Indole-3-piperazinyl derivatives: novel chemical class of 5-HT(6) receptor antagonists.
N(1)-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT(6) receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT(6) receptor. The compound 7a (K(i) = 3.4 nM, functional assay IC(50) = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.
Discovery Research, Medicinal Chemistry, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500 034, India. ramakrishna_nirogi@yahoo.co.in
Ramakrishna V S
RV
Nirogi
Amol D
AD
Deshpande
Ramasastri
R
Kambhampati
Rajesh Kumar
RK
Badange
Laxman
L
Kota
Anand V
AV
Daulatabad
Anil K
AK
Shinde
Ishtiyaque
I
Ahmad
Vishwottam
V
Kandikere
Pradeep
P
Jayarajan
P K
PK
Dubey
D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; 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
D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor