Synthesis and Pharmacological Activity of Triazole Derivatives Inhibiting Eosinophilia

Abstract

In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the airway through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-tria zole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally (ip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD50 value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D4 (LTD4) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23c as a novel candidate for the treatment of chronic asthma. Further studies are now underway.

Design and Synthesis of New Bioactive 1,2,4-Triazoles, Potential Antitubercular and Antimicrobial Agents

“…The 1,2,4-triazole, as well found to exhibit antiasthmatic [14] , antiviral (ribavirin) [15] , antifungal (fluconazole) [16] , antimicrobial [17,18] , antibacterial [19][20][21] , insecticidal [22] , hypnotic [23] , cytotoxic [24] , antitubercular [25] and hypotensive [26,27] activities. This moiety was also found in potent agonist and antagonist receptor ligands [28,29] in HIV-1 protease inhibitors [30] and in thrombin inhibitors [31] .…”

Synthesis and evaluation of antibacterial and antioxidant activity of novel 2-phenyl-quinoline analogs derivatized at position 4 with aromatically substituted 4H-1,2,4-triazoles

“…The solid that separated out on cooling was filtered and crystallized to give their corresponding carbohydrazide 9-11. 2-Phenylquinoline-4-carbohydrazide (9 …”

“…They possess broad spectrum of activities against most of the yeasts and filamentous fungi 2 . Among azoles, 1H-1,2,4-triazole derivatives are considered to be more interesting as they possess important pharmacological activities such as antifungal 3,4 , antiviral 5 , antioxidant [6][7][8] , antiasthmatic 9 , anticonvulsant 10 , antidepressant 11 , antithyroid 12 , anti-HIV 13 , anti-inflammatory 14 and anticancer [15][16][17] .…”

Synthesis and Biological Activities Evaluation of New Spiro Heterocycles Containing 1,2,4-Triazole, Piperidine and Sulfonamide Moieties

“…A survey of the literature has shown that compounds having azole derivatives to possess diverse biological activity and are widely used in a medicinal chemistry [15][16][17][18]. The 1,2,4-triazole derivatives has received a considerable attention in view of their diverse pharmacological activities [19][20][21][22] such as antimicrobial [23,24] sedative, anticonvulsant [25], anti-inflammatory properties [26]and anticancer agents. They are also use as intermediates in obtaining colour photosensitive materials as well as toners, inks and other photographic materials such as magenta coupler in a photosensitive emulsion layer [27][28][29][30].…”