title: Synthesis of some urea and thiourea derivatives of 3-phenyl/ethyl-2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidine and their antagonistic effects on haloperidol-induced catalepsy and oxidative stress in mice.
abstract: A series of 3-phenyl/ethyl-2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7-yl urea and thiourea derivatives were designed and synthesized. All the compounds have been evaluated for their antiparkinsonian activity in catalepsy induced by haloperidol in mice. A majority of the compounds exhibited significant antiparkinsonian activity after intraperitoneal administration. The most active compound carries methoxy group at 2-position of the phenyl ring. Some of the potent compounds were selected for biochemical estimations of malondialdehyde, glutathione, superoxide dismutase and glutathione peroxidase from brain homogenate to highlight the neuroprotective properties associated with them. The results obtained in the present study may lead to the development of a suitable approach to the treatment of Parkinson's disease and may be the starting point for the future drug design.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seventh October, Misurata, Libya. azamfaizul@yahoo.co.in
authors.forename: Faizul
authors.initials: F
authors.lastname: Azam
authors.forename: Ismail A
authors.initials: IA
authors.lastname: Alkskas
authors.forename: Musa A
authors.initials: MA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D018726:Anti-Dyskinesia Agents; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006220:Haloperidol; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D014508:Urea / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D018726:Anti-Dyskinesia Agents; D000978:Antiparkinson Agents; D011743:Pyrimidines; D008315:Malondialdehyde; D014508:Urea; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D013890:Thiourea; D006220:Haloperidol