title: Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility.
abstract: Catechol O-methyltransferase (COMT) is the enzyme responsible for the O-methylation of endogenous neurotransmitters and of xenobiotic substances and hormones incorporating catecholic structures. COMT is a druggable biological target for the treatment of various central and peripheral nervous system disorders, including Parkinson's disease, depression, schizophrenia, and other dopamine deficiency-related diseases. The purpose of this perspective is fourfold: (i) to summarize the physiological role of COMT inhibitors in central and peripheral nervous system disorders; (ii) to provide the history and perspective of the medicinal chemistry behind the discovery and development of COMT inhibitors; (iii) to discuss how the physicochemical properties of recognized COMT inhibitors are understood to exert influence over their pharmacological properties; and (iv) to evaluate the clinical benefits of the most relevant COMT inhibitors.
authors: Department of Research & Development, BIAL - Portela & Ca, S.A. , À Avenida da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal.
authors: László E
authors: LE
authors: Kiss
authors: Patrício
authors: P
authors: Soares-da-Silva
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use; D000818:Animals; D002384:Catalysis; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002396:Catechols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D009570:Nitriles / Q000627:therapeutic use; D010069:Oxadiazoles / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats
chemical_list: D000098:Acetophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; D010069:Oxadiazoles; D011355:Prodrugs; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase; C433466:nebicapone; C549349:opicapone