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Medicinal Chemistry and the Pharmacy Curriculum

Article  in  American Journal of Pharmaceutical Education · October 2011

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 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

REVIEWS
Medicinal Chemistry and the Pharmacy Curriculum
M.O. Faruk Khan, PhD, MPharm,a Michael J. Deimling, PhD,b and Ashok Philip, PhDc
a
College of Pharmacy, Southwestern Oklahoma State University
b
Philadelphia College of Osteopathic Medicine, School of Pharmacy – Georgia Campus
c
Union University School of Pharmacy
Submitted March 17, 2011; accepted May 18, 2011; published October 11, 2011.

The origins and advancements of pharmacy, medicinal chemistry, and drug discovery are interwoven
in nature. Medicinal chemistry provides pharmacy students with a thorough understanding of drug
mechanisms of action, structure-activity relationships (SAR), acid-base and physicochemical proper-
ties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. A compre-
hensive understanding of the chemical basis of drug action equips pharmacy students with the ability to
answer rationally the “why” and “how” questions related to drug action and it sets the pharmacist apart
as the chemical expert among health care professionals. By imparting an exclusive knowledge base,
medicinal chemistry plays a vital role in providing critical thinking and evidence-based problem-solving
skills to pharmacy students, enabling them to make optimal patient-specific therapeutic decisions. This
review highlights the parallel nature of the history of pharmacy and medicinal chemistry, as well as the
key elements of medicinal chemistry and drug discovery that make it an indispensable component of the
pharmacy curriculum.
Keywords: curriculum, medicinal chemistry, history of pharmacy, drug discovery

INTRODUCTION Act of 1990 (OBRA 1990) increased the clinical responsi-

It was not until the mid 19th century that pharmacy bility of pharmacists by requiring them to counsel Medic-
emerged as a professional entity in the United States. In aid patients and participate in prospective and retrospective
1869, William Proctor Jr defined pharmacy as the “art of drug utilization review programs. Responding to this chal-
preparing and dispensing medicine” which “embodies the lenge, US colleges and schools of pharmacy moved toward
knowledge and skill requisite to carry them out to prac- offering the PharmD program.1
tice.”1 Thus, preparation and dispensing have been at the The advent of this new direction for the pharmacy
heart of pharmacy practice since the beginning of the pro- profession prompted an increase in the clinical coursework
fession, with sound knowledge of chemical compatibility, in the pharmacy curriculum. Unfortunately, this paradigm
solubility, and stability of the drugs deemed essential to shift also initiated a debate over the relevance of medicinal
effectively accomplish the “preparation” component of the chemistry, a basic pharmaceutical science, in pharmacy
prescription.1 education. The Accreditation Council for Pharmacy Edu-
Over the last 4 decades, the role of a pharmacist pro- cation (ACPE) Standard No. 13 clearly states the need to
gressively shifted from being a compounder and supplier provide a thorough scientific foundation for the achieve-
of pharmaceutical products to a service and information ment of desired professional outcomes.3 To achieve this
provider, and eventually to a comprehensive patient care goal, ACPE requires the curriculum to contain biomedical
provider.2 In 1990, Hepler and Strand called for a paradigm sciences, pharmaceutical sciences, social/behavioral/
shift to “pharmaceutical care,” a concept that is defined as administrative sciences, and clinical sciences.3 Additional
“the responsible provision of drug therapy for the purpose guidelines specify the medicinal chemistry requirements
of achieving definite outcomes that improve a patient’s under the umbrella of pharmaceutical sciences (Table 1).
quality of life.”2 The Omnibus Budget Reconciliation Important historic milestones and the interrelationship
between drug discovery and development, medicinal chem-
Corresponding Author: M. O. Faruk Khan, BPharm, MPharm, istry, and the pharmacy profession are highlighted in the
PhD, Department of Pharmaceutical Sciences, College of table in Appendix 1.4-16 While drug development and me-
Pharmacy, Southwestern Oklahoma State University, 100 dicinal chemistry are purely scientific, the pharmacy pro-
Campus Drive, Weatherford, OK 73096. Email: faruk.khan@ fession deals with the art of preparing and dispensing as well
swosu.edu; Tel: 580-774-3064; Fax: 580-774-7020. as providing optimal pharmaceutical care with therapeutic
1
 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

Table 1. The Study Objectives for Medicinal Chemistry in the transfer (Kosower, 1955); induced-fit theory of drug action
Pharm D Curriculum3 (Koshland, 1958); concepts of drug latentiation (Harper,
d Physico-chemical properties of drug molecules in 1959) and prodrug (Albert, 1960); application of mathe-
relation to drug ADME matical methods to medicinal chemistry and transformation
d Chemical basis of pharmacology and therapeutics of SAR studies into quantitative SAR (QSAR) (Hansch and
d Fundamental pharmacophores for drugs used to others, 1960s); and application of artificial intelligence to
treat disease drug research (Chu, 1974).10
d Structure activity relationships in relation to
Medicinal chemistry is defined as an interdependent
drug-target interactions
mature science that is a combination of applied (medi-
d Chemical pathways of drug metabolism
cine) and basic (chemistry) sciences. It encompasses the
d Application to making drug therapy decisions
discovery, development, identification, and interpretation
of the mode of action of biologically active compounds at
the molecular level. Medicinal chemistry may be viewed
agents. In pharmacy, the hallmark of the new millennium as the melting pot of synthetic chemistry and molecular
has been the tremendous advancements made in the area pharmacology that emphasizes the study of SAR of drug
of pharmacogenomics, whereby dosages of medications molecules; it therefore requires a clear understanding of
are tailored to individual patients based on specific genomic both chemical and pharmacological principles. At an insti-
patterns, polymorphisms, and therapeutic responses to se- tutional level in the United States, medicinal chemistry first
lect drugs. Thus, pharmacogenomics is a rapidly developing started as the division of pharmaceutical chemistry (1909-
area that lends the application of biotechnology principles 1920), was modified to the division of medicinal products
to the efficient practice of pharmacy. (1920-1948) and later got its name, the division of medic-
inal chemistry, from the American Chemical Society.16
HISTORY OF MEDICINAL CHEMISTRY Medicinal chemistry continues to play a major role in
From a fertile mix of ancient folk medicine and early drug research and development, taking advantage of newer
natural-product chemistry, medicinal chemistry emerged techniques and increased knowledge of different branches
about 150 years ago as a distinct discipline. This area of of related sciences. The roots of modern medicinal chem-
study received formal recognition 78 years ago with its istry, however, lie in all branches of chemistry and biology,
inclusion in the 4-year BSPharm degree curriculum.1,6 which began its journey in the battle against diseases in the
The 19th century may be viewed as the birth period of revered hands of Ehrlich who dreamed of a “magic bullet”
modern medicinal chemistry with the introduction of side to combat all infectious diseases. Out of 114 US colleges
chain theory of drug action in 1885 by Berlin immunol- and schools of pharmacy, 20 have separate medicinal
ogist Ehrlich.8 Later in 1891, he coined the term chemo- chemistry departments, all of which grant a PhD degree in
therapy and defined it as “the chemical entities exhibiting this area of study. Of the approximately 40 new colleges
selective toxicities against particular infectious agent.”4 and schools of pharmacy that have emerged since 2000,
The modern drug receptor theory originated from this side none has a separate medicinal chemistry department.17
chain theory, which was supported during the same period
(mid-1890s) by Cambridge physiologist Langley who de- Intellectual Domains of Medicinal Chemistry:
scribed it in his publications as “receptive substances.” Scopes and Importance in Pharmacy
The importance of receptors for understanding diverse The 2 intellectual domains of medicinal chemistry that
biological processes was recognized initially by Ehrlich are of value in pharmacy are drug design and development
and Langley and then followed by Clark in the 1930s. Re- and ADMET (absorption, distribution, metabolism, excre-
search on enzyme specificity (lock-and-key theory) by tion, and toxicity) assessments. Interpretation of mode of
Fischer in 1894 and Henry’s hypothesis on enzyme- action at the molecular level and construction of SAR of
substrate complex formation in 1903 are recognized as drug molecules or biologically active compounds are im-
key advancements in the principles of drug action and mod- portant scopes of the drug design and discovery domains,
ern medicinal chemistry.9 Grimm’s and Erlenmeyer’s con- which in turn are vital facets of medicinal chemistry. Ad-
cepts of isosterism and bioisoterism (1929-1931) also had ditionally, ADMET assessments of therapeutic drug clas-
a tremendous impact on the understanding of structure ac- ses that have a significant influence on therapeutic decision
tivity relationship (SAR) of drugs and development of mod- making are essential components of pharmacy education.
ern medicinal chemistry.7 Other notable advancements in As experts in the therapeutic use of medications and phar-
understanding of drug action and design that were made in maceutical care, pharmacists routinely provide therapeutic
the mid to late 20th century include: intervention of charge evaluations, recommendations, and counseling to patients
2
 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

