120443-15-4Relevant articles and documents
Synthesis of chiral thioacetals and thioethers
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, (2008/06/13)
Thioacids, thiols, an acid, and an aldehyde are used to produce chiral thioacetals of the general formula. STR1 The compounds are leukotriene antagonists.
Development of a novel series of styrylquinoline compounds as high- affinity leukotriene D4 receptor antagonists: Synthetic and structure- activity studies leading to the discovery of (±)-3-[[[3-[2-(7-chloro-2- quinolinyl)-(E)-ethenyl]phenyl][[3-(dimethylamino)-3- oxopropyl]thio]methyl]thio]propionic acid
Zamboni,Belley,Champion,Charette,DeHaven,Frenette,Gauthier,Jones,Leger,Masson,McFarlane,Metters,Pong,Piechuta,Rokach,Therien,Williams,Young
, p. 3832 - 3844 (2007/10/02)
Based on LTD4 receptor antagonist activity of 3-(2-quinolinyl-(E)- ethenyl)pyridine (2) found in broad screening, structure-activity studies were carried out which led to the identification of 3-[[[3-[2-(7-chloro-2- quinolinyl)-(E)-ethenyl]phenyl][[3-(dimethylamino)-3- oxopropyl]thio]methyl]thio]propionic acid (1, MK-571) as a potent and orally active LTD4 receptor antagonist. These studies demonstrated that a phenyl ring could replace the pyridine in 2 without loss of activity, that 7-halogen substitution in the quinoline group was optimal for binding, that the (E)- ethenyl linkage was optimal, that binding was enhanced by incorporation of a polar acidic group or groups in the 3-position of the aryl ring, and that two acidic groups could be incorporated via a dithioacetal formed from thiopropionic acid and the corresponding styrylquinoline 3-aldehyde to yield compounds such as 20 (IC50 = 3 nM vs [3H]LTD4 binding to the guinea pig lung membrane). It was found that one of the acidic groups could be transformed into a variety of the amides without loss of potency and that the dimethylamide 1 embodied the optimal properties of intrinsic potency (IC50 = 0.8 nM on guinea pig lung LTD4 receptor) and oral in vivo potency in the guinea pig, hyperreactive rat, and squirrel monkey. The evolution of 2 to 1 involves the increase of >6000-fold in competition for [3H]LTD4 binding to guinea pig lung membrane and a >40-fold increase in oral activity as measured by inhibition of antigen-induced dyspnea in hyperreactive rats.
2-substituted quinoline dioic acids and pharmaceutical compositions
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, (2008/06/13)
Compounds having the formula: STR1 are antagonists of leukotrienes and inhibitors of their biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
ASYMMETRIC DITHIOACETALS III: THE PREPARATION OF THE ENANTIOMERS OF 3-((((3-(2-(7-CHLOROQUINOLIN-2-YL)-(E)-ETHENYL)PHENYL)-3-DIMETHYLAMINO-3-OXOPROPYLTHIO)METHYL)THIO)PROPIONIC ACID (L-660,711) (MK-571), AN ANTAGONIST OF LEUKOTRIENE D4
Young, Robert N.,Gauthier, Jacques Yves,Therien, Michel,Zamboni, Robert
, p. 967 - 978 (2007/10/02)
The application of a novel method for the preparation of chiral dithioacetals to the synthesis of the enantiomers of L-660,711, an antagonist of leukotriene D4, is described.Reaction of 3-(t-butyldiphenylsilyloxymethyl)benzaldehyde or isophthal
Synthesis of Unsymmetrical Dithioacetals: An Efficient Synthesis of a Novel LTD4 Antagonist, L-660,711
McNamara, J. M.,Leazer, J. L.,Bhupathy, M.,Amato, J. S.,Reamer, R. A.,et al.
, p. 3718 - 3721 (2007/10/02)
An efficient four-step synthesis of the potent LTD4 antagonist L-660,711 (1) is described.The key step involves selective conversion of aldehyde 2 to the unsymmetrical dithioacetal 7, via O-trimethylsilyl hemithioacetal 10.This specific cleavage of the carbon-oxygen bond of a mixed O,S-acetal permits the unprecedented synthesis of unsymmetrical dithioacetals.
2-Substituted quinoline dioic acids
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, (2008/06/13)
Compounds having the formula: are antagonists of leukotrienes and inhibitors of their biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
