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    • 1. 发明授权
      US4604389A Benzazepine derivatives 失效
    • Benzazepine derivatives
    • 苯扎西平衍生物
    • US4604389A
    • 1986-08-05
    • US732204
    • 1985-05-08
    • Manfred Reiffen , Klaus Noll , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • Manfred Reiffen , Klaus Noll , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • A61K31/55 , A61P9/06 , C07C59/64 , C07D223/16 , C07D233/16 , C07D243/04 , C07D405/12 , C07D491/04 , C07D491/056 , C07D521/00
    • C07D223/16 , C07C59/64 , C07D243/04 , C07D405/12 , C07D491/04
    • This invention relates to benzazepine derivatives of formula I ##STR1## wherein A is --CH.sub.2 CH.sub.2 -- or --CH.dbd.CH--;R.sub.1 is hydrogen, chlorine, bromine, C.sub.1 -C.sub.3 alkyl, amino, C.sub.1 -C.sub.3 alkylamino, C.sub.1 -C.sub.3 dialkylamino, acylamino, hydroxy, C.sub.1 -C.sub.3 alkoxy or phenyl C.sub.1 -C.sub.3 alkoxy;R.sub.2 is hydrogen, chlorine, bromine, hydroxy, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or phenyl C.sub.1 -C.sub.3 alkoxy or, together with R.sub.1, can be C.sub.1 -C.sub.3 alkylenedioxy;R.sub.3 is hydrogen, chlorine, bromine or C.sub.1 -C.sub.3 alkoxy;R.sub.4 is hydrogen, benzyl, C.sub.1 -C.sub.3 alkyl or C.sub.3 -C.sub.5 alkenyl;R.sub.5 is hydrogen, halogen, C.sub.1 -C.sub.3 alkyl or C.sub.1 -C.sub.3 alkoxy;R.sub.6 is hydrogen, C.sub.1 -C.sub.3 alkyl or C.sub.1 -C.sub.3 alkoxy or, together with R.sub.5, can be a C.sub.1 -C.sub.2 alkylenedioxy;X is an imino, optionally substituted by a benzyl or C.sub.1 -C.sub.3 alkyl, or is oxygen, sulphur, sulphinyl or sulphonyl;Y is an imino, optionally substituted by a benzyl or C.sub.1 -C.sub.3 alkyl, or is methylene or carbonyl;m and n are each independently 2, 3 or 4; and nontoxic, pharmaceutically acceptable addition salts thereof. These compounds have valuable pharmacological properties, particularly the effect of lowering heart rate and reducing the O.sub.2 requirement of the heart.
    • 本发明涉及式I的苯并氮杂衍生物，其中A是-CH 2 CH 2 - 或-CH = CH-; R1是氢，氯，溴，C1-C3烷基，氨基，C1-C3烷基氨基，C1-C3二烷基氨基，酰氨基，羟基，C1-C3烷氧基或苯基C1-C3烷氧基; R2是氢，氯，溴，羟基，C1-C3烷基，C1-C3烷氧基或苯基C1-C3烷氧基，或与R1一起可以是C1-C3亚烷基二氧基; R3是氢，氯，溴或C1-C3烷氧基; R4是氢，苄基，C1-C3烷基或C3-C5烯基; R5是氢，卤素，C1-C3烷基或C1-C3烷氧基; R 6是氢，C 1 -C 3烷基或C 1 -C 3烷氧基，或与R 5一起可以是C 1 -C 2亚烷基二氧基; X是任选被苄基或C 1 -C 3烷基取代的亚氨基，或是氧，硫，亚磺酰基或磺酰基; Y是任选被苄基或C 1 -C 3烷基取代的亚氨基，或亚甲基或羰基; m和n各自独立地为2,3或4; 和无毒的药学上可接受的加成盐。 这些化合物具有有价值的药理学特性，特别是降低心率并降低心脏O2需求的作用。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 3. 发明授权
      US4616011A Novel indole derivatives and pharmaceutical compositions containing same 失效
    • Novel indole derivatives and pharmaceutical compositions containing same
    • 新型吲哚衍生物和含有它们的药物组合物
    • US4616011A
    • 1986-10-07
    • US675084
    • 1984-11-26
    • Manfred Reiffen , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • Manfred Reiffen , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • A61K31/55 , A61P9/06 , A61P9/08 , A61P9/10 , A61P25/02 , C07C59/64 , C07D209/14 , C07D209/16 , C07D209/18 , C07D223/16 , C07D403/12 , C07D405/14
    • C07D223/16 , C07C59/64 , C07D209/16 , C07D209/18 , C07D403/12
