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IJRPC 2011, 1(3) Sathyaraj et al. ISSN: 22312781
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY
Review Article
Available online at www.ijrpc.com
RECENT TRENDS IN PHARMACEUTICAL CHEMISTRY FOR DRUG
DISCOVERY
Sathyaraj A
Department of Chemistry, Krishna University, Machilipatnam, Andhra Pradesh, India.
*Corresponding Author: arsathya.pharma@gmail.com
ABSTRACT
Pharmaceutical chemistry is used to the development and assessment of therapeutic
compounds. And the Pharmaceutical chemistry encompasses drug design, drug
synthesis, and the evaluation of drug efficacy (how effective it is in treating a condition)
and drug safety. Drug discovery is the core of pharmaceutical chemistry. The drug
discovery process includes all the stages of drug development, from targeting a disease or
medical condition to toxicity studies in animals, or even, by some definitions, testing the
drug on human subjects. The field of pharmaceutical chemistry is diverse and involves
many areas of expertise. Natural-product and analytical chemists isolate and identify
active components from plant and other natural sources. Theoretical chemists construct
molecular models of existing drugs to evaluate their properties. These computational
studies help medicinal chemists and bioengineers design and synthesize compounds with
enhanced biological activity. Pharmaceutical chemists evaluate the bioactivity of drugs
and drug metabolites. Toxicologists assess drug safety and potential adverse effects of
drug therapy. When a drug has been approved for human studies, clinicians and
physicians monitor patients' response to treatment with the new drug. The impact of
pharmaceutical chemistry on the normal human life span and on the quality of life
enjoyed by most people is hard to overestimate.
Keywords: Drug Design, Drug Synthesis, Evaluation of Drug Efficacy and Drug safety.
INTRODUCTION
Pharmaceutical chemists are involved in the trained pharmacists and physicians how to
development and assessment of therapeutic prepare medicinal remedies from natural
compounds. Pharmaceutical chemistry organic products or inorganic materials. Herbal
encompasses drug design, drug synthesis, and medications and folk remedies dating back to
the evaluation of drug efficacy (how effective it ancient Egyptian, Greek, Roman, and Asian
is in treating a condition) and drug safety. Prior societies were administered without any
to the nineteenth century, schools of pharmacy knowledge of their biological mechanism of
action. It was not until the early 1800s that
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IJRPC 2011, 1(3) Sathyaraj et al. ISSN: 22312781
scientists began extracting chemicals from plants between the drug and its target in biological
with purported therapeutic properties to isolate systems. Molecular modeling software depicts
the active components and identify them. By three-dimensional images of a chemical.
discovering and structurally characterizing Mathematical operations adjust the positions of
compounds with medicinal activity, chemists the atoms in the molecule in an attempt to
are able to design new drugs with enhanced accurately portray the size and shape of the
potency and decreased adverse side effects. drug, and the location of any charged groups.
Chemists can vary the atoms or groups within
Pharmaceutical Chemistry in Drug Discovery the model and predict the effect the
and Novel Drug Delivery System transformation has on the molecular properties
Drug discovery is the core of pharmaceutical of the drug. In this way, new compounds can be
chemistry. The drug discovery process includes designed.
all the stages of drug development, from Advances in technology have made it possible
targeting a disease or medical condition to for medicinal chemists to synthesize a vast
toxicity studies in animals, or even, by some number of compounds in a relatively short time,
definitions, testing the drug on human subjects. a process referred to as combinatorial chemistry. In
Typically, conditions that affect a larger this technique, one part of a molecule is
percentage of the population receive more maintained, as different chemical groups are
attention and more research funding. Antiulcer attached to its molecular framework to produce
drugs and cholesterol- reducing agents are a series of similar molecules with distinct
currently the therapeutic areas of greatest structural variations. Combinatorial libraries of
emphasis. To develop a drug to target a specific these molecular variants are thus created.
