Terminal Phenoxy Group as a Privileged Moiety of the Drug Scaffold-A Short Review of Most Recent Studies 2013-2022

Abstract

The terminal phenoxy group is a moiety of many drugs in use today. Numerous literature reports indicated its crucial importance for biological activity; thus, it is a privileged scaffold in medicinal chemistry. This review focuses on the latest achievements in the field of novel potential agents bearing a terminal phenoxy group in 2013-2022. The article provided information on neurological, anticancer, potential lymphoma agent, anti-HIV, antimicrobial, antiparasitic, analgesic, anti-diabetic as well as larvicidal, cholesterol esterase inhibitors, and antithrombotic or agonistic activities towards the adrenergic receptor. Additionally, for selected agents, the Structure-Activity-Relationship (SAR) is also discussed. Thus, this study may help the readers to better understand the nature of the phenoxy group, which will translate into rational drug design and the development of a more efficient drug. To the best of our knowledge, this is the first review devoted to an in-depth analysis of the various activities of compounds bearing terminal phenoxy moiety.

Keywords: adrenergic receptor activity; analgesic activity; anti-HIV activity; anticancer activity; antidiabetic; antimicrobial; drug scaffold; lymphoma; neurological disorder; phenoxy group.

Figure 1

Unsubstituted terminal phenoxy group or substituted with R substituent.

Figure 2

Drugs currently used in the treatment of neurological disorders.

Figure 3

Antiviral drugs.

Figure 4

Cardiac drugs.

Figure 5

Analgesic drugs currently used in treatment.

Figure 6

Antimicrobial drugs.

Figure 7

Anti-cholesterol drugs.

Figure 8

Diuretic drugs.

Figure 9

Anti-leukemia drugs.

Figure 10

Other drugs with various biological activities.

Figure 11

Auxiliary substances bearing phenoxy moiety.

Figure 12

The novel potential agents for a neurological disorder bearing a phenoxy group.

Figure 13

Schematic representation of the developed pharmacophore model in which the terminal phenoxy group plays the role of mimicking the phenylalanine side chain.

Figure 14

The novel potential agents with anticancer activity bearing a phenoxy group.

Figure 15

Schematic representation of H-π interactions (black dots) formed by a phenoxyphenyl moiety with STAT3 (R is the rest of the compound structure).

Figure 16

The novel potential BTK inhibitors bearing a phenoxy group.

Figure 17

Schematic representation of the pi-stacking (blue lines) interaction formed by a phenoxy group with a BTK enzyme. The black dots represent hydrogen bonds.

Figure 18

The novel potential agents with antimicrobial activity bearing a phenoxy group.

Figure 19

Schematic representation of the hydrophobic interactions (lines) formed by a phenoxy group with an active site of cytochrome 450 14α-sterol demethylase enzyme CYP51 (R is the rest of the compound structure).

Figure 20

The novel potential agents with anti-HIV activity bearing a phenoxy group.

Figure 21

Schematic representation of the π–π interaction (blue lines) formed by a phenoxy group (R is the rest of the compound structure).

Figure 22

The novel potential agents with anti-parasitic activity bearing a phenoxy group.

Figure 23

The novel potential agents with analgesic activity bearing a phenoxy group.

Figure 24

Schematic representation of the π–π interaction (blue lines) formed by a phenoxy group (R is the rest of the compound structure).

Figure 25

The novel potential agents with anti-diabetic activity bearing a phenoxy group.

Figure 26

The novel potential agents with other activity bearing a phenoxy group.