- PROCESSES AND COMPOUNDS FOR THE PREPARATION OF SUBSTITUTED NAPHTHYLINDOLE DERIVATIVES
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The present invention provides processes for the preparation of substituted naphthyl indole derivatives of formula (I) that can be used as inhibitors of plasminogen activator inhibitor-1 (PAI-I) . In certain embodiments of the invention, the processes involve reactions that include one or more of an Oppenauer oxidation, a Fischer indole synthesis, a methyl ether cleavage, or coupling a substituted methyl tetrazole with a substituted naphthol.
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Page/Page column 10; 20-21
(2008/06/13)
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- Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
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This invention provides PAI-1 inhibiting compounds of Formula I: wherein: R1, R2, R3, and R4 are eachH, alkyl,, alkanoyl, halo, OH, aryl optionally substituted with R8, perfluoroalkyl, alkoxy, amino, alkylamino, dialkylamino, perfluoroalkoxy; R5 is H, alkyl, perfluoroalkyl, aryl optionally substituted with R8, alkanoyl, aroyl optionally substituted with R8; R6 is H, alkyl, alkylaryl, benzyl optionally substituted with R8, alkanoyl, aroyl optionally substituted with R8; R7 is H, alkyl, alkylaryl, aryl optionally substituted with R8; n is 0-6; A is COOH, or an acid mimic such as tetraazole, SO3H, PO3H2, tetronic acid, etc.; R8 is H, alkyl, cycloalkyl, alkanoyl, halo, OH, perfluoroalkyl, alkoxy, amino, alkylamino, dialkylamino, perfluoroalkoxy; or a pharmaceutically acceptable salt thereof; as well as pharmaceutical compositions and methods of treatment using these compounds.
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- Acylation of 2-Methoxynaphthalene with Acyl Clorides in the Presence of a Catalytic Amount of Lewis Acids
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The regiochemistry of the reaction of 2-methoxynaphthalene 1 with benzoyl chloride 2a using a catalytic amount of Lewis acid is strongly influenced by the identity of the acid catalyst employed as well as by the reaction temperature.By using InCl3, FeCl3, SnCl4 or ZnCl2 and heating at 160 deg C, 2-benzoyl-6-methoxynaphthalene 4a is selectively produced along with 1-benzoyl-7-methoxynaphthalene 5a, while in the case of AlCl3, SbCl5 or TiCl4, 1-benzoyl-2-methoxynaphthalene 3a is the major product. 2-Acyl-6-methoxynaphthalenes 4b-e can be selectively obtained using InCl3 and the corresponding acyl chlorides 2b-e in place of 2a.In the presence of a stoichiometric amount of InCl3, the reaction of 1 with 2a also gives 4a as the predominant product along with 5a even at 50 deg C.This reaction appears to involve isomerisation of 3a to 4a and 5a.
- Pivsa-Art, Sommai,Okuro, Kazumi,Miura, Masahiro,Murata, Satoru,Nomura, Masakatsu
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p. 1703 - 1708
(2007/10/02)
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