14. HIV Integrase Inhibitors: From Diketo Acids to Heterocyclic Templates: History of HIV Integrase Medicinal Chemistry at Merck West Point and Merck Rome (IRBM) Leading to Discovery of Raltegravir

  1. Nouri Neamati
  1. Melissa S. Egbertson1,
  2. Neville J. Anthony1 and
  3. Vincenzo Summa2

Published Online: 28 SEP 2011

DOI: 10.1002/9781118015377.ch14

HIV-1 Integrase: Mechanism and Inhibitor Design

HIV-1 Integrase: Mechanism and Inhibitor Design

How to Cite

Egbertson, M. S., Anthony, N. J. and Summa, V. (2011) HIV Integrase Inhibitors: From Diketo Acids to Heterocyclic Templates: History of HIV Integrase Medicinal Chemistry at Merck West Point and Merck Rome (IRBM) Leading to Discovery of Raltegravir, in HIV-1 Integrase: Mechanism and Inhibitor Design (ed N. Neamati), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/9781118015377.ch14

Editor Information

  1. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, California, USA

Author Information

  1. 1

    Medicinal Chemistry Department, Merck Research Laboratories, West Point, Pennsylvania, USA

  2. 2

    Medicinal Chemistry Department, IRBM P. Angeletti—Merck Research Laboratories, Rome, Italy

Publication History

  1. Published Online: 28 SEP 2011
  2. Published Print: 9 SEP 2011

Book Series:

  1. Wiley Series in Drug Discovery and Development

Book Series Editors:

  1. Binghe Wang

ISBN Information

Print ISBN: 9780470184745

Online ISBN: 9781118015377

SEARCH

Keywords:

  • HIV integrase inhibitors;
  • heterocyclic rings;
  • polar heterocyclic substituents, 5-position

Summary

This chapter contains sections titled:

  • Introduction

  • First Leads

  • SAR of Diketo Acid Series

  • Diketo Acid Is Replaced

  • SAR of Diaryl Diketones

  • Replacement of Diaryl Diketone

  • Combination of 1,6-Naphthyridine and Amide to Give New Lead Structures

  • Another Template

  • Proof of Concept

  • Search for More Potent Analog of 16-2: 5-Position Heterocycles and 5-Position Amides

  • Development of Potent Analog of 16-2

  • Development of IRBM Hydroxypyrimidinones: Raltegravir

  • Summary: Diketo Acids as Leads for Integrase Inhibitor Development

  • Acknowledgments

  • References