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

Objective

Introduction

Review of Survey

Pharmacophore-based Drug Design

Drug Design

Computer Aided Drug Design

Future Use

Conclusion

References

CONTENTS

1

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

INTRODUCTION OF PHARMACOPHORE

‘’The schematic representation of nature of bioactive functional group’s

along with their interatomic distance is known as pharmacophore’’

3

1 I want a new drug: G-protein-coupled receptors in drug development

AbstractHuey 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.

Review of Survey

2 Pharmacophore modeling and applications in drug discovery: challenges and recent advances

AbstractPharmacophore 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

Pharmacophore-based Drug Design

Activity data

Test activity

Buy or synthesise ‘hits’

Generate

pharmacophore

Search compound

library for actives

5

“A substances used in

the diagnosis,

treatment or

prevention of disease.

Drug Design

The process of finding drug by design.

Based on what the drug targeting?

Metabolic or Signaling pathway

Specific for disease or pathology.

Drugs

Bind to active site & Work.

6

O

NMe

HO

HO

MORPHINE

Example,

Analgesic

Anti-Alzheimer

Anti-Diabetic

Anti-Histamine

Pharmacophore-based Drug

7

3D Pharmacophore

8

Computer aided drug design

O

N

Ar

9

O

N

Ar

11.3o

150o

18.5o

7.098 A

2.798 A

4.534 A

3D Pharmacophore

10

HBA

Ionic

vdW

11.3o

150o

18.5o

7.098 A

2.798 A

4.534 A

Bonding type

pharmacophore

11

Future use

This review may helpful for researcher in development of drugsby pharmacophore modeling. computer aided drug design (CADD)strategies have been applied successfully in drug developmentprocesses.

The current status of CADD includes both modeling andinformatics with equal and synergistic contributions. Although a lothas been done in this area over the past twenty years, there is still alot of scope left for future growth.

12

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

Kramer, J.A., Sagartz, J.E. and Morris, D.L. (2007) Nature

London) 6, 636–649.

References

An introduction to Medicinal Chemistry – Graham L Patrick

1Ehrlich, P. (1909) Ueber den jetzigen Stand der

Chemotherapie. Ber. Dtsch. Chem.Ges. 42,

17–47

14

Drug Discovery Today, Volume 11, Issues 11–12, June 2006, Pages 481-493

Sabine Schlyer, Richard Horuk

Drug Discovery Today, Volume 15, Issues 11–12, June

2010, Pages 444-450 Sheng-Yong Yang

Thank You