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29 条记录 (耗时 0.019 秒)

    Medrogestrone production
    1.
    发明授权
    Medrogestrone production 失效
    甲基孕酮生产

    公开(公告)号：US5428151A

    公开(公告)日：1995-06-27

    申请号：US239187

    申请日：1994-05-05

    申请人： Michael W. Winkley ,  Robert D. Mitchell

    发明人： Michael W. Winkley ,  Robert D. Mitchell

    IPC分类号： C07J7/00 ,  C07J53/00 ,  C07J71/00 ,  C07J75/00

    CPC分类号： C07J53/002 ,  C07J7/0045

    摘要： A process for the production of medrogestone, in which, in an intermediate step, the solvate 3.beta.,5.alpha.,6.beta.-trihydroxy-6.alpha.,17.alpha.-dimethylpregnan-20-one monomethanolate is obtained as a solid, stable compound by displacing the organic solvent from a solution of of 3.beta.,5.alpha.,6.beta.-trihydroxy-6.alpha.,17.alpha.-dimethylpregnan-20-one with a lower alkanol, and a Diels-Alder adduct of 6-methylene-17.alpha.-methylpregn-4-ene-3,20-dione with maleic anhydride is used as an intermediate for production of the corresponding dicarboxylic acid salt for removal of 6-methylene-17.alpha.-methylpregn-4-ene-3,20-dione contamination of the desired product. Another intermediate, 6.beta.-hydroxy-6.alpha.,17.alpha.-dimethylpregn-4-ene-3,20-dione, has been found to prevent smooth muscle proliferation and is useful in the treatment of atherosclerosis and restinosis.

    摘要翻译： 制备孕激素的方法，其中在中间步骤中获得作为固体稳定化合物的溶剂合物3β，5α，6β-三羟基-6α，17α-二甲基孕烷-20-酮单甲醇化物 从3β，5α，6β-三羟基-6α，17α-二甲基孕烷-20-酮与低级链烷醇的溶液中取代有机溶剂，并将6-亚甲基-17α- 甲基孕-4-烯-3,20-二酮与马来酸酐用作制备相应二羧酸盐的中间体，用于除去6-亚甲基-17α-甲基孕-4-烯-3,20-二酮污染物 所需产品。 已经发现另一种中间体6β-羟基-6α，17α-二甲基孕-4-烯-3,20-二酮可以预防平滑肌增生，并且可用于治疗动脉粥样硬化和再狭窄。

    2,3,4,5-tetrahyd ro-1H-[1,2,5]triazocino(1,2-a)[1,2,4]benzotriazin-7(8H)-ones, thiones and derivatives
    3.
    发明授权
    2,3,4,5-tetrahyd ro-1H-[1,2,5]triazocino(1,2-a)[1,2,4]benzotriazin-7(8H)-ones, thiones and derivatives 失效

