Pyrrolo[3,2- c]quinoline derivatives: a new class of kynurenine-3-hydroxylase inhibitors

• Published in: Farmaco (Società chimica italiana : 1989) Vol. 54; no. 3; pp. 152 - 160
• Main Authors: Heidempergher, Franco, Pevarello, Paolo, Pillan, Antonio, Pinciroli, Vittorio, Della Torre, Arturo, Speciale, Carmela, Marconi, Marina, Cini, Massimo, Toma, Salvatore, Greco, Felicita, Varasi, Mario
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier SAS 31.03.1999; Elsevier; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Enzyme inhibition; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Hydroxylase; Kynurenine; Kynurenine 3-Monooxygenase; Life Sciences & Biomedicine; Liver - enzymology; Medical sciences; Miscellaneous; Mixed Function Oxygenases - antagonists & inhibitors; Molecular Structure; Neuropharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyrroles - chemical synthesis; Pyrroles - pharmacology; Quinolines - chemical synthesis; Quinolines - pharmacology; Rats; Science & Technology; Kynurenine; Enzyme inhibition; Hydroxylase; QUINOLINIC ACID; 3-HYDROXYLASE; enzyme inhibition; METABOLISM; KYNURENINE PATHWAY; CHEMISTRY; kynurenine; RAT-BRAIN; hydroxylase; Rat; Enzyme; Nitrogen heterocycle; Liver; Rodentia; Enzyme inhibitor; Tricyclic compound; In vitro; Modeling; Vertebrata; Mammalia; Structure activity relation; Animal; Molecular model; Kynurenine 3-monooxygenase; Aromatic compound; Oxidoreductases; Chemical synthesis
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(99)00009-9

A series of pyrrolo[3,2- c]quinoline derivatives were synthesised and evaluated as inhibitors of selected enzymes of the kynurenine pathway. 7-Chloro-3-methyl-1 H-pyrrolo[3,2- c]quinoline-4-carboxylic acid ( 7a) was found to be a relatively potent and selective inhibitor of kynurenine-3-hydroxylase (KYN-3-OHase). A molecular modelling study showed a good superimposition of 7a with PNU-156561 and kynurenine the natural substrate of KYN-3-OHase.