Synthesis, hepatotoxic evaluation and antipyretic activity of nitrate ester analogs of the acetaminophen derivative SCP-1.

Authors :: Das M
Bhattacharjee S
Fronczek FR
Bazan NG
Trudell ML
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2018 Dec 15; Vol. 28 (23-24), pp. 3798-3801. Date of Electronic Publication: 2018 Sep 17.
Publication Year :: 2018
Abstract: A series of nitrate ester analogues of the acetaminophen derivative SCP-1 were prepared by triflic acid catalyzed O-acylation of SCP-1 with chloroalkanoyl chlorides followed by nitration with silver nitrate. The chloroesters and corresponding nitrate esters were obtained in high yields. Preliminary hepatotoxicity studies revealed nitrate esters 5b (MD-38) and 5c (MD-39) to be well tolerated by human hepatocytes and had little effect on the three cytochrome P450 enzymes tested (CYP3A4, CYP2E1 and CYP2D6). In addition, the nitrate ester 5c (MD-39) exhibited antipyretic activity similar to acetaminophen.<br /> (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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