In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors

Herein we report the synthesis, PDE-4B and TNF-alpha inhibitory activities of a few dibenzo[b,d]furan-1-yl-thiazole derivatives. The hydroxycyclohexanol amide derivatives 14, 18, 24, 29, 31 and 33 exhibited promising in vitro PDE-4B and TNF-alpha inhibitory activities. Compound 24 showed good systemic availability in preclinical animal models and was also found to be non-toxic (exploratory mutagenicity test). Further it exhibited promising results in in vivo asthma/COPD and Uveitis models. (C) 2016 Elsevier Ltd. All rights reserved.