公开(公告)号：US4181719A

公开(公告)日：1980-01-01

申请号：US909846

申请日：1978-05-26

申请人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

发明人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

IPC分类号： A61K31/22 ,  A61K31/485 ,  A61K31/52 ,  A61K31/54 ,  A61K31/615 ,  C07C67/08

CPC分类号： A61K31/485 ,  A61K31/22 ,  A61K31/52 ,  A61K31/54

摘要： N-acetyl-para-aminophenyl N'-acetylaminothioalkanoates I are new analgesic compounds with greatly reduced hepatotoxic effects, when taken in overdose, relative to N-acetyl-para-aminophenol. They are prepared by reacting an N-acetylaminothioalkanoic acid IV with a reactive organic chloride V to form a mixed anhydride II and then reacting the latter with N-acetyl-para-aminophenol. The mixed anhydrides II are new and useful intermediates. Alternatively the derivatives I may be prepared by reacting the acid IV with bis-(4-nitrophenyl) sulfite to form a para-nitrophenyl N-acetylaminothioalkanoic acid ester VIII, reducing the latter to a para-aminophenyl N-acetylaminothioalkanoate VII, and acetylating this product. The esters VII and VIII are new and useful intermediates. Both reactions may pass through S-blocked intermediates, which are also new. Pharmaceutical compositions containing the derivatives I are disclosed, and also analgesic methods using them.

摘要翻译： N-乙酰基 - 对氨基苯基N'-乙酰基氨基硫代链烷酸酯I是新的止痛化合物，相对于N-乙酰基对氨基苯酚，当服用过量时，肝毒性作用大大降低。 它们通过使N-乙酰氨基硫代链烷酸IV与反应性有机氯化物V反应以形成混合酐II，然后使其与N-乙酰基对氨基苯酚反应来制备。 混合酸酐II是新的和有用的中间体。 或者，衍生物I可以通过使酸IV与双 - （4-硝基苯基）亚硫酸酯反应以形成对硝基苯基N-乙酰氨基硫代链烷酸酯VIII，将其还原成N-乙酰基氨基硫代链烷酸异对氨基苯酯VII，并将其乙酰化 产品。 酯VII和VIII是新的和有用的中间体。 这两种反应都可能通过S型阻塞的中间体，这也是新的。 公开了含有衍生物I的药物组合物，以及使用它们的镇痛方法。

公开(公告)号：US4405800A

公开(公告)日：1983-09-20

申请号：US360312

申请日：1982-03-22

申请人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

发明人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

IPC分类号： A61K31/22 ,  A61K31/485 ,  A61K31/52 ,  A61K31/54 ,  C07D309/08

CPC分类号： A61K31/485 ,  A61K31/22 ,  A61K31/52 ,  A61K31/54

摘要： N-Acetyl-para-aminophenyl N'-acetylaminothioalkanoates I are new analgesic compounds with greatly reduced hepatotoxic effects, when taken in overdose, relative to N-acetyl-para-aminophenyl. They are prepared by reacting an N-acetylaminothioalkanoic acid IV with a reactive organic chloride V to form a mixed anhydride II and then reacting the latter with N-acetyl-para-aminophenol. The mixed anhydrides II are new and useful intermediates. Alternatively the derivatives I may be prepared by reacting the acid IV with bis-(4-nitrophenyl) sulfite to form a para-nitrophenyl N-acetylaminothioalkanoic acid ester VIII, reducing the latter to a para-aminophenyl N-acetylaminothioalkanoate VII, and acetylating this product. The esters VII and VIII are new and useful intermediates. Both reactions may pass through S-blocked intermediates, which are also new. Pharmaceutical compositions containing the derivatives I are disclosed, and also analgesic methods using them.

