Pyrrolo[3,2-c]quinoline derivatives: a new class of kynurenine-3-hydroxylase inhibitors.
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-1H-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.
Heidempergher
F
F
Pharmacia & Upjohn, Chemistry Department, Milan, Italy.
Pevarello
P
P
Pillan
A
A
Pinciroli
V
V
Della Torre
A
A
Speciale
C
C
Marconi
M
M
Cini
M
M
Toma
S
S
Greco
F
F
Varasi
M
M
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D050601:Kynurenine 3-Monooxygenase; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
C120225:7-chloro-3-methyl-1H-pyrrolo(3,2-c)quinoline-4-carboxylic acid; D004791:Enzyme Inhibitors; D011758:Pyrroles; D011804:Quinolines; D006899:Mixed Function Oxygenases; D050601:Kynurenine 3-Monooxygenase