Symakalim | 129518-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: Symakalim
• 英文别名: EMD 56010；(-)-2,2-dimethyl-4R-(1,6-dihydro-1-methyl-6-oxo-3-pyridazinyl-oxy)-6-cyano-3S-chromanol；(3S,4R)-3-hydroxy-2,2-dimethyl-4-(1-methyl-6-oxopyridazin-3-yl)oxy-3,4-dihydrochromene-6-carbonitrile
• CAS: 129518-57-6
• 化学式: C₁₇H₁₇N₃O₄
• 分子量: 327.34
• InChiKey: RIBYSHCVSQIIJE-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Symakalim 生成 Toluene-4-sulfonic acid (3S,4R)-6-cyano-2,2-dimethyl-4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-chroman-3-yl ester
  参考文献：
  名称：

  Bergmann Rolf, Gericke Rolf, Arch. Pharm., 327 (1994) N 3, S 169- 173

  摘要：

  DOI：
• 作为产物：
  描述：

  2,2-二甲基-2H-1-苯并吡喃-6-甲腈 在 Mn(III)salen <(S,S)-4> 吡啶 、 sodium hypochlorite 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 Symakalim
  参考文献：
  名称：

  Enantiomerically Pure Epoxychromans via Asymmetric Catalysis

  摘要：

  A practical and highly effective process for the asymmetric epoxidation of several 2,2-dimethylchromene derivatives is reported. Catalysis by Mn(salen) complex 4 in all cases affords epoxychromans with > 90% ee, and this method has been applied to the synthesis of two recently developed antihypertensive agents in enantiomerically pure form.

  DOI：

  10.1016/s0040-4039(00)93426-9

文献信息

• The Influence of Substituents in 3-Position on the Activity of Chroman-Type Potassium Channel Activators
  作者：Rolf Bergmann、Rolf Gericke

  DOI：10.1002/ardp.19943270308

  日期：——

  pyridone residue. 3‐Chloro derivatives 16 and 19 resulted on heating the mesylate or tosylate with LiCl in DMF. Bromination of chromene 20 led to 21. ‐ All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats with a dose of 1 mg/kg.

  色原醇 1 的 Swern 氧化导致酮 3 伴随着相邻 4-位的氯化。使用 Leuckart 条件，色满酮 2 被转化为烯胺 5。 - 4 - 溴色烯 - 3 - 甲醛 8，这是通过来自 7 的 Vilsmeier - Arnold 反应获得的，结果证明是插入吡啶酮残基的合适中间体。3-氯衍生物 16 和 19 通过在 DMF 中用 LiCl 加热甲磺酸酯或甲苯磺酸酯而产生。色烯 20 的溴化导致 21。 - 在自发性高血压大鼠中以 1 mg/kg 的剂量测试所有化合物的口服抗高血压活性。
• Chromanderivate
  申请人：MERCK PATENT GmbH

  公开号：EP0363883A1

  公开（公告）日：1990-04-18

  Die Erfindung betrifft neue Chromanderivate der Formel I worin R¹, R², R³, R⁴ R⁵ R⁶ R⁷ R⁸ und Z die in Patentanspruch 1 angegebene Bedeutungen haben, sowie ihre Salze zeigen Wirkungen auf das cardiovaskuläre System und können verwendet werden zur Behandlung bzw. Prophylaxe von Herzinsuffizienz, Angina pectoris, Blut­hochdruck, Inkontinenz und Alopezie.

  本发明涉及式 I 的新色烷衍生物 其中 R¹、R²、R³、R⁴ R⁵ R⁶ R⁷ R⁸ 和 Z 具有权利要求 1 中给出的含义、 以及它们的盐类对心血管系统有作用，可用于治疗或预防心力衰竭、心绞痛、高血压、尿失禁和脱发。
• Diazabicycloalkene derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0571822A1

  公开（公告）日：1993-12-01

  A compound of formula (I) possesses excellent potassium channel opening activity and is effective on various diseases arising from contractions of blood vessels, bronchial smooth muscles, etc., for example, ischemic heart diseases exemplified by angina pectoris, asthma, pollakisuria, sequela of subarachnoid hemorrhage, peripheral arterioinfarct, and so on. The compound has potent and long-lasting antihypertensive activity, with the onset of the action being slow, excellent activity in increasing renal blood flow, and high safety, and is therefore particularly useful as an antihypertensive.    The substituents are as defined in the specification.

  式（I）化合物具有优异的钾通道开放活性，对血管、支气管平滑肌等收缩引起的各种疾病有效，例如心绞痛、哮喘、蛛网膜下腔出血后遗症、外周动脉梗塞等缺血性心脏病。该化合物具有强效、持久的降压活性，起效缓慢，在增加肾血流量方面具有极佳的活性，安全性高，因此作为降压药特别有用。 取代基如说明书中所定义。
• 4-Heterocyclyloxy-2H-1-benzopyran potassium channel activators
  作者：Rolf Bergmann、Volker Eiermann、Rolf Gericke

  DOI：10.1021/jm00172a013

  日期：1990.10

  The reaction of 2,4-dihydroxypyridine (2) with 3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (1) yielded the 4-[(1,2-dihydro-2-oxo-4-pyridyl)oxy] compound 3a, accompanied by small amounts of the isomeric 4-(1,2-dihydro-4-hydroxy-2-oxo-1-pyridyl) compound 4. This could also be prepared by hydrogenation of the benzyloxy derivative 5. Reaction of 3,6-pyridazinediol (10) with 1 (R = CN) gave the 4-[(1,6-dihydro-6-oxo-3-pyridazinyl)oxy] compound 11a, which in turn rearranged on heating with NaH in DMSO into the 4-(1,6-dihydro-3-hydroxy-6-oxo-1-pyridazinyl) compound 12. A series of 6-substituted analogues (R = CO2Me, CSNH2, NO2, Br) of 3a and 11a were synthesized. N-Alkylation led to compounds 14a-c (R = Me, Et, CHMe2). The 4-heterocyclyloxychromenes 9 and 16a were obtained by alkaline hydrolysis of their 3-camphorsulfonates. The racemic pyridazinyloxy compounds 11a and 14a could be resolved via their diastereomeric camphorsulfonates or camphanates. The differences between the 4-heterocyclyloxychromanols and the isomeric N-substituted compounds 4 and 12 were elucidated in the course of extensive NMR investigations. While in DMSO the former appeared to be conformationally flexible molecules the latter were rigid. All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats, using doses of 1 mg/kg. High and long lasting activities were found for the pyridyloxy compounds 3a and 3d, the pyridazinyloxy compound 11a, and its N-alkylation products, as well as for the 3S,4R-enantiomers 20a and 22a. (-)-(3S,4R)-3,4-Dihydro-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)oxy]-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (22a) was selected for further development.
• BERGMANN, ROLF;EIERMANN, VOLKER;GERICKE, ROLF, J. MED. CHEM., 33,(1990) N0, C. 2759-2767
  作者：BERGMANN, ROLF、EIERMANN, VOLKER、GERICKE, ROLF

  DOI：——

  日期：——