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Synthesis 2020; 52(24): 3693-3713
DOI: 10.1055/s-0040-1707287
review

Syntheses of Analogues of Propofol: A Review

Ivaylo V. Dimitrov∗
a   Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand   Email: i.dimitrov@auckland.ac.nz
,
Elina E. K. Suonio
b   School of Environment, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
› Author AffiliationsThe authors would like to thank the Auckland Cancer Society Research Centre for financial support.
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Abstract

Propofol (2,6-diisopropylphenol) is an intravenous sedative/hypnotic agent that is used extensively for introduction and maintenance of general anaesthesia, sedation of critically ill patients and procedural sedation (e.g., endoscopy). Propofol has a rapid onset and offset of action and shows only minimal accumulation upon prolonged use. Propofol is only sparingly soluble in water and is currently marketed in 10% soybean oil-based lipid emulsion. Propofol’s anaesthetic properties were discovered over forty years ago, and it has been in clinical use for over thirty years. The main use of propofol remains as an anaesthetic but, over the years, analogues have been developed with varying properties from anticancer, anticonvulsant and antioxidant. In addition, large synthetic efforts have been made towards improving propofol’s water-solubility, its activity, and elucidating its structure–activity­ relationship and exact mechanism of action have been made. This review provides an overview of the research pertaining to propofol-like molecules and covers the efforts of synthetic chemists towards propofol analogues over the last 40 years.

1 Introduction

2 History

3 Early Work

4 Improving Water Solubility

5 The Importance of the Phenol

6 Exploring the Structure–Activity Relationship and Attempts to Improve Activity

7 Anticancer Activity

8 Anticonvulsant Properties

9 Antioxidant Activity

10 Photoactive Labelling to Elucidate Mechanism of Action

11 Photoregulation

12 Conclusion

Key words

propofol analogues - synthesis - anesthetic - medicinal chemistry


Publication History

Received: 31 May 2020

Accepted after revision: 22 August 2020

Article published online:
05 October 2020

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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