3-Ethoxy-N'-hydroxypropanimid amide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-Ethoxy-N'-hydroxypropanimid amide
• 英文别名: 3-Ethoxy-N-hydroxypropanimidamide；3-ethoxy-N'-hydroxypropanimidamide
• 化学式: C₅H₁₂N₂O₂
• 分子量: 132.162
• InChiKey: PUUNZGQTFBFHIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Ethoxy-N'-hydroxypropanimid amide 在 sodium hydride 作用下， 反应 24.0h， 生成 5-[3-(2-Ethoxy-ethyl)-[1,2,4]oxadiazol-5-yl]-1,4,5,6-tetrahydro-pyrimidine; compound with trifluoro-acetic acid
  参考文献：
  名称：

  Synthesis and Biological Characterization of 1,4,5,6-Tetrahydropyrimidine and 2-Amino-3,4,5,6-tetrahydropyridine Derivatives as Selective m1 Agonists

  摘要：

  Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Asn382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.

  DOI：

  10.1021/jm960467d
• 作为产物：
  描述：

  3-乙氧基丙腈 在 盐酸羟胺 、 三乙胺 作用下， 以 乙醇 为溶剂， 生成 3-Ethoxy-N'-hydroxypropanimid amide
  参考文献：
  名称：

  Substituted 3-(1,2,4-Oxadiazol-5-yl)-5-Phenylpiperidines

  摘要：

  该发明涉及新型取代哌啶类化合物，以及其制备方法，用于治疗和/或预防疾病的用途，以及用于生产治疗和/或预防疾病的药物的用途，特别是心血管疾病和肿瘤疾病。

  公开号：

  US20120129831A1

文献信息

• SUBSTITUTED PIPERIDINES
  申请人：Heimbach Dirk

  公开号：US20100305111A1

  公开（公告）日：2010-12-02

  The invention relates to novel substituted piperidines, to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular diseases and tumour diseases.

  这项发明涉及新型取代哌啶类化合物，以及其制备方法，用于治疗和/或预防疾病，以及用于生产治疗和/或预防疾病的药物，特别是心血管疾病和肿瘤疾病。
• Substituted piperidines
  申请人：Bayer Intellectual Property GmbH

  公开号：US08202862B2

  公开（公告）日：2012-06-19

  The invention relates to compounds of the formula to processes for the preparation thereof, and to the use thereof for treatment and/or prophylaxis of cardiovascular diseases and tumour diseases.

  本发明涉及以下配方的化合物、其制备方法以及用于治疗和/或预防心血管疾病和肿瘤疾病的用途。
• HETEROARYL-SUBSTITUTED PIPERIDINES
  申请人：Heimbach Dirk

  公开号：US20120214788A1

  公开（公告）日：2012-08-23

  The invention relates to novel heteroaryl-substituted piperidines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular diseases and tumour diseases.

  本发明涉及新型杂环芳基取代的哌啶，其制备方法，以及它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是心血管疾病和肿瘤疾病。
• Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type. Synthesis and structure-activity relationships
  作者：Per Sauerberg、Jens W. Kindtler、Lone Nielsen、Malcolm J. Sheardown、Tage Honore

  DOI：10.1021/jm00106a033

  日期：1991.2

  A series of 3-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines (2a-q) were synthesized and tested for central muscarinic cholinergic receptor binding affinity by using [H-3]oxotremorine-M and [H-3]QNB as ligands and in a functional assay using guinea pig ileum. The analogues with unbranched C1-8-alkyl substituents (2a-g) were agonist, whereas the compounds with branched or cyclic substituents (2h-m) were antagonists. The alkyl ether analogues (2o-q) were also agonists but had lower receptor binding affinity than the corresponding alkyl analogues. The 3-(5-alkyl-1,2,4-oxadiazol-3-yl)-1,2,5,6-tetrahydro-1-methylpyridine analogues had only very low affinity for the central muscarinic receptors and were weak antagonists in the ileum assay. A few 3-(3-butyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydro-1-methylpyridines substituted with methyl or hydrogen in the 1-, 5-, or 6-position were synthesized and tested. N-Desmethyl analogue 7 was a potent muscarinic agonist, whereas N-desmethyl-5-methyl analogue 11 and N-methyl-6-methyl analogue 13 both were antagonists with lower muscarinic receptor affinity. The 3-(3-butyl-1,2,4-oxadiazol-5-yl)quinuclidine (17) and tropane (15) analogues were both very potent antagonists with high affinity for central muscarinic receptors. The ratio [IC50(QNB)/IC50(Oxo-M)] x 0.162 proved to be a good indicator of the efficacy of the compounds in the guinea pig ileum assay.
• SAUERBERG, PER;KINDTLER, JENS W.;NIELSEN, LONE;SHEARDOWN, MALCOLM J.;HONO+, J. MED. CHEM., 34,(1991) N, C. 687-692
  作者：SAUERBERG, PER、KINDTLER, JENS W.、NIELSEN, LONE、SHEARDOWN, MALCOLM J.、HONO+

  DOI：——

  日期：——