7-(3-hydroxyphenyl)-1,4-dimorpholino-7-phenylpyrido<3,4-d>pyridazine | 57696-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 7-(3-hydroxyphenyl)-1,4-dimorpholino-7-phenylpyrido<3,4-d>pyridazine
• 英文别名: 7-m-Hydroxy-phenyl-1,4-dimorpholino-pyrido<3,4-d>pyridazin；3-(1,4-di-morpholin-4-yl-pyrido[3,4-d]pyridazin-7-yl)-phenol；3-(1,4-Dimorpholin-4-ylpyrido[3,4-d]pyridazin-7-yl)phenol
• CAS: 57696-56-7
• 化学式: C₂₁H₂₃N₅O₃
• 分子量: 393.445
• InChiKey: IOGNXWOSUXMUFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-(m-benzyloxyphenyl)pyrido<3,4-d>pyridazine-1,4-(2H,3H)dione 在 三氟乙酸 作用下， 反应 2.0h， 生成 7-(3-hydroxyphenyl)-1,4-dimorpholino-7-phenylpyrido<3,4-d>pyridazine
  参考文献：
  名称：

  Studies on the syntheses of N-heterocyclic compounds. XXVI. Syntheses of pyrido(3,4-d)pyridazine derivatives. III.

  摘要：

  一种新的合成路线用于1,4-二吗啉基-7-苯基吡啶并[3,4-d]哒嗪（1）的合成，这是一种有效的利尿剂。通过催化氢化3-氰基-2-氧代-6-苯基-4（1H）-吡啶甲酸乙酯（2）进行氯化反应和后续脱氯反应，得到3-氰基-6-苯基-4-吡啶甲酸乙酯（6），该物质也可以通过3-氰基-6-苯基-2-硫代-4（1H）-吡啶甲酸乙酯（3）的脱硫反应得到。6通过环状亚胺（10）或酸酐（11）转化为7-苯基吡啶并[3,4-d]哒嗪-1,4（2H,3H）-二酮（12），后者是合成1的关键中间体。1的几种同系物也可以通过这些方法制备。1,4,5-三氯-7-苯基吡啶并[3,4-d]哒嗪（18）中的三个氯基团与吗啉发生亲核

  DOI：

  10.1248/cpb.23.2306

文献信息

• Analysis of 1,4-dimorpholino-7-phenylpyrido[3,4-d]pyridazine (DS-511) and its metabolites in biological specimens. III. Fluorodensitometric method for the simultaneous determination of DS-511 and its metabolites in urine and bile.
  作者：MOTOAKI KUWAYAMA、SOHACHIRO MIYAKE、KOHEI NISHIKAWA

  DOI：10.1248/cpb.28.2158

  日期：——

  A simple and rapid fluorodensitometric method for the simultaneous determination of 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) and its metabolites in urine and bile was established. The biological specimens containing DS-511 and its metabolites were separated into lipophilic and hydrophilic layers by extraction with ethyl acetate. The hydrophilic layer was incubated at 37° for 24 hr with β-glucuronidase and arylsulfatase, then separated again into two layers by a similar extraction procedure. The lipophilic layers were purified by two-dimensional thin-layer chromatography with chloroform-methanol (10 : 1) and ethyl acetate-benzene (3 : 2). The hydrophilic layer was passed through a column of Amberlite XAD-2 (100-200 mesh), eluting with ethanol, and the eluate was purified by stepwise thin-layer chromatography with ethyl acetatebenzene (3 : 2) and chloroform-methanol (2 : 1). After moistening the air-dried chromatogram with 1-butanol, the fluorescent spots were quantitatively determined with a spectrodensitometer in the fluorescence mode. The recoveries and the coefficients of variation (c. v.) with this method were 89-116% (c. v. 6-14%) for lipophilic compounds and 93.0-95.0% (c. v. 5-6%) for hydrophilic compounds at concentrations between 0.1-1.0 μg/ml in biological specimens. This method could be used to analyze biological specimens from rats and dogs after administration of DS-511 and should also be applicable to human specimens.

