalent within area of responsibility)<5

:

1

:

3 2

5-9 4 4 91CL20 2 3 5 4 6>20 5” 1 2 7 12c

Educational backgroundOrganic chemistry 10 7 16 18 27plus biochemistry 2 0 4 1 1plus pharmacology 2 2plus medicina l chemistry 1 3plus pharmacy 1 2plus bioorganic 1 1Other 2d 7e

aFour replies indicated >30 years experience; bfour replies indicated responsibility for 30-40 PhDs, one reply indicated respon-sibility for 60 PhDs; cfour replies indicated responsibility for 3140 PhDs, two replies indicated responsibility for >40 PhDs;dtwo replies indicated industrial chemistry as educational background; ereplies indicated physical organic chemistry (4), medi-

cine (l), biological chemistry (1) or pharmacognosy (1) as part of their educational background.

molecular basis for drug design is expanding sorapidly that scientists cannot afford the luxury oftaking ten or more years for ‘on the job’ training. Thepoint is surely not whether one can teach how todesign drugs but whether one can teach some prin-ciples and language to be used as tools and where thismight be done most efficiently. What these tools arewill provide the basis for a curriculum in medicinalchemistry.

search for new types of drug action, most leads weregenerated by screening. Since then we have had aperiod in which a more rational approach has emergedbased upon a knowledge of enzymes and receptors astargets. In this period the dialogue between thechemist and biologist became very important andchemists had to learn much more about the biologicaltargets and how to match the chemistry of drugs tobind to these targets.

The practice of medicinal chemistry and its role in We have now entered another phase where techno-

drug research has been continuously changing over logy has provided the opportunity for automatedthe years due to changes in technology, scientific screening against a range of biological targets usingunderstanding, and the approaches to drug research. radioligand binding or enzyme assays, in addition toForty years ago, research in the pharmaceutical indus- screens against microorganisms. When a new lead istry was dominated by organic chemists. Medicinal generated one requires outstanding organic chemistrychemists were rather rare and were often referred to as to follow it up as rapidly as possible by synthesizingpharmaceutical chemists. Indeed, recognition of the analogues. Surely, one has also to select the targetscience of medicinal chemistry as a chemical sub- molecules for synthesis but the planning requires adiscipline was in its infancy. The Journal of brief time compared with the time spent on actuallyMedicinal Chemistry emerged only in 1957. In the synthesizing them. Only a few medicinal chemistry



758

Table IX. Summations of answers to Question 3 by country: if you were to employ a synthetic organic chemistwho will join yourcompany o become medicinalchemist, tateA: your priorities for additional educationagainst he listedsubjects rated accordingto priority where is low and S is hi.& priority) and B: indicate the stageat which eachsubiectshouldbe taught, wherea = under-graduate;b = graduatestudent,c = postdoctoralappointment,d = only yrt industry. s

Subject Priorities or additionaleducationar ? Score

Stage,for eachinga b c d

Germany (11 replies)

Synthetic methodologyMechanistic synthesisPhysical organic chemistryBioloaical chemistryQSAR

i

Comuutational modellinaAnalytical chemist ry cProcess chemistryKnowledge of drug actionDrug metabolismPharmacokineticsProdrugsPrinciples of pharmacologyPhysiologyMolecular biologyToxicologyMicrobiologyPharmaceuticsMaximum scoreMinimum score

Japan (22 replies)

Synthetic methodologyMechanistic synthesisPhysical organic chemistryBiological chemistryQSARComputational modellingAnalytical chemistryProcess chemistry

Knowledge of drug actionDrug metabolismPharmacokineticsProdrugsPrinciples of pharmacologyPhysiologyMolecular biologyToxicologyMicrobiologyPharmaceuticsMaximum scoreMinimum score

Italy (9 replies)

Synthetic methodologyMechanistic synthesisPhysical organic chemistry

Biological chemistryQSARComputational modellingAnalytical chemistryProcess chemistryKnowledge of drug actionDrug metabolismPharmacokineticsProdrugsPrinciples of pharmacologyPhysiologyMolecular biologToxicologyMicrobiologyPharmaceuticsMaximum scoreMinimum score

1 i

t10

52134

454

i116II109

1617910

;84

121010

i712484



759

Table IX. Continued

UK (17 replies)

Subject Priorities for additional educationa

Synthetic methodologyMechanistic synthesisPhysical organic chemistryBiological chemistryQSARComputational modellingAnalytical chemistryProcess chemistryKnowledge of drug actionDrug metabolismPharmacokineticsProdrugs

Principles of pharmacologyPhysiologyMolecular biologyToxicologyMicrobiologyPharmaceuticsMaximum score

USA (30 replies)

Synthetic methodologyMechanistic synthesisPhysical organic chemistryBiological chemistryQSARComputational modelling

Analytical chemistryProcess chemistryKnowledge of drug actionDrug metabolismPharmacokineticsProdrugsPrinciples of pharmacologyPhysiologyMolecular biologyToxicologyMicrobiologyPharmaceuticsMaximum scoreMinimum score

1 i 3Stage for teaching

4 5 Score a b C d

001

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31391097

44

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51134

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17146451117421

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114

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275944

64466042

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7178108

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365242

1012127

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1804

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32420

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aThe number of responses for each subject is shown for the respective priorities and stage for teaching. Returns for the latter add up to

more than 100% because many respondents indicated that subjects should be acquired at more than one educational stage. The scorerepresents the sums of the number of answers times the priority values.