    • This invention relates to novel indole derivatives of the formula ##STR1## wherein A represents a --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, ##STR2## group and B represents a methylene, carbonyl, or thiocarbonyl group or A represents a --CO--CO-- or ##STR3## group and B represents a methylene group, E represents an alkylene group or a 2-hydroxy-n-propylene, 2-hydroxy-n-butylene, or 3-hydroxy-n-butylene group,G represents an alkylene group,R.sub.1 represents a hydrogen, chlorine, or bromine atom or a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, hydroxyl, alkoxy, or phenylalkoxy group,R.sub.2 represents a hydrogen, chlorine, or bromine atom or a hydroxyl, alkoxy, phenylalkoxy, or alkyl group orR.sub.1 and R.sub.2 together represent an alkylenedioxy group,R.sub.3 represents a hydrogen, chlorine, or bromine atom or an alkyl group,R.sub.4 represents a hydrogen atom or an alkyl or phenylalkyl group,R.sub.5 represents a hydrogen, fluorine, chlorine, or bromine atom or an alkyl, hydroxyl, alkoxy, or phenylalkoxy group,R.sub.6 represents a hydrogen atom or an alkoxy group, andR.sub.7 represents a hydrogen atom or an alkenyl, alkyl or phenylalkyl group,and the acid additional salts thereof. These compounds, which may be obtained by use of known methods, have valuable pharmacological properties, particularly a heart rate-lowering activity.
    • 本发明涉及式（I）的新的吲哚衍生物，其中A代表-CH2-CH2-，-CH = CH-，IMA组，B代表亚甲基，羰基或硫代羰基，或A代表 -CO-CO-或基，B表示亚甲基，E表示亚烷基或2-羟基正丙烯，2-羟基 - 正丁烯或3-羟基 - 正丁烯基 ，G表示亚烷基，R 1表示氢，氯或溴原子或三氟甲基，硝基，氨基，烷基氨基，二烷基氨基，烷基，羟基，烷氧基或苯基烷氧基，R 2表示氢，氯或溴原子或 羟基，烷氧基，苯基烷氧基或烷基，或者R 1和R 2一起表示亚烷基二氧基，R 3表示氢，氯或溴原子或烷基，R 4表示氢原子或烷基或苯基烷基，R 5表示 氢，氟，氯或溴原子或烷基，羟基，烷氧基或苯基烷氧基，R6代表 氢原子或烷氧基，R7表示氢原子或烯基，烷基或苯基烷基，及其酸加成盐。 可以通过使用已知方法获得的这些化合物具有有价值的药理学性质，特别是心率降低活性。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 4. 发明授权
      US4584293A Aminotetralin derivatives 失效
    • Aminotetralin derivatives
    • 氨基四氢萘衍生物
    • US4584293A
    • 1986-04-22
    • US732199
    • 1985-05-08
    • Manfred Reiffen , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • Manfred Reiffen , Joachim Heider , Volkhard Austel , Norbert Hauel , Walter Kobinger , Christian Lillie
    • A61K31/55 , A61P9/06 , A61P9/08 , A61P9/10 , C07C45/00 , C07C45/51 , C07C49/755 , C07C57/58 , C07C59/64 , C07C205/56 , C07D223/16 , C07D243/04 , C07D491/056 , C07D521/00
    • C07D223/16 , C07C205/56 , C07C45/00 , C07C45/513 , C07C49/755 , C07C57/58 , C07C59/64 , C07D231/12 , C07D233/56 , C07D243/04 , C07D249/08
    • This invention related to new aminotetralin derivatives of formula I ##STR1## wherein ##STR2## B is methylene or, when A is --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH--, --NH--CO-- or --CH.sub.2 --CO--, B can also be carbonyl or thiocarbonyl;E is a C.sub.2 -C.sub.4 straight-chain alkylene, optionally substituted by a C.sub.1 -C.sub.3 alkyl, or is 2-hydroxy-n-propylene, 2-hydroxy-n-butylene or 3-hydroxy-n-butylene;R.sub.1 is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, nitro, amino, C.sub.1 -C.sub.3 alkylamino, C.sub.1 -C.sub.3 dialkylamino, C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkylthio, hydroxy, C.sub.1 -C.sub.3 alkoxy or phenyl C.sub.1 -C.sub.3 alkoxy;R.sub.2 is hydrogen, chlorine, bromine, hydroxy, C.sub.1 -C.sub.3 alkoxy phenyl C.sub.1 -C.sub.3 alkoxy, or C.sub.1 -C.sub.3 alkyl or, together with R.sub.1, can be a C.sub.1 -C.sub.2 alkylenedioxy;R.sub.3 and R.sub.4 are each independently selected from hydrogen, fluorine, chlorine, bromine, C.sub.1 -C.sub.3 alkyl, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, amino, C.sub.1 -C.sub.3 alkylamino, or C.sub.1 -C.sub.3 dialkylamino, or together can be methylenedioxy; andR.sub.5 is hydrogen, C.sub.3 -C.sub.5 alkenyl, C.sub.1 -C.sub.3 alkyl, or phenyl C.sub.1 -C.sub.3 alkyl, and nontoxic, pharmaceutically acceptable addition salts thereof which have valuable pharmacological properties, particularly a long-lasting heart rate lowering effect and the effect of reducing the O.sub.2 requirement of the heart.
