Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility.

摘要: Catechol O-methyltransferase (COMT) is the enzyme responsible for O-methylation of endogenous neurotransmitters and xenobiotic substances hormones incorporating catecholic structures. COMT a druggable biological target treatment various central peripheral nervous system disorders, including Parkinson's disease, depression, schizophrenia, other dopamine deficiency-related diseases. The purpose this perspective fourfold: (i) to summarize physiological role inhibitors in disorders; (ii) provide history medicinal chemistry behind discovery development inhibitors; (iii) discuss how physicochemical properties recognized are understood exert influence over their pharmacological properties; (iv) evaluate clinical benefits most relevant inhibitors.