disease, researchers try to understand the Every chemical that is synthesized must be
biological mechanism responsible for that tested for biological activity. In vitro testing
condition. If the biochemical pathways leading involves biological assays outside a living
up to the diseases are understood, scientists system. For example, if the desired effect of a
attempt to design drugs that will block one or drug is to inhibit a particular enzyme, the
several of the steps of the disease's progress. enzyme can be isolated from an organ and
Alternatively, drugs that boost the body's own studied in a test tube. New technologies have
defense mechanism may be appropriate. made it possible to assay large numbers of
How do chemists "discover" drugs? Often there compounds in a short period. High-throughput
is an existing remedy for a condition, and drug screening allows pharmaceutical chemists
scientists will evaluate how that drug exerts its to test between 1,000 and 100,000 chemicals in a
actions. Once the drug's structure is known, the single day! A compound that demonstrates
drug can serve as a prototype or "lead some biological activity will undergo further
compound" for designing more effective tests, or it may be chemically modified to
therapeutic agents of similar chemical structure. enhance its activity. As a consequence, chemical
Lead compounds are molecules that have some libraries consisting of potentially therapeutic
biological activity with respect to the condition compounds are developed. Each of these
under investigation. However, the lead compounds can then serve as leads for the
compound may not be effective in combating development of new drugs to be screened.
the disease, or it may produce undesirable side Once a drug shows promise in vitro as a
effects. Lead optimization involves chemical therapeutic agent, it must also be screened for
modifications to the lead compound to produce toxic properties. Adverse drug side effects are
a more potent drug, or one with fewer or often due to the interaction of the drug with
decreased adverse effects. biological molecules other than the desired
Computers have transformed the drug target. It is very rare that a drug interacts with
discovery process. Rational drug design only one type of molecule in a living system.
involves computer-assisted approaches to Drug selectivity refers to the ability of the
designing molecules with desired chemical compound to interact with its target, not with
properties. Rational drug design is based on a other proteins or enzymes in the system. To
molecular understanding of the interactions investigate drug toxicity, animal studies are
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IJRPC 2011, 1(3) Sathyaraj et al. ISSN: 22312781
performed. These studies also estimate administered a placebo. In a double-blind study,
mutagenicity, that is, whether the compound neither the physician nor the patient knows
under investigation damages genetic material. whether the drug, a placebo, or a related remedy
Rarely does a drug pass through a biological has been administered. Therapy is monitored by
system unchanged. Most drugs undergo an outside group.
chemical transformations (in a process known as Phase III and phase IV clinical trials involve
drug metabolism) before they are excreted from larger populations. During phase III trials,
the body. The drug transformation products which can last two to eight years, a drug is often
(metabolites) must be identified so that their brought to market. Phase IV studies continue
toxicological profiles can be determined. after the drug is being marketed.
Since the 1970s more attention has been given to
drug formulation and methods of drug delivery. Combinatorial Chemistry in Drug Discovery
Historically, drugs have been administered Combinatorial chemistry is a sophisticated set of
orally, as a pill or a liquid, or in an injectable techniques used to synthesize, purify, analyze,
form. The goal of drug-delivery systems is to and screen large numbers of chemical
enable controlled and targeted drug release. compounds, far faster and cheaper than was
Today, many medications are commonly previously possible. The direct precursor of
introduced as inhalants or in a time-release combinatorial chemistry was the solid-phase
formulation, either encapsulated in a synthesis of polypeptides developed by
biodegradable polymer or by means of a American biochemist Robert Bruce Merrifield in
transdermal patch. the 1960s, followed by the advances in
laboratory automation since then. Initial
Pharmaceutical Chemistry in Clinical Trials development of the field has been led by the
Once scientists and government regulatory pharmaceutical industry in the search for new
agencies have determined the drug candidate to drugs, but its applications are spreading into
be relatively safe, it can enter into clinical trials. other fields of chemistry. Other terms associated
The clinical stage involves four phases of testing with this field are parallel array synthesis and
on human volunteers. Animal studies and in high-throughput chemistry.
