Medicinal Chemistry is the Chemistry Discipline Concerned With the Design

8/12/2019 Medicinal Chemistry is the Chemistry Discipline Concerned With the Design

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ASSIGNMENT

ON

Medicinal Chemistry

(definition, scopes, limitations andaromatic and

heteroaromatic compounds)

Course name: Medicinal Chemistry I

Course code: PHRM -302

SUBMITTED TO:

MEHREEN RAHMAN

Lecturer

Department of Pharmacy

SUBMITTED BY:

SAMIYA KHONDAKER RINTA

ID: 2010-3-70-048

Submission date: 28thJanuary, 2014


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MEDICINAL CHEMISTRY

Medicinal chemistry is the chemistry discipline concerned with the design, development,

synthesis, biochemical effects, regulatory and ethical aspects of pharmaceutical drugs for clinical

use in the treatment of disease. It is a highly interdisciplinary science combining organic

chemistry with biochemistry, computational chemistry, biology, molecular biology, physiology,pharmacology statistics, and physical chemistry to identify, develop and synthesize chemical

agents that have a therapeutic use and also to evaluate the properties of existing drugs.

Medicinal chemistry provides pharmacy students with a thorough understanding of drug

mechanisms of action, structure-activity relationships (SAR), acid-base and physicochemical

properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles.

A comprehensive 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.

Scopes of Medicinal Chemistry

1. Rational design and synthesis of lead compounds and modification of novel biologicallyactive molecules.

2. New drug discovery technologies, including HTS and combinatorial chemistry.3. Computational and virtual approaches in synthesis and modeling.4. Therapeutic strategies and emerging targets.5. Evaluation and development of chemical structural feature (structure-activity relationship),

physico-chemical property, stability.

6. Development of new drug target and delivery, such as prodrug/co-drug strategies.7.

Studies involving the use of NMR, X-ray crystallography, CD and other biophysicaltechniques.

8. Structural basis for in vitro/vivo mechanisms of action and molecular recognition (e.g., drug-receptor interactions).

9. Evaluation and development of pharmacokinetic (ADME) parameters; side-effects andadverse effects; and toxicological investigations of new drug compounds.

10.Purification and proper characterization of the new chemicals.Limitations of Medicinal Chemistry

Medicinal chemistry has become the most time-consuming step in the drug discovery process,

and new discovery technologies are likely to increase the burden on lead optimization and

refinement. Although medicinal chemists are able to optimize hits/leads very quickly and

successfully with regard to potency, improving the kinetic, metabolic and toxicological

properties of a compound remains as a difficult obstacle and a limitation.

The search for new drugs to treat a wide range of human ailments such as heart disease and

cancer remain a great challenge to the pharmaceutical and biotechnology industries and it is still


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where medicinal chemistry has limited information and progress.

There are limited success rates for new biological targets. Recent data indicate that productivity

has not kept pace with increasing resource allocation to the drug discovery process. Large

numbers of drugs fail in pre-clinical stages due to poor pharmacokinetics and oral bioavailability.

Moreover large amount of expenses occur in these research processes. This is responsible for thevery high cost of bringing a drug to market.

With the pressure to increase the number of drugs receiving market approval, the science of

medicinal chemistry needs to change in order to address the high attrition rates in pre-clinical

and early clinical earlier on in development.

AROMATIC AND HETEROAROMATIC COMPOUNDS

Aromatic compounds: These compounds are hydrocarbons having a closed ring of alternate

single and double bonds with delocalized electrons. The chemically simplest aromatic

hydrocarbon is benzene.

Figure 1: Benzene

Heterocyclic compounds:These compounds are also aromatic compounds. In these compounds,

at least one carbon atom is replaced by one of the heteroatoms oxygen, nitrogen, or sulfur.

Examples of non-benzene compounds with aromatic properties are furan, a five-membered ring

that includes an oxygen atom, and pyridine, a six-membered ring containing one nitrogen atom.

Figure 2: Pyridine Figure 3: Furan

Differences between aromatic hydrocarbons and heterocyclic compounds

Aromatic hydrocarbons Heterocyclic compounds

Compounds contain carbon and hydrogen

atoms only.

Compounds have at least one carbon atom

replaced by one of the heteroatoms oxygen,

nitrogen, or sulfur.

Have higher C:H ratio than heterocyclic

compounds.

Have lower C:H ratio than aromatic

hydrocarbons.

Electron donating capacity of benzene is more

than pyrimidine (a 6-membered heterocyclic

compound) but less than furan (a 5-membered

heterocyclic compound).

Electron donating capacity of furan is more than

benzene due to the electron-donating effects of

the oxygen heteroatom and pyrimidine has less

electron donating capacity than benzene.


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Resonance energy of benzene is 130-

140kJ/mol, which is higher than that of 5-

membered heterocyclic compounds, like furan

and pyrrole.

Resonance energy of 5-membered heterocyclic

compounds like furan is 67 kJ/mol and that of

pyrrole is 88 kJ/mol, both of which are less than

resonance energy of benzene.

Benzene is less reactive than furan, a 5-

membered heterocyclic compounds because of

absence of lone pair electrons.

5-membered heterocyclic compounds, like furan,

are more reactive than benzene because of lone

pair electrons.

Benzene undergoes electrophilic aromatic

substitution reactions more readily than 6-

membered heterocyclic compounds, like

pyrimidine.

6-membered heterocyclic compounds, like

pyridine, enter into electrophilic aromatic

substitution reactions only under vigorous

conditions.

Benzene undergoes electrophilic aromatic

substitution reactions less readily than 5-

membered heterocyclic compounds, like

pyrrole.


pyrrole, enter more readily into electrophilic

aromatic substitution reactions than benzene.

Benzene does not undergo diazotization and

Reimer-Tiemann reactions.


pyrrole, undergo diazotization and Reimer-

Tiemann reactions.

No lone pair electrons are involved in

satisfying the criteria for aromaticity.

In 5-membered heterocyclic compounds, lone

pair electrons from N, O or S is involved in

occupying a p orbital in order to satisfy the

criteria for aromaticity.

Benzene shows more aromaticity than

heterocyclic compounds.

Since one or more of the atoms in the aromatic

ring is of an element other than carbon so the

ring's aromaticity is less than that of benzene.

Since in aromatic hydrocarbons, lone pair

electrons are not in the aromatic ring,

protonation does not does not affect

aromaticity of the compound.

Since in 5-membered heterocyclic compounds,

lone pair electrons are in the aromatic ring,

protonation destroys aromaticity of the

compound.


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REFERENCES

Bahl, A. and Bahl, B.S. (2006) A Textbook of Organic Chemistry, 18th

edition, Rajendra

Ravindra Printers: New Delhi.

Jones,

R. A. (2009) The Chemistry of Heterocyclic Compounds.John Wiley & Sons:

New York

Katritzky,A. R. (2003) Short Course on Heterocyclic Chemistry University of Florida

Krchnak, V. and Dalton C. (2002) GRABBING GOLDEN: Medicinal chemists may soon reap

the benefits of solid-phase split-and-pool combichem techniques.Modern Drug Discovery.

Khurana J.M. (2006) ORGANIC CHEMISTRY: Chemistry of Heterocyclic Compounds

University of Delhi

Lombardino, J. G. and Lowe,J. A. (2004) THE ROLE OF THE MEDICINAL CHEMIST IN

DRUG DISCOVERYTHEN AND NOWNature Reviews: Drug Discovery

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Medicinal Chemistry is the Chemistry Discipline Concerned With the Design