N-(2,5-dimethyl-1H-pyrrol-1-yl)-N-methyl-6-(4-morpholinyl)-3-pyridazineamine | 75841-99-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2,5-dimethyl-1H-pyrrol-1-yl)-N-methyl-6-(4-morpholinyl)-3-pyridazineamine
• 英文别名: N-(2,5-Dimethyl-1H-pyrrol-1-yl)-N-methyl-6-morpholino-3-pyridazineamine；N-(2,5-dimethylpyrrol-1-yl)-N-methyl-6-morpholin-4-ylpyridazin-3-amine
• CAS: 75841-99-5
• 化学式: C₁₅H₂₁N₅O
• 分子量: 287.365
• InChiKey: CIFHXAFCNLSMAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(6-氯哒嗪-3-基)吗啉 在 盐酸 、 sodium hydride 、 一水合肼 作用下， 以 溶剂黄146 为溶剂， 反应 53.5h， 生成 N-(2,5-dimethyl-1H-pyrrol-1-yl)-N-methyl-6-(4-morpholinyl)-3-pyridazineamine
  参考文献：
  名称：

  Antihypertensives. N-1H-Pyrrol-1-yl-3-pyridazinamines

  摘要：

  The hypothesis that the side effects of hydralazine, such as mutagenicity and lupus erythematosus like syndrome, might be due to the NHNH2 group prompted us to incorporate part of this moiety into a pyrrole ring. Therefore, we prepared a series of N-1H-pyrrol-1-yl-3-pyridazinamines and a limited number of N-1H-pyrrol-1-yl-1-phthalazinamines by reaction of 3-hydrazinopyridazines and 1-hydrazinophthalazines with gamma-diketones. Most of these compounds, especially in the pyridazine series, showed moderate to strong antihypertensive activity in spontaneously hypertensive rats. The decrease in blood pressure generally had a slow onset after either oral or intravenous administration. N-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine hydrochloride (30) (MDL 899) showed no mutagenic activity in several tests and is now in clinical trials in patients.

  DOI：

  10.1021/jm00374a024

文献信息

• N-Pyrrolyl-pyridazineamines and their use as antihypertensive agents
  申请人：Gruppo Lepetit S.p.A.

  公开号：US04247551A1

  公开（公告）日：1981-01-27

  New-pyrrolyl-3-pyridazineamines having a further aminic substituent in the position 6. The compounds are useful as antihypertensive agents and may be prepared from 6-amino substituted-3-hydrazino pyridazines and .beta.-dicarbonyl compounds. The use of the novel compounds as antihypertensives and compositions containing the novel compounds as active ingredients are also claimed.

  具有位置6进一步氨基取代物的新吡咯基-3-吡啶嗪胺类化合物。这些化合物可用作降压药物，并可从6-氨基取代-3-叠氮基吡啶嗪和β-二羰基化合物制备。还声称将这些新化合物用作降压药物，并含有这些新化合物作为活性成分的组合物。
• 6-Amino substituted N-pyrrolyl-3-pyridazine amines, their preparation, and pharmaceutically antihypertensive compositions containing them
  申请人：GRUPPO LEPETIT S.P.A.

  公开号：EP0009655A1

  公开（公告）日：1980-04-16

  New N-pyrrolyl-3-pyridazine-amines having a further aminic substituent in the 6 position of the formula (I), wherein R, R1, R2 and R3 are hydrogen or lower alkyl, R4 is e.g hydrogen or lower alkyl, R5 and R6 are e.g. lower alkyl or taken together with the adjacent nitrogen atom represent a saturated 5 - 6 membered heterocyclic ring which may contain a further heteroatom, R7 and R8 represent hydrogen or, taken together, a 1,3-butadienylene radical forming a benzo system fused with the pyridazine ring, for example N-2,5-dimethyl-1H-pyrrol-1-yl)- 6-morpholino-3-pyridazineamine or N-(2,5-dimethyl-1H-pyrrol- 1-yl)-4-(4-hydroxypiperidino)-1-phthalazineamine, and their pharmaceutically acceptable salts are made e.g. by contacting a hydrazino derivate of the formula (II), wherein the substituents have the same meaning as above or an acid addition salt thereof with a dicarbonyl compound of the formula (III), wherein the substituents have the same meaning as above, or a functional derivative thereof in the presence of an acid catalyst at a temperature between 15°C and 120°C. The new compounds can be used as antihypertensive agents.

  在式 (I) 的 6 位具有另一个氨基取代基的新型 N-吡咯烷-3-哒嗪胺、 其中 R、R1、R2 和 R3 为氢或低级烷基，R4 如为氢或低级烷基，R5 和 R6 如为R5和R6是低级烷基，或与相邻的氮原子一起代表一个饱和的 5 - 6 个成员的杂环，该杂环可能含有另一个杂原子，R7和R8代表氢，或与 1、例如 N-2,5-二甲基-1H-吡咯-1-基）-6-吗啉基-3-哒嗪胺或 N-(2,5-二甲基-1H-吡咯-1-基)-4-(4-羟基哌啶基)-1-酞嗪胺及其药学上可接受的盐。例如，将式（II）的肼基衍生物（其中取代基的含义同上）或其酸加成盐与式 （III）的二羰基化合物（其中取代基的含义同上）或其官能衍生物在酸催化剂存在下于 15°C 至 120°C 的温度下接触。 新化合物可用作降压药。
• Process for preparing N-pyrrolyl-pyridazineamine derivatives
  申请人：GRUPPO LEPETIT S.P.A.

  公开号：EP0054816A1

  公开（公告）日：1982-06-30

  The present invention refers to a new process for preparing N-2,3,4,5-substituted-1H-pyrrol-1-yl)-6-substituted amino-3-pyridazineamine, known as antihypertensive agents. The process is characterized in that a suitable 3,6-dihalogenopyridazine is reacted with hydrazine hydrate or other hydrazine derivatives of formula NH2 NHR, the obtained compound is reacted with a suitable dicarbonyl compound yielding first an alcandione-bis-[6-halogen-3-pyridazinyl]-hydrazone, and then a 6-halogen-3-pyrrolylpyridazineamine derivative which is in turn reacted with an amine to yield the desired compounds.

  本发明涉及一种制备 N-2,3,4,5-取代-1H-吡咯-1-基)-6-取代氨基-3-哒嗪胺的新工艺，这种胺被称为抗高血压药。该工艺的特点是将一种合适的 3,6-二卤哒嗪与水合肼或其他式 NH2 NHR 的肼衍生物反应，得到的化合物与一种合适的二羰基化合物反应，首先得到一种阿坎二酮-双-[6-卤素-3-哒嗪基]-腙，然后得到一种 6-卤素-3-吡咯哒嗪胺衍生物，该衍生物又与胺反应，得到所需的化合物。
• US4247551A
  申请人：——

  公开号：US4247551A

  公开（公告）日：1981-01-27
• US4385179A
  申请人：——

  公开号：US4385179A

  公开（公告）日：1983-05-24