Design and synthesis of novel sulfonamide-containing bradykinin hB(2) receptor antagonists. Synthesis and structure-relationships of α,α-tetrahydropyranylglycine.
Bioorg Med Chem
; 20(6): 2091-100, 2012 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-22342268
ABSTRACT
A series of α,α-cycloalkylglycine sulfonamide compounds of general formula 1 has previously been identified by our group as selective human B(2)(hB(2)) receptor antagonists. Here we report the in vitro and in vivo BK antagonist activity of a further evolution of the series, consisting in compounds of the general formula 2, containing either an alkyl piperazine or a 4-alkyl piperidine ring bearing various positively charged groups (R'). These studies unexpectedly revealed quite a flat nanomolar/subnanomolar SAR for the binding affinity, while differences were seen in the in vitro functional activities. We propose that variations in the residence time may explain these results.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfonamides
/
Bradykinin B2 Receptor Antagonists
/
Glycine
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2012
Document type:
Article
Affiliation country:
Italia