Dehydroabietylamine derived bistetrazoles from ultrasound-assisted pseudo-seven-component Ugi reactions act as efficient and selective inhibitors of cholinesterases

• Main Authors: Niels V. Heise (Author), Antonia Schmidt (Author), Jördis-Ann Schüler (Author), René Csuk (Author)
• Format: Book
• Published: Elsevier, 2024-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2772-4174; 10.1016/j.ejmcr.2023.100124
• Keywords: Dehydroabietylamine; Tetrazoles; Cholinesterases; Inhibition; Ugi reaction; Pharmacy and materia medica; RS1-441; Other systems of medicine; RZ201-999
• Source: European Journal of Medicinal Chemistry Reports, Vol 10, Iss , Pp 100124- (2024)

The reaction of dehydroabiethylamine (DHA) with isocyanides and formaldehyde produces varying products depending on the conditions employed. In a 4-component Ugi reaction using benzyl isocyanide, paraformaldehyde, and TMS-azide, the anticipated tetrazole is formed. Nevertheless, other isocyanides were unsuccessful in these conditions. Upon substituting paraformaldehyde with formalin and utilizing ultrasound instead, bis-tetrazole formation was obtained in a pseudo-7-component reaction. A bis-benzyl-substituted tetrazole 5 demonstrated significant AChE and BChE inhibition in Ellman's assays. Molecular modeling corroborated these results, with compound 5 identified as a mixed-type inhibitor for both enzymes.