vitro testing continue during clinical Whereas classical synthetic chemistry involves
investigations of a drug. Drug-therapy the stepwise synthesis and purification of a
evaluation is very costly and time consuming. single compound at a time, combinatorial
Phase I clinical trials evaluate drug tolerance and chemistry makes it possible to synthesize
safety in a small group of healthy adult thousands of different molecules in a relatively
volunteers. Phase II trials continue to assess the short amount of time, usually without the
drug's safety and effectiveness in a larger intermediate separation of compounds involved
population. Volunteers participating in phase I in the synthetic pathway, and with a high
trials understand that they are receiving degree of automation. Such procedures result in
experimental therapy. While those patients the production of new compounds faster and in
involved in phase II clinical trials are made greater numbers than is possible with standard
aware of the medication and any known side synthetic methods. The first and still the most
effects, some of the volunteers may be common type of combinatorial synthesis
administered a placebo (a compound with no involves attaching a molecular species onto a
pharmacological activity against the condition macroscopic substrate such as a plastic bead and
being treated) rather than the drug being performing one or several well-characterized
studied. In a blind study, only the physician chemical reactions on the species. After each
administering therapy knows whether the reaction, the product mixture can be split among
patient is receiving the drug or a placebo. Both several reaction containers and then recombined
groups of patients are monitored, and after the reaction (a procedure called mix and
physicians or clinicians evaluate whether there split), or else carried out in parallel containers.
is significant improvement in the condition of The resulting mixture of compounds is referred
the group receiving the experimental drug, to as a molecular library and can contain many
compared with those individuals who were thousands of individual compounds. The
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IJRPC 2011, 1(3) Sathyaraj et al. ISSN: 22312781
analysis, or screening, of these libraries to considered, as the complexity and limitations of
identify the compounds of interest, along with drug discovery programs that are based on
their subsequent isolation and identification, can biochemical screens of large compound
be completed by a variety of methods. One collections have been major factors in
example is iterative deconvolution; it involves the stimulating the growth of this modality.
successive identification of each of the units
backward along the chain of synthesized units. CONCLUSION
Another, called positional scanning, requires the The field of pharmaceutical chemistry is diverse
multiple synthesis of a library, each time and involves many areas of expertise. Natural-
varying the location of a known unit along the product and analytical chemists isolate and
chain and comparing the activities of the identify active components from plant and other
resulting libraries. More recent advances in natural sources. Theoretical chemists construct
library screening involve the "tagging" of a molecular models of existing drugs to evaluate
substrate with tiny radio frequency transmitters their properties. These computational studies
or unique two-dimensional barcodes. Another help medicinal chemists and bioengineers
important recent advance by researchers allows design and synthesize compounds with
combinatorial syntheses to be carried out in enhanced biological activity. Pharmaceutical
solution, which further extends the scope and chemists evaluate the bioactivity of drugs and
utility of this field. drug metabolites. Toxicologists assess drug
Although the initial applications of safety and potential adverse effects of drug
combinatorial and high-throughput chemistry therapy. When a drug has been approved for
have occurred in the pharmaceutical field, the human studies, clinicians and physicians
same techniques are now being used monitor patients' response to treatment with the
successfully to aid in the discovery of new new drug. The impact of pharmaceutical
catalysts, polymers, and high temperature chemistry on the normal human life span and on
superconductors. the quality of life enjoyed by most people is
hard to overestimate.
Pharmaceutical Chemistry for Drug Discovery Each of the aforementioned technological
Significance of Recent Trends reviews the state modalities is viewed in terms of practical
of the art and aims to determine the significance examples and commercial activity. Outsourcing
of technology and market trends in arises as a prominent theme in the applications
pharmaceutical chemistry for advancing realm, with special emphasis on companies with
productivity in drug discovery. Although the primary operations in countries with developing
fundamental task of medicinal chemists has not economies, notably China, India, and Russia.
changed drastically over time, the chemical and Among 32 companies considered, structure-
computational tools and perspectives at their based drug design is the most prevalent activity
disposal have advanced significantly. One in with most players emphasizing the fragment-
particular, fragment-based drug design, stands based variation. Virtual screening is the second-
out as promising major improvements in most prevalent modality, whereas natural
research productivity. products, diversity-oriented synthesis, and
We examine pharmaceutical chemistry-related chemogenomics appear in only a small minority
approaches and methodologies that drug of cases.
discovery organizations employ in an effort to A thorough analysis of recent trends in
increase productivity in early drug discovery pharmaceutical chemistry and evaluation of
and decrease attrition at later pipeline stages. their significance for advancing productivity in
Key topics considered include structure-based drug discovery is presented.
drug design, fragment-based drug design, This report includes:
natural products-based drug design, diversity- 1. A critical evaluation of chemical and
oriented synthesis, and chemogenomics. An computational technological modalities,
overall assessment of the current and potential their current and potential value, and
value of these approaches is presented. Various their commercial manifestations.
flavors of computer-aided drug design are also
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