This document discusses pharmacophore modeling and computer-aided drug design. It begins with objectives of studying pharmacophore modeling methods and techniques for lead prioritization and optimization. An introduction defines pharmacophore as the schematic representation of bioactive functional groups and their distances. It then reviews surveys on G-protein coupled receptors in drug development and advances in pharmacophore modeling applications. The document outlines the process of pharmacophore-based drug design and provides an example using morphine. It also shows 3D pharmacophores and how computer-aided design is used. It concludes that pharmacophore approaches have been major tools in drug discovery and various methods have been applied successfully in virtual screening and lead optimization.

1. PROJECTED BY:-VINOD G.TONDE
GUIDED BY:- PROF. RANE P. V.
8/2/2014
RAJMATA JIJAU SHIKSHAN PRASARAK MANDAL’s
COLLEGE OF PHARMACY
DUDULGAON, PUNE- 412105

2. CONTENTS
Objective
Introduction
Review of Survey
Pharmacophore-based Drug Design
Drug Design
Computer Aided Drug Design
Future Use
Conclusion
References
1

3. OBJECTIVE
To concept of pharmacophore modeling & drug designing.
To study the new advance in pharmacophore modeling and drug
designing.
To study the methods of pharmacophore modeling & drug
designing.
To study the concentration lead prioritization & lead
optimization
2

4. INTRODUCTION OF PHARMACOPHORE
‘’The schematic representation of nature of bioactive functional group’s
along with their interatomic distance is known as pharmacophore’’
3

5. Review of Survey
1 I want a new drug: G-protein-coupled receptors in drug development
Abstract
Huey Lewis and the News summed it up nicely in their 1980s hit record: ‘I want a new drug, one that won’t
make me sick, one that won’t make me crash my car, or make me feel three feet thick’. The song could be
an anthem for drug discovery in the pharmaceutical industry. We all want new and better drugs with fewer
side effects, which are effective for combating the major diseases of our time: cancer, heart disease,
obesity and autoimmune diseases.
2 Pharmacophore modeling and applications in drug discovery: challenges and recent advances
Abstract
Pharmacophore approaches have become one of the major tools in drug discovery after the past century's
development. Various ligand-based and structure-based methods have been developed for improved
pharmacophore modeling and have been successfully and extensively applied in virtual screening, de
novo design and lead optimization. Despite these successes, pharmacophore approaches have not
reached their expected full capacity, particularly in facing the demand for reducing the current expensive
overall cost associated with drug discovery and development.
4

6. Pharmacophore-based Drug Design
Activity data
Test activity
Buy or synthesise ‘hits’
Generate
pharmacophore
Search compound
library for actives
5

7. Drug Design
The process of finding drug by design.
 Based on what the drug targeting?
Metabolic or Signaling pathway
“A substances used in
the diagnosis,
treatment or
prevention of disease.
Specific for disease or pathology.
Drugs
Bind to active site & Work.
6

8. HO
O
NMe
HO
MORPHINE
Pharmacophore-based Drug
Example,
Analgesic
Anti-Alzheimer
Anti-Diabetic
Anti-Histamine
7

9. 3D Pharmacophore
8
Computer aided drug design

10. O
N
Ar
9

11. O
3D Pharmacophore
N
Ar
11.3o
150o
2.798 A
18.5o
7.098 A
4.534 A
10

12. HBA
Bonding type
pharmacophore
Ionic
vdW
11.3o
150o
2.798 A
18.5o
7.098 A
4.534 A
11

13. Future use
This review may helpful for researcher in development of drugs
by pharmacophore modeling. computer aided drug design (CADD)
strategies have been applied successfully in drug development
processes.
The current status of CADD includes both modeling and
informatics with equal and synergistic contributions. Although a lot
has been done in this area over the past twenty years, there is still a
lot of scope left for future growth.
12

14. Conclusions
Pharmacophore approaches have become one of the major tools in drug discovery
after the past century’s development.
Various ligand-based and structure-based methods have been developed for
improved pharmacophore modeling and have been successfully and extensively applied
in virtual screening, de novo design and lead optimization.
The Pharmacophore based drug design is useful in discovery and development of
drugs of belonging to various categories like anti-Alzheimer's agents, kinase 2
inhibitors, antidyslipidemic , Anti-diabetic and many more.
13

15. 
References
1Ehrlich, P. (1909) Ueber den jetzigen Stand der
Chemotherapie. Ber. Dtsch. Chem.Ges. 42,
17–47
An introduction to Medicinal Chemistry – Graham L Patrick
Kramer, J.A., Sagartz, J.E. and Morris, D.L. (2007) Nature
London) 6, 636–649.
Drug Discovery Today, Volume 11, Issues 11–12, June 2006, Pages 481-493
Sabine Schlyer, Richard Horuk
14
Drug Discovery Today, Volume 15, Issues 11–12, June
2010, Pages 444-450 Sheng-Yong Yang

16. Thank You