摘要翻译： N-乙酰基对氨基苯基N'-乙酰氨基硫代链烷酸酯I是新的止痛化合物，相对于N-乙酰基对氨基苯基，服用过量时，肝毒性作用大大降低。 它们通过使N-乙酰氨基硫代链烷酸IV与反应性有机氯化物V反应以形成混合酐II，然后使其与N-乙酰基对氨基苯酚反应来制备。 混合酸酐II是新的和有用的中间体。 或者，衍生物I可以通过使酸IV与双 - （4-硝基苯基）亚硫酸酯反应以形成对硝基苯基N-乙酰氨基硫代链烷酸酯VIII，将其还原成N-乙酰基氨基硫代链烷酸异对氨基苯酯VII，并将其乙酰化 产品。 酯VII和VIII是新的和有用的中间体。 这两种反应都可能通过S型阻塞的中间体，这也是新的。 公开了含有衍生物I的药物组合物，以及使用它们的镇痛方法。

公开(公告)号：US4482495A

公开(公告)日：1984-11-13

申请号：US026329

申请日：1979-04-02

申请人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

发明人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

IPC分类号： A61K31/22 ,  A61K31/485 ,  A61K31/52 ,  A61K31/54 ,  C07C149/00 ,  C07C149/243 ,  C07C149/43 ,  C07D309/08

CPC分类号： A61K31/485 ,  A61K31/22 ,  A61K31/52 ,  A61K31/54

摘要： N-acetyl-para-aminophenyl N'-acetylaminothioalkanoates I are new analgesic compounds with greatly reduced hepatotoxic effects, when taken in overdose, relative to N-acetyl-para-aminophenol. They are prepared by reacting an N-acetylaminothioalkanoic acid IV with a reactive organic chloride V to form a mixed anhydride II and then reacting the latter with N-acetyl-para-aminophenol. The mixed anhydrides II are new and useful intermediates. Alternatively the derivatives I may be prepared by reacting the acid IV with bis-(4-nitrophenyl) sulfite to form a para-nitrophenyl N-acetylaminothioalkanoic acid ester VIII, reducing the latter to a para-aminophenyl N-acetylaminothioalkanoate VII, and acetylating this product. The esters VII and VIII are new and useful intermediates. Both reactions may pass through S-blocked intermediates, which are also new. Pharmaceutical compositions containing the derivatives I are disclosed, and also analgesic methods using them.

摘要翻译： N-乙酰基 - 对氨基苯基N'-乙酰基氨基硫代链烷酸酯I是新的止痛化合物，相对于N-乙酰基对氨基苯酚，当服用过量时，肝毒性作用大大降低。 它们通过使N-乙酰氨基硫代链烷酸IV与反应性有机氯化物V反应以形成混合酐II，然后使其与N-乙酰基对氨基苯酚反应来制备。 混合酸酐II是新的和有用的中间体。 或者，衍生物I可以通过使酸IV与双 - （4-硝基苯基）亚硫酸酯反应以形成对硝基苯基N-乙酰氨基硫代链烷酸酯VIII，将其还原成N-乙酰基氨基硫代链烷酸异对氨基苯酯VII，并将其乙酰化 产品。 酯VII和VIII是新的和有用的中间体。 这两种反应都可能通过S型阻塞的中间体，这也是新的。 公开了含有衍生物I的药物组合物，以及使用它们的镇痛方法。

公开(公告)号：US4361703A

公开(公告)日：1982-11-30

申请号：US246234

申请日：1981-03-23

申请人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

发明人： George Margetts ,  Roderic S. Andrews ,  Jean Legros

IPC分类号： A61K31/22 ,  A61K31/485 ,  A61K31/52 ,  A61K31/54 ,  C07C69/773

CPC分类号： A61K31/485 ,  A61K31/22 ,  A61K31/52 ,  A61K31/54

摘要： N-acetyl-para-aminophenyl N'acetylaminothioalkanoates I are new analgesic compounds with greatly reduced hepatotoxic effects, when taken in overdose, relative to N-acetyl-para-aminophenol. They are prepared by reacting an N-acetylaminothioalkanoic acid IV with a reactive organic chloride V to form a mixed anhydride II and then reacting the latter with N-acetyl-para-aminophenol. The mixed anhydrides II are new and useful intermediates. Alternatively the derivatives I may be prepared by reacting the acid IV with bis-(4-nitrophenyl) sulfite to form a para-nitrophenyl N-acetylaminothioalkanoic acid ester VIII, reducing the latter to a para-aminophenyl-N-acetylaminothioalkanoate VII, and acetylating this product. The esters VII and VIII are new and useful intermediates. Both reactions may pass through S-blocked intermediates, which are also new. Pharmaceutical compositions containing the derivatives I are disclosed, and also analgesic methods using them.

