- ISOQUINOLINESULFONYL DERIVATIVE AS RHO KINASE INHIBITOR
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The present invention discloses a class of isoquinolinesulfonyl derivatives as RHO kinase inhibitors, and pharmaceutical compositions thereof, and relates to pharmaceutically acceptable uses thereof. Specifically, the present invention relates to a compound as represented by formula (I), or a pharmaceutically acceptable salt thereof.
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- Formation of N-substituted 4- and 7-oxo-4,5,6,7-tetrahydroindoles revisited: A mechanistic interpretation and conversion into 4- and 7-oxoindoles
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An efficient method for the preparation of 4-oxo-4,5,6,7-tetrahydroindoles was successfully applied to the synthesis of N-substituted 7-oxo-4,5,6,7- tetrahydroindoles for the first time. Both isomers where converted into their corresponding 4- and 7-oxoindoles in good yields utilizing a novel aromatization protocol. Based on the impurity profile obtained, however, different mechanisms for the formation of the 4- and 7-oxo-4,5,6,7-tetrahydroindole derivatives are discussed. In addition, the reaction sequences appear to be stereospecific allowing for the direct introduction of a chiral center α to the nitrogen and preparation of enantiomerically enriched products.
- Montalban, Antonio Garrido,Baum, Sven M.,Cowell, Justin,McKillop, Alexander
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experimental part
p. 4276 - 4279
(2012/09/25)
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- New and general nitrogen heterocycle synthesis: Use of heteropoly acids as a heterogeneous recyclable catalyst
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An efficient synthetic method of six-and five-member nitrogen heterocyclic compounds was developed. Nitrogen heterocyclic compounds were prepared by condensation of the-dicarbonyl compounds with the corresponding-or-amino alcohols, subsequent cyclization, and spontaneous aromatization in the presence of a catalytic amount of Keggin-type heteropoly acids under very mild conditions. Copyright
- Hekmatshoar, Rahim,Sadjadi, Sodeh,Sadjadi, Samaheh,Heravi, Majid M.,Beheshtiha, Yahya S.,Bamoharram, Fatemeh F.
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experimental part
p. 1708 - 1716
(2010/07/15)
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- Synthesis of 3-Acylpyrroles, 3-(Alkoxycarbonyl)pyrroles, 1,5,6,7-Tetrahydro-4H-indol-4-ones and 3-Benzoylpyridines Based on Staudinger-Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds with 2- and 3-Azido-1,1-dialkoxy- alkanes
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The Staudinger-aza-Wittig reaction of 1,3-dicarbonyl compounds with 2-azido-1,1-diethoxyethane and subsequent cy- clization allowed an efficient synthesis of a variety of pyrroles, 1,5,6,7-tetrahydro-4H-indol-4-ones, and of a pyridine. Georg Thieme Verlag
- Bellur, Esen,Yawer, Mirza A.,Hussain, Ibrar,Riahi, Abdolmajid,Fatunsin, Olumide,Fischer, Christine,Langer, Peter
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experimental part
p. 227 - 242
(2009/06/24)
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- Tricyclic indole and dihydroindole derivatives as new inhibitors of soluble guanylate cyclase
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The synthesis of new tricyclic fused indole and dihydroindole derivatives and preliminary results from their in vitro inhibitory activity against soluble guanylate cyclase (sGC) are presented.
- Spyridonidou, Katerina,Fousteris, Manolis,Antonia, Marazioti,Chatzianastasiou, Athanasia,Papapetropoulos, Andreas,Nikolaropoulos, Sotiris
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supporting information; experimental part
p. 4810 - 4813
(2010/04/26)
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- Synthesis of functionalized pyrroles and 6,7-dihydro-1H-indol-4(5H)-ones by reaction of 1,3-dicarbonyl compounds with 2-azido-1,1-diethoxyethane
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The condensation of 1,3-dicarbonyl compounds with 2-azido-1,1- diethoxyethane and subsequent cyclization allowed an efficient synthesis of a variety of pyrroles and 6,7-dihydro-1H-indol-4(5H)-ones.
