1373876-06-2Relevant academic research and scientific papers
Dipeptidyl peptidase inhibitors for the preparation of iodo, chloro, iodo intermediate and method
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Paragraph 0113; 0114, (2016/10/10)
The invention provides an iodination preparation method for a dipeptidyl peptidase inhibitor, chlorination and iodination intermediates of the dipeptidyl peptidase inhibitor and preparation methods for the intermediates. According to the invention, an intermediate chlorinated compound is subjected to iodination in an organic solvent, and then a compound represented by a formula I and a salt thereof are prepared from an iodinated compound and used as the dipeptidyl peptidase inhibitor, wherein in the formula 1 descried in the invention, R1 is selected from an aryl group, a heteroaryl group and an alkyl group, or from an aryl group, a heteroaryl group and an alkyl group substituted by an alkyl or alkoxy group whose substituent groupp has a carbon atom number of C1 to C8, and X is an alkylene group with a carbon atom number of C1 to C8. Compared with conventional methods which prepare the compound represented by the formula I from brominated compounds, the method provided by the invention has the advantages of a substantial increase in yield and no need for column chromatographic purification, thereby facilitating industrial synthesis.
Reductive amination of dipeptidyl peptidase inhibitors for the preparation method, intermediate and method
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Paragraph 0147; 0151; 0152, (2016/11/24)
The invention provides a reductive amination preparation method for a dipeptidyl peptidase inhibitor, intermediate ester, alcohol and aldehyde compounds used for preparation of the dipeptidyl peptidase inhibitor and preparation methods for the intermediates. According to the invention, an ester compound is produced from an intermediate chlorinated compound in an organic solvent and is then hydrolyzed to obtain alcohol, the alcohol is oxidized to obtain aldehyde, and then a compound represented by a formula I is prepared from an aldehyde compound through reductive amination, wherein in the formula 1 descried in the invention, R1 is selected from an aryl group, a heteroaryl group and an alkyl group, or from an aryl group, a heteroaryl group and an alkyl group substituted by an alkyl or alkoxy group whose substituent group has a carbon atom number of C1 to C8, and X is an alkylene group with a carbon atom number of C1 to C8. Compared with conventional methods which prepare the compound represented by the formula I from brominated compounds, the method provided by the invention has the advantages of a substantial increase in yield, great improvement of stability of the compound represented by the formula I and no need for column chromatographic purification, thereby facilitating industrial synthesis.
Synthesis and evaluation of structurally constrained imidazolidin derivatives as potent dipeptidyl peptidase IV inhibitors
Wang, Liutang,Zhang, Bin,Ji, Jianxin,Li, Bogang,Yan, Jufang,Zhang, Weiyu,Wu, Yong,Wang, Xuechao
experimental part, p. 3318 - 3322 (2009/12/01)
To find potent and selective inhibitors of dipeptidyl peptidase IV (DPP-IV), we synthesized a series of 2-cyanopyrrolidine derivatives with constrained imidazolidin ring and tested their activities against DPP-IV. Most of them exhibited submicromolar inhibitory activities against DPP-IV. The most potent compound among these is (S)-1-(2-(2-(3-(3,4-dimethoxyphenyl)-2-oxoimidazolidin-1-yl)ethyl-amino)acetyl)pyrrolidine-2-carbonitrile (6n), which is a 2 nM DPP-IV inhibitor.
