6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1 receptor antagonists: structure-activity exploration of eastern and western parts.
SAR explorations of the eastern and western parts of recently disclosed 2-aminoquinoline MCH1R-antagonists are reported. Eastern part investigations confirmed a high degree of structural freedom, and a number of additional single digit nanomolar antagonists were identified. Investigations of the western part also confirmed the initial SAR analysis, requiring a para-substituted phenyl ring spaced from the 6-amide by two connecting atoms. The exploration led to the discovery of a novel sub-series with a 4-biphenylcarboxamide western part, also exhibiting single digit nanomolar affinity.
Ulven
Trond
T
7TM Pharma A/S, Fremtidsvej 3, DK-2970 Hørsholm, Denmark.
Little
Paul Brian
PB
Receveur
Jean-Marie
JM
Frimurer
Thomas M
TM
Rist
Oystein
O
Nørregaard
Pia K
PK
Högberg
Thomas
T
D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011804:Quinolines; D017481:Receptors, Somatostatin