- Bellur, Esen,Langer, Peter
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p. 2151 - 2154
(2007/10/03)
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- Efficient synthesis of pyrroles and 4,5,6,7-tetrahydroindoles via palladium-catalyzed oxidation of hydroxy-enamines
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Facile and one-pot synthetic route of poly-substituted pyrroles and 4-oxo-4,5,6,7-tetrahydroindoles is established, which consists of three steps: (1) palladium-catalyzed oxidation of hydroxy-enamines by using tetrakis(triphenylphosphine)palladium and mesityl bromide oxidation system, (2) intramolecular cyclization, and (3) dehydration.
- Aoyagi, Yutaka,Mizusaki, Toshihiko,Shishikura, Masahiro,Komine, Takashi,Yoshinaga, Tokuji,Inaba, Haruko,Ohta, Akihiro,Takeya, Koichi
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p. 8533 - 8538
(2007/10/03)
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- Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers
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A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv1.5 blockers. In in vitro studies, several compounds exhibited very good potency for blockade of Kv1.5. Compound 8i showed good selectivity for blockade of Kv1.5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ventricular ERP.
- Wu, Shengde,Fluxe, Andrew,Janusz, John M.,Sheffer, James B.,Browning, Greg,Blass, Benjamin,Cobum, Keith,Hedges, Richard,Murawsky, Michael,Fang, Bin,Fadayel, Gina M.,Hare, Michelle,Djandjighian, Laurent
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p. 5859 - 5863
(2007/10/03)
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- Selective cleavage of Cbz-protected amines
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(MatrixPresented) Under conditions of catalytic Ni(0) and in most cases just over 1 equiv of Me2NH·Br3/K2CO3 or Cs2CO3, a Cbz-protected nitrogen, which is part of a heteroaromatic ring, can
- Lipshutz, Bruce H.,Pfeiffer, Steven S.,Reed, Anthony B.
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p. 4145 - 4148
(2007/10/03)
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- o-Nitrobenzyl as a photocleavable nitrogen protecting group for indoles, benzimidazole, and 6-chlorouracil
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The potential for the o-nitrobenzyl group as an alternative nitrogen protecting group for various indoles, benzimidazole, and 6-chlorouracil was determined. Treatment of the appropriate N-H containing substrate with LiH or NaH in DMF followed by o-nitrobenzyl bromide afforded reasonable yields of N-alkylated products. To effect removal of this group, simple photolysis with 300 nm light afforded good yields of starting substrate.
- Voelker, Troy,Ewell, Tim,Joo, Jean,Edstrom, Eric D.
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p. 359 - 362
(2007/10/03)
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- Facile and efficient synthesis of pyrroles and indoles via palladium-catalyzed oxidation of hydroxy-enamines and -amines
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The palladium-catalyzed oxidation of hydroxy-enamines, which were obtained by the condensation of β-aminoalcohols and carbonyl compounds, proceeded to give the corresponding polysubstituted pyrroles and 4,5,6,7-tetrahydroindoles in good yields. The treatment of o-(2-hydroxyethyl)aniline with the palladium catalyst also gave indole in 78% yield.
- Aoyagi, Yutaka,Mizusaki, Toshihiko,Ohta, Akihiro
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p. 9203 - 9206
(2007/10/03)
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- Chemo-enzymatic synthesis and characterization of L-tryptophans selectively 13C-enriched or hydroxylated in the six-membered ring using transformed Escherichia coli cells
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L-(3a-13C)- and L-(6-13C)tryptophan have been synthesized from simple labelled compounds via a single reaction scheme based on the conversion of 1,3-cyclohexanedione into indole.The labelled indoles have been converted in one step into the corresponding L-tryptophans using transformed Escherichia coli cells with large amounts of the enzyme, tryptophan synthease.The same reaction scheme has been used for the synthesis of 4- and 7-indolol.These hydroxyindoles together with 5-indolol have been converted into 4-, 7- and 5-hydroxy-L-tryptophan, respectively, using theEscherichia coli cells.The latter compound is the immediate precursor of the neurotransmitter, serotonin.It appears that 7-indolol is the only indole derivative which is converted faster than unsubstituted indole by the enzyme, tryptophan synthease.With the preparation of L-(3a-13C)- and L-(6-13C)tryptophan, we have completed the series of indoles and L-tryptophans with a stable isotope (13C, 15N or 2H) in the aromatic ring.In this paper, we also discuss the NMR parameters of these mono-isotopically labelled systems.
