79874-87-6Relevant academic research and scientific papers
An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-Induced Drug Resistance to Enhance the Efficacy of Myocardial Protection
Zhou, Wen,Zhang, Bin,Fan, Keyu,Yin, Xiaojian,Liu, Jinfeng,Gou, Shaohua
, (2021/04/19)
Purpose: Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia-induced drug resistance. Methods: In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown, and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed. Results: Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin. Conclusion: Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.
Acetazolamide derivative, preparation method thereof and application thereof in preparation of medicine for treating coronary heart disease
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Paragraph 0024, (2020/12/05)
The invention relates to an acetazolamide derivative, a preparation method thereof and an application of the acetazolamide derivative in preparation of a medicine for treating coronary heart disease.The acetazolamide derivative is an acetazolamide derivative I obtained by bonding a carbonic anhydrase inhibitor acetazolamide Ac and a non-steroidal anti-inflammatory drug which is represented by aspirin As and has a carboxylic acid group through a linking group, and the structural general formula is shown as a formula 1 shown in the specification, wherein in the formula 1, OOC-NSAID represents anon-steroidal anti-inflammatory drug in which one carboxylic acid proton is lost, representative are acetazolamide derivatives containing aspirin or indomethacin, and the acetazolamide derivative I has good activity of inhibiting carbonic anhydrase 9, can effectively improve myocardial anoxia injury in an anoxia microenvironment, and is applied to preparation of the medicine for treating coronaryheart disease.
Synthesis and Evaluation of Novel Erlotinib-NSAID Conjugates as More Comprehensive Anticancer Agents
Zhang, Yanmei,Tortorella, Micky D,Liao, Jinxi,Qin, Xiaochu,Chen, Tingting,Luo, Jinfeng,Guan, Jiantong,Talley, John J,Tu, Zhengchao
, p. 1086 - 1090 (2015/10/20)
A series of novel anticancer agents were designed and synthesized based on coupling of different nonsteroidal anti-inflammatory drugs (NSAIDs) with the epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib. Both the antiproliferative and pharmacokinetic activity of the target compounds were evaluated using HCC827 and A431 tumor cell lines. Among the derivatives made, compounds 10a, 10c, and 21g showed superb potency, comparable to that of erlotinib. Furthermore, preliminary SAR analysis showed that when the NSAIDs were conjugated via linkage to C-6 OH versus linkage to C-7 OH of the quinazoline nucleus, superior anticancer activity was achieved. Finally, the in vitro pharmacokinetic profile of several conjugates demonstrated the desired dissociation kinetics as the coupled molecules were effectively hydrolyzed, releasing both erlotinib and the specific NSAID in a time-dependent manner. The conjugation strategy represents a unique and simplified approach toward combination therapy, particularly for the treatment of cancers where both EGFR overexpression and inflammation play a direct role in disease progression.
Evaluation of nitrate-substituted pseudocholine esters of aspirin as potential nitro-aspirins
Gilmer, John F.,Moriarty, Louise M.,Clancy, John M.
, p. 3217 - 3220 (2008/02/05)
Herein we explore some designs for nitro-aspirins, compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t1/2 ～ 1 min) but generating exclusively the corresponding nitro-salicylate. The one exception, an N-propyl, N-nitroxyethyl aminoethanol ester produced 9.2% aspirin in molar terms indicating that the nitro-aspirin objective is probably achievable if due cognisance can be paid to the demands of the activating enzyme. Even at this low level of aspirin release, this compound is the most successful nitro-aspirin reported to date in the key human plasma model.
