Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity

European Journal of Medicinal Chemistry
Angela Di CapuaMaurizio Anzini

Abstract

A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers were previously synthesized and the potential anti-inflammatory and antinociceptive activities of these compounds were evaluated in vivo. The compounds displayed a very good activity against both carrageenan-induced hyperalgesia and oedema in the rat paw test. Therefore, in a very preliminary test, compounds (8a,b) showed antiproliferative activity in the HaCaT (aneuploid immortal keratinocyte from adult human skin) cell models. On these basis, our research continued with the synthesis of fluorinated derivatives (8c,d, 9b-d, and 10b-d) with the aim of improving the pharmacokinetic profile of the previous active compounds. Substitution of a hydrogen atom by a fluorine atom may change the conformational preferences of the molecules due to stereoelectronic effects and also fluorine atom may be able to exert the metabolic obstruction reducing the "first-pass effect". Compound 10b exhibited a prominent in vivo anti-inflammatory and antinociceptive activities, in addition its antiproliferative power in an in vitro model of human skin cancer is herein described.

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Citations

Nov 15, 2017·Applied Biochemistry and Biotechnology·Nivya JamesK Ramanathan
Mar 7, 2018·Applied Biochemistry and Biotechnology·Nivya James, K Ramanathan
May 22, 2019·BMC Cancer·Chia-Chi LiuChi-Shiun Chiang
May 10, 2017·Cell Biochemistry and Biophysics·Nivya James, K Ramanathan
Jul 1, 2019·European Journal of Medicinal Chemistry·Navneet KishoreAkhilesh Kumar Verma
Mar 5, 2021·Respiratory Medicine·Ourania S KotsiouSotirios G Zarogiannis
Jul 16, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Lorenzo FloriVincenzo Calderone

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