2-Amino-5-sulfanyl-1,3,4-thiadiazoles: A new series of selective cyclooxygenase-2 inhibitors

Abstract

Suppression of pain and inflammation still continues to be a challenge despite the availability of a number of non-steroidal anti-inflammatory drugs (NSAIDs). This is because NSAIDs do not only exhibit a different spectrum of analgesic, anti-pyretic and anti-inflammatory effects but also cause gastrointestinal (GI) complications ranging from dyspepsia to fatal upper GI tract bleeding and perforation (1). Efforts to improve the adverse effect profile of the current NSAIDs have been focused on developing prodrugs (2) or modifications of marketed formulations (3). These approaches have been only partially successful. A recent approach is development of selective cyclooxygenase (COX)-2 inhibitors (4-6). COX is the key enzyme that catalyzes the conversion of arachidonic acid to prostaglandins and thromboxans. There are two types of cyclooxygenase enzymes, COX-1 and COX-2. Currently available NSAIDs inhibit both COX-1 and COX-2 enzymes. Inhibition of COX-1 reduces basal production of cytoprotective prostaglandins (PGs) PGE2 and PGI2 and hence causes ulceration while inhibition of COX-2 inhibits inflammation. Complete inhibition of COX-1 is therefore not preferred and drugs that inhibit the COX-2 enzyme are better anti-inflammatory agents (7,8).Owing to the continuous efforts in exploring the structural insights to aid the design (9, 10) and synthesis of safer novel anti-inflammatory agents, 2-amino-5-sulfanyl--1,3,4-thiadiazole was identified as the central nucleus. To date, 2-amino-5-sulfanyl--1,3,4-thiadiazole derivatives have not been reported to exhibit anti-inflammatory and A new series of cyclooxygenase-2 inhibitors with 2-amino--5-sulfanyl-1,3,4-thiadiazole as the central scaffold unit has been synthesized. The newly synthesized compounds were characterized by analytical and spectral methods. Compounds were screened for cyclooxygenase inhibitory activity by the colorimetric COX (ovine) inhibitor screening assay, anti-inflammatory activity by the carrageenean induced rat paw oedema test and analgesic activity by the tail flick method. Some compounds exhibited significant biological activity.

11C-Labeled Analogs of Indomethacin Esters and Amides for Brain Cyclooxygenase-2 Imaging: Radiosynthesis, in Vitro Evaluation and in Vivo Characteristics in Mice

“…COX Inhibitory Activity The inhibitory activity of the compounds (2-6) for the COX enzyme and selectivity index (SI) was determined in vitro, including celecoxib and indomethacin as a reference COX inhibitor, using a colorimetric COX (ovine) inhibitor screening assay, 26) in which arachidonic acid was used as the substrate and N,N,NЈ,NЈ-tetramethylphenylenediamine (TMPD) as the cosubstrate. The IC 50 value was calculated from the concentration-inhibition response curve.…”

Regiospecific synthesis of some novel N-nucleosides of 4-amino-5-substituted-1,2,4-triazole-3-thiones and their in-vitro antimicrobial activity

“…For example, a large number of 1,2,4-triazolecontaining ring system have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, central nervous system (CNS) stimulants, sedatives, anxyolytic, antimicrobial agents [3,4]. Derivatives of 1,2,4-triazole and 1,3,4-thiadiazole condensed nucleus systems (triazolothiadiazoles) found to have diverse pharmacological activities including unique anti-inflammatory, anti-edema, and analgesic properties [5][6][7][8][9]. Also, there are known drugs containing the 1,2,4-triazole group e.g.…”

Synthesis of 5-arylidine amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamides endowed with potent antioxidants and anticancer activity induces growth inhibition in HEK293, BT474 and NCI-H226 cells

“…The biological activity of the compounds is mainly dependent on their molecular structures (Salimon et al ., 2010). A vast number of 1,3,4-thiadiazoles have been reported as potential pharmacologically active compounds with antimicrobial (Patil and Biradar, 2001; Zamani et al ., 2004; Sharma et al ., 2006), antiviral (Pandey et al ., 2004), antitubercular (Oruc et al ., 2004; Desai et al ., 1984), anticonvulsant (Shrivastava et al ., 1999; Kumar et al ., 2003; Gupta et al ., 2008; Stillings et al ., 1986; Jatav et al ., 2008), CNS depressant (Jatav et al ., 2008), hypoglycaemic (Hanna et al ., 1995; Pattan et al ., 2009), anti-inflammatory (Sharma et al ., 2008; Varandas et al ., 2005) and anticancer (Noolvi et al ., 2011; Kumar et al ., 2010) properties. At the same time, the 1,3,4-thiadiazole fragment appears in a number of clinically used drugs such as acetazolamide; methazolamide; butazolamide (diuretic); sulfamethiazole (antibacterial); cefazolin, cefazedone (antibiotic); atibeprone (anti-depressant); glybuthiazole, glybuzole (antidiabetic); and tebuthiuron (insecticide) (Wilson and Gisvold, 1991; Abrahum, 2003; Supran et al ., 2003).…”