RU2323221C9 - SUBSTITUTED ESTERS OF 1,2,3,7-TETRAHYDROPYRROLO[3,2-f][1,3]BENZOXAZIN-5-CARBOXYLIC ACIDS, PHARMACEUTICAL COMPOSITION, METHOD FOR THEIR PREPARING (VARIANTS) AND USING - Google Patents
SUBSTITUTED ESTERS OF 1,2,3,7-TETRAHYDROPYRROLO[3,2-f][1,3]BENZOXAZIN-5-CARBOXYLIC ACIDS, PHARMACEUTICAL COMPOSITION, METHOD FOR THEIR PREPARING (VARIANTS) AND USING Download PDFInfo
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Abstract
FIELD: organic chemistry, medicine, pharmacy, chemical technology.
SUBSTANCE: invention relates to novel substituted esters of 1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazin-5-carboxylic acids of the general formula (1): or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates possessing the antiviral effect. In compounds of the general formula (1) each R1 and R4 represents independently of one another a substitutes of amino group chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 1-4 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and possibly an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R2 represents alkyl substitute chosen from hydrogen atom, optionally substituted mercapto group, optionally substituted amino group, optionally substituted hydroxyl; R3 represents lower alkyl or cycloalkyl; R5 represents a substitute of cyclic system chosen from hydrogen atom, optionally substituted linear or branched alkyl comprising 3-12 carbon atoms, optionally substituted cycloalkyl comprising 3-10 carbon atoms, optionally substituted aryl or optionally substituted and optionally an annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides; R6 represents a substitute of cyclic system chosen from hydrogen atom, halogen atom, cyano group, optionally substituted aryl or optionally substituted and optionally annelated heterocyclyl that can be aromatic or nonaromatic and comprising from 3 to 10 atoms in ring with one or some heteroatoms chosen from nitrogen, oxygen or sulfur atoms or their oxides. Also, invention relates to methods for treatment, drugs and pharmaceutical compositions using compounds of this invention. Proposed compounds can be used as active components of drugs used in treatment of such diseases as infectious hepatitis, human immunodeficiency, atypical pneumonia and avian influenza.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods of synthesis.
22 cl, 3 tbl, 6 dwg, 7 ex
Description
Claims (23)
где R1 и R4 независимо друг от друга представляют собой заместитель аминогруппы, выбранный из водорода, необязательно замещенного линейного или разветвленного алкила, содержащего 1-4 атомов углерода, необязательно замещенного циклоалкила, содержащего 3-10 атомов углерода, необязательно замещенного арила или необязательно замещенного и возможно аннелированного гетероциклила, который может быть ароматическим или неароматическим и содержать от 3 до 10 атомов в кольце, с одним или несколькими гетероатомами, выбранными из азота, кислорода или серы или их оксидов;
R2 представляет собой алкильный заместитель, выбранный из водорода, необязательно замещенной меркаптогруппы, необязательно замещенной аминогруппы, необязательно замещенного гидроксила;
R3 представляет собой низший алкил или циклоалкил;
R5 представляет собой заместитель циклической системы, выбранный из водорода, необязательно замещенного линейного или разветвленного алкила, содержащего 3-12 атомов углерода, необязательно замещенного циклоалкила содержащего 3-10 атомов углерода, необязательно замещенного арила или необязательно замещенного и необязательно аннелированного гетероциклила, который может быть ароматическим или неароматическим и содержать от 3 до 10 атомов в кольце, с одним или несколькими гетероатомами, выбранными из азота, кислорода или серы или их оксидов;
R6 представляет собой заместитель циклической системы, выбранный из водорода, атома галогена, цианогруппы, необязательно замещенного арила или необязательно замещенного и необязательно аннелированного гетероциклила, который может быть ароматическим или неароматическим и содержать от 3 до 10 атомов в кольце, с одним или несколькими гетероатомами, выбранными из азота, кислорода или серы или их оксидов, за исключением соединений, где
каждый из R1, R2, R5,R6 представляет собой водород, R3 означает алкил с по меньшей мере 4 атомами углерода, и R4 представляет собой алкил, замещенный диалкиламино или гетероциклическим остатком, таким как пирролидино или морфолино, или R3-означает этил, а R4 означает алкил с 2-3-атомами углерода, замещенный гидрокси или диалкиламиногруппой, где алкил имеет до 4 атомов углерода, алкенил, содержащий до 3 атомов углерода, циклоалкил, содержащий до 6 атомов углерода, в частности, 2-гидроксиэтил, изопропил, пропенил, циклогексил, этил, диэтиламиноэтил; либо
