((2S,5R)-5-phenylmorpholin-2-yl)methanol | 1349829-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: ((2S,5R)-5-phenylmorpholin-2-yl)methanol
• 英文别名: [(2S,5R)-5-phenylmorpholin-2-yl]methanol
• CAS: 1349829-37-3
• 化学式: C₁₁H₁₅NO₂
• 分子量: 193.246
• InChiKey: IXGKTMLLLCYDRF-QWRGUYRKSA-N

物化性质

• 沸点：
  343.1±27.0 °C(Predicted)
• 密度：
  1.096±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ((2S,5R)-5-phenylmorpholin-2-yl)methanol 在 tris-(dibenzylideneacetone)dipalladium(0) 、 5-(diisopropylphosphino)-1',3',5'-triphenyl-1'H-1,4'-bipyrazole 、 三乙胺 、 lithium tert-butoxide 作用下， 以 六甲基磷酰三胺 、 2-甲基-2-丁醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-((2R,5R)-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]-oxazin-6-yl)-5-phenylmorpholin-2-yl)acetonitrile
  参考文献：
  名称：

  Identification of Morpholino-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ones as Nonsteroidal Mineralocorticoid Antagonists

  摘要：

  A novel series of morpholine-based non steroidal mineralocorticoid receptor antagonists is reported. Starting from a pyrrolidine HTS hit 9 that possessed modest potency but excellect selectivity versus related nuclear hormone receptors, a series of libraries led to identification of morpholine lead 10. After further optimization, cis disubstituted morpholine 22 was discovered, which showed a 45-fold boost in binding affinity and corresponding functional potency compared to 13. While 22 had high clearance in rat, it provided sufficient exposure at high doses to favorably assess in vivo efficacy (increased urinary Na+/K+ ratio) and safety. In contrast to rat, the dog and human MetID and PK profiles of 22 were adequate, suggesting that it could be suitable as a potential clinical asset.

  DOI：

  10.1021/acs.jmedchem.7b01515
• 作为产物：
  描述：

  N-(2-hydroxy-1-phenylethyl)-4-methylbenzenesulfonamide 在 甲醇 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 四(三苯基膦)钯 、 乙醇 、 iron(III) chloride hexahydrate 、 水 、 magnesium 、 N-甲基吗啉氧化物 作用下， 以 乙醚 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 21.0h， 生成 ((2S,5R)-5-phenylmorpholin-2-yl)methanol
  参考文献：
  名称：

  一锅反应对取代吗啉的非对映选择性合成

  摘要：

  在顺序Pd（0）催化的Tsuji–Trost / Fe（III）催化的杂环化作用下，已从乙烯基环氧乙烷和氨基醇实现了各种取代吗啉的非对映选择性合成。使用相同的策略，获得了2,6-，2,5-和2,3-二取代的吗啉，2,5,6-和2,3,5-三取代的吗啉，收率和非对映选择性都非常好。

  DOI：

  10.1021/acs.orglett.8b03141

文献信息

• MORPHOLINE COMPOUNDS
  申请人：Casimiro-Garcia Agustin

  公开号：US20110281854A1

  公开（公告）日：2011-11-17

  Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.

  矿物皮质激素受体拮抗剂（MRa），含有这类抑制剂的药物组合物以及利用这类抑制剂治疗哺乳动物，包括人类，例如糖尿病肾病和高血压。
• A One-Pot Reaction toward the Diastereoselective Synthesis of Substituted Morpholines
  作者：Thomas Aubineau、Janine Cossy

  DOI：10.1021/acs.orglett.8b03141

  日期：2018.12.7

  The diastereoselective synthesis of various substituted morpholines has been achieved from vinyloxiranes and amino-alcohols under sequential Pd(0)-catalyzed Tsuji–Trost/Fe(III)-catalyzed heterocyclization. Using the same strategy, 2,6-, 2,5-, and 2,3-disubstituted as well as 2,5,6- and 2,3,5-trisubstituted morpholines were obtained in good to excellent yields and diastereoselectivities.

  在顺序Pd（0）催化的Tsuji–Trost / Fe（III）催化的杂环化作用下，已从乙烯基环氧乙烷和氨基醇实现了各种取代吗啉的非对映选择性合成。使用相同的策略，获得了2,6-，2,5-和2,3-二取代的吗啉，2,5,6-和2,3,5-三取代的吗啉，收率和非对映选择性都非常好。
• Identification of Morpholino-2<i>H</i>-pyrido[3,2-<i>b</i>][1,4]oxazin-3(4<i>H</i>)-ones as Nonsteroidal Mineralocorticoid Antagonists
  作者：David W. Piotrowski、Kentaro Futatsugi、Agustin Casimiro-Garcia、Liuqing Wei、Matthew F. Sammons、Michael Herr、Wenhua Jiao、Sophie Y. Lavergne、Steven B. Coffey、Stephen W. Wright、Kun Song、Paula M. Loria、Mary Ellen Banker、Donna N. Petersen、Jonathan Bauman

  DOI：10.1021/acs.jmedchem.7b01515

  日期：2018.2.8

  A novel series of morpholine-based non steroidal mineralocorticoid receptor antagonists is reported. Starting from a pyrrolidine HTS hit 9 that possessed modest potency but excellect selectivity versus related nuclear hormone receptors, a series of libraries led to identification of morpholine lead 10. After further optimization, cis disubstituted morpholine 22 was discovered, which showed a 45-fold boost in binding affinity and corresponding functional potency compared to 13. While 22 had high clearance in rat, it provided sufficient exposure at high doses to favorably assess in vivo efficacy (increased urinary Na+/K+ ratio) and safety. In contrast to rat, the dog and human MetID and PK profiles of 22 were adequate, suggesting that it could be suitable as a potential clinical asset.