RESEARCH ARTICLE Application of novel precursors derived from carbazolo condensed azepinones to the direct single step synthesis of corresponding isoxazole and pyrazole annulated analogues of medicinal importance Meenakshi Agrawal & Sonika Jain & Anshu Agarwal & Jaya Dwivedi & Swapnil Sharma & D. Kishore Received: 4 October 2011 / Accepted: 26 January 2012 / Published online: 7 March 2012 # Institute of Oriental Medicine, Kyung Hee University 2012 Abstract Exceedingly facile protocols based on the reac- tivity of corresponding oxoketenedithioacetal (4), 2-(dime- thylaminomethylene) ketone (5), β-oxoenolether (6) and α, β-unsaturated ketone (7) resulted from 7-ethyl-3,4 dihy- droazepino[3,2-b] carbazole-2,5 (1H,7H)-dione (3) on its reaction with base catalyzed condensation of (a) CS 2 + MeI (b) DMF-DMA (c) H-COOEt and (IV) C 6 H 5 CHO respective- ly, has been explored to provide an easy access of their isoxazole and pyrazole annulated analogues (8–13) of medic- inal interest. The key compound 3 from which, the synthesis proceeded was in turn realized on the reaction of commercial 3-amino-9-ethyl carbazole (1) with ethyl succinyl chloride, under the conditions of Friedel-Crafts acylation followed by cyclocondensation of the resulting intermediate 2 with PPA. Isoxazolo and pyrazolo annulated analogues of carbazolo condensed azepinone derivatives (8–13) were screened for their in-vitro antimicrobial potential against various bacterial and fungal species. Besides this pyrazole derivative (8) was also evaluated for its CNS depressant potential in mice using photoactometer. Keywords Friedel-Crafts acylations . 3-amino-9-ethyl carbazole . Ethyl ester of succinyl chloride . Oxoketnedithioacetal . 2-(dimethylaminomethylene) ketone . Dimethyl formamide dimethyl acetal . Oxoenolether . Chalcone . Isoxazole . Pyrazole Introduction The development of efficient methodologies to facilitate the preparation of compound libraries from molecules having proven record of bio-efficacy is an intense area of research in medicinal chemistry. Due to the vast commercial success of the materials derived from carbazoles, azacarbazoles and pyr- idocarbazoles, various methods to incorporate these on to the bioactive pharmacophores which have the previous history of being biologically active have been widely explored (Martin and Prasad 2006; Liger et al. 2007). Recently, benzazepines of the general formula (A) namely-paullone have been shown to constitute a class of cyclin-dependent kinase inhibitors for which antiproliferative activity against the tumor cell lines (of in vitro cell line) has been demonstrated (Schultz et al. 1999; Kunick et al. 2004a, b; Bertrand et al. 2003). In addition to this, paullone has also found application in the treatment of human leukemia (Kohfeld et al. 2007), breast cancer and in tumors due to its potent inhibitory action on glycogen syn- thase kinase 3 (GSK-3) (Kunick et al. 2004a, b; Leost et al. 2000) and mitochondrial malate dehydrogenase (Knockaert et al. 2002). H N HN O R (A) Literature has been replete with examples showing that heterocycles which incorporate carbazoles (Mulwad and Patel 2005), azepinones (Kunick and Link 1995), isoxazoles M. Agrawal (*) : S. Jain : A. Agarwal : J. Dwivedi : D. Kishore Department of Chemistry, Banasthali University, Banasthali, Rajasthan 304022, India e-mail: meenakshi.agrawal2011@gmail.com S. Sharma Department of Pharmacy, Banasthali University, Banasthali, Rajasthan 304022, India Orient Pharm Exp Med (2012) 12:141–150 DOI 10.1007/s13596-012-0060-8