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

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• 作者：Gopalan Balasubramanian^a ; Sukunath Narayanan^a ; Lavanya Andiappan^a ; Thirunavukkarasu Sappanimuthu^a ; Saravanan Thirunavukkarasu^a ; Shamundeeswari Sundaram^a ; Saravanakumar Natarajan^a ; Naresh Sivaraman^a ; Sridharan Rajagopal^a ; Fakrudeen Ali Ahamed Nazumudeen^b ; Sanjeev Saxena^b ; Santosh L. Vishwakarma^b ; Shridhar Narayanan^b ; Ganapavarapu V.R. Sharma^a ; Chidambaram V. Srinivasan^a ; Narasimhan Kilambi^a ; ^{narasimhank@orchidpharma.com" class="auth_mail" title="E-mail the corresponding author} ; ^{k_narasimhan99@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{ipm@orchidpharma.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PDE ; phosphodiesterase ; TNF-α ; tumour necrosis factor ; nm ; nanomolar ; IL ; interleukin ; μM ; micromolar ; @ ; at ; PBMC ; peripheral blood mononuclear cells ; LPS ; lipopolysaccharides ; COPD ; chronic obstructive pulmonary disease ; CC ; column chromatography ; HCl ; hydrochloric acid ; h ; hour ; rt ; room temperature ; mp ; melting point ; ND ; not done ; cpm ; counts per minute ; CHCl3 ; chloroform ; MDC/CH2Cl2 ; methylene dichloride ; MeOH ; methanol ; EtOAc ; ethylacetate ; HOBt ; hydroxybenzotriazole ; DMAP ; dimethylaminop
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：24
• 期：22
• 页码：5702-5716
• 全文大小：3924 K

文摘

Herein we report the synthesis, PDE-4B and TNF-α 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-α 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.