    • 本发明涉及新的式I的氨基蝶呤衍生物，其中B是亚甲基，或当A是-CH 2 -CH 2 - 时，-CH = CH-，-NH-CO-或-CH 2 -CO-，B也可以是羰基或硫代羰基; E是任选被C 1 -C 3烷基取代的C 2 -C 4直链亚烷基，或是2-羟基 - 正丙烯，2-羟基 - 正丁烯或3-羟基 - 正丁烯; R1是氢，氟，氯，溴，三氟甲基，硝基，氨基，C1-C3烷基氨基，C1-C3二烷基氨基，C1-C3烷基，C1-C3烷硫基，羟基，C1-C3烷氧基或苯基C1-C3烷氧基; R2是氢，氯，溴，羟基，C1-C3烷氧基苯基C1-C3烷氧基或C1-C3烷基，或与R1一起可以是C1-C2亚烷基二氧基; R 3和R 4各自独立地选自氢，氟，氯，溴，C 1 -C 3烷基，羟基，C 1 -C 3烷氧基，硝基，氨基，C 1 -C 3烷基氨基或C 1 -C 3二烷基氨基，或一起可以是亚甲二氧基; 并且R 5是氢，C 3 -C 5烯基，C 1 -C 3烷基或苯基C 1 -C 3烷基，以及其无毒的药学上可接受的加成盐，其具有有价值的药理学性质，特别是持久的心率降低效果和降低 心脏的O2要求。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 10. 发明授权
      US4134980A Phenylalkylamino-alkyl derivatives of quinazolinone and phthalazinone 失效
    • Phenylalkylamino-alkyl derivatives of quinazolinone and phthalazinone
    • 喹唑啉酮和酞嗪酮的苯基烷基氨基 - 烷基衍生物
    • US4134980A
    • 1979-01-16
    • US827142
    • 1977-08-24
    • Wolfgang Eberlein , Volkhard Austel , Joachim Heider , Jurgen Dammgen , Rudolf Kadatz , Christian Lillie , Walter Kobinger
    • Wolfgang Eberlein , Volkhard Austel , Joachim Heider , Jurgen Dammgen , Rudolf Kadatz , Christian Lillie , Walter Kobinger
    • C07D239/91 , A61K31/50 , A61K31/502 , A61K31/505 , A61K31/517 , A61P9/06 , A61P9/12 , B01J23/00 , C07D237/00 , C07D237/32 , C07D239/88 , C07D239/90 , C07D317/00 , C07D319/00 , C07D405/12 , C07D491/04 , C07D491/056 , C07D239/72
    • C07D491/04 , C07D237/32 , C07D239/90
    • Compounds of the formula ##STR1## wherein A is ##STR2## where R.sub.1 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.2 is alkoxy of 1 to 3 carbon atoms;R.sub.3 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.2, methylenedioxy or ethylenedioxy;R.sub.4 is hydrogen, alkyl of 1 to 3 carbon atoms or benzyl;R.sub.5 is hydrogen or alkyl of 1 to 3 carbon atoms;R.sub.6 is hydrogen or alkoxy of 1 to 3 carbon atoms;R.sub.7 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.6, methylenedioxy or ethylenedioxy; andN is 2 or 3;And non-toxic, pharmacologically acceptable acid addition salts thereof; the compounds as well as their salts are useful as heart rate reducers and mild antihypertensives.This invention relates to novel N-(phenylalkylaminoalkyl)-substituted quinazolinones and phthalazinones and nontoxic acid addition salts thereof, as well as to various methods of preparing these compounds.More particularly, the present invention relates to a novel class of N-substituted quinazolinones and phthalazinones represented by the formula ##STR3## wherein A is ##STR4## where R.sub.1 is hydrogen or alkyl of 1 to 3 carbon atoms; R.sub.2 is alkoxy of 1 to 3 carbon atoms;R.sub.3 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.2, methylenedioxy or ethylenedioxy;R.sub.4 is hydrogen, alkyl of 1 to 3 carbon atoms or benzyl;R.sub.5 is hydrogen or alkyl of 1 to 3 carbon atoms;R.sub.6 is hydrogen or alkoxy of 1 to 3 carbon atoms;R.sub.7 is alkoxy of 1 to 3 carbon atoms or, together with R.sub.6, methylenedioxy or ethylenedioxy; andN is 2 or 3;Or a non-toxic, pharmacologically acceptable acid addition salt thereof.A preferred sub-genus thereunder is constituted