Abstract
An improved and rapid synthesis of mefenamic acid based indole derivatives has been achieved via the ligand free Cu-catalyzed coupling-cyclization method under ultrasound irradiation. This simple, straightforward and inexpensive one-pot method involved the reaction of a terminal alkyne derived from mefenamic acid with 2-iodosulfanilides in the presence of CuI and K2CO3 in PEG-400. The reaction proceeded via an initial C[sbnd]C bond formation (the coupling step) followed by C[sbnd]N bond formation (the intramolecular cyclization) to afford the mefenamic acid based indole derivatives in good to acceptable yields. Several of these compounds showed inhibition of PDE4 in vitro and the SAR (Structure Activity Relationship) within the series is discussed. The compound 3d has been identified as a promising and selective inhibitor of PDE4B (IC50 = 1.34 ± 0.46 µM) that showed TNF-α inhibition in vitro (IC50 = 5.81 ± 0.24 µM) and acceptable stability in the rat liver microsomes.
Original language | English |
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Article number | 127112 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 30 |
Issue number | 10 |
DOIs | |
State | Published - 15 May 2020 |
Externally published | Yes |
Keywords
- Cu
- Indole
- Mefenamic acid
- PDE4
- Ultrasound
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry