143816-48-2Relevant academic research and scientific papers
Utilities of olefin derivatives
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Page/Page column 15, (2008/06/13)
Compounds having an activity to enhance the expression of apoAI are provided. Compounds of formula (I): in which Ar1 and Ar2 are independently a phenyl, naphthyl, or monocyclic or bicyclic aromatic heterocyclic group, which may be optionally substituted; —X— is —N═CZ2-, —CY2═CZ2-, —CY2Y3—CHZ2-, —S—, —O—, or the like; Y1, Y2, Y3, Z1 and Z2 are independently a hydrogen, a halogen, a lower alkyl, a phenyl, or the like; Z1 and Z2 may be independently a linker group that may combine with Ar2 and Ar1 to form a condensed ring; m is 0 or 1, and n is 0 to 2; a prodrug thereof, a pharmaceutically acceptable salt or solvate of them; are disclosed.
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.
