407-75-0Relevant academic research and scientific papers
SARTAN ANALOGUE
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, (2019/07/23)
The invention concerns a sartan analogue on basis of a sartan which sartan comprises an alkyl group or an alkoxy group, wherein the sartan analogue only differs from the sartan by a replacement of the alkyl group or the alkoxy group or replacement of a methyl residue or a hydrogen residue of the alkyl group or of the alkoxy group by a fluorine atom.
18F-Labeled Derivatives of Irbesartan for Angiotensin II Receptor PET Imaging
Hoffmann, Matthias,Chen, Xinyu,Hirano, Mitsuru,Arimitsu, Kenji,Kimura, Hiroyuki,Higuchi, Takahiro,Decker, Michael
, p. 2546 - 2557 (2018/11/23)
The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18F-labeled derivative of the drug irbesartan, one of the most prescribed angiotensin II type 1 receptor (AT1R) antagonists, for in vivo positron emission tomography (PET). This allows the in vivo measurement of AT1R expression, and thus the evaluation of functional changes in its expression under pathophysiological conditions. We followed various synthetic approaches optimized for the introduction of fluorine into different positions of the aliphatic side chain of irbesartan. Radioligand binding studies revealed that fluorine atoms at specified positions (α-position (IC50=6.6 nm) and δ-position (IC50=8.5 nm) of the aliphatic side chain) do not alter the binding properties of irbesartan (IC50=1.6 nm). After successful radiolabeling with fluorine-18 in a radiochemical yield of 11 %, we observed high renal uptake in healthy rats and pigs, which could be decreased by pretreatment with the parent compound irbesartan.