  建立了一种简单快速的荧光密度测定法，用于同时测定尿液和胆汁中的1,4-二氨基-7-苯基吡啶并[3,4-d]哒嗪（DS-511）及其代谢产物。用乙酸乙酯萃取，将含有DS-511及其代谢产物的生物样本分为亲脂层和亲水层。将亲水层在37℃下与β-葡萄糖醛酸酶和芳基硫酸酶一起孵育24小时，然后用类似的萃取程序再次分为两层。用氯仿-甲醇（10:1）和乙酸乙酯-苯（3:2）进行二维薄层色谱法纯化亲脂层。将亲水层通过Amberlite XAD-2（100-200目）柱，用乙醇洗脱，用乙酸乙酯-苯（3:2）和氯仿-甲醇（2:1）进行逐步薄层色谱法纯化洗脱液。用1-丁醇润湿风干的色谱图后，用分光密度计在荧光模式下定量测定荧光点。在生物样本中浓度为0.1-1.0μg/ml时，该方法的回收率和变异系数（CV）分别为：亲脂化合物89-116%（CV 6-14%），亲水化合物93.0
• OKA Y.; ITOH K.; MIYAKE A.; TADA N.; OMURA K.; TOMIMOTO M.; YURUGI S., CHEM. AND PHARM. BULL.<CPBT-AL>, 1975, 23, NO 10, 2306-2317
  作者：OKA Y.、 ITOH K.、 MIYAKE A.、 TADA N.、 OMURA K.、 TOMIMOTO M.、 YURUGI S.

  DOI：——

  日期：——
• Studies on the syntheses of N-heterocyclic compounds. XXVI. Syntheses of pyrido(3,4-d)pyridazine derivatives. III.
  作者：YOSHIKAZU OKA、KATSUMI ITOH、AKIO MIYAKE、NORIO TADA、KIYOSHI OMURA、MITSUMI TOMIMOTO、SHOJIRO YURUGI

  DOI：10.1248/cpb.23.2306

  日期：——

  A new synthetic route to 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (1), a potent diuretic, has been investigated. Chlorination and the subsequent dechlorination by catalytic hydrogenation of ethyl 3-cyano-2-oxo-6-phenyl-4 (1H)-pyridinecarboxylate (2) gave ethyl 3-cyano-6-phenyl-4-pyridinecarboxylate (6), which was also obtained by desulfurization of ethyl 3-cyano-6-phenyl-2-thioxo-4 (1H)-pyridinecarboxylate (3). 6 was led to 7-phenylpyrido [3, 4-d] pyridazine-1, 4 (2H, 3H)-dione (12), a key intermediate in the synthesis of 1, by way of cyclic imide (10) or anhydride (11). Several homologs of 1 could also be prepared by employing these procedures. Reactivity of the three chloro groups in 1, 4, 5-trichloro-7-phenylpyrido [3, 4-d] pyridazine (18) towards nucleophilic substitution with morpholine is discussed.

  一种新的合成路线用于1,4-二吗啉基-7-苯基吡啶并[3,4-d]哒嗪（1）的合成，这是一种有效的利尿剂。通过催化氢化3-氰基-2-氧代-6-苯基-4（1H）-吡啶甲酸乙酯（2）进行氯化反应和后续脱氯反应，得到3-氰基-6-苯基-4-吡啶甲酸乙酯（6），该物质也可以通过3-氰基-6-苯基-2-硫代-4（1H）-吡啶甲酸乙酯（3）的脱硫反应得到。6通过环状亚胺（10）或酸酐（11）转化为7-苯基吡啶并[3,4-d]哒嗪-1,4（2H,3H）-二酮（12），后者是合成1的关键中间体。1的几种同系物也可以通过这些方法制备。1,4,5-三氯-7-苯基吡啶并[3,4-d]哒嗪（18）中的三个氯基团与吗啉发生亲核