Synthetic approaches and pharmacological activity of 1,3,4-oxadiazoles: a review of the literature from 2000-2012

Abstract

This review provides readers with an overview of the main synthetic methodologies for 1,3,4-oxadiazole derivatives, and of their broad spectrum of pharmacological activities as reported over the past twelve years.

Figure 1

Isomers of oxadiazole.

Figure 2

Structures of raltegravir and zibotentan, drugs that are in late stage clinical development.

Figure 3

Number of publications in the last twelve years involving 1,3,4-oxadiazole.

Scheme 1

Retrosynthetic analysis of 5-substituted-2-amino-1,3,4-oxadiazole.

Scheme 2

5-Aryl-2-amino-1,3,4-oxadiazole obtained from acylhydrazides and cyanogen bromide.

Scheme 3

5-Aryl-2-amino-1,3,4-oxadiazole obtained from acylhydrazides and di(benzotriazol-1-yl)methanimine.

Scheme 4

5-Substituted-1,3,4-oxadiazol-2-amines from of cyclization reaction of semicarbazones.

Scheme 5

Synthesis of 1,3,4-oxadiazol-2-amines from of cyclization reaction of acylthiosemicarbazides with iodine.

Scheme 6

Synthesis of 5-aryl-2-amino-1,3,4-oxadiazole from acylthiosemicarbazide and 1,3-dibromo-5,5-dimethylhydantoin.

Scheme 7

Synthesis of 5-aryl-2-amino-1,3,4-oxadiazole from acylthiosemicarbazide and tosyl chloride.

Scheme 8

Synthesis of 5-substituted-1,3,4-oxadiazole-2-thiols.

Figure 4

5-Aryl-1,3,4-oxadiazole-2-thiols obtained by reaction of acylhydrazide with carbon disulfide.

Scheme 9

Retrosynthetic analysis of 2,5-diaryl(alkyl)-1,3,4-oxadiazoles.

Scheme 10

Synthesis of asymmetrical 2-(2,4-dichloro-5-fluorophenyl)-5-aryl-1,3,4-oxadiazoles.

Scheme 11

Synthesis of 2,5-dissubstituted-1,3,4-oxadiazole derivatives of ibuprofen.

Scheme 12

Cyclization of diacylhydrazine with thionyl chloride. 50 [28], 51 [29] and 52 [30].

Scheme 13

Cyclodehydration of diacylhydrazine using triphenylphosphine oxide and triflic anhydride.

Scheme 14

Cyclodehydration reaction of diacylhydrazines using EDC.

Scheme 15

Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from 1,2-diacylhydrazines and silica-supported dichlorophosphate.

Scheme 16

Synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from 1,2-diacylhydrazines and zirconium(IV) chloride.

Scheme 17

Effect of halogens in the formation of 1,3,4-oxadiazoles.

Scheme 18

Preparation of 1,3,4-oxadiazoles from 1,2-diacylhydrazines using XtalFluor-E.

Scheme 19

Synthesis of 1,3,4-oxadiazoles from carboxylic acids and hydrazides using HATU and Burgess reagent.

Scheme 20

Synthesis of 2,5-dissubstituted-1,3,4-oxadiazoles using CDI and triphenylphosphyne.

Scheme 21

Synthesis of 1,3,4-oxadiazoles using Deoxo-Fluor.

Scheme 22

Synthesis of 2,5-disubstituted-1,3,4-oxadiazoles using microwave heating.

Scheme 23

Synthesis of 1,3,4-oxadiazolines from N-acylhydrazones using acetic anhydride.

Scheme 24

Synthesis of 2,5-diaryl-1,3,4-oxadiazoles from benzohydrazide and aromatic aldehydes.

Scheme 25

Synthesis of 1,3,4-oxadiazoles from N-arylidenearoylhydrazides and Cu(OTf)₂.

Scheme 26

Oxidative cyclization of N-acylhydrazones using chloramine-T.

Scheme 27

Synthesis of 1,3,4-oxadiazoles using trichloroisocyanuric acid (TCCA).

Scheme 28

Oxidative cyclization of acylhydrazones using N-chlorosuccinimide and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU).

Scheme 29

Oxidative cyclization of N-acylhydrazones using Dess-Martin periodinane.

Scheme 30

Nafion catalized 1,3,4-oxadiazole synthesis.

Scheme 31

Reaction of cinnamic acid hydrazide with triethyl orthoesters.

Scheme 32

Synthesis α-keto-1,3,4-oxadiazole.

Scheme 33

Synthesis of dissubstituted 1,3,4-oxadiazoles from four components in a one-pot procedure.

Scheme 34

Synthesis of 1,3,4-oxadiazoles by the Huisgein reaction.

Scheme 35

Acylation of tetrazoles with acetic and benzoic anhydrides.

Figure 5

Disubstituted-1,3,4-oxadiazoles with antibacterial and antifungal activity.

Figure 6

1,3,4-Oxadiazoles with anti-mycobacterial activity.

Figure 7

1,3,4-Oxadiazoles with anticonvulsant activity.

Figure 8

1,3,4-Oxadiazoles with anti-inflammatory activity.

Figure 9

1,3,4-Oxadiazoles with analgesic activity.

Figure 10

1,3,4-Oxadiazoles with antitumor activity.

Figure 11

Structures of raltegravir (162) and derivatives.

Figure 12

1,3,4-Oxadiazoles with inhibitory activity against human immunodeficiency virus type 1 (HIV-1).

Figure 13

1,3,4-Oxadiazoles with inhibitory activity against HIV and hepatitis C virus.

Figure 14

Vasorelaxant activity of 1,3,4-oxadiazoles.

Figure 15

1,3,4-Oxadiazole as enzyme inhibitors.

Figure 16

1,3,4-Oxadiazoles showing inhibitors activity against enzymes.

Figure 17

Other 1,3,4-oxadiazole derivatives as enzymes inhibitors.

Figure 18

Other biological and pharmacological activities of 1,3,4-oxadiazoles derivatives.