    公开(公告)号：US4935515A

    公开(公告)日：1990-06-19

    申请号：US432245

    申请日：1989-11-06

    申请人： Michael W. Winkley ,  James L. Diebold

    发明人： Michael W. Winkley ,  James L. Diebold

    IPC分类号： C07D487/04

    CPC分类号： C07D487/04

    摘要： Disclosed herein are novel 1,2,3,4,5,6-hexahydro[1,3,6]triazocino[1,2-a]benzimidazole of Formulas I and II: ##STR1## wherein R.sup.1 may be phenyl, m- or p-nitrophenyl, m- or p-methylsulfonylaminophenyl, napthtyl, naphthyl mono-substituted by nitro or methylsulfonylamino, benzofurazanyl, 2-pyrimidinyl, 2- or 4-pyridinyl, 2- or 4-naphthyridinyl, pyrazinyl, isoquinolinyl, or quinolinyl;R.sup.2 may be hydrogen; C.sub.1 -C.sub.8 alkyl; phenyl(C.sub.1 -C.sub.4)alkyl or substituted-phenyl(C.sub.1 -C.sub.4)alkyl, in which phenyl may have one to three substituents selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, fluorine, chlorine or bromine; phenyl or substituted-phenyl in which the phenyl substituents are the same as for substituted-phenyl (C.sub.1 -C.sub.4)alkyl; 2- or 4-pyrimidinyl; pyrazinyl; imidazolyl; C.sub.1 -C.sub.4 alkanoyl; halo or dihalo-(C.sub.1 -C.sub.4)alkanoyl, in which halo is fluoro or chloro; benzoyl or benzoyl substituted on the phenyl ring by one or two C.sub.1 -C.sub.4 alkyl groups; C.sub.1 -C.sub.4 alkanoyloxy; C.sub.1 -C.sub.4 alkylamino(C.sub.1 -C.sub.4 alkanoyl; C.sub.1 -C.sub.4 alkyloxycarbonyl; C.sub.1 -C.sub.4 alkylaminocarbonyl; phenylaminocarbonyl in which phenyl may have one to three C.sub.1 -C.sub.4 alkyl groups; phenyloxy or naphthyloxy-(C.sub.1 -C.sub.4)alkyl in which the phenyl or naphthyl ring may be substituted by one to three C.sub.1 -C.sub.4 alkyl groups; C.sub.1 -C.sub.4 alkylsulfonyl; (C.sub.1 -C.sub.4)alkyl- or N-di-(C.sub.1 -C.sub.4 alkyl)carboxamido(C.sub.1 -C.sub.4)alkyl; N-phenyl or substituted phenyl-carboxamido-(C.sub.1 -C.sub.4)alkyl in which phenyl may be substituted as above for C.sub.1 -C.sub.4 alkyl-substituted phenyl; cyano; amidino in which each N atom is substituted by a C.sub.1 -C.sub.4 alkyl group; and C.sub.1 -C.sub.4 alkylguanidino; andR.sup.3 and R.sup.4 are, independently, selected from hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, fluorine and chlorine, or acid addition salts thereof. Compounds of formulas I and II having certain values of R.sup.2 are antiarrhythmic or antiischaemic agents. The remaining values of R.sup.2 provide intermediate compounds of formulas I and II.Also disclosed herein a novel tetrahydro-3-substituted-7-substituted-1H[1,2,5]triazepino[1,2-a][1,2,4]benzotriazines, wherein the 7 substituent may be --SMe, --Cl or Br and the 3 substituent is the same as R.sup.2 in formulas I and II above. These compounds also serve as intermediates for the production of the antiarrhythmic agents for formula II above.

    N-substituted-hexahydro-1,2,5-triazepines
    4.
    发明授权
    N-substituted-hexahydro-1,2,5-triazepines 失效
    N-取代 - 六氢-1,2,5-三氮杂

    公开(公告)号：US4801706A

    公开(公告)日：1989-01-31

    申请号：US187187

    申请日：1988-04-28

    申请人： Michael W. Winkley ,  James L. Diebold

    发明人： Michael W. Winkley ,  James L. Diebold

    IPC分类号： C07D255/02 ,  A61K31/55

    CPC分类号： C07D255/02 ,  Y02P20/55

    摘要： Disclosed herein are N-substituted-hexahydro-1,2,5-triazepines of formula I, which is ##STR1## or a pharmaceutically acceptable acid addition salt thereof, wherein R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1 -C.sub.4 alkyl;R.sup.1 is (R.sup.6).sub.2 --CH--(CH.sub.2).sub.n -- in which n is 0, 1, 2 or 3 and R.sup.6 is p-fluoro, chloro or methoxyphenyl; andR.sup.3 is hydrogen and R.sup.2 is benzoyl, 2,6-dimethyl or diethylbenzoyl, 2,6-dichlorobenzoyl, N-methyl, ethyl or propylcarboxamido, N-phenylcarboxamido, N-2,6-dimethyl or diethylphenylcarboxamido, N-2,6-dichlorophenylcarboxamido, N-methyl, ethyl or propylacetamido, N-phenylacetamido, N-2,6-dimethyl or diethylphenylacetamido, or N-2,6-dichlorophenylacetamido orR.sup.2 and R.sup.3 are the same and are N-methyl, ethyl or propylcarboxamido, benzoyl, 2,6-dimethyl or diethlbenzoyl, 2,6-dichlorobenzoyl, benzyl, 2,6-dimethyl or diethlbenzoyl, 2,6-dichlorobenzoyl, or a removable amino protective group. Also disclosed are N-substituted-hexahydro-1,2,5-triazepines of formula II in which R.sup.1 of formula I is replaced by R.sup.7 which is C.sub.1 -C.sub.4 alkyl, and R.sup.2 and R.sup.3 of formula I are replaced by R.sup.8 and R.sup.9 which are, respectively, N-2,6-dimethyl, diethyl or dichlorophenylcarboxamido or N-2,6-dimethyl, diethyl or dichlorophenylacetamido and hydrogen. The compounds of the invention have antiarrhythmic properties or are intermediates for the preparation thereof.

