8-(2,6-difluorobenzyl)-5,8-dihydro-2-[4-(ethylaminocarbonylamino)phenyl]-3-(N-methyl-N-benzylaminomethyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester | 229484-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 8-(2,6-difluorobenzyl)-5,8-dihydro-2-[4-(ethylaminocarbonylamino)phenyl]-3-(N-methyl-N-benzylaminomethyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester
• 英文别名: Ethyl 8-(2,6-difluorobenzyl)-3-((benzyl(methyl)amino)methyl)-2-(4-(3-ethylureido)phenyl)-5-oxo-5,8-dihydroimidazo[1,2-a]pyrimidine-6-carboxylate；ethyl 3-[[benzyl(methyl)amino]methyl]-8-[(2,6-difluorophenyl)methyl]-2-[4-(ethylcarbamoylamino)phenyl]-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylate
• CAS: 229484-80-4
• 化学式: C₃₄H₃₄F₂N₆O₄
• 分子量: 628.679
• InChiKey: YCJOYRXLFOTOAW-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  8-(2,6-difluorobenzyl)-5,8-dihydro-2-[4-(ethylaminocarbonylamino)phenyl]-3-(N-methyl-N-benzylaminomethyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 以83%的产率得到8-(2,6-difluorobenzyl)-5,8-dihydro-2-(4-ethylaminocarbonylaminophenyl)-3-(N-methyl-N-benzylaminomethyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of homo-bivalent GnRHR ligands

  摘要：

  G protein coupled receptors (GPCRs) are important drug targets in pharmaceutical research. Traditionally, most research efforts have been devoted towards the design of small molecule agonists and antagonists. An interesting, yet poorly investigated class of GPCR modulators comprise the bivalent ligands, in which two receptor pharmacophores are incorporated. Here, we set out to develop a general strategy for the synthesis of bivalent compounds that are projected to bind to the human gonadotropin-releasing hormone receptor (GnRHR). Our results on the dimerisation of a known GnRHR antagonist, with as key step the Huisgen 1,3-cycloaddition, and their ability to bind to and antagonize GnRH-induced GnRHR stimulation, are presented here. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.04.065
• 作为产物：
  描述：

  8-(2,6-difluorobenzyl)-5,8-dihydro-3-(N-methyl-N-benzylaminomethyl)-2-(4-nitrophenyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester 在 吡啶 、 盐酸 、 铁粉 作用下， 以 乙醇 为溶剂， 生成 8-(2,6-difluorobenzyl)-5,8-dihydro-2-[4-(ethylaminocarbonylamino)phenyl]-3-(N-methyl-N-benzylaminomethyl)-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester
  参考文献：
  名称：

  一类新的有效的非肽促黄体生成激素释放激素（LHRH）拮抗剂：2-苯基咪唑并[1,2-a]嘧啶-5-酮的设计与合成。

  摘要：

  报道了新型的非肽黄体生成激素释放激素（LHRH）受体拮抗剂2-苯基咪唑并[1,2-a]嘧啶-5-酮的设计与合成。在这项研究中描述的化合物中，我们确定了具有纳摩尔体外功能拮抗作用的强效拮抗剂15b。结果可能表明，具有连接至五元环的苯基侧基的杂环5-6环系统是小分子LHRH拮抗剂支架的重要结构特征。

  DOI：

  10.1016/s0960-894x(02)00372-4

文献信息

• Nitrogen-containing heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06194419B1

  公开（公告）日：2001-02-27

  A compound of the formula: wherein one of A and D is N and the other is C, or both are N; B is N or C; m is 0-3; R1, R2 and R3 each is (i) H or (ii) a group bound via C, N, O or S; R4 is a group bound via C; R5 is H or a group bound via C or O; R6 is H or a group bound via C; R7 is a homo- or hetero-cyclic group which may be substituted; or a salt thereof possesses excellent gonadotropin-releasing hormone antagonizing activity, and is useful as a prophylactic or therapeutic agent for sex hormone-dependent diseases, and so forth.

  该式的化合物： 其中A和D中的一个是N，另一个是C，或者两者都是N；B是N或C；m为0-3；R1、R2和R3分别是(i) H或(ii) 通过C、N、O或S结合的基团；R4是通过C结合的基团；R5是H或通过C或O结合的基团；R6是H或通过C结合的基团；R7是可能被取代的同源或异源环基团；或其盐具有出色的促性腺激素释放激素拮抗活性，并且可用作性激素依赖性疾病的预防或治疗剂等。
• Preventives/remedies for alzheimer's disease
  申请人：——

  公开号：US20030134863A1

  公开（公告）日：2003-07-17

  The present invention provides an agent for the prophylaxis or treatment of Alzheimer's disease. The agent for the prophylaxis or treatment of Alzheimer's disease of the present invention containing a compound having a GnRH antagonistic action shows low toxicity and has a superior preventive and therapeutic effect on Alzheimer's disease.

  本发明提供了一种用于预防或治疗阿尔茨海默病的药剂。本发明的用于预防或治疗阿尔茨海默病的药剂含有具有GnRH拮抗作用的化合物，显示出低毒性，并对阿尔茨海默病具有卓越的预防和治疗效果。
• MEDICINAL SOLUTIONS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1374855A1

  公开（公告）日：2004-01-02

  The present invention relates to a pharmaceutical solution containing a physiologically active non-