- Berg, E. M. M. van den,Jansen, F. J. H. M.,Goede, A. T. J. W. de,Baldew, A. U.,Lugtenburg, J.
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p. 287 - 297
(2007/10/02)
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- Studies on Sugar Nitro-olefins. Part 7. Synthesis of 3-(Alditol-1-yl)-1,2,3,5,6,7-hexahydro- and -1,5,6,7-tetrahydro-indol-4-ones. X-Ray Molecular Structure of (3S)-3-(1,2,3,4,5-Penta-O-acetyl-D-galacto-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-one
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Raney nickel reduction of (3R)-2-hydroxyimino-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-glucopentitol-1-yl)-3,5,6,7-tetrahydrobenzofuran-4(2H)-ones (5) gives (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-ones (6) in high yields.Deacetylation of compounds (6) with catalytic sodium methoxide in methanol affords the corresponding (pentitol-1-yl)indolones (7).Compounds (6) can be transformed into the 3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-1,5,6,7-tetrahydroindol-4-ones (8) by treatment with 2,3-dichloro-5,6- dicyano-1,4-benzoquinone.The structure of (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-one (6a) was confirmed by an X-ray structure determination.
- Dianez, Maria J.,Galan, Jose,Gomez-Sanchez, Antonio,Lopez-Castro, Amparo,Rico, Manuel
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p. 581 - 588
(2007/10/02)
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- A FACILE SYNTHESIS OF 4-OXO-4,5,6,7-TETRAHYDROINDOLES
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Condensation of 1,3-cyclohexanedione with chloroacetaldehyde followed by dehydration gave 4-oxo-4,5,6,7-tetrahydrobenzofuran in a good yield.The tetrahydrobenzofuran was quantitatively converted into 4-oxo-4,5,6,7-tetrahydroindoles.
- Matsumoto, Masakatsu,Watanabe, Nobuko
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p. 2313 - 2316
(2007/10/02)
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- Protecting groups for the pyrrole nitrogen atom. The 2-chloroethyl, 2-phenylsulfonylethyl, and related moieties
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The 2-chloroethyl and 2-phenylsulfonylethyl moieties are versatile protecting groups for the pyrrole nitrogen atom.The 2-chloroethyl group is easily attached under phase transfer conditions using 1,2-dichloroethane.The 2-phenylsulfonylethyl moiety is read
- Gonzalez, Carlos,Greenhouse, Robert,Tallabs, Ramon,Muchowski, Joseph M.
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p. 1697 - 1702
(2007/10/02)
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- 1,3-Cyclohexanedione derivatives
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Novel cyclohexanone derivatives of general formula: STR1 (wherein R1 is a hydrocarbon group of 1 to 15 carbon atoms) and new cyclohexanone derivatives of general formula: STR2 (wherein R1 and R2 each is a hydrocarbon group of 1 to 15 carbon atoms) are produced by an electrooxidative coupling of 1,3-cyclohexanedione with a vinyl ether of general formula: (wherein R1 is as defined above) in the presence or absence of an alcohol of general formula: (wherein R2 is as defined above). These new cyclohexanone derivatives can be easily converted to N-substituted or unsubstituted-4-oxo-4,5,6,7-tetrahydroindoles, which are of value as intermediates for the production of N-substituted or unsubstituted-4-hydroxyindoles and, thence, to pindolol and its analogs.
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- A FACILE SYNTHESIS OF 4-HYDROXYINDOLE VIA ELECTROCHEMICAL OXIDATIVE C-C COUPLING
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4-hydroxyindole (1a), a useful intermediate for Pindolol (1b), has been prepared via electrooxidative coupling of 1,3-cyclohexadione with ethyl vinyl ether followed by ammonolysis and dehydrogenation.
- Torii, Sigeru,Uneyama, Kenji,Onishi, Takashi,Fujita, Yoshiji,Ishiguro, Michihiro,Nishida, Takashi
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p. 1603 - 1604
(2007/10/02)
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