experts may be needed to provide the drug-design numbers of compounds for structure optim ization

‘know-how’. It must be appreciated, however, that this places an even greater premium on the ability to‘know-how’ of drug design has now become even conduct a perceptive structure-activity analysis of themore important. The possibility of using techniques as data being generated. Furthermore it has become evenin combinatorial chemistry to rapidly generate large more critical in drug design to incorporate at an early



760

stage the requirements for achieving satisfactorypharmacokinetic behaviour of drugs in vivo. Thusmedicinal chemists need a great awareness of thechemical factors affecting drug distribution and drugtoxicity. Organic chemists enter the industry comple-tely unaware of these issues. Medicinal chemists arerequired to analyse and solve them. In the currentclimate of large research teams and specialists atypical team will probably include a fe w experts inNMR or mass spectroscopy, crystallography, chemicalcomputation and modelling, a fe w experienced medi-cinal chemists to relate biology to structure-activityanalysis and to solve absorption, distribution, metabo-lism, and excretion problems, but the majority of theteam will be the many organic chemists involved inthe synthesis. Of course, being in a team implies thatthe various sub-disciplines are mutually supportive.The medicinal and organic chemists are not working

in isolation but are strongly interactive and helpingone another solve the many technical problems thatarise. Perhaps this situation underlies the strong biastowards organic chemists revealed in the replies to thequestionnaire.

It is also important to note that the questionnairewas sent to the research directorate of large internatio-nal pharmaceutical companies. These possess thelarge research teams. Small companies generally donot have a wide range of specialists. They are muchmore dependent on generalists who can cover variousaspects, eg, to have productive dialogue with biolo-gists, understand drug-design and structure-activityanalysis, and be able to synthesize compounds.

Furthermore they usually lack the infrastructure toprovide company training in medicinal chemistry.Probably, therefore, their requirements and attitudestowards university-trained medicinal chemists will bequite different.

The teaching of medicinal chemistry

As indicated by the replies to the questionnaire, manyof the large research-based pharmaceutical companieshave established internal courses to teach the prin-ciples of medicinal chemistry to their newly hiredorganic chemists. There are also the one week resi-dential intensive postgraduate courses [ 121 held at, eg,

University of Kent in Canterbury, UK, Drew Univer-

sity, Madison, New Jersey, USA, Leiden-Amsterdam,The Netherlands and Leysin, Switzerland. Their greatpopularity (they are generally oversubscribed) atteststo the support given by companies in sending theiryoung medicinal chemists to attend.

Some universities provide the opportunity for post-graduate chemistry students to attend courses appro-priate to medicinal chemistry during their researchtraining. Generally these have departments of medici-nal chemistry and may be in schools or faculties ofpharmacy. There is a general perception amongstorganic chemists, however, that organic chemistry inschools of pharmacy is not of the highest standard andtherefore it would be advantageous if, in some way,there could be a working collaboration between thedepartments of medicinal chemistry and organicchemistry. This was clearly apparent in the replies tothe questionnaire. It is proposed to pursue this enquiry

by taking it to the universities which teach medicinalchemistry.

References and notes

I

2

3

4

5

6

Membership of the Section Comm ittee was JG Topliss (President). N Koga

(Vice-President). WD Busse (Secretary). CG Wernuth (past President),

CR Ganellin, LA Mitscher

The mem bers were CR Ganel n (Chairman). WD Busse (Bayer, W uppertal,

Germa ny), P Lmdberg (Astra, HLssle, MBlndal, Sweden), LA Mitscher

(University of Kanas, USA), G Tarzla (Unwersity of Urbino, Italy),

CG Wermuth (UniversitC Louis-Pasteur, Strasbourg, France) and R Ziegler

(Sandoa. Basel. Switzerland)

We are grateful to D Two me y and M Ganel n for helpful discussion about

construction of the questionnaire

We thank N Koga (Daiichi Pharmaceutical) and J Ide (Sankyo) for arrangingdistribution of the questionn aire in Japan

We thank T Kr&ner (Bayer A C. Wuppertal) for assistance with the analysis

of the returned answer&

WD Busse and CR Ganel n (1993) In: Trm & !n Drug Research (Claassen V,

ed) Elsevier. Amste rdam , 1993, 305-315

Letters and the questionnaire were sent to companies in France and Italy by

CG Wermuth and G Tarzia respectively

Letters and the questionnaire were sent to US companies by LA Mitscher or

JG Topliss

CR Ganellin, LA Mitscher. JG Topliss (1995) In: Annua/ Reporfs of

Medicinal Chemisr,-y (Bristol J. ed) ACS. Vol 30, Ch 33, 329-338

T Rotunda (1994) Requisiti e Formazione profession& de1 Chimico

Farmaceutico del Industria, XI Convegno Narionale, Divisione di Chimica

Farmaceu tica, Societa Chimica Italiana, Ba ri, 2-S October 1994

CC Wermuth. CR Ganellin. R Imh of, P Lindberg. LA Mitscher (1996)

Glossary of Ter ms lised m Medwnal Chem my. Pure Appl Chem (in press)

CR Ganel n (1995) Syllabus for u Short Postgraduate Course in Medicinal

Chemis try, Chemistry International, Blackwell Science. Oxford, 17, 212-214

Documents

Vocational Training for Medicinal Chemists