and other health care professionals regarding safe, appro- a vital part of the drug discovery team. Readers are directed
priate, and cost-effective use of medications. With current to an extensive review of the historical perspective of
emphasis on intense clinical training, pharmacists also are the role of the medicinal chemist in drug discovery by
equipped with skills to evaluate scientific literature and Lomberdino and Lowe III for more information.19 In this
develop evidence-based patient-specific pharmacotherapy article, we present a drug discovery case story below to
plans. Thus, by offering a sound knowledge base of the highlight the medicinal chemists’ role in the complex but
chemical basis of drug action, its stability, SAR, mecha- exciting drug discovery process.
nism of action, pharmacology, and ADMET, medicinal
chemistry instills critical-thinking and problem-solving Drug Development Case Study: Development
skills in students that are essential for the making of a com- of Omeprazole.
petent pharmacist. In the late 1960s, a subdivision of AstraZeneca Re-
search and Development started a research project to find
Medicinal Chemistry in Drug Design and Discovery drugs capable of inhibiting gastric acid secretion for use in
A summary of important techniques and tools used in patients with peptic ulcer disease (Figure 1).20 The project
drug design and discovery are listed in Table 2. Because a produced a drug that was highly effective in rats but not in
detailed discussion of these scientific techniques is beyond humans. The project was abandoned for a time, but in
the scope of this paper, interested readers are encouraged to 1972 was revived, this time using a dog model.
read the sixth edition of Burger’s Medicinal Chemistry and A literature search identified a report by another
Drug Discovery, Volume 1.18 We believe that a systematic pharmaceutical company of an antisecretory compound
review of these scientific backgrounds during a pharma- pyridylthioacetamide. The second company dropped the
cist’s educational years is fundamental to imparting a project because of the severe acute toxicity associated with
thorough foundational knowledge and promotes lifelong this drug. The observed toxicity was attributed to the thio-
learning skills. amide group and a decision to modify this group by incor-
Medicinal chemists play a crucial role in driving the porating it into or in between heterocyclic ring systems was
drug discovery project by relying on their knowledge and made. In 1973, a benzimidazole derivative, H124/26, was
expertise in modern organic chemistry, biology of the dis- discovered that had powerful antisecretory properties and
ease, in vitro and in vivo pharmacological screening, and lacked acute toxicity. The compound was patent protected
pharmacokinetic characteristics, with the goal of maximiz- by a Hungarian company for use in tuberculosis; however,
ing efficacy while minimizing side effects. Additionally, a its sulfoxide metabolite (timoprazole) was not covered by
firm understanding of ADMET issues related to medicines the patent, and in 1974 it was found to have even more
in the market for a target disease, regulatory affairs for antisecretory potency than H124/26. Unfortunately, long-
similar drugs, drugs in the pipeline, scientific literature, term toxicological studies revealed its ability to cause en-
and technological advances make the medicinal chemist largement of the thyroid gland due to inhibition of iodine
uptake. Through a literature search, the research team iden-
tified substituted mercapto-benzimidazoles, which had no
Table 2. Important Techniques Used in Drug Development
effect on iodine uptake. When these substitutents were added
and Medicinal Chemistry17
to timoprazole, the effects on thyroid and thymus glands
d Quantitative structure-activity relationship (QSAR) were eliminated without a reduction in the antisecretory
d Molecular modelling
effect of timoprazole. The most potent drug identified in
d Virtual screening and docking
1977, picoprazole, initially was associated with necrotiz-
d Drug target binding forces

d Combinatorial library design

ing vasculitis in dogs; however, this effect was limited to
d Bioinformatics
one breed of beagle with antibodies to intestinal worms.
d Structure based drug design This effect was not reproduced in other strains or in non-
d X-ray crystallography parasitized dogs; thus, picoprazole was given approval for
d Nuclear Magnetic Resonance and Mass spectroscopy initial studies in humans and showed a good antisecretory
d Electron cryomicroscopy of biological macromolecules effect with a long duration.20
d Peptidomimetics About the same time as the picoprazole discovery
d Analog design (1977), the final step in acid secretion, the proton pump,
d Rational drug design
was discovered. In the early 1980s, researchers found that
d Chirality
the substituted benzimidazoles blocked the proton pump
d Study of structural basis for toxicity
process/action. Because weak bases exhibit a tendency
d Use of natural products as drug leads
to accumulate in the acidic compartment, more electron
3
 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

