首页 | 本学科首页   官方微博 | 高级检索  
     检索      


Stereoselective synthesis of (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanols targeted to the C1 domain of protein kinase C
Authors:Alexandros Kiriazis  Gustav Boije af Gennäs  Virpi TalmanElina Ekokoski  Timo Ruotsalainen  Irene KylänlahtiTobias Rüffer  Gloria Wissel  Henri XhaardHeinrich Lang  Raimo K TuominenJari Yli-Kauhaluoma
Institution:a Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
b Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
c Technische Universität Chemnitz, Fakultät für Naturwissenschaften, Institut für Chemie, Strasse der Nationen 62, D-09111 Chemnitz, Germany
d Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland
Abstract:Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. By using the X-ray crystal structure of the PKCδ C1b domain combined with molecular modeling, we discovered (3-aminodecahydro-1,4-methanonaphthalen-2-yl)methanol as a novel C1 domain ligand. The stereoselective synthesis of this tricyclic γ-amino alcohol was based on two successive Diels-Alder reactions to construct the six continuous stereocenters of the key intermediate.
Keywords:Diels-Alder reaction  Protein kinase C  Molecular modeling  Curtius-Schmidt rearrangement
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号