Antinociceptive effects of new pyrazoles compounds mediated by the ASIC-1α channel, TRPV-1 and μMOR receptors

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

“…As pain is a hallmark of tissue damage and inflammatory processes (Baral et al, 2019), pyrazole analogs with antinociceptive and anti-inflammatory activities are important to analgesic drug development. The pyrazole compounds with fluorine at para (17), meta (18), and ortho (19) positions on the phenyl ring demonstrated an antinociceptive effect in the previous studies (de Oliveira et al, 2017;Florentino et al, 2019). This effect was associated with the activation of the opioid receptor and blockage of the acid-sensing ion channel subtype 1α (ASIC-1α).…”

Development of pyrazole derivatives in the management of inflammation

“…Some pyrazole derivatives ( 44–45 ; 73 ; 74 ; 103–107 ; 109 ; 110 ) modulate both first (neurogenic) and second (inflammatory) phases of formalin test [39,68,74,76,78,83] while certain derivatives ( 22 ; 38–40 ; 68 ; 77 ) only decreased the pain reaction at the inflammatory phase [31,44,45,61]. Compounds 43–45 and 109 [68,76] reduced pain response to intraplantar injection of acidified saline, capsaicin, or glutamate that supports the involvement of ASIC‐1α channel, TRPV‐1 receptor, and glutamatergic pathways, respectively. Considering tissue acidosis and production of chemical mediators as dominant in inflamed tissues, the block of cation channels activated by protonation and nonselective cation channels (ASIC and TRPV, respectively) seems to be an additional and direct target for NSAIDs against hyperalgesia [84,85].…”

“…The electrophysiological recording demonstrated the blockade of the ion current of the acid‐sensing ion channel subtype 1α (ASIC‐1α) and transient receptor potential vanilloid subtype 1 (TRPV‐1) by LQFM020, 021, and 039 ( 43–45 ). While some of these derivatives increase the current of µMOR [68], the aryl‐pyrazole derivatives ( 101 ; 102 ) [69], and fused‐benzenesulfonamide derivatives [70] blocked the T‐type calcium current channel. Additionally, the aryl‐pyrazole derivatives ( 101 ; 102 ) were categorized as lower hERG (α‐subunit of potassium channel) inhibitors [69].…”

“…The carboxamide derivatives with methyl ( 52 ) [81] and propyl ( 48 ) [66], groups conferred a better anti‐inflammatory activity than diclofenac sodium and dexamethasone, respectively, as well as with nitrophenyl ( 54 ) and fluorophenyl ( 55 ) moieties compared to indomethacin [77]. 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].…”

Electrochemically enabled oxidative aromatization of pyrazolines

“…2 One prominent example is sildenafil ( 3 ), a phosphodiesterase inhibitor for treatment of erectile dysfunction (Chart 1). Furthermore, pyrazoles exhibit metabolic, 3 cardiac, 4 and gastrointestinal effects, 5 antibacterial, 6 antipsychotic, 7 anti-inflammatory, 8 antinociceptive 9 properties and are promising candidates for the development of new anticancer drugs. 10 Pyrazoles are widely found in active compounds in agrochemicals, e.g.…”