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    • 97. 发明公开
    • Substituted 9,10-anthracene-bis hydrazones and pharmaceutical compositions containing same
    • 取代的9,10-蒽二基 - 腙和含有它们的药物组合物。
    • EP0018850A1
    • 1980-11-12
    • EP80301480.2
    • 1980-05-07
    • AMERICAN CYANAMID COMPANY
    • Murdock, Keith ChadwickDurr, Frederick Emil
    • C07C133/08C07C133/12C07C159/00C07D233/52C07D239/18C07D295/18A61K31/15A61K31/415A61K31/505A61K31/42
    • C07D295/13C07C17/32C07C47/453C07C47/457C07C47/47C07C47/55C07C47/57C07C47/575C07C251/72C07C281/18C07C2603/24C07D213/42C07D213/77C07D233/52C07D239/18C07D243/04C07D307/52C07D317/70C07D333/20C07C22/04
    • There are disclosed anthracene-9,10- bis- carbonyl- lydrazones and derivatives thereof useful for inhibiting the growth of transplanted mouse tumors, and for inducing the regression and/or palliation of leukemia and related cancers.
      The compounds can be represented by the formula:
      wherein Z is a trivalent moiety selected from the group consisting of those of the formulae:
      wherein n is 0, 1, 2 or 3 and R is hydrogen, lower alkyl, cycloalkyl, phenyl or benzyl; R 1 is of hydrogen or lower alkyl; R 2 is selected from the group consisting of monovalent moieties of the formulae:
      wherein p is 1, 2 or 3, q is 0, 1 or 2, R' is hydrogen or lower alkyl, R" is lower alkyl R 7 is a moiety of the formula:
      wherein m is 2, 3, 4 or 5, R 1 , R' and R" are as hereinbefore defined and the moiety -NR'R" may be pyrrolidino, piperidino, morpholino or N-methylpiperazino, X isoxo (O=), thioxo (S=) or imino (R'-N=) wherein R' is as hereinbefore defined), and R 3 , R 4 , R 5 and R 6 are each individually selected from the group consisting of hydrogen, halogen, hydroxy, nitro, amino, sulfonamido, lower alkyl; and the pharmacologically acceptable acid-addition and quaternary ammonium salts thereof.
      These compunds can be prepared by reaction of 9,10- anthracenedialdehyde with a hydrazine. The dialdehyde is obtained from the reaction of anthracene with paraformaldehyde and hydrochloric acid, giving the 9,10-bis-(chloromethyl)anthracene derivative, which then is treated with sodium in ethanol. Or anthracene can be reacted with vinylene carbonate, to give a cyclic carbonate which is hydrol- ised to the diol, which in turn is treated with lead tetraacetate in acetic acid to give the 9,10-anthracenedicarboxaldehyde. Or 9,10-anthracenediacetonitrile, a substituted hydrazine hyrochloride, sodium acetate and Raney nickel is reduced with hydrogen to give the anthracene bis-hydrazone.
    • 有游离缺失盘蒽9,10双carbonyllydrazones和衍生物用于移植小鼠的肿瘤的生长抑制它们的有用的,并且用于诱导白血病和相关的癌症的消退和/或减轻。 化合物可以通过下式表示: worin Z是选自的那些式餐饮中选择的三价基团: - (CH 2)N - @ =和 - @ H-CH = worin n为0,1 或3,R是氢2,低级烷基,环烷基,苯基或苄基; R 1是氢或低级烷基的; R 2是选自式餐饮单价部分由......组成: worin p是1,2或3,q为0,1或2,R“是氢或低级烷基,R sec是低级烷基,R 7是一个 下式的基团: worin m为2,3,4或5,R 1,R分钟和R秒是如前定义的和部分-NR分钟ř秒可以被哌啶子基,吗啉代或N-甲基哌嗪基, X是氧代(O =),氢硫代(S =)或亚氨基的(R min N =)worin R“是如之前定义),和R3,R4,R5和R6各自独立地为选自的组, 卤素,羟基,硝基,氨基,磺酰氨基,低级烷基; 和药理学上可接受的酸加成和它们的季铵盐。 这些侃,陈万平可以通过与肼9,10- anthracenedialdehyde的反应来制备。 二醛选自蒽的与多聚甲醛和盐酸的反应获得,给予9,10-双(氯甲基)蒽衍生物,其然后被处理以在乙醇钠。 或蒽可以与碳酸亚乙烯酯进行反应,得到的环状碳酸酯的所有其hydrolised成二醇,这又在乙酸中的治疗用四乙酸铅,得到9,10- anthracenedicarboxaldehyde。 或9,10- anthracenediacetonitrile,一个substituiertem肼hyrochloride,乙酸钠和阮内镍与氢气,得到蒽双 - 腙减少。