Figure 1. Development of Omeprazole.

donating substituents were added to the pyridine ring of dents by linking basic sciences to clinical practices.26 This
picoprazole to increase its pKa and maximize its accumu- led some medicinal chemistry educators to apply problem-
lation in parietal cells. The changes led to the identification based learning methodology in their teaching of medicinal
of omeprazole, with a pKa of 4.0 (about 1 unit higher than chemistry content to pharmacy students. Medicinal chem-
pKa of picoprazole). The higher pKa also increased the rate istry-based case studies were developed to solve clinical
of acid-mediated conversion of this agent to its active spe- problems through group discussions. These case studies
cies. The methoxy substitution in the benzimidozole ring led to a marked improvement in the problem-solving skills
also made the compound more stable to conversion at neu- of the students, reiterating the significance of medicinal
tral pH.20 Subsequent clinical studies led to omeprazole chemistry as a critical component of pharmaceutical-care
marketed as Prilosec (1989), the first among a new class directed learning.26-28 Roche and Zito developed comput-
of proton-pump inhibitors (PPIs), for the treatment of gas- erized case studies emphasizing medicinal chemistry prin-
tric acidity and ulcers. ciples in the practice of pharmacy. Positive outcomes were
reported for identifying relevant therapeutic problems, con-
Innovations in Medicinal Chemistry Education in ducting thorough and mechanistic SAR analyses of drug
Academic Pharmacy product choices provided, evaluating SAR findings in terms
With evidence-based patient-centered care taking a of patient needs and desired therapeutic outcomes, and solv-
prominent role in current pharmacy practice, creative ways ing patient-related therapeutic problems.29,30 This teaching
to reinforce medicinal chemistry content are being actively methodology reinforced the indispensability of medicinal
pursued by educators. Among these, structurally based ther- chemistry in the pharmacy curriculum. This method of in-
apeutic evaluation (SBTE), an innovative concept devel- struction also has been addressed in the SBTE approach.
oped by Alsharif and colleagues, uses knowledge of drug Sound knowledge of functional group chemistry of
structures in making therapeutic decisions and emphasizes drug molecules, along with ADMET parameters, is funda-
the relevance of medicinal chemistry to the pharmacist. All mental to selection of appropriate agent and/or formulation,
7 criteria of therapeutic decision making (drug history/drug understanding of routes of drug administration, and dos-
response, patient compliance, current medical history, past ages.31 Functional groups are critical to receptor binding,
medical history, side effects, biopharmaceutics, and phar- influence the mode of drug action, and serve as predictors of
macodynamics) are addressed in this SBTE approach and their potency. Accordingly, the development of computer-
used by students to solve therapeutic problems for each based tutorials containing structures, receptor biochemis-
class of drugs.21 Also, professional practice skills like prob- try, and functional group chemistry, has been a milestone in
lem solving and decision-making, learning from problem- the development of the technology-driven medicinal chem-
solving experiences, communicating, teaching, educating, istry instructional model for pharmacy curriculum. Indeed,
and collaborating are reinforced by SBTE.22 SBTE has evaluation of this instructional model has revealed its over-
proven to be a valuable tool for curriculum integration whelmingly positive impact on pharmacy students’ perfor-
and interdisciplinary teaching; as evidenced by student rec- mance.32 metabolic reactions are dependent on classical
ognition of medicinal chemistry as an extremely valuable chemical reactivity of the drugs’ functional groups and
tool for the scientific practice of pharmacy.23-25 The success their local electronic and steric characteristics. Relying
of the SBTE approach clearly highlights that medicinal on their knowledge of functional group chemistry (Figure
chemistry and pharmacy education are inseparable and 2), the pharmacy student can comprehend reported drug
are inherently bonded in their origin and future directions. metabolites and rationally predict potential drug metabolic
Partial replacement of the traditional lecture-based outcomes.7 Such knowledge and expertise, critical to un-
teaching approach with problem-based learning consider- derstanding pharmacokinetic and pharmacodynamic char-
ably improved the problem-solving skills of medical stu- acteristics of drugs, are unique to pharmacists and certainly
4
 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