R2, R5, R6 представляет собой водород, R1 означает метил, фенил, R3 - этил, R4 представляет собой метил, н-бутил.1. Substituted esters of 1,2,3,7-tetrahydropyrrolo [3,2-f] [1,3] benzoxazine-5-carboxylic acids of the general formula 1 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts, and / or hydrates
where R 1 and R 4 independently represent an amino substituent selected from hydrogen, optionally substituted linear or branched alkyl containing 1-4 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms, optionally substituted aryl or optionally substituted and optionally annelated heterocyclyl, which may be aromatic or non-aromatic and contain from 3 to 10 atoms in the ring, with one or more heteroatoms selected from nitrogen, oxygen, or EASURES or their oxides;
R 2 represents an alkyl substituent selected from hydrogen, an optionally substituted mercapto group, an optionally substituted amino group, an optionally substituted hydroxyl;
R 3 represents lower alkyl or cycloalkyl;
R 5 is a cyclic system substituent selected from hydrogen, optionally substituted linear or branched alkyl containing 3-12 carbon atoms, optionally substituted cycloalkyl containing 3-10 carbon atoms, optionally substituted aryl, or optionally substituted and optionally annelated heterocyclyl, which may be aromatic or non-aromatic and contain from 3 to 10 atoms in the ring, with one or more heteroatoms selected from nitrogen, oxygen or sulfur or their oxides;
R 6 is a cyclic system substituent selected from hydrogen, a halogen atom, a cyano group, an optionally substituted aryl or an optionally substituted and optionally annelated heterocyclyl, which may be aromatic or non-aromatic and contain from 3 to 10 atoms in the ring, with one or more heteroatoms, selected from nitrogen, oxygen or sulfur or their oxides, with the exception of compounds where
each of R 1 , R 2 , R 5 , R 6 is hydrogen, R 3 is alkyl with at least 4 carbon atoms, and R 4 is alkyl substituted with a dialkylamino or heterocyclic radical, such as pyrrolidino or morpholino, or R 3 is ethyl, and R 4 is alkyl with 2-3 carbon atoms, substituted with hydroxy or dialkylamino group, where alkyl has up to 4 carbon atoms, alkenyl containing up to 3 carbon atoms, cycloalkyl containing up to 6 carbon atoms, in particular 2-hydroxyethyl, isopropyl, propenyl, cyclohexyl, ethyl, diethylaminoethyl; or
R 2 , R 5 , R 6 is hydrogen, R 1 is methyl, phenyl, R 3 is ethyl, R 4 is methyl, n-butyl.
где R1, R2, R4 и R5 имеют вышеуказанные значения; Аг представляет собой арил или 5-6-членный гетероциклил, включающий, по крайней мере, один гетероатом, выбранный из N, О или S.2. The compounds according to claim 1, which are ethyl esters of 9-aryl (or heterocyclyl) -1,2,3,7-tetrahydro-pyrrolo [3,2-f] [1,3] benzoxazine-5-carboxylic acids total formulas 1.1 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and / or hydrates
where R 1 , R 2 , R 4 and R 5 have the above meanings; Ag is aryl or a 5-6 membered heterocyclyl comprising at least one heteroatom selected from N, O or S.
где R2, R4 и R5 имеют вышеуказанные значения; Ar1 представляет собой арил или пиридил.3. The compounds according to claim 1, which are ethyl esters of 9-aryl (or pyridyl) -7-methyl-1,2,3,7-tetrahydro-pyrrolo [3,2-f] [1,3] benzoxazine-5 β-carboxylic acids of the general formula 1.2 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and / or hydrates
where R 2 , R 4 and R 5 have the above meanings; Ar 1 represents aryl or pyridyl.
где R4 и R5 и Ar1 имеют вышеуказанные значения; R3 4 и R4 4 независимо друг от друга представляют собой заместитель аминогруппы, выбранный из водорода, необязательно замещенного алкила, необязательно замещенного циклоалкила, необязательно замещенного арила или необязательно замещенного гетероциклила или R3 4 и R4 4, вместе с атомом азота, с которым они связаны, образуют через R3 4 и R4 4 необязательно замещенный азагетероциклил или гуанидил.4. The compounds according to claim 3, which are ethyl esters of 6-aminomethyl-9-aryl (or pyridyl) -7-methyl-1,2,3,7-tetrahydropyrrolo [3,2-f] [1,3] benzoxazine -5-carboxylic acids of the general formula 1.3
where R 4 and R 5 and Ar 1 have the above meanings; R 3 4 and R 4 4 independently represent an amino substituent selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heterocyclyl or R 3 4 and R 4 4 , together with a nitrogen atom, with which they are linked, form optionally substituted azaheterocyclyl or guanidyl via R 3 4 and R 4 4 .
