梁曉天, 趙知中, 于潤海, 莫若瑩, 陈明熾. 降压药物的研究——苯駢噻二嗪类化合物的合成J. 药学学报, 1963, 10(6): 345-358.
引用本文: 梁曉天, 趙知中, 于潤海, 莫若瑩, 陈明熾. 降压药物的研究——苯駢噻二嗪类化合物的合成J. 药学学报, 1963, 10(6): 345-358.
LIANG XIAO-TIAN, ZHAO ZHI-ZHONG, YU YUN-HAI, MO RUO-YING AND CHEN MING-ZHI, . SYNTHETIC STUDIES OF COMPOUNDS RELATED TO CHLOROTHIAZIDEJ. Acta Pharmaceutica Sinica, 1963, 10(6): 345-358.
Citation: LIANG XIAO-TIAN, ZHAO ZHI-ZHONG, YU YUN-HAI, MO RUO-YING AND CHEN MING-ZHI, . SYNTHETIC STUDIES OF COMPOUNDS RELATED TO CHLOROTHIAZIDEJ. Acta Pharmaceutica Sinica, 1963, 10(6): 345-358.

降压药物的研究——苯駢噻二嗪类化合物的合成

SYNTHETIC STUDIES OF COMPOUNDS RELATED TO CHLOROTHIAZIDE

  • 摘要: 为了寻找更有效的苯駢噻二嗉类的降压药物,合成了五个类型化合物共五十二个.(1)間位氯代苯胺与过量氯磺酸反应(另加三氯化磷),产生的双磺酰氯与氫氧化铵或脂族胺,芳香胺,脂环胺等作用可得到相应的双磺酰胺.間位三氟甲基苯胺先轉变成2-三氟甲基-4氨基-苯磺酸后再氯磺化、氨化可得到相应的双磺酰胺.苯胺經氯磺化、氨化得到三磺酰胺.(2)磺酰胺与脂族醛、芳香醛作用,縮合成苯駢噻二嗪类化合物.这些化合物不溶于水及酸而溶于碱,因此可利用此性质,进行化合物的純制.三磺酰胺与甲醛反应得到三环化合物,而与乙醛反应得苯駢噻二嗪衍生物.(3)双磺酰胺与酮也可进行縮合,但此醛类困难.

     

    Abstract: 6-Chloro-7-sulfamyl-l,2,4-benzothiadiazine-1,1-dioxide (chlorothiazide) is an orally effective diuretic and is being employed for the treatment of hypertension. Many workers have reported the chemistry and pharmacology of this compound and its analogs. But the mechanism of the antihypertensive action has not been fully elucidated. It seemed to be of interest to us to analyse the structural features conducive to diuretic and antihypertensive activities. Five types of compounds have been prepared for the purpose of studying the relationship between chemical structure and biological activities and of searching for a better antihypertensive agent. Physical data of these compounds were assembled in tables 1 to 12 in the Chinese text. Most of the compounds prepared were derived from 4-amino-6-chloro-l,3-benzenedisulfonamide, but compounds containing trifluoromethyl were also made. The intermediate disulfonamides were prepared by chlorosulfonation of m-chloroaniline with chlorosulfonic acid in large excess (ocassionally with added phosphorus trichloride or sodium chloride), followed by treatment with ammonia or with simple aliphatic and aromatic amines. The sulfonamides were condensed with aldehydes and ketones to give substituted 1,2,4-benzothiadiazine-1,1-dioxide. Pharmacologic studies will be reported elsewhere.

     

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