by compounds of the formula I whereR.sub.1 and R.sub.5 are each hydrogen, methyl, ethyl, n-propyl or isopropyl;R.sub.4 is hydrogen, methyl, ethyl, n-propyl, isopropyl or benzyl;R.sub.2, r.sub.3 and R.sub.7 are each methoxy, ethoxy, n-propoxy or isopropoxy;R.sub.6 is hydrogen, methoxy, ethoxy, n-propoxy or isopropoxy;R.sub.2 and R.sub.3, together with each other, are methylenedioxy or ethylenedioxy;R.sub.6 and R.sub.7, together with each other, are methylenedioxy or ethylenedioxy; andn is 2 or 3;and non-toxic, pharmacologically acceptable acid addition salts thereof.A further, especially preferred sub-genus thereunder is constituted by compounds of the formula I whereR.sub.2 and R.sub.3 are methoxy in the 6- and 7-position, respectively, or, together with each other, methylenedioxy or ethylenedioxy;R.sub.4 is hydrogen or methyl;R.sub.5 is hydrogen;R.sub.6 is hydrogen or methoxy in the 3-position;R.sub.7 is methoxy in the 4-position or, together with R.sub.6, methylenedioxy or ethylenedioxy; andn is 2 or 3;and non-toxic, pharmacologically acceptable acid addition salts thereof.The compounds embraced by formula I may be prepared by the following methods:Method ABy reacting a compound of the formula ##STR5## wherein R.sub.2, R.sub.3, A and n have the same meanings as in formula I, andZ is a leaving-group, such as chlorine, bromine, iodine, alkylsulfonyloxy or arylsulfonyloxy,with a phenylalkylamine of the formula ##STR6## wherein R.sub.4, R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I.The reaction is carried out in an inert solvent, such as ether, tetrahydrofuran, methylformamide, dimethylformamide, dimethylsulfoxide, chlorobenzene or benzene, and depending upon the reactivity of substituent Z, at a temperature between -50 and +250.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage.Method BBy reacting a compound of the formula ##STR7## wherein A, R.sub.2 and R.sub.3 have the same meanings as in formula I, with a phenylalkylamine of the formula ##STR8## wherein R.sub.4, R.sub.5, R.sub.6 and n have the same meanings as in formula I, andZ has the same meanings as in formula II.The reaction is carried out in an inert solvent, such as acetone, dimethylformamide, dimethylsulfoxide or chlorobenzene, and, depending upon the reactivity of substituent Z, at a temperature between 0 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, an alkali metal amide or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage.Method CBy reacting an aldehyde of the formula ##STR9## wherein R.sub.2, R.sub.3, A and n have the same meanings as in formula I, or an acetal thereof, with an amine of the formula III in the presence of catalytically activated hydrogen.The reductive amination is carried out with hydrogen in the presence of a hydrogenation catalyst, such as palladized charcoal, at a hydrogen pressure of 5 atmospheres, in a solvent, such as methanol, ethanol or dioxane, and at a temperature between 0 and 100.degree. C, but preferably between 20 and 80.degree. C.Method DBy reacting an amine of the formula ##STR10## wherein R.sub.2, R.sub.3, R.sub.4, A and n have the same meanings as in formula I, with a phenylalkyl compound of the formula ##STR11## wherein R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I, andZ has the same meanings as in formula II.The reaction is carried out in an inert solvent, such as acetone, methylene