The importance of molecular design principles in delivering high quality pharmaceutical candidates

Thomas E. Prisinzano

doi:10.1007/978-1-4939-1399-2_5

The importance of molecular design principles in delivering high quality pharmaceutical candidates

Thomas E. Prisinzano

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

1 Scopus citations

Abstract

High throughput screening of large chemical libraries of compounds is a proven way to identify novel chemical entities that target a biological system of interest. This technology is being used by industry and a growing number of academic screening centers for drug discovery campaigns. Unfortunately, many of the components of screening libraries have poor drug-like properties and require optimization. Typical components of a screening hit that need to be optimized include water solubility, reduced potential for toxicity, and metabolic stability. Presently, methods to alter individual molecular properties are not well elucidated. This chapter will discuss the molecular design principles that have been used successfully to alter the physiochemical properties of molecules through medicinal chemistry. Insights will be provided into the differences in approaches needed for optimization of a biological probe for target validation versus that of a hit to lead campaign, the design of more drug-like libraries, and the over-reliance of potency in optimization campaigns.

Original language	English
Title of host publication	Discovering and Developing Molecules with Optimal Drug-Like Properties
Pages	177-191
Number of pages	15
ISBN (Electronic)	9781493913992
DOIs	https://doi.org/10.1007/978-1-4939-1399-2_5
State	Published - Jan 1 2015

Bibliographical note

Funding Information:
This chapter is based in part on a short course in Contemporary Medicinal Chemistry given by Professors Lester A. Mitscher and Thomas E. Prisinzano provided by the International Organization for Chemical Sciences in Development (IOCD). The author wishes to thank the National Institute on Drug Abuse (DA018151) for financial support of the medicinal chemistry described in the case study. The content is the sole responsibility of the author and does not necessarily represent the official views of the National Institute on Drug Abuse, National Institutes of Health.

Publisher Copyright:
© American Association of Pharmaceutical Scientists 2015.

ASJC Scopus subject areas

Medicine (all)

Access to Document

10.1007/978-1-4939-1399-2_5

Cite this

@inbook{617fa022cfb243be987321370ac7d315,

title = "The importance of molecular design principles in delivering high quality pharmaceutical candidates",

abstract = "High throughput screening of large chemical libraries of compounds is a proven way to identify novel chemical entities that target a biological system of interest. This technology is being used by industry and a growing number of academic screening centers for drug discovery campaigns. Unfortunately, many of the components of screening libraries have poor drug-like properties and require optimization. Typical components of a screening hit that need to be optimized include water solubility, reduced potential for toxicity, and metabolic stability. Presently, methods to alter individual molecular properties are not well elucidated. This chapter will discuss the molecular design principles that have been used successfully to alter the physiochemical properties of molecules through medicinal chemistry. Insights will be provided into the differences in approaches needed for optimization of a biological probe for target validation versus that of a hit to lead campaign, the design of more drug-like libraries, and the over-reliance of potency in optimization campaigns.",

author = "Prisinzano, {Thomas E.}",

note = "Funding Information: This chapter is based in part on a short course in Contemporary Medicinal Chemistry given by Professors Lester A. Mitscher and Thomas E. Prisinzano provided by the International Organization for Chemical Sciences in Development (IOCD). The author wishes to thank the National Institute on Drug Abuse (DA018151) for financial support of the medicinal chemistry described in the case study. The content is the sole responsibility of the author and does not necessarily represent the official views of the National Institute on Drug Abuse, National Institutes of Health. Publisher Copyright: {\textcopyright} American Association of Pharmaceutical Scientists 2015.",

year = "2015",

month = jan,

day = "1",

doi = "10.1007/978-1-4939-1399-2_5",

language = "English",

isbn = "9781493913985",

pages = "177--191",

booktitle = "Discovering and Developing Molecules with Optimal Drug-Like Properties",

}

TY - CHAP

T1 - The importance of molecular design principles in delivering high quality pharmaceutical candidates

AU - Prisinzano, Thomas E.

N1 - Funding Information: This chapter is based in part on a short course in Contemporary Medicinal Chemistry given by Professors Lester A. Mitscher and Thomas E. Prisinzano provided by the International Organization for Chemical Sciences in Development (IOCD). The author wishes to thank the National Institute on Drug Abuse (DA018151) for financial support of the medicinal chemistry described in the case study. The content is the sole responsibility of the author and does not necessarily represent the official views of the National Institute on Drug Abuse, National Institutes of Health. Publisher Copyright: © American Association of Pharmaceutical Scientists 2015.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - High throughput screening of large chemical libraries of compounds is a proven way to identify novel chemical entities that target a biological system of interest. This technology is being used by industry and a growing number of academic screening centers for drug discovery campaigns. Unfortunately, many of the components of screening libraries have poor drug-like properties and require optimization. Typical components of a screening hit that need to be optimized include water solubility, reduced potential for toxicity, and metabolic stability. Presently, methods to alter individual molecular properties are not well elucidated. This chapter will discuss the molecular design principles that have been used successfully to alter the physiochemical properties of molecules through medicinal chemistry. Insights will be provided into the differences in approaches needed for optimization of a biological probe for target validation versus that of a hit to lead campaign, the design of more drug-like libraries, and the over-reliance of potency in optimization campaigns.

AB - High throughput screening of large chemical libraries of compounds is a proven way to identify novel chemical entities that target a biological system of interest. This technology is being used by industry and a growing number of academic screening centers for drug discovery campaigns. Unfortunately, many of the components of screening libraries have poor drug-like properties and require optimization. Typical components of a screening hit that need to be optimized include water solubility, reduced potential for toxicity, and metabolic stability. Presently, methods to alter individual molecular properties are not well elucidated. This chapter will discuss the molecular design principles that have been used successfully to alter the physiochemical properties of molecules through medicinal chemistry. Insights will be provided into the differences in approaches needed for optimization of a biological probe for target validation versus that of a hit to lead campaign, the design of more drug-like libraries, and the over-reliance of potency in optimization campaigns.

UR - http://www.scopus.com/inward/record.url?scp=84944096758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944096758&partnerID=8YFLogxK

U2 - 10.1007/978-1-4939-1399-2_5

DO - 10.1007/978-1-4939-1399-2_5

M3 - Chapter

AN - SCOPUS:84944096758

SN - 9781493913985

SP - 177

EP - 191

BT - Discovering and Developing Molecules with Optimal Drug-Like Properties

ER -

The importance of molecular design principles in delivering high quality pharmaceutical candidates

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this