ORIGINAL RESEARCH Synthesis and biological evaluation of 2-amino-5-sulfanyl-1,3, 4-thiadiazole derivatives as antidepressant, anxiolytics and anticonvulsant agents Rajesh Sharma • Ganesh Prasad Misra • Jitendra Sainy • Subhash Chandra Chaturvedi Received: 15 July 2009 / Accepted: 13 January 2010 / Published online: 10 February 2010 Ó Springer Science+Business Media, LLC 2010 Abstract A new series of 2-amino-5-sulfanyl-1,3,4-thia- diazole derivatives has been synthesized. The newly syn- thesized compounds were characterized by analytical and spectral methods. Compounds were screened for central nervous system activity. Compounds 1, 5, 7, 10, 14 exhibited significant antidepressant, anxiolytic and anti- convulsant activity in comparison to the reference drugs. Keywords 2-Amino-5-sulfanyl-1,3,4-thiadiazole Á Antidepressant Á Anxiolytic and anticonvulsant activity Introduction Substituted thiadiazole derivatives have been found to show diverse pharmacological activities such as analgesic (Schenone et al., 2006), antidepressant and anxiolytic (Clerici and Pocar, 2001), anticonvulsant (Stillings et al., 1986; Chapleo et al., 1986), anti-inflammatory (Mullican et al., 1993), antimicrobial (Servi et al., 2005), antituber- cular (Oruc ¸ et al., 2004), antitumor (Matysiak, 2006) and antiviral (Jones et al., 1965) activity. A series of 2-amino- 5-sulfanyl-1,3,4-thiadiazoles originally been synthesized and evaluated for antidepressant and anxiolytic activity by Clerici and Pocar (2001). Due to their effect on central nervous system (CNS) it was considered worthwhile to synthesize some new derivatives to evaluate for antide- pressant, anxiolytic and anticonvulsant activity. The syn- thetic pathway is given in Scheme 1. Materials and methods Chemistry Melting points were determined in an open capillary tube and uncorrected. Purity of the compounds was checked on pre-coated silica gel G plates (0.2 mm thickness, Merck, India) using iodine vapor as visualizing agent. Infrared spectra were recorded on a Perkin Elmer Paragon 1000 IR spectrometer (USA) and 1 H-NMR spectra were obtained on a Bruker DRX-300 MHz FT NMR spectrometer (USA) in CDCl 3 . All chemical shifts were reported as d (ppm) values. Mass spectra were recorded on a Jeol SX-102 mass spectrometer (Japan). Elemental analyses were performed on an Elemental Vario EL II/Carlo N 1108 (Italy) and satisfactory results ±0.4% of calculated values (C, H, N) were obtained. All the reagents used in the present work were of synthetic grade (Aldrich, Germany, Lancaster, UK). The various substitution was made on sulfanyl and amino group of 2-amino-5-sulfanyl-1,3,4-thiadiazole nucleus. The various substituents are presented in Table 1. Synthesis of compounds Synthesis of 4-[5-chlorophenylamino)-1,3,4- thiadiazole-2-yl-sulphanyl]-benzenesulphonamide (1) 2-Amino-5-sulfanyl-1,3,4-thiadiazole (I) (0.01 mol, 1.31 g) was suspended in a minimum quantity of water and a R. Sharma (&) Á G. P. Misra Á J. Sainy School of Pharmacy, Devi Ahilya Vishwavidyalaya, Thakshyasila Campus, Khandwa Road, Indore, Madhya Pradesh 452 001, India e-mail: rbsm73@yahoo.co.in S. C. Chaturvedi College of Pharmacy, IPS Academy, A.B. Road, Rau, Indore, Madhya Pradesh 452 001, India 123 Med Chem Res (2011) 20:245–253 DOI 10.1007/s00044-010-9308-3 MEDICINAL CHEMISTR Y RESEARCH