121175-61-9Relevant academic research and scientific papers
3,4-Dihydro-2H-1-benzopyran-2-carboxylic Acids and Related Compounds as Leukotriene Antagonists
Cohen, Noal,Weber, Giuseppe,Banner, Bruce L.,Lopresti, Rocco J.,Schaer, Beatrice,et al.
, p. 1842 - 1860 (2007/10/02)
Evaluation of a series of 3,4-dihydro-2H-1-benzopyran-2-carboxylic acids linked to the 2-hydroxyacetophenone pharmacophore present in the standard peptidoleukotriene antagonist FPL 55712 (1) has led to the discovery of Ro 23-3544 (7), an antagonist possessing greater potency and duration of action vs LTD4 than the standard (aerosol route of administration, guinea pig bronchoconstriction model).Interestingly, this compound also potently inhibited bronchoconstriction induced by LTB4 whereas 1 did not.Attempts to establish structure-activity relationships in this series involved modifications in the 2-hydroxyacetophenone moiety, the linking chain, and the chroman system.All variations produced analogues which were either inactive or possessed reduced potency relative to acid 7.Optical resolution of 7 was achieved by two methods.Absolute configurations of the enantiomers were determined via X-ray crystallographic analyses of an intermediate as well as a salt of the S enantiomer.Although the enantiommers exhibited similar potencies in in vitro assays and in vivo when administered intravenously, significant differences were observed in the guinea pig bronchoconstriction model vs LTC4 and LTD4 when administered by the aerosol route (S antipode 15-fold more potent).The properties of 7 have been compared with several recently reported leukotriene antagonists.
Lewis Acid Mediated Nucleophilic Substitution Reactions of 2-Alkoxy-3,4-dihydro-2H-1-benzopyrans: Regiochemistry and Utility in the Synthesis of 3,4-Dihydro-2H-1-benzopyran-2-carboxylic Acids
Cohen, Noal,Schaer, Beatrice,Saucy, Gabriel,Borer, Rene,Todaro, Louis,Chiu, Anne-Marie
, p. 3282 - 3292 (2007/10/02)
The Lewis acid mediated nucleophilic substitution reactions of a variety of 2-alkoxy-, 2-hydroxy-, and 2-(acyloxy)-3,4-dihydro-2H-1-benzopyrans (chromans) have been studied within the context of developing new synthetic routes to chroman-2-carboxylic acids, certain of which have utility as antioxidants and drug intermediates.The scope and limitations of these transformations have been determined.Treatment of 2-methoxychromans in the α-tocopherol structural class (9, 25) with cyanotrimethylsilane in the presence of TiCl4 or BF3 etherate generally leads in good yield to the desired 2-cyanochromans 10 and 26.On the other hand, ketals of the type 19 react less efficiently, giving poor to moderate yields of the cyanochromans 36 along with regioisomeric products (37, 38).Spiro-fused ketals such as 28 exhibit dichotomous behavior dependent on the Lewis acid employed, while the pyranochroman 34b affords 35 in good yield.Thus the regioselectivity of these processes appears to be highly dependent on substrate structure and the nature of the Lewis acid.
