Chemical and pharmacological characterization of the TRPML calcium channel blockers ML-SI1 and ML-SI3 was written by Leser, Charlotte;Keller, Marco;Gerndt, Susanne;Urban, Nicole;Chen, Cheng-Chang;Schaefer, Michael;Grimm, Christian;Bracher, Franz. And the article was included in European Journal of Medicinal Chemistry in 2021.HPLC of Formula: 58333-75-8 This article mentions the following:
The members of the TRPML subfamily of non-selective cation channels (TRPML1-3) are involved in the regulation of important lysosomal and endosomal functions, and mutations in TRPML1 are associated with the neurodegenerative lysosomal storage disorder mucolipidosis type IV. In literature only two TRPML inhibitors, compound I : ML-SI1 and compound II : ML-SI3, have been published, albeit without clear information about stereochem. details. In this investigation authors developed total syntheses of both inhibitors. ML-SI1 was only obtained as a racemic mixture of inseparable diastereomers and showed activator-dependent inhibitory activity. The more promising tool is ML-SI3, hence ML-SI1 was not further investigated. For ML-SI3 authors confirmed by stereoselective synthesis that the trans-isomer is significantly more active than the cis-isomer. Separation of the enantiomers of trans-ML-SI3 further revealed that the (-)-isomer is a potent inhibitor of TRPML1 and TRPML2 (IC50 values 1.6 and 2.3μM) and a weak inhibitor (IC50 12.5μM) of TRPML3, whereas the (+)-enantiomer is an inhibitor on TRPML1 (IC50 5.9μM), but an activator on TRPML 2 and 3. The anal. of 12 analogs and aromatic analog of ML-SI3 gave first insights into structure-activity relationships in this chemotype, and showed that a broad variety of modifications in both the N-arylpiperazine and the sulfonamide moiety is tolerated. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8HPLC of Formula: 58333-75-8).
4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.HPLC of Formula: 58333-75-8
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem