- SUBSTITUTED INDOLES
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Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 51
(2009/08/14)
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- A study of 5-nitroindole alkylation
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A detailed study of the 5-nitroindole alkylation, the key step in the synthesis of Zafirlukast, is presented. A broad distribution of alkyl derivatives has been found. 2,3- And 1,3-dialkylindoles can be selectively obtained in a ZnBr2-catalyzed
- Kozmik, Vaclav,Kosata, Bedrich,Svoboda, Jiri,Kuchar, Miroslav
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p. 679 - 690
(2008/02/01)
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- Investigation into the acidification process of zafirluskast nitroacid leads to a surprising improvement in product quality
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An investigation into the acidification step of the zafirlukast nitroacid process was conducted by varying a range of parameters, including acid molarity, addition time, final pH, and temperature. A significant and unexpected improvement in product quality was achieved by using dilute rather than concentrated acid, independent of the final pH, and without a reduction in yield. The change to the dilute-acid process could be accommodated within the constraints of the existing registered process.
- Ancell, Claire L.,Derrick, Ian,Moseley, Jonathan D.,Stott, Jeffery A.
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p. 808 - 813
(2013/09/03)
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- A general method for C3 reductive alkylation of indoles
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General indole C3 reductive alkylation conditions have been developed. The scope of this reaction includes C2 unsubstituted indoles, aryl and alkyl aldehydes, as well as N-H and N-alkyl indole substrates.
- Mahadevan, Anu,Sard, Howard,Gonzalez, Mario,McKew, John C.
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p. 4589 - 4591
(2007/10/03)
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- Bicyclic carbamates and methods of treating inflammatory diseases using the same
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A compound of the formula STR1 wherein R is defined herein is useful as an anti-inflammatory agent.
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- Evolution of a series of peptidoleukotriene antagonists: Synthesis and structure/activity relationships of 1,3,5-substituted indoles and indazoles
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1,3,5-Substituted indoles and indazoles have been studied as receptor antagonists of the peptidoleukotrienes. The best of these compounds generally had a methyl group at the N1 position, a [(cyclopentyloxy)carbonyl]amino or 2-cyclopentylacetamido or N'-cyclopentylureido group at the C-5 position, and an arysulfonyl amide group as part of the acidic chain at the C-3 position of the ring. Such compounds had in vitro dissociation constants K(B) in the range 10-9-10-11 M on guinea pig trachea against LTE4 as agonist and inhibition constants (K(i)) ≤ 10-9 M on guinea pig parenchymal membranes against [3H]LTD4. A number of compounds were orally effective at doses ≤1 mg/kg in blocking LTD4-induced 'dyspnea' in guinea pigs. Compound 45 [N-[4-[[5-[[cyclopentyloxy)carbonyl]amino]-1-methylindol-3-yl]methyl]- 3-methoxybenzoyl]-2-methyl]benzenesulfonamide, ICI 204,219; pK(B) = 9.67 ± 0.13, K(i) = 0.3 ± 0.03 nM, po ED50 = 0.3 mg/kg] is currently under clinical investigation for asthma. In the indole series, certain alkylsulfonyl amides possessing a 3-cyanobenzyl substituent at the N-1 position (60, 61) were produced that had K(B) ≤ 10-9 M on guinea pig trachea.
- Matassa,Maduskuie Jr.,Shapiro,Hesp,Snyder,Aharony,Krell,Keith
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p. 1781 - 1790
(2007/10/02)
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- Indole and indazole keto sulphones as leukotriene antagonists
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This invention provides a series of novel keto sulfones of formula I STR1 in which the group =A-- is selected from =C(Ra)-- and =N-- and the other radicals have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.
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- Heterocyclic amide derivatives and pharmaceutical use
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The invention concerns novel, pharmaceutically useful, amide derivatives of certain benzoheterocyclylalkanoic acids (and related tetrazoles and acylsulphonamides) of the formula I and salts thereof, wherein the radicals R1, R2, L, X, Y, Z, A1, Q, A2 and M have the meanings set out in the specification. The invention also includes pharmaceutical compositions incorporating a formula I compound or a salt thereof, a process for the manufacture of the said compound, together with intermediates for use in the latter process. STR1
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