ORIGINAL RESEARCH Synthesis and analgesic, anti-inflammatory activities of 3-(3-methoxyphenyl)-2-substituted amino-quinazolin-4 (3H)-ones V. Alagarsamy • M. Gopinath • P. Parthiban • B. Subba Rao • K. Murali • V. Raja Solomon Received: 16 March 2010 / Accepted: 18 August 2010 / Published online: 16 September 2010 Ó Springer Science+Business Media, LLC 2010 Abstract A variety of novel 3-(3-methoxyphenyl)-2- substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methoxy- phenyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3- methoxyphenyl)-quinazolin-4(3H)-one was synthesized from 3-methoxy aniline. The title compounds were inves- tigated for analgesic, anti-inflammatory, and ulcerogenic behavior. Among these the compound 2-(1-methyl butyli- dene-hydrazino)-3-(3-methoxyphenyl)-3H-quinazolin-4-one (AS3) emerged as the most active compound for the analgesic activity, while the compound 2-(1-ethyl propyl- idene-hydrazino)-3-(3-methyoxyphenyl)-3H-quinazolin-4- one (AS2) showed most potent anti-inflammatory activity of the series and these compounds are moderately more potent when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid. Keywords Quinazoline  Analgesic  Anti-inflammatory  Ulcer index Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are com- monly prescribed for the treatment of acute and chronic inflammation, pain, and fever. However, long-term clinical usage of NSAIDs is associated with significant side effects of gastrointestinal lesions, bleeding, and nephrotoxicity. Therefore, the discovery of new safer anti-inflammatory drugs represents a challenging goal for such a research area (Van Ryn, 1971; Van Ryn and Botting, 1995; Van Ryn et al., 2000; Beuck, 1999). As part of our ongoing medicinal chemistry research program we found that quinazolines and condensed quinazolines exhibit potent central nervous system (CNS) activities including analge- sic, anti-inflammatory (Alagarsamy et al., 2003a), and anticonvulsant (Alagarsamy et al., 2006). Quinazolin- 4(3H)-ones with 2,3-disubstitution are reported to possess significant analgesic, anti-inflammatory (Abdel-Rahman et al., 2003; Chambhare et al., 2003), and anticonvulsant effects (Santagati et al., 1995). Previously we have docu- mented some lead compound 2-phenyl-3-substituted quin- azolines (Alagarsamy et al., 2002), 2-methyl-3-substituted quinazolines (Alagarsamy et al., 2003b), 2-methylthio-3- substituted quinazolines (Alagarsamy et al., 2004), and 2, 3-disubstituted quinazolines (Alagarsamy et al., 2003c) that exhibited good analgesic and anti-inflammatory activities. The present work is an extension of our ongoing efforts toward the development and identification of new molecules for analgesic and anti-inflammatory activities with minimal gastrointestinal ulceration side effects. The present work is an extension of our ongoing efforts toward V. Alagarsamy (&)  P. Parthiban  B. Subba Rao Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, MNR Nagar, Sangareddy, Gr. Hyderabad 502 294, India e-mail: drvalagarsamy@gmail.com M. Gopinath Department of Pharmaceutical Chemistry, Ratnam Institute of Pharmacy, Pidathapolur, Nellore 524 346, India K. Murali Department of Pharmaceutical Chemistry, C.L. Baid Metha College of Pharmacy, Thorappakkam, Chennai 600 097, India V. Raja Solomon Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, India 123 Med Chem Res (2011) 20:946–954 DOI 10.1007/s00044-010-9417-z MEDICINAL CHEMISTR Y RESEARCH