Synthesis of stable and selective inhibitors of human galectins-1 and -3.
Bioorg Med Chem
; 16(16): 7811-23, 2008 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-18674915
ABSTRACT
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-(beta-D-galactopyranosyl)-but-2-enoate 15 with inhibitory potency of 313 microM against galectin-1 and best dimers were bis-lactoside 68 and 75 having both inhibitory properties of 160 microM against Galectin-3.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Galectin 1
/
Galectin 3
/
Galactosides
/
Glycosides
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2008
Document type:
Article
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM