A Review of the Recent Development in the Synthesis and Biological Evaluations of Pyrazole Derivatives

Abstract

Pyrazoles are five-membered heterocyclic compounds that contain nitrogen. They are an important class of compounds for drug development; thus, they have attracted much attention. In the meantime, pyrazole derivatives have been synthesized as target structures and have demonstrated numerous biological activities such as antituberculosis, antimicrobial, antifungal, and anti-inflammatory. This review summarizes the results of published research on pyrazole derivatives synthesis and biological activities. The published research works on pyrazole derivatives synthesis and biological activities between January 2018 and December 2021 were retrieved from the Scopus database and reviewed accordingly.

Keywords: biological activities; derivatives; heterocycle; pyrazole; recent development; synthesis.

Figure 1

Naturally occurring bioactive compounds containing the pyrazole scaffold.

Figure 2

Some biologically active molecules containing pyrazole conjugates.

Scheme 1

Synthesis of the substituted pyrazoles using hydrazine [6].

Scheme 2

Synthetic route to the formation of celecoxib, deracoxib, and mavacoxib using hydrazine [7].

Scheme 3

Synthesis of 5-aryl-3-trifluoromethyl pyrazole derivatives in the presence of a silver catalyst [11].

Scheme 4

Synthesis of the arylpyrazoles from secondary β-enamino diketone and arylhydrazine [12].

Scheme 5

Synthesis of pyrazole derivatives via the cyclo-condensation of cross-conjugated enynones with hydrazines [13].

Scheme 6

Synthesis of polysubstituted-4-trifluoromethylpyrazoles using ketones and trifluoroacetyl diazoester [14].

Scheme 7

Synthetic route to 4-difluoromethyl pyrazole derivatives using Sc(OTf)₃ as the catalyst [15].

Scheme 8

Synthesis of pyrazole-based triarylmethanes using a gold catalyst [16].

Scheme 9

Synthesis of pyrazole derivatives via copper-catalyzed an oxidative coupling reaction [17].

Scheme 10

Synthesis of the pyrazole derivatives from aldehyde hydrazones via a copper-catalyzed oxidative coupling reaction [17].

Scheme 11

Synthesizing of pyrazoles derivatives via an iodine-catalyzed reaction [18].

Scheme 12

Synthesis of the pyrazole derivatives in the presence of terminal oxidant and copper salt [19].

Scheme 13

Synthesis of the pyrazole derivatives from β,γ-unsaturated hydrazones [19].

Scheme 14

Synthesis of pyrazole derivatives via the dipolar cycloaddition of terminal ethynyl pyridines with tosylhydrazides [20].

Scheme 15

Synthesis of pyrazole derivatives from α,β-unsaturated N-tosylhydrazones and N-heteroaryl chlorides [21].

Scheme 16

Synthetic route to the formation of spirocyclic pyrazole via 1,3-dipolar cycloadditions of diazo intermediates with alkynes [22].

Scheme 17

Synthesis of dihydro-pyrrolo-pyrazoles from vinyl sulfones [23].

Scheme 18

Synthesis of the trisubstituted tetrahydropyrano [2,3-c]pyrazoles domino Rauhut−Currier cyclization reaction [24].

Scheme 19

Synthetic route to forming polysubstituted pyrazoles from Glaser coupling/annulation of alkynes with hydrazines [25].

Scheme 20

Synthesis of tetrahydropyrazole-fused heterocycles from Morita−Baylis−Hillman (MBH) carbonates [26].

Scheme 21

Synthesis of bispyranopyrazole under a support heterogeneous catalytic system [27].

Scheme 22

Synthesis of fused pyrazole derivatives using 4-toluenesulfonic as the catalyst [28].

Scheme 23

Synthetic route to the formation of fused pyrazole [29].

Scheme 24

Synthetic route to the formation of pyrazole triflate using N-phenyltriflamide in pyridine [29].

Scheme 25

Synthetic route to the formation of the JNJ-18038683 heterocyclic compound [29].

Scheme 26

Synthesis of pyrazole derivatives via the microwave reaction of arylhydrazines with 3-aminocrotonitrile [30].

Figure 3

Structures of pyrazole derivatives with anti-inflammatory activity.

Figure 4

Structures of the pyrazole derivative with anti-inflammatory activity.

Figure 5

Structures of promising pyrazole derivatives with anti-inflammatory and analgesic activity.

Figure 6

Pyrazole hybrids with anticancer activity.

Figure 7

Structures of pyrazole derivatives with anticancer activity.

Figure 8

Structures of pyrazole derivatives acting as anticancer agents.

Figure 9

Structures of promising pyrazole derivatives with antibacterial activity.

Figure 10

Pyrazole derivative with antifungal activity.

Figure 11

Structures of pyrazole derivatives as antifungal agents.

Figure 12

Structures of pyrazole hybrids with antidiabetic activity.

Figure 13

Structures of pyrazoles derivatives with antileishmanial activity.

Figure 14

Structures of pyrazoles derivatives as potent antimalarial agents.

Figure 15

Structures of promising pyrazole derivatives with antioxidant activity.

Figure 16

Structures of pyrazole hybrids with antioxidant activity.

Figure 17

Structures of pyrazole hybrids with antitubercular activity.

Figure 18

Structures of pyrazole a derivative acting as promising agrochemical agents.