chloride, dimethylformamide, dimethylsulfoxide or chlorobenzene, and, depending upon the reactivity of substituent Z, at a temperature between 0 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The presence of an acid-binding agent, such as an alkali metal alcoholate, an alkali metal hydroxide, an alkali metal carbonate, especially potassium carbonate, or a tertiary organic base, particularly triethylamine or pyridine, or of a reaction accelerator, such as potassium iodide, is of advantage.Method EFor the preparation of a quinazolinone derivative of the formula I, by reacting a benzoxazin-4-one of the formula ##STR12## wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as in formula I, with an alkylenediamine of the formula wherein R.sub.4, R.sub.5, R.sub.6 and R.sub.7 have the same meanings as in formula I.The reaction is advantageously carried out in a solvent, such as benzene, dioxane, a lower alkanoic acid such as glacial acetic acid, or dimethylformamide, and optionally in the presence of an acid catalyst at a temperature between 50 and 150.degree. C, but preferably at the boiling point of the particular solvent which is used. The preferred solvent is glacial acetic acid. The reaction may, however, also be performed without a solvent.If the end product of methods A through E is a compound of the formula I wherein R.sub.4 is benzyl, the same may be de-benzylated to yield the corresponding compound wherein R.sub.4 is hydrogen. The de-benzylation is preferably effected by means of catalytic hydrogenation, for example with hydrogen in the presence of a catalyst such as palladized charcoal, in a solvent such as ethanol or ethylacetate, at a temperature between 25 and 75.degree. C and at a hydrogen pressure of 1 to 7 atmospheres.On the other hand, if the end product of methods A through E is a compound of the formula I wherein R.sub.4 is hydrogen; the same may be alkylated at the bridge nitrogen atom to form the corresponding compound where R.sub.4 is alkyl. The alkylation is carried out with a conventional alkylating agent, for example with an alkyl halide such as methyl iodide, ethyl iodide or isopropyl bromide, or with a dialkylsulfate such a dimethylsulfate, in a solvent such as acetone, dimethylformamide or dioxane, optionally in the presence of an inorganic or tertiary organic base, at a temperature between 0 and 50.degree. C. A methylation may also be effected by reaction with a mixture of formaldehyde and formic acid, preferably at the boiling point of said mixture.The compounds embraced by formula I are organic bases and therefore form acid addition salts with inorganic or organic acids. Examples of non-toxic, pharmacologically acceptable acid addition salts are those formed with hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, lactic acid, tartaric acid, maleic acid, 8-chlorotheophylline or the like.The starting compounds of the formulas II through X are either described in the literature or may be prepared by known methods, as described in the examples below.
    • 其中A是其中R 1是氢或1至3个碳原子的烷基的式“IMAGE”的化合物; R 2是1至3个碳原子的烷氧基; R3为1〜3个碳原子的烷氧基，或与R2一起亚甲二氧基或亚乙二氧基; R4是氢，1至3个碳原子的烷基或苄基; R5是氢或1〜3个碳原子的烷基; R6是氢或1〜3个碳原子的烷氧基; R 7为1〜3个碳原子的烷氧基，或与R6一起亚甲二氧基或亚乙二氧基; 和N IS 2 OR 3; 和非毒性，药理学上可接受的酸添加量; 化合物作为其有效的有效的H
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Espacenet 法律信息 同族专利 专利引用
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