Design and synthesis of 3,4-dihydro-2H-benzo[h]chromene derivatives as potential NF-κB inhibitors

Abstract A novel class of NF-κB inhibitors were designed and synthesized based on KL-1156 (6-hydroxy-7-methoxychroman-2-carboxylic acid phenyl amide) which is unambiguously considered to be a promising inhibitor for the translocation step of NF-κB. Especially in this study we focused on the modifying the chroman moiety of KL-1156 into four parts for exploring the SAR studies linked with physical properties of substituents resulted the development of novel 1a – k , 2a – f , 3a – d and 4a – d derivatives of 3,4-dihydro-2 H -benzo[ h ]chromene. From the SAR studies we were very delightfully identified that several new N -aryl-3,4-dihydro-2 H -benzo[ h ]chromene-2-carboxamide derivatives ( 1a – k ) exhibited good inhibitory activity and anti-proliferative activity than parent lead compound KL-1156 , among them 1i exhibited outstanding inhibitory effect on LPS-induced NF-κB transcriptional activity and anti-proliferative activity on NCI-H23 lung cancer cell lines than KL-1156 .