Discovery of 3,6-dihydro-2H-pyran as a morpholine replacement in 6-aryl-1H-pyrazolo[3,4-d]pyrimidines and 2-arylthieno[3,2-d]pyrimidines: ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR).
Bioorg Med Chem Lett
; 20(2): 640-3, 2010 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-19963384
ABSTRACT
The morpholine hinge-region binding group on a series of pyrazolopyrimidine and thienopyrimidine mammalian target of rapamycin (mTOR) inhibitors was replaced with 3,6-dihydro-2H-pyran (DHP), giving compounds of equivalent potency and selectivity versus PI3K. These results establish the DHP group as a hinge-region binding motif for the preparation of highly potent and selective mTOR inhibitors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrans
/
Pyrazoles
/
Pyridines
/
Pyrimidines
/
Morpholines
/
Protein Serine-Threonine Kinases
/
Intracellular Signaling Peptides and Proteins
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2010
Type:
Article
Affiliation country:
United States