Figure 2. Identification of functional groups showing few common metabolic routes; phase I: (1) ester hydrolysis by esterases, (2)
N-dealkylation by CYP enzymes, (3) O-delakylation by CYPs, (4) p-hydroxylation by CYPs; relative rates are: (1) .. (2) . (3) ;
(4); phase II: (5) glucuronidation (or sulphate conjugation), (6) N-acetylation; relative rates are: (5) .. (6). (Adopted from7)

derived from medicinal chemistry instruction in pharmacy play a critical role in sustaining the drug discovery and
school. development process. The subject areas that are fundamen-
tal to drug discovery also serve as sources for a complete
DISCUSSION knowledge base of the diseases and their safe and economic
A review of the evolution and progression of the treatments. By encompassing these into the pharmacy cur-
pharmacy profession reveals that the uniqueness of this riculum, pharmacists become invaluable to maintaining the
profession is the pharmacist’s comprehensive expertise in health and well-being of the community.
medicines and other pharmaceutical products compared The rigorous pharmacy curriculum is intended to im-
with that of other health care professionals. Because med- part a sound knowledge base and prepare the pharmacy
icines are primarily chemical entities, early histories of student to play a central and a dynamic role among health
both pharmacy and medicinal chemistry overlap and are in- care professionals post licensure. Medicinal chemistry,
herently bonded to each other. From the beginning of the a key component of the pharmaceutical science founda-
academic pharmacy program in the United States, medicinal tion, plays a crucial role in the development of such a com-
chemistry has been an “indispensible” component of its cur- petency. The Pharmacy Practice Activity Classification by
riculum. The pharmacists’ unique knowledge of a medicine’s the American Pharmacists Association recognizes phar-
design, pharmacological action, manufacture, storage, use, macist’s other historic roles in pharmaceutical industry,
supply, and handling has elevated the profession to its ap- administration, regulatory agencies, professional associa-
propriate place in the health care sector. These areas of ex- tions, public health, and academia.34 Thus, even from a his-
pertise also led to legislation that increased the pharmacist’s torical perspective, in addition to an interest in knowledge
legal role in patient care, the result of which is today’s phar- enrichment about therapeutic agents, the significance of
maceutical care. Pharmacists cannot afford to ignore their drug research and drug development in the pharmacy cur-
identity as medication safety experts if they want to success- riculum has never diminished, but rather increased.
fully perform and hold on to this assigned responsibility.
The interwoven nature of medicinal chemistry and CONCLUSION
pharmacy are evident in their origins (Appendix 1), as well This article emphasizes the relevance of medicinal
as in the important medicinal chemistry-related intellectual chemistry in the pharmacy curriculum, its role in the evo-
domains. Being a competent pharmacist requires a sound lution of pharmacy, and its paradigm shift to pharmaceu-
knowledge of each of these domains. By embracing the tical care, as well as its history and intellectual domains.
discipline of medicinal chemistry, the pharmacy profession Medicinal chemistry provides a comprehensive under-
can reap enormous benefits. Medicinal chemistry, a unique standing of the underlying principles of drug action and
component of the pharmacy curriculum, imparts vital behavior within the body, which is fundamental to today’s
knowledge and critical-thinking skills to pharmacy students pharmaceutical care and patient counseling. Because ap-
and sets them apart as chemical experts among health care prehensions regarding the relevance of medicinal chemis-
professionals.33 This specialized set of proficiencies in me- try continue to exist, a change in the approach to how
dicinal chemistry and drug discovery, poises the pharmacist medicinal chemistry content is presented is necessary to
as the leader of the health care team in efforts aimed at better fit this basic science into the pharmacy curriculum
providing patient-specific evidence-based care. Medici- under the newly set goals. Some educators are already
nal chemists, as the entrepreneurs and innovators of ther- engaged in this endeavour. Future research/reviews should
apeutic agents, the most important armor of health care, address the scope of medicinal chemistry in the pharmacy
5
 American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

curriculum with appropriate drug class examples. Histori- 15. Xiang X-D, Sun X, Briceno G, Lou Y, Wang K-A, Chang H,
cally, medicinal chemistry has developed hand-in-hand with Wallace-Freedman WG, Chen S-W, Schultz PG. A combinatorial
approach to materials discovery. Science. 1995;268(5218):1738-1740.
the pharmacy profession and has always been at the forefront
16. Timmerman H. Reflection of medicinal chemistry since the
of drug design and discovery. The components of drug de- 1950s. Compr Med Chem II. 2007;8:7-15.
sign and discovery contribute to the pharmacy student’s 17. AACP Institutional Members. http://www.aacp.org/about/
foundational knowledge base and will have a tremendous membership/institutionalmembership/Pages/usinstitutionalmember.
impact in advancing the professional leadership of a phar- aspx. Accessed August 15, 2011.
macist in the pharmaceutical and health care sectors. 18. Burger A. Burger’s Medicinal Chemistry Vol 1. 6th ed. Hoboken,
NJ:John Wiley & Sons, Inc.; 2003.
19. Lomberdino JG, Lowe III JA. The role of medicinal chemist in
ACKNOWLEDGEMENTS drug discovery – then and now. Nat Rev Drug Discov. 2004;3(10):
The authors wish to thank Dr. Gayle Brazeau, Dean, 853-862.
University of New England College of Pharmacy, for her 20. Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor
careful review and constructive suggestions in the manu- expedition: the case histories of omeprazole and esomeprazole. Nat
script preparation. The authors are indebted to Kimberly Rev Drug Discov. 2003;2(2):132-139.
21. Alsharif NZ, Theesen KA, Roche VF. Structurally based
Lindsey, PharmD, BCPS, for a critical review of the therapeutic evaluation: a therapeutic and practical approach to
manuscript. teaching medicinal chemistry. Am J Pharm Educ. 1997;61(1):55-60.
22. Alsharif NZ, Destache CJ, Roche VF. Teaching Medicinal
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6
 Appendix 1. Relationship Between the History of Drug Discovery and Development, Medicinal Chemistry, and Pharmacy1-16
History of Drug Discovery and Development
2735 B.C. 1600 B.C. 400 B.C. 1200s 1500s 1600-1800 1800s 1900s
1. Chinese Egyptian Hippocrates, 1. Alchemists: First half of this 1. Isolation of 1. Salicylic acid 1. Synthesis of barbital
scholar-emperor medicine: Discarides, senna, camphor, century: benzoic acid and synthesis by Kolbe by Fischer and
Sheng Nung: vegetable Pliny, Galen: rhubarb, tamarind, Paracelsus: Father ephedrine (1887) (mid-19th century), Mering (1903)
ch’ang shang to origin metallic salts nutmeg were of today’s medicinal/ paved new synthetic dyes by
treat malaria and galenicals described in pharmaceutical dimension in drug Perkin (1856),
Arabian medical chemistry to discovery from aspirin by Dresser
treatise prepare medicine plant origin (1889) are the
milestones in modern
drug discovery
2. Babylonian - 2. 1240: German 2. Synthesis of 2. Ehrlich’s “Side 2. Henry’s hypothesis
Assyrian Emperor urea paved the chain theory” (1885) on enzyme-substrate
culture: 250 Frederick II: new tool of drug and chemotherapy complex (1903)
vegetable drugs Issued Magna discovery (1891); Fischer’s
Charta of lock-and-key
medicinal chemist theory (1894) are
important
advancements in
drug design and

7
discovery.
3. Grimm’s and
Erlenmeyer’s concepts
of isosterism and
bioisosterism
(1929-1931)
4. Charge transfer
by kosower
(1955), induced-fit
theory by Koshland
(1958), drug
latentiation by Harper
(1959) and prodrug by
Albert (1960),
Hansch’s QSAR
American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

(1960s) and
artificial intelligence
in drug research by
Chu (1974)

(Continued)
 Appendix 1. (Continued )
History of Drug Discovery and Development
2735 B.C. 1600 B.C. 400 B.C. 1200s 1500s 1600-1800 1800s 1900s
5. Purification of
insulin by Benting
and Best (1922),
isolation of penicillin
by Fleming (1929),
discovery of sulfa
antibacterials by
Trefouël, Nitti and
Bovet (1935) and total
synthesis of insulin by
Kamder et al. (1975)
6. Solid phase organic
synthesis (1960s) and
Merrifield’s Nobel
prize for this discovery
in 1984, combinatorial

