Synthesis of stable and selective inhibitors of human galectins-1 and -3

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• 作者：Denis Giguè ; re ; Marc-André ; Bonin ; Philipe Cloutier ; Ramesh Patnam ; Christian St-Pierre ; Sachiko Sato ; René ; Roy
• 关键词：Glycomimetic ; Galectins ; Galactoside ; Cancer ; HIV
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 August 2008
• 年：2008
• 卷：16
• 期：16
• 页码：7811-7823
• 全文大小：319 K

文摘

The syntheses of glycolytically stable galactosides and lactosides have been made toward the selective inhibition of human galectins-1 and -3. Transition metal-catalyzed cross-coupling reactions were used to create carbon–carbon bond formation (Sonogashira, Suzuki, Heck, Glaser). Additionally, Hantzsch condensation was used to create novel 2-aminothiazoles which reacted with a panel of acylating and sulfonylating reagents. Moreover, dimeric galactosides and lactosides bearing triazoles, regiospecifically prepared using copper-catalyzed Huisgen azide-alkyne [1,3]-dipolar cycloaddition, provided efficient galectins-1 and -3 inhibitors. Best monovalent inhibitor among the tested series was (E)-methyl 2-phenyl-4-(β-d-galactopyranosyl)-but-2-enoate 15 with inhibitory potency of 313 μM against galectin-1 and best dimers were bis-lactoside 68 and 75 having both inhibitory properties of 160 μM against Galectin-3.