Synthesis and biological evaluation of novel N 1 -phenylsulphonyl indole derivatives as potent and selective 5-HT 6 R ligands for the treatment of cognitive disorders

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 31; no. sup1; pp. 1 - 15
• Main Authors: Nirogi, Ramakrishna V S, Bandyala, Thrinath Reddy, Gangadasari, Pamuletinarasimha Reddy, Khagga, Mukkanti
• Format: Journal Article
• Language: English
• Published: England 01.11.2016
• Subjects: Antipsychotic Agents - chemical synthesis; Antipsychotic Agents - metabolism; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Cognition Disorders - drug therapy; Cognition Disorders - metabolism; Dose-Response Relationship, Drug; Humans; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Ligands; Molecular Structure; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Receptors, Serotonin - metabolism; Structure-Activity Relationship; novel object recognition test; 5-Hydroxytryptamine-6 receptor; structure–activity relationship; animal models; cognition; central nervous system
• ISSN: 1475-6366; 1475-6374
• DOI: 10.3109/14756366.2015.1103233

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-HT receptor (5-HT R) 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.