Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT) was written by Ding, Yun;O’Keefe, Heather;DeLorey, Jennifer L.;Israel, David I.;Messer, Jeffrey A.;Chiu, Cynthia H.;Skinner, Steven R.;Matico, Rosalie E.;Murray-Thompson, Monique F.;Li, Fan;Clark, Matthew A.;Cuozzo, John W.;Arico-Muendel, Christopher;Morgan, Barry A.. And the article was included in ACS Medicinal Chemistry Letters in 2015.Electric Literature of C11H16ClNO2 This article mentions the following:
The aggrecan degrading metalloprotease ADAMTS-4 has been identified as a novel therapeutic target for osteoarthritis. Here, the authors use DNA-encoded Library Technol. (ELT) to identify novel ADAMTS-4 inhibitors from a DNA-encoded triazine library by affinity selection. Structure-activity relationship studies based on the selection information led to the identification of potent and highly selective inhibitors. For example I has IC50 of 10 nM against ADAMTS-4, with >1000-fold selectivity over ADAMT-5, MMP-13, TACE, and ADAMTS-13. These inhibitors have no obvious zinc ligand functionality. In the experiment, the researchers used many compounds, for example, 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3Electric Literature of C11H16ClNO2).
6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (cas: 2328-12-3) belongs to tetrahydroisoquinoline derivatives. Tetrahydroisoquinoline, as a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. An oxidative C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents is mediated by diethyl azodicarboxylate (DEAD). This C-H activation under metal-free conditions delivers target compounds, including some naturally occurring alkaloids, in good yields.Electric Literature of C11H16ClNO2
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem