[Pyrrolo(2,3-c)quinolines and pyrrolo(3,4-d)quinolines--synthesis and investigation of lipoxygenase inhibition].
The Paal-Knorr synthesis of the cyclic hemiketonacetal 4 yields the pyrrole-2,4-dicarboxylic acid diesters 1c and 7 via the cyclic hemiaminals 5 and 6; while the pyrrole-2-carboxylic acid ester 9 is formed from the 1,4-diketon 10. Under reducing conditions 1c and their 4-carboxylic acid 8 give the pyrrolo[3,4-c]quinoline carboxylic acid ester 2a; the cyclic hydroxamic acid 11 and the lactam 12 of the pyrrolo[2,3-c]quinoline type are obtained from compound 9. The isomeric compounds of the pyrrolo[3,4-c]quinoline series 16, 17 and 18, respectively, are synthesized from the pyrroles 14 and 15; the cyclic hemiacetal 13 was used as educt. The tricyclic hydroxamic acids 16 and 17 weakly inhibit the 5-lipoxygenase (IC50 > 10 microM, relating to the formation of LTB4 of human whole blood).
Görlitzer
K
K
Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
Fabian
J
J
Frohberg
P
P
Drutkowski
G
G
D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase