2504-32-7Relevant articles and documents
Chemoselective ester/ether C–O cleavage of methyl anisates by aluminum triiodide
Sang, Dayong,Yi, Cuicui,He, Zhoujun,Wang, Jiahui,Tian, Juan,Yao, Ming,Shi, Hong
supporting information, p. 1469 - 1472 (2018/03/13)
The aluminum triiodide mediated chemoselective ester/ether C–O cleavage of methyl anisates was investigated. o-Anisate undergoes ether cleavage at low temperatures in carbon disulfide, cyclohexane and acetonitrile. Further cleavage of the ester group occurs at elevated temperatures to afford salicylic acid. The cleavage of p-anisate is solvent-dependent. In cyclohexane, the ester and ether groups were cleaved non-selectively to give equimolar amounts of p-anisic acid and methyl p-hydroxybenzoate. The ester group was preferentially cleaved in acetonitrile, compared to ether group cleavage in carbon disulfide. The ester cleavage reaction was improved using pyridine as an acid scavenger additive. Reasons for the contrasting reactivity of anisates towards AlI3 were explored, and the methods were applied to cleavage of the tert-butyl ester of acemetacin which gave different products under these conditions.
Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans
Xie, Gang,Zhou, Dingying,Cheng, Ka-Wing,Wong, Chi C.,Rigas, Basil
, p. 1195 - 1202 (2013/05/22)
Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite in the liver microsomes and rats. PTI additionally undergoes cytochromes P450 (CYP)-mediated hydroxylation at its tyrosol moiety and O-demethylation at its indomethacin moiety. Of the five major human CYPs, CYP3A4 and CYP2D6 catalyze the hydroxylation and O-demethylation reactions of PTI, respectively; whereas CYP1A2, 2C9 and 2C19 are inactive towards PTI. In contrast to PTI, indomethacin is primarily O-demethylated by CYP2C9, which prefers acidic substrates. The hydrolyzed and O-demethylated metabolites of PTI are further glucuronidated and sulfated, facilitating drug elimination and detoxification. We observed substantial inter-species differences in the metabolic rates of PTI. Among the liver microsomes from various species, PTI was the most rapidly hydrolyzed, hydroxylated and O-demethylated in mouse, human and rat liver microsomes, respectively. These results reflect the differential expression patterns of carboxylesterase and CYP isoforms among these species. Of the human microsomes from various tissues, PTI underwent more rapid carboxylesterase- and CYP-catalyzed reactions in liver and intestine microsomes than in kidney and lung microsomes. Together, our results establish the metabolic pathways of PTI, reveal significant inter-species differences in its metabolism, and provide insights into the underlying biochemical mechanisms.
Design, synthesis and insulin-sensitizing activity of indomethacin and diclofenac derivatives
Zhang, Jiquan,Wang, Jianta,Wu, Haoshu,He, Yaoyao,Zhu, Gaofeng,Cui, Xing,Tang, Lei
scheme or table, p. 3324 - 3327 (2010/03/31)
A series of aromatic acetic acid compounds were designed and synthesized on the basis of Non-steroidal anti-inflammatory drugs indomethacin and diclofenac. Compounds 5a, 7a, 5h, 7h and 17 could strongly promote insulin-regulated differentiation of 3T3-L1 cells in vitro. They acted as full or partial PPARγ agonist, or improved insulin resistance through non-PPARγ pathway.