ys-121 and Inflammation

ys-121 has been researched along with Inflammation* in 2 studies

Other Studies

2 other study(ies) available for ys-121 and Inflammation

Article	Year
Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid. Journal of medicinal chemistry, 2008, Sep-11, Volume: 51, Issue:17 A novel class of potent 5-lipoxygenase (5-LO) product synthesis inhibitors based on the structure of pirinixic acid (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid, compound 1) is presented. Systematic profiling of 1, i.e., esterification of the carboxylic acid, alpha-substitution, and replacement of the o-dimethylaniline by 6-aminoquinoline, leads to potent suppressors of 5-LO product formation in activated polymorphonuclear leukocytes, exemplified by ethyl 2-[4-chloro-6-(quinoline-6-ylamino)-pyrimidin-2-ylsulfanyl]octane-1-carboxylate (6d, IC50 = 0.6 microM). These derivatives may possess potential for intervention with inflammatory and allergic diseases. Topics: Aminoquinolines; Cells, Cultured; Esterification; Humans; Hypersensitivity; Inflammation; Leukocytes; Lipoxygenase; Lipoxygenase Inhibitors; Pyrimidines; Structure-Activity Relationship	2008
Pirinixic acid derivatives as novel dual inhibitors of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase. Journal of medicinal chemistry, 2008, Dec-25, Volume: 51, Issue:24 Dual inhibition of the prostaglandin (PG) and leukotriene (LT) biosynthetic pathway is supposed to be superior over single interference, both in terms of efficacy and side effects. Here, we present a novel class of dual microsomal PGE(2) synthase-1/5-lipoxygenase (5-LO) inhibitors based on the structure of pirinixic acid [PA, 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)acetic acid, compound 1]. Target-oriented structural modification of 1, particularly alpha substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue, resulted in potent suppression of mPGES-1 and 5-LO activity, exemplified by 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (7b, IC(50) = 1.3 and 1 microM, respectively). Select compounds also potently reduced PGE(2) and 5-LO product formation in intact cells. Importantly, inhibition of cyclooxygenases-1/2 was significantly less pronounced. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacological profile and a potential for therapeutic use. Topics: Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Cyclooxygenase 1; Cyclooxygenase 2; Drug Design; Enzyme Activation; Enzyme Inhibitors; Humans; Inflammation; Inhibitory Concentration 50; Intramolecular Oxidoreductases; Lipoxygenase Inhibitors; Models, Chemical; Prostaglandin-E Synthases; Pyrimidines	2008

Article

Year

Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid.

Journal of medicinal chemistry, 2008, Sep-11, Volume: 51, Issue:17

A novel class of potent 5-lipoxygenase (5-LO) product synthesis inhibitors based on the structure of pirinixic acid (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid, compound 1) is presented. Systematic profiling of 1, i.e., esterification of the carboxylic acid, alpha-substitution, and replacement of the o-dimethylaniline by 6-aminoquinoline, leads to potent suppressors of 5-LO product formation in activated polymorphonuclear leukocytes, exemplified by ethyl 2-[4-chloro-6-(quinoline-6-ylamino)-pyrimidin-2-ylsulfanyl]octane-1-carboxylate (6d, IC50 = 0.6 microM). These derivatives may possess potential for intervention with inflammatory and allergic diseases.

Topics: Aminoquinolines; Cells, Cultured; Esterification; Humans; Hypersensitivity; Inflammation; Leukocytes; Lipoxygenase; Lipoxygenase Inhibitors; Pyrimidines; Structure-Activity Relationship

2008

Pirinixic acid derivatives as novel dual inhibitors of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase.

Journal of medicinal chemistry, 2008, Dec-25, Volume: 51, Issue:24

Dual inhibition of the prostaglandin (PG) and leukotriene (LT) biosynthetic pathway is supposed to be superior over single interference, both in terms of efficacy and side effects. Here, we present a novel class of dual microsomal PGE(2) synthase-1/5-lipoxygenase (5-LO) inhibitors based on the structure of pirinixic acid [PA, 2-(4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylthio)acetic acid, compound 1]. Target-oriented structural modification of 1, particularly alpha substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue, resulted in potent suppression of mPGES-1 and 5-LO activity, exemplified by 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (7b, IC(50) = 1.3 and 1 microM, respectively). Select compounds also potently reduced PGE(2) and 5-LO product formation in intact cells. Importantly, inhibition of cyclooxygenases-1/2 was significantly less pronounced. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacological profile and a potential for therapeutic use.

Topics: Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Cyclooxygenase 1; Cyclooxygenase 2; Drug Design; Enzyme Activation; Enzyme Inhibitors; Humans; Inflammation; Inhibitory Concentration 50; Intramolecular Oxidoreductases; Lipoxygenase Inhibitors; Models, Chemical; Prostaglandin-E Synthases; Pyrimidines

2008