17327-34-3Relevant academic research and scientific papers
Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-indolecarboxamides: Identification of 4--1-methylindol-3-yl>methyl>-3-methoxy-N-benzamide, ...
Jacobs, Robert T.,Bernstein, Peter R.,Cronk, Laura A.,Vacek, Edward P.,Newcomb, Lisa F.,et al.
, p. 1282 - 1297 (2007/10/02)
The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4--1-methylindol-3-yl>methyl>-3-methoxy-N-benzamide (38p, ZENECA ZD 3523), which has been chosen for clinical evaluation.This compound exhibited a Ki of 0.42 nM for displacement of LTD4 on guinea pig lung membranes, a pKB of 10.13 +/- 0.14 versus LTE4 on guinea pig trachea, and an oral ED50 of 1.14 μmol/kg opposite LTD4-induced bronchoconstriction in guinea pigs.The R enantiomer was found to be modestly more potent than the S enantiomer 38o.Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity.Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist.The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99percent enantiomeric purity.
Estimation of hydrocarbon solubilities in hydrofluorocarbons
Puy, Michael Van Der,Poss, Andrew J.,Persichini, Phillip J.,Ellis, Lois A. S.
, p. 215 - 224 (2007/10/02)
A new solubility parameter, SP, for hydrofluorocarbons (HFCs) has been developed (SP = 1.175 ln(np) + 0.025H - 0.063F - 0.028α - 0.018β where np depends on the molar volume and the molar refractivity; H and F are the number of hydrogens and fluorines, respectively, in the molecule; and α and β are the respective numbers of H-C-F and H-C-C-F connections).Values of SP have been used to predict if an HFC would be a good solvent for various hydrocarbons at 25 deg C.Within an isomeric HFC family, the individual HFCs having the greatest solvency for hydrocarbons were those having the maximum separation of fluorines from hydrogens.Hildebrand solubility parameters, δ, are compared with the semi-empirical SP values.Syntheses for 10 new compounds are given: 3,3,4,4,5,5,6,6,7,7-decafluorononane, 1,1,1,2-tetrafluoro-2-(trifluoromethyl)-3-methylbutane, 1,1,1,2,2-pentafluoro-3-methylbutane, 1,1,1,2,2,3,3,4,4-nonafluoro-5-methylhexane, 1,1,1,2,2,3,3,4,4-nonafluoroheptane, 1,1,1,2-tetrafluoro-2-(trifluoromethyl)butane, 1,1,1-trifluoro-3-(trifluoromethyl)butane, 1,1,1,2,2,3,3,5-octafluorohexane, 1,1,1,2,2-pentahydroperfluorooctane and 1,1,1,2,2-pentahydroperfluorodecane.
