Synthesis and Primary Cytotoxic Screening of Some 3- Sulfonamide Substituted Benzamido-benzimidazolones


avatar Ghadam Ali Khodarahmi 1 , * , avatar Pei-Yu Chen 2 , 3 , avatar Gholam-Hosein Hakimelahi 1 , 4 , avatar Ji-Wang Chern 2

Department of Medicinal Chemistry, Faculty of Pharmacy, Isfahan Univercity of Medical Sciences , Isfahan, Iran
School of Pharmacy, National Taiwan University, Taipei, Taiwan
Maine Medical Center Research Institute, Scarborough, ME, USA
Institutes of Chemistry and Biomedical Sciences, Academia Sinica, Taipei, Taiwan

how to cite: Khodarahmi G A, Chen P, Hakimelahi G, Chern J. Synthesis and Primary Cytotoxic Screening of Some 3- Sulfonamide Substituted Benzamido-benzimidazolones. Iran J Pharm Res. 2005;4(1):e128226.


Several cycline dependent kinase 2 (CDK2) inhibitors with different chemical structures have been introduced. The hinge region of CDK2 (residues 81–84) contains a set of hydrogen bond donor and acceptor sites some of which must be satisfied for potent inhibitor binding. The benzimidazolone skeleton may provide such interactions. Accordingly, 3-sulfonamide substituted benzamido-benzimidazolones 24-31 were prepared starting from benzoic acid to give the acyl chloride 1 which was reacted with different amines to afford the acids 2-9. The acids were changed to their corresponding acyl chlorides 10-17. Reaction of 10-17 with o-nitropheyl hydrazine gave the nitro derivatives 18-25 followed by reduction of the nitro groups to give 26-33 which were then reacted with ethyl chloroformate to give the target compounds 34-41. The 3-pyridyl derivative 47 was prepared starting with chlorosulfonyl benzoyl chloride to give the acid 43 which was changed to the corresponding acyl, nitro and amino derivatives 44, 45 and 46, respectively, followed by the final ring closure reaction to give 47. The dibenzimidazolinoe derivative 49 was also obtained from the reaction of isopropenyl-benzimidazolone 48 and 3-chloro sulfonyl benzoyl chloride. The target compounds were then tested against the cancer cell lines, Hepa G2, HT-29, CL1-5 and AGS. Results indicated that the target compounds did not show reasonable cell growth inhibition comparing to the positive and negative controls.