So far, in addition to halogen atoms, other non-metallic atoms can become part of the aromatic heterocycle, and the target ring system is still aromatic.Kumar, Kunal; Wang, Peng; Wilson, Jessica; Zlatanic, Viktor; Berrouet, Cecilia; Khamrui, Susmita; Secor, Cody; Swartz, Ethan A.; Lazarus, Michael; Sanchez, Roberto; Stewart, Andrew F.; Garcia-Ocana, Adolfo; DeVita, Robert J. researched the compound: Methyl 3-bromopropanoate( cas:3395-91-3 ).HPLC of Formula: 3395-91-3.They published the article 《Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor》 about this compound( cas:3395-91-3 ) in Journal of Medicinal Chemistry. Keywords: harmine derivative preparation DYRK1A inhibitory activity diabetes SAR. We’ll tell you more about this compound (cas:3395-91-3).
Recently, our group identified that harmine is able to induce β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. Since, harmine suffers from a lack of selectivity, both against other kinases and CNS off-targets, we therefore sought to expand structure-activity relationships for harmine’s DYRK1A activity, to enhance selectivity for off-targets while retaining human β-cell proliferation activity. We carried out optimization of the 9-N-position of harmine to synthesize 29 harmine-based analogs. Several novel inhibitors showed excellent DYRK1A inhibition and human β-cell proliferation capability. An optimized DYRK1A inhibitor, compound I, was identified as a novel, efficacious in vivo lead candidate. Compound I also demonstrates improved selectivity for kinases and CNS off-targets, as well as in vivo efficacy for β-cell proliferation and regeneration at lower doses than harmine. Collectively, these findings demonstrate that compound I is a much improved in vivo lead candidate as compared to harmine for the treatment of diabetes.
《Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor》 provides a strategy for the preparation of materials with excellent comprehensive properties, which is conducive to broaden the application field of this compound(Methyl 3-bromopropanoate)HPLC of Formula: 3395-91-3.
Reference:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem