C-branched iminosugars: α-glucosidase inhibition by enantiomers of isoDMDP, isoDGDP, and isoDAB-L-isoDMDP compared to miglitol and miglustat.
J Org Chem
; 78(15): 7380-97, 2013 Aug 02.
Article
em En
| MEDLINE
| ID: mdl-23688199
ABSTRACT
The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 45% from d-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K(i) 0.081 µM for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
1-Desoxinojirimicina
/
Inibidores da Angiogênese
/
Inibidores Enzimáticos
/
Imino Açúcares
/
Inibidores de Glicosídeo Hidrolases
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article