где R4 и R5 и Ar1 имеют вышеуказанные значения.5. The compounds according to claim 4, which are ethyl esters of 9-aryl (or pyridyl) -6-dimethylaminomethyl-7-methyl-1,2,3,7-tetrahydropyrrolo [3,2-f] [1,3] benzoxazine -5-carboxylic acids of the general formula 1.4
where R 4 and R 5 and Ar 1 have the above meanings.
где Ar1 имеет вышеуказанные значения.6. The compounds according to claim 5, which are ethyl esters of 9-aryl (or pyridyl) -3,7-dimethyl-6-dimethylaminomethyl-1,2,3,7-tetrahydropyrrolo [3,2-f] [1,3 ] benzoxazine-5-carboxylic acids of the General formula 1.5
where Ar 1 has the above meanings.
7. The compound according to claim 6, which is 3,7-dimethyl-6-dimethylaminomethyl-9- (3-pyridyl) -1,2,3,7-tetrahydro-pyrrolo [3,2-f] ethyl ester [1 , 3] benzoxazine-5-carboxylic acid of the formula 1.5.1
где R1, R2, R3, R4, R5 и R6 имеют вышеуказанное значение.8. The method of producing esters of 1,2,3,7-tetrahydro-pyrrolo [3,2-f] [1,3] benzoxazine-5-carboxylic acids according to any one of claims 1 to 7, which consists in the interaction of 5-hydroxy esters -1H-indole-3-carboxylic acids of general formula 2 with aldehydes of general formula 3 and primary amines of general formula 4
where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the above meaning.
где R1, R2, R3, R4, R5 и R6 имеют значение указанное выше.9. The method of producing esters of 1,2,3,7-tetrahydro-pyrrolo [3,2-f] [1,3] benzoxazine-5-carboxylic acids according to any one of claims 1 to 7, which consists in the interaction of 4-aminomethyl esters -5-hydroxy-1H-indole-3-carboxylic acids of the general formula 5 with aldehydes of the general formula 3
where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the meaning indicated above.
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
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RU2006117558/04A RU2323221C9 (en) | 2006-05-23 | 2006-05-23 | SUBSTITUTED ESTERS OF 1,2,3,7-TETRAHYDROPYRROLO[3,2-f][1,3]BENZOXAZIN-5-CARBOXYLIC ACIDS, PHARMACEUTICAL COMPOSITION, METHOD FOR THEIR PREPARING (VARIANTS) AND USING |
US12/600,251 US8329689B2 (en) | 2006-05-23 | 2007-05-17 | Substituted indoles and a method for the production and use thereof |
PCT/RU2007/000246 WO2007136302A2 (en) | 2006-05-23 | 2007-05-17 | Active substances, pharmaceutical composition and a method for the production and use thereof |
EP20070747937 EP2036889A4 (en) | 2006-05-23 | 2007-05-17 | Substituted indoles and a method for the production and use thereof |
PCT/RU2007/000244 WO2007136300A2 (en) | 2006-05-23 | 2007-05-17 | Substituted indoles and a method for the production and use thereof |
EA200901412A EA016633B1 (en) | 2006-05-23 | 2007-05-17 | Substituted indoles and a method for the production and use thereof |
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RU2006117558/04A RU2323221C9 (en) | 2006-05-23 | 2006-05-23 | SUBSTITUTED ESTERS OF 1,2,3,7-TETRAHYDROPYRROLO[3,2-f][1,3]BENZOXAZIN-5-CARBOXYLIC ACIDS, PHARMACEUTICAL COMPOSITION, METHOD FOR THEIR PREPARING (VARIANTS) AND USING |
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RU2007106408/04A Division RU2332421C1 (en) | 2006-05-23 | 2007-02-21 | Active subctances, pharmaceutical composition, method of their production and application |
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RU2006117558A RU2006117558A (en) | 2007-12-10 |
RU2323221C2 RU2323221C2 (en) | 2008-04-27 |
RU2323221C9 true RU2323221C9 (en) | 2010-03-27 |
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Non-Patent Citations (1)
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Indian Journal of Heterocyclic Chemistry, 2005, 15(2), 113-116. J. Am. Chem. Soc., 1949, 71, p.609-612. * |
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