106435-53-4Relevant articles and documents
Microwave-assisted α-halogenation of 2-methylquinolines with tetrabutylammonium iodide and 1,2-dichloroethane (1,2-dibromoethane)
Xie, Yuanyuan,Li, Lehuan
, p. 3892 - 3895 (2014)
A simple and efficient methodology permitting the halogenation of 2-methylquinolines into 2-(chloromethyl)quinolines or 2-(bromomethyl)quinolines in the tetrabutylammonium iodide and 1,2-dichloroethane (1,2-dibromoethane) system has been developed for the first time. The halogenation can be rapidly completed with good to excellent yields and high selectivity under microwave irradiation.
5-lipoxygenase-activating protein (FLAP) inhibitors. Part 4: Development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin- 2-ylmethoxy)-1 H -indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor
Stock, Nicholas S.,Bain, Gretchen,Zunic, Jasmine,Li, Yiwei,Ziff, Jeannie,Roppe, Jeffrey,Santini, Angelina,Darlington, Janice,Prodanovich, Pat,King, Christopher D.,Baccei, Christopher,Lee, Catherine,Rong, Haojing,Chapman, Charles,Broadhead, Alex,Lorrain, Dan,Correa, Lucia,Hutchinson, John H.,Evans, Jilly F.,Prasit, Peppi
experimental part, p. 8013 - 8029 (2012/03/08)
The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2- ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem.2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett.2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB4 inhibition with longer drug preincubation times (15 min vs 5 h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC50 of 76 nM for inhibition of LTB4 in human blood (5 h incubation) and excellent preclinical toxicology and pharmacokinetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients.
Substituted tetralins, chromans and related compounds in the treatment of asthma
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, (2008/06/13)
PCT No. PCT/US87/02734 Sec. 371 Date Apr. 11, 1990 Sec. 102(e) Date Apr. 11, 1990 PCT Filed Oct. 19, 1987Substituted tetralins, chromans and related compounds which, by inhibiting 5-lipoxygenase enzyme and/or blocking leukotriene receptors, are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction and related disease states in mammals; pharmaceutical compositions comprising said compounds; a method of treatment with said compounds; and intermediates useful in the synthesis of said compounds.