    摘要翻译： 本文公开了式I的N-取代 - 六氢-1,2,5-三氮杂，其为I或其药学上可接受的酸加成盐，其中R 4和R 5独立地为氢或C 1 -C 4烷基; R1是（R6）2-CH-（CH2）n-，其中n是0,1,2或3，R6是对氟，氯或甲氧基苯基; 并且R 3是氢，R 2是苯甲酰基，2,6-二甲基或二乙基苯甲酰基，2,6-二氯苯甲酰基，N-甲基，乙基或丙基甲酰胺基，N-苯基甲酰胺基，N-2,6-二甲基或二乙基苯基甲酰胺基，N-2,6 乙基或丙基乙酰氨基，N-苯基乙酰胺基，N-2,6-二甲基或二乙基苯基乙酰胺基，或N-2,6-二氯苯乙酰氨基或R2和R3相同，为N-甲基，乙基或丙基甲酰胺基， 苯甲酰基，2,6-二甲基或二乙基苯甲酰基，2,6-二氯苯甲酰基，苄基，2,6-二甲基或二乙基苯甲酰基，2,6-二氯苯甲酰或可除去的氨基保护基。 还公开了式II的N-取代 - 六氢-1,2,5-三氮杂，其中式I的R 1被作为C 1 -C 4烷基的R 7代替，式I的R 2和R 3被R 8和R 9取代， 分别为N-2,6-二甲基，二乙基或二氯苯基甲酰胺基或N-2,6-二甲基，二乙基或二氯苯乙酰氨基和氢。 本发明的化合物具有抗心律失常性质或者是其制备的中间体。

    Process for preparing indoline-2-carboxylic acids via alpha-hydroxy-2-nitrobenzenepropanoic acid
    8.
    发明授权
    Process for preparing indoline-2-carboxylic acids via alpha-hydroxy-2-nitrobenzenepropanoic acid 失效

    公开(公告)号：US4585879A

    公开(公告)日：1986-04-29

    申请号：US700371

    申请日：1985-02-11

    申请人： Michael W. Winkley ,  Ronald J. McCaully

    发明人： Michael W. Winkley ,  Ronald J. McCaully

    IPC分类号： C07D209/42

    CPC分类号： C07D209/42

    摘要： Disclosed herein is a process for obtaining indoline-2-carboxylic acid (or derivatives thereof) comprising the following steps: (a) reducing .alpha.-oxo-2-nitrobenzenepropanoic acid to .alpha.-hydroxy-2-nitrobenzenepropanoic acid, (b) replacing the hydroxyl group of the latter with a chlorine atom utilizing a selected Vilsmeier chlorinating reagent at temperatures of at least 20.degree. C., (c) reducing the nitro group of the resulting .alpha.-chloro-2-nitrobenzenepropanoic acid to obtain .alpha.-chloro-2-aminobenzenepropanoic acid, and (d) cyclizing the latter in aqueous base to form the desired indoline-2-carboxylic acid. Alternately, steps (c) and (d) may be combined in a one pot step by using, for example, a Raney nickel-hydrazine reducing medium.

    Aminoalkyl ethers of 2,2'- and 3,3'-dihydroxybenzil
    9.
    发明授权
    Aminoalkyl ethers of 2,2'- and 3,3'-dihydroxybenzil 失效
    2,2（40-和3,3 {40-二羟基苯甲醚）的氨基烷基醚

    公开(公告)号：US3962334A

    公开(公告)日：1976-06-08

    申请号：US603556

    申请日：1975-08-08

    申请人： Gerhard R. Wendt ,  Michael W. Winkley

    发明人： Gerhard R. Wendt ,  Michael W. Winkley

    IPC分类号： C07D295/092 ,  C07C93/06

    CPC分类号： C07D295/088

    摘要： Dialkylaminoalkyl ethers of 2,2'- and 3,3'-dihydroxybenzil are prepared by reacting the dithallium salt of 2,2'- or 3,3'-dihydroxybenzil with a dialkylaminoalkylchloride. The products have antiarrhythmic activity.

    摘要翻译： 通过使2,2'-或3,3'-二羟基苯甲醚的二钠盐与二烷基氨基烷基氯化物反应来制备2,2'-和3,3'-二羟基苯甲亚胺的二烷基氨基烷基醚。 该产品具有抗心律失常活性。