کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1358144 | 981321 | 2016 | 8 صفحه PDF | دانلود رایگان |
Based on our recently reported selective hMAO-A inhibitors, on which, the intramolecular cyclization led to a very interesting change of isoform selectivity. A series of selective hMAO-B inhibitors (3a–3u) with novel scaffold of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one were designed and synthesized. Compound 3u (IC50 = 221 nM) exhibited the best inhibitory activity and isoform selectivity against hMAO-B, superior to selegiline (IC50 = 321 nM), which is a commercial selective hMAO-B inhibitor used to Parkinson’s disease. Modeling study indicated that the selectivity of our compounds to hMAO-B is determined by at least two residues, i.e., Ile 199 and Cys 172 (or corresponded Phe 208 and Asn 181 of hMAO-A). These data support further studies to assess rational design of more efficiently selective hMAO-B inhibitors.
Novel tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one as potential selective hMAO-B inhibitors were designed and synthesized. Modeling study indicated that the hMAO-B selectivity is determined by at least two residues, i.e., Ile 199 and Cys 172.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 24, Issue 8, 15 April 2016, Pages 1741–1748