MK-0591

Names

[ Name ]:
MK-0591

[Synonym ]:
1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-α,α-dimethyl-5-(2-quinolinylmethoxy)-
quiflapon
3-[1-[(4-chlorophenyl)methyl]-5-(quinolin-2-ylmethoxy)-3-tert-butylsulfanyl-indol-2-yl]-2,2-dimethyl-propanoic acid
3-[3-(tert-Butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoic acid
3-[3-(1,1-dimethylethylthio)-5-(quinolin-2-ylmethoxy)-1-(4-chlorophenylmethyl)indol-2-yl]-2,2-methylpropionic acid
3-[3-(1,1-dimethylethylthio)-5-(quinolin-2-ylmethoxy)-1-(4-chlorophenylmethyl)indol-2-yl]-2,2-dimethylpropionic acid
3-[1-(4-Chlorobenzyl)-3-[(2-methyl-2-propanyl)sulfanyl]-5-(2-quinolinylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoic acid
Quiflapon [INN]
1-((4-Chlorophenyl)methyl)-3-((1,1-dimethylethyl)thio)-a,a-dimethyl-5-(2-quinolinylmethoxy)-1H-indole-2-propanoic Acid
3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid
MK 0591
3-(tert-Butylthio)-1-(p-chlorobenzyl)-a,a-dimethyl-5-(2-quinolylmethoxy)indole-2-propionic Acid
MK-0591

Biological Activity

[Description]:

MK591 (free acid) is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay.

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> FLAP

Research Areas >> Inflammation/Immunology

[Target]

IC50 value: 1.6 nM (FLAP)[1].

[In Vitro]

MK591 (free acid) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). MK591 (free acid) has no effect on rat 5-lipoxygenase. MK591 (free acid) has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs[1].

[In Vivo]

MK591 (free acid) is a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK591 (free acid) is observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response) [1]. Pups were treated with either vehicle or MK591 (free acid) 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with MK-0591 (free acid) untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation[2].

[References]

[1]. Brideau C, et al. Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1992 Jun;70(6):799-807.

[2]. Park MS, et al. 5-Lipoxygenase-activating protein (FLAP) inhibitor MK-0591 prevents aberrant alveolarization in newborn mice exposed to 85% oxygen in a dose- and time-dependent manner. Lung. 2011 Feb;189(1):43-50.

[Related Small Molecules]

MK886 | GSK2190915 | AM679 | MK591 | AM 103

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
751.3±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₃₄H₃₅ClN₂O₃S

[ Molecular Weight ]:
587.171

[ Flash Point ]:
408.2±32.9 °C

[ Exact Mass ]:
586.205688

[ PSA ]:
89.65000

[ LogP ]:
8.31

[ Vapour Pressure ]:
0.0±2.6 mmHg at 25°C

[ Index of Refraction ]:
1.617

[ Storage condition ]:
2-8℃

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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