title: Synthesis, anticonvulsant, sedative and anxiolytic activities of novel annulated pyrrolo[1,4]benzodiazepines.
abstract: Four new pentacyclic benzodiazepine derivatives (PBDTs 13-16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.
authors.affiliation: Medicinal Chemistry Laboratory, Gunapati Venkata Krishnareddy Biosciences Private Limited, Plot No. 28A, Industrial Development Area Nacharam, Hyderabad 500076, India. kumaraswamy.s@gvkbio.com.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Sorra
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan. cschen7@mail.cmu.edu.tw.
authors.forename: Chien-Shu
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan. cfchang@mail.cmu.edu.tw.
authors.forename: Chi-Fen
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Medicinal Chemistry Laboratory, Gunapati Venkata Krishnareddy Biosciences Private Limited, Plot No. 28A, Industrial Development Area Nacharam, Hyderabad 500076, India. pusulurisrinivas@gvkbio.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Pusuluri
authors.affiliation: Chemistry Division, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500085, India. kmukkanti@yahoo.com.
authors.forename: Khagga
authors.initials: K
authors.lastname: Mukkanti
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan. crw@mail.cmu.edu.tw.
authors.forename: Chi-Rei
authors.initials: CR
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan. thchuang@mail.cmu.edu.tw.
authors.forename: Ta-Hsien
authors.initials: TH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D010424:Pentobarbital / Q000633:toxicity; D010852:Picrotoxin / Q000633:toxicity; D012021:Reflex, Abnormal / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013331:Strychnine / Q000633:toxicity
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D006576:Heterocyclic Compounds, 4 or More Rings; D006993:Hypnotics and Sedatives; D010424:Pentobarbital; D010852:Picrotoxin; D013331:Strychnine; C000598175:18-thia-6,14,16,19,20-pentaazapentacyclo(12.6.0.0(2,6).0(8,13).0(15,19))icosa-1(20),8,10,12,15-pentaene-7,17-dione