Synthesis and pharmacological evaluation of aryl aminosulfonamide derivatives as potent 5-HT(6) receptor antagonists.
A series of novel aryl aminosulfonamides was designed and synthesized as 5-HT(6) receptor ligands. Many compounds screened in a functional reporter gene based assay displayed potent antagonistic activity with Kb values in the range of 0.02-10nM. The lead compound 11m exemplified in this series showed good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. The compound was selected for detailed profiling.
Nirogi
Ramakrishna V S
RV
Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in
Daulatabad
Anand V
AV
Parandhama
G
G
Mohammad
Shaikh
S
Sastri
K R
KR
Shinde
Anil K
AK
Dubey
P K
PK
D000818:Animals; D003071:Cognition / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D003577:Cytochrome P-450 Enzyme System