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

F Heidempergher; P Pevarello; A Pillan; V Pinciroli; A Della Torre; C Speciale; M Marconi; M Cini; S Toma; F Greco; M Varasi

doi:10.1016/s0014-827x(99)00009-9

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

Farmaco. 1999 Mar 31;54(3):152-60. doi: 10.1016/s0014-827x(99)00009-9.

Authors

F Heidempergher¹, P Pevarello, A Pillan, V Pinciroli, A Della Torre, C Speciale, M Marconi, M Cini, S Toma, F Greco, M Varasi

Affiliation

¹ Pharmacia & Upjohn, Chemistry Department, Milan, Italy.

PMID: 10371028
DOI: 10.1016/s0014-827x(99)00009-9

Abstract

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.

MeSH terms

Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Kynurenine 3-Monooxygenase
Liver / enzymology
Mixed Function Oxygenases / antagonists & inhibitors*
Molecular Structure
Pyrroles / chemical synthesis*
Pyrroles / pharmacology
Quinolines / chemical synthesis*
Quinolines / pharmacology
Rats

Substances

7-chloro-3-methyl-1H-pyrrolo(3,2-c)quinoline-4-carboxylic acid
Enzyme Inhibitors
Pyrroles
Quinolines
Mixed Function Oxygenases
Kynurenine 3-Monooxygenase