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降冰片-2-烯-7-酮作为生理触发的一氧化碳释放前药。

Norborn-2-en-7-ones as physiologically-triggered carbon monoxide-releasing prodrugs.

作者信息

Kueh Jui Thiang Brian, Stanley Nathan J, Hewitt Russell J, Woods Laura M, Larsen Lesley, Harrison Joanne C, Rennison David, Brimble Margaret A, Sammut Ivan A, Larsen David S

机构信息

Department of Chemistry , University of Otago , Dunedin , New Zealand . Email:

Department of Pharmacology , University of Otago , Dunedin , New Zealand . Email:

出版信息

Chem Sci. 2017 Aug 1;8(8):5454-5459. doi: 10.1039/c7sc01647f. Epub 2017 May 30.

DOI:10.1039/c7sc01647f
PMID:28970925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5609517/
Abstract

A prodrug strategy for the release of the gasotransmitter CO at physiological pH, based upon 3-bromo-norborn-2-en-7-one Diels-Alder cycloadducts of 2-bromomaleimides and 2,5-dimethyl-3,4-diphenylcyclopentadienone has been developed. Examples possessing protonated amine and diamine groups showed good water solubility and thermal stability. Half-lives for CO-release in TRIS-sucrose buffer at pH 7.4 ranged from 19 to 75 min at 37 °C and 31 to 32 h at 4 °C. Bioavailability in rats was demonstrated by oral gavage and showed a dose dependent vasorelaxant effect in pre-contracted rat aortic rings with an EC of 1.6 ± 0.9 μM. Increased intracellular CO levels following exposure were confirmed using a CO specific fluorescent probe.

摘要

基于2-溴马来酰亚胺与2,5-二甲基-3,4-二苯基环戊二烯酮的3-溴降冰片-2-烯-7-酮狄尔斯-阿尔德环加成物，已开发出一种在生理pH值下释放气体递质CO的前药策略。具有质子化胺基和二胺基的示例显示出良好的水溶性和热稳定性。在37℃时，在pH 7.4的TRIS-蔗糖缓冲液中释放CO的半衰期为19至75分钟，在4℃时为31至32小时。通过口服灌胃证明了在大鼠中的生物利用度，并且在预收缩的大鼠主动脉环中显示出剂量依赖性的血管舒张作用，EC为1.6±0.9μM。使用CO特异性荧光探针证实了暴露后细胞内CO水平的增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/a652ca09d4da/c7sc01647f-f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/b78a78939de6/c7sc01647f-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/c12c3e1bd75e/c7sc01647f-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/a652ca09d4da/c7sc01647f-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/33cb1d7d4dd8/c7sc01647f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/6fc42609e9db/c7sc01647f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/4639e9238527/c7sc01647f-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/c843bda8927f/c7sc01647f-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/1225ce1288bc/c7sc01647f-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/750ad98b88c2/c7sc01647f-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/2197272b36e2/c7sc01647f-s4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/b78a78939de6/c7sc01647f-f4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50f4/5609517/a652ca09d4da/c7sc01647f-f6.jpg

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3
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