摘要翻译： N-乙酰基对氨基苯基乙酰氨基硫代烷酸酯I是新的止痛化合物，相对于N-乙酰基对氨基苯酚，当服用过量时，肝毒性作用大大降低。 它们通过使N-乙酰氨基硫代链烷酸IV与反应性有机氯化物V反应以形成混合酐II，然后使其与N-乙酰基对氨基苯酚反应来制备。 混合酸酐II是新的和有用的中间体。 或者，可以通过使酸IV与双 - （4-硝基苯基）亚硫酸酯反应以形成对硝基苯基N-乙酰氨基硫代链烷酸酯VIII，将其还原成对氨基苯基-N-乙酰氨基硫代烷酸酯VII并将乙酰化 这个产品。 酯VII和VIII是新的和有用的中间体。 这两种反应都可能通过S型阻塞的中间体，这也是新的。 公开了含有衍生物I的药物组合物，以及使用它们的镇痛方法。

公开(公告)号：US09283235B2

公开(公告)日：2016-03-15

申请号：US10474868

申请日：2002-04-09

申请人： Christopher Wood ,  George Margetts

发明人： Christopher Wood ,  George Margetts

IPC分类号： A61P5/00 ,  A61P5/08 ,  A61P5/46 ,  C07J71/00 ,  C07J41/00 ,  A61K31/58

CPC分类号： A61K31/58 ,  C07J71/00

摘要： Use of a compound of formula (I) or a 3-enol C1-4 alkanoate ester thereof in the manufacture of a medicament for the intermittent treatment of a condition of a human or non-human mammal in which said mammal has an abnormally high serum concentration of an adrenal hormone: Wherein R1, R2, R5, and R6 are the same or different and each is hydrogen or C1 to 4? alkyl; R3 is hydrogen C1 to 4? alkyl, C1 to 4? alkenyl or C1 to 4? alkynyl; R4 is hydroxy, C1 to 4? alkanoyloxy, a group of formula (II) or (III) Wherein R7 is (CH2)n, where n is an integer of from 0 to 4, R8 is hydrogen, C1 to 4? alkyl, hydroxy or NH2 and R9 and R10 are the same or different and each is hydrogen or C1 to 4? Alkyl; or R3 and R4 together are oxo, ethylenedioxy or propylenedioxy. The invention has practical benefits for the treatment of man and other animals with diseases associated with abnormal production of adrenal steroids. The invention also shows that sustained suppression of the adrenal hormones is not required to achieve relief of symptoms in these conditions.

摘要翻译： 式（I）化合物或其3-烯醇C 1-4链烷酸酯在制备用于间歇治疗所述哺乳动物具有异常高血清的人或非人哺乳动物状况的药物中的用途 肾上腺激素浓度：其中R1，R2，R5和R6相同或不同，分别为氢或C1至4？ 烷基; R3是氢C1〜4 烷基，C1〜4 烯基或C1〜4 炔基; R4是羟基，C1〜4 烷氧基，式（II）或（III）的基团，其中R7是（CH2）n，其中n是0-4的整数，R8是氢，C1〜4的烷氧基， 烷基，羟基或NH 2，R 9和R 10相同或不同，各自为氢或C 1至4 烷基; 或者R 3和R 4一起是氧代，亚乙二氧基或亚丙二氧基。 本发明具有治疗具有与肾上腺类固醇异常生成相关的疾病的人和其他动物的实际益处。 本发明还表明，在这些情况下，不需要持续抑制肾上腺激素来缓解症状。