1. In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors
- Author
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Ganapavarapu Veera Ragh Sharma, Sanjeev Saxena, Narasimhan Kilambi, Lavanya Andiappan, C.V. Srinivasan, Gopalan Balasubramanian, Saravanakumar Natarajan, Shridhar Narayanan, Santosh L. Vishwakarma, Fakrudeen Ali Ahamed Nazumudeen, Thirunavukkarasu Sappanimuthu, Sukunath Narayanan, Sridharan Rajagopal, Saravanan Thirunavukkarasu, Shamundeeswari Sundaram, and Naresh Sivaraman
- Subjects
0301 basic medicine ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Peripheral blood mononuclear cell ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,In vivo ,Furan ,Amide ,Drug Discovery ,medicine ,Humans ,Furans ,Molecular Biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Tumor Necrosis Factor-alpha ,Organic Chemistry ,medicine.disease ,In vitro ,Cyclic Nucleotide Phosphodiesterases, Type 4 ,Dibenzofuran ,Thiazoles ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Phosphodiesterase 4 Inhibitors ,Mutagenicity Test ,Uveitis - Abstract
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.
- Published
- 2016