8
chemistry by Geysen
et al. (1984) and high
throughput screening,
molecular modeling
and rational drug design
History of Medicinal Chemistry
2735 B.C. 1600 B.C. 400 B.C. 1200s 1500-1550 1600-1800 1800s 1900s
1. Chinese Egyptian Hippocrates, 1. Alchemists: Paracelsus: Father 1. Isolation of 1. Both milestones 1. The milestones
scholar- medicine: Discarides, Contributed to of today’s medicinal/ benzoic acid and 1 and 2 above are mentioned in
emperor Sheng vegetable Pliny, Galen: develop pharmaceutical ephedrine are the also considered the the drug design
Nung: ch’ang origin metallic salts medicinal chemistry to milestones in important and development
shang to treat and galenicals chemistry prepare medicine medicinal milestones above (1-6) are
malaria chemistry for medicinal also considered
chemistry era important
milestones in the
American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

modern medicinal
chemistry.

(Continued)
 Appendix 1. (Continued )
History of Medicinal Chemistry
2735 B.C. 1600 B.C. 400 B.C. 1200s 1500-1550 1600-1800 1800s 1900s
2. Babylonian - 2. German 2. Synthesis of 2. This is indeed the 2. Medicinal
Assyrian culture: 250 Emperor urea, the birth of birth period of chemistry received
vegetable drugs Frederick II: new science of modern medicinal formal recognition
Issued Magna organic medicinal chemistry with the in academic
Charta of chemistry inclusion of pharmacy in 1932
medicinal chemist Ehrlich’s “Side
chain theory” and
chemotherapy and
Fischer’s lock-and-
key theory
3. American
Chemical Society
started
Division of
Pharmaceutical
Chemistry
(1909-1920),

9
then Division
of Medicinal
Products (1920-
1948), which
finally took the
name of Division
of Medicinal
Chemistry in 1948.
History of Pharmacy, Academic Pharmacy and Medicinal Chemistry in Academic Pharmacy
2735 B.C. 1600 B.C. 400 B.C. 1100s 1500-1550 1600-1800 1800s 1900s
1. Chinese Egyptian Hippocrates, Public pharmacy Paracelsus: Father 1777: the first 1. Philadelphia College 1. 4-Year B.S. Pharmacy
scholar- medicine: Discarides, began in Italy, of preparing pharmacy of Pharmacy – the degree as the requirement
emperor Sheng vegetable Pliny, Galen: France and medicine that a school first institute for for pharmacy licensure
Nung: ch’ang origin – metallic salts elsewhere pharmacy does. in France awarding pharmacy in the U.S. in 1932, with
American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

shang to treat Examples of and Galenicals – Essentially the Diploma in America medicinal chemistry as an
malaria ancient examples of same as the in 1821. essential component in
apothecary apothecary/ medicinal its curriculum.
pharmacy chemistry

(Continued)
 Appendix 1. (Continued )

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History of Pharmacy, Academic Pharmacy and Medicinal Chemistry in Academic Pharmacy
2735 B.C. 1600 B.C. 400 B.C. 1100s 1500-1550 1600-1800 1800s 1900s
2. Babylonian - 2. William Proctor 2. University of Southern
Assyrian Jr. defined pharmacy California started first 6-Year
culture: 250 in 1869 as the “art (2 1 4) Doctor of Pharmacy
vegetable drugs of preparing and (Pharm. D.) degree in 1960,
These are dispensing medicine” while most institutes
examples of selected 5-year (2 1 3) B.S.
ancient Pharmacy degree as standard
apothecary with medicinal chemistry and
pharmaceutics as the core
requirements.
3. The “Paradigm Shift”:
Omnibus Budget
Reconciliation Act 1990
(OBRA 1990) increased
the responsibility of
pharmacists by incorporating

10
the key concept of
“Pharmaceutical Care” as
the major role of pharmacist.
4. 6-Year (2 1 4) Pharm. D.
degree became the standard
requirement for pharmacy
licensure all over the U.S.
to achieve the desired
outcome
by the paradigm shift.
5. ACPE Standard 13
(Curriculum
Core – Knowledge, Skills,
Attitudes, and Values) has
clearly stated the need of
American Journal of Pharmaceutical Education 2011; 75 (8) Article 161.

medicinal chemistry in
Pharm. D. curriculum in its
revised appendix B effective
since 2007.