title: Design, synthesis, and preliminary in vitro and in vivo pharmacological evaluation of 2-{4-[4-(2,5-disubstituted thiazol-4-yl)phenylethyl]piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles as atypical antipsychotic agents.
abstract: A series of 2-{4-[4-(2,5-disubstituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8-naphthyridine-3-carbonitriles were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized either by microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by microanalysis. The D(2) and 5-HT(2A) affinity of the synthesized compounds was screened in vitro by radioligand displacement assays on membrane homogenates isolated from rat striatum and rat cortex, respectively. Furthermore, all the synthesized compounds were screened for their in vivo pharmacological activity in Swiss albino mice. The D(2) antagonism studies were performed using climbing mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine-induced head twitches in mice. It was observed that none of the new chemical entities exhibited catalepsy and 10f is the most active among the synthesized compounds with 5-HT(2A)/D(2) ratio of 1.1286 although the standard drug risperidone exhibited 5-HT(2A)/D(2) ratio of 1.0989.
authors.affiliation: Chemistry Group, Birla Institute of Technology & Science, Pilani, Rajasthan, India. kvgcs@yahoo.com
authors.forename: Kondapalli Venkata
authors.initials: KV
authors.lastname: Gowri Chandra Sekhar
authors.forename: Vajja Samabasiva
authors.initials: VS
authors.lastname: Rao
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Aravalli Satish
authors.initials: AS
authors.lastname: Reddy
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Mutyala Murali
authors.initials: MM
authors.lastname: Krishna Kumar
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D005260:Female; D008297:Male; D051379:Mice; D008872:Microwaves; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D009287:Naphthyridines; D009570:Nitriles; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists