Synthesis and biological evaluation of novel N1-phenylsulphonyl indole derivatives as potent and selective 5-HT6R ligands for the treatment of cognitive disorders.
A series of 1-[3-(4-methyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole and 1-[3-(4-ethyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole derivatives were designed and synthesized as 5-HT6receptor (5-HT6R) ligands. The lead compound 1-[4-methyl-3-(4-methyl piperazin-1-yl methyl) phenylsulfonyl]-1H-indole dihydrochloride (6b), in this series, has shown potent in vitro binding affinity, selectivity, good pharmacokinetics (PK) profile and activity in the animal models of cognition.
a Discovery Research, Suven Life Sciences Limited , Hyderabad , India and.
Ramakrishna V S
RV
Nirogi
a Discovery Research, Suven Life Sciences Limited , Hyderabad , India and.|b Centre for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad , Hyderabad , India.
Thrinath Reddy
TR
Bandyala
a Discovery Research, Suven Life Sciences Limited , Hyderabad , India and.
Pamuletinarasimha Reddy
PR
Gangadasari
b Centre for Chemical Sciences and Technology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad , Hyderabad , India.
Mukkanti
M
Khagga
D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
C000614174:1-(4-methyl-3-(4-methyl piperazin-1-yl methyl)phenylsulfonyl)-1H-indole dihydrochloride; D014150:Antipsychotic Agents; D007211:Indoles; D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor
5-Hydroxytryptamine-6 receptor; animal models; central nervous system; cognition; novel object recognition test; structure–activity relationship