(Piperidinylalkoxy)chromones: Novel Antihistamines with Additional Antagonistic Activity against Leukotriene D4

Abstract

A series of novel chromone derivatives, in which the chromone moiety is connected to a (diphenylmethylene)-, (diphenylmethyl)-, or (diphenylmethoxy)piperidine via an alkyloxy spacer, were synthesized as antiallergic and antiasthmatic agents. In addition to their potent antihistaminic activity, the compounds also inhibit contraction in guinea pig ileum induced by leukotriene D4. When analyzed by radioligand binding assays in guinea pig lung membranes, one of the compounds, 7-[[3-[4-(diphenylmethylene)piperidin-1- yl]propyl]oxy]-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran, showed dissociation constants (KD) of 5.62 nM and 2.34 microM for H1- and LTD4-receptors, respectively. In vivo at the dose of 10 mg/kg, the compound inhibited the histamine- and LTD4-induced increase of vascular permeability in guinea pigs by 95 and 30%, respectively. The inhibition of LTD4-induced increase in vascular permeability by the compound was increased to 56% when a dose of 50 mg/kg was employed. Similar to terfenadine, the compound does not readily occupy the brain H1-receptors when given intraperitoneally to mice, implying no sedating side effects.

Dietary aloin, aloesin, or aloe-gel exerts anti-inflammatory activity in a rat colitis model

“…The results of this study indicate that aloesin is a strong inhibitor of LTB 4 release, suggesting that aloesin may reduce the accumulation of neutrophils and leukocytes within the mucosa. Zhang et al (1995) reported that the chromone moiety effectively inhibits a LTD4-induced increase in vascular permeability. Huang et al (1991) found that the chromone moiety in the benzopyran-4-one ring led to a significant increase in leukotriene D4 receptor binding affinity.…”

Selective, competitive and mechanism-based inhibitors of human cytochrome P450 2J2

“…2 Fig. 2)-4-(diphenylmethoxy)piperidine [30] and 1,1-difluoro-2-phenylethane [31] were prepared as described previously.…”

Agentes antiasmáticos modernos: antagonistas de receptores de leucotrienos cisteínicos

“…Como exemplos de agentes terapêuticos broncodilatadores podemos citar: os agonistas β 2 adrenérgicos 44 , anticolinérgicos 45 , metilxantinas 46 e moduladores de canais de potássio 41 . Por sua vez, os corticosteróides 47 , antagonistas de bradicinina 48 , anti-histamínicos 49 , inibidores de fosfolipase A 2 (PLA 2 -i) 50 , inibidores de tromboxana sintase (TXSi) 51 , antagonistas de receptores de TXA 2 (TPant) 52 , antagonistas de receptores de PAF (PAFant) 53 , inibidores de LTA 4 -hidrolase 54 , inibidores de 5-lipoxigenase (5-LO-i) 55 , são exemplos de agentes antiinflamatórios, úteis para o tratamento do processo asmático.…”