Synthesis of pyrazoles containing benzofuran and trifluoromethyl moieties as possible anti-inflammatory and analgesic agents

Abstract

Searching for new anti-inflammatory and analgesic agents, we have prepared a series of novel pyrazoles containing benzofuran and trifluoromethyl moieties. The pyrazole derivatives have been synthesized via two routes starting from 5-(3-(trifluoromethyl)phenyl azo) salicylaldehyde. The first route involved the synthesis of 2-acetylbenzofuran and then treatment with aldehydes to afford the corresponding chalcones. The cyclization of the latter chalcones with hydrazine hydrate led to the formation of new pyrazoline derivatives. The second route involved the synthesis of benzofuran-2-carbohydrazide and then treatment with formylpyrazoles, chalcones and ketene dithioacetal derivatives to afford the corresponding pyrazole derivatives. Some of the synthesized compounds exhibited anti-inflammatory and analgesic activities.

Synthesis and Utility of α,β‐Unsaturated Ketone Bearing Naphthalene and Benzofuran Rings in the Synthesis of Some N‐heterocycles with Their Antiviral and Antitumor Activity Evaluation

“…The mass spectra were measured with a GC Finnigan MAT SSQ‐7000 mass spectrometer. Follow‐up of the reactions and checking the purity of the compounds were made by thin‐layer chromatography on silica gel‐precoated aluminum sheets (type 60, F 254, Merck, Darmstadt, Germany) 1‐(5‐((3‐(trifluoromethyl)phenyl)diazenyl)benzofuran‐2‐yl)ethanone 1 .…”

Development of pyrazole derivatives in the management of inflammation

“…The anti‐inflammatory or antinociceptive potential of some derivatives ( 22 ; 38–40 ; 43 ; 44 ; 46 ; 68 ; 77 ; 82–96 ; 98 ; 99 ; 103–109 ) was demonstrated in a nonspecific abdominal writhing test [29,31,41,42,44,45,61,63–65,71–76]. The anti‐inflammatory activity of several compounds ( 10–14 ; 16–19 ; 22–24 ; 27–33 ; 38 ; 40–44 ; 46 ; 49 ; 51 ; 54 ; 55 ; 57 ; 58 ; 60–67 ; 73 ; 74 ; 76 ; 79–87 ; 89–91 ) was assessed in carrageenan‐induced paw edema [16,18,26,27–29,31,32,35,36,37–42,46–49,52–55,61,71,77–79]. Furthermore, the antiedematogenic effect of some derivatives ( 15 ; 34–37 ; 50 ; 109 ) has been evaluated with formalin [30,34,38,76,80] and histamine‐induced paw edema ( 52 ) [81], in addition to xylene ( 48 ) [66] and croton oil‐induced ear edema ( 77 ; 109 ) [44,76].…”

“…The central analgesic effect, as well as spinal [61,64,74,75] or supraspinal mechanisms [33,76,79,83] of pyrazole derivatives, has been explored using tail‐flick ( 22 ; 97 ; 100 ; 103–108 ) and/or hot plate ( 68–72 ; 81 ; 109 ; 110 ) tests. An increase in latency to thermal stimulus response suggests antinociceptive property, as demonstrated for LQFM008 ( 73 ) in both tests [78].…”

“…Addition of fluorine group to phenyl ring (fluorophenyl moiety) ( 43–45 ; 110 ) elicited a significant anti‐inflammatory and antinociceptive activity [46,68,72,73,82,83]. According to Hong and colleagues (2017), the introduction of hydrophobic groups, such as phenyl, 4‐fluorophenyl, and trifluoromethyl in compounds 79–81, improved the antinociceptive and antiedematogenic activities of some derivatives [79]. The presence of fluoromethyl [51] and nitrophenyl [65] groups ameliorates the anti‐inflammatory and antinociceptive activities of 3,5‐bis(fluoromethyl)phenyl ( 59 ) and diaminopyrazole ( 88 ).…”

Synthesis of some novel pyrazoline‐thiazole hybrids and their antimicrobial activities

“…Pyrazole, five‐member heterocyclic ring with two adjacent nitrogen atoms, has gained a great attention in pharmaceutical and chemical industries . A large number of pyrazoles showed various biological activities such as anticancer, antihistaminic, pesticidal, antifungal, anti‐rheumatoid arthritis, anticonvulsant, antidepressant, antipyretic, antibacterial, antituberculosis, antiviral, and anti‐inflammatory activities.…”