Successful reduction of off-target hERG toxicity by structural modification of a T-type calcium channel blocker was written by Choi, Yeon Jae;Seo, Jae Hong;Shin, Kye Jung. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2014.SDS of cas: 58333-75-8 This article mentions the following:
To obtain an optimized T-type calcium channel blocker with reduced off-target hERG toxicity, we modified the structure of the original compound by introducing a zwitterion and reducing the basicity of the nitrogen. Among the structurally modified compounds we designed, compounds 5 and 6, which incorporate amides in place of the original compound’s amines, most appreciably alleviated hERG toxicity while maintaining T-type calcium channel blocking activity. Notably, the benzimidazole amide 5 selectively blocked T-type calcium channels without inhibiting hERG (hERG/T-type ≥ 220) and L-type channels (L-type/T-type = 96), and exhibited an excellent pharmacokinetic profile in rats. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8SDS of cas: 58333-75-8).
4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.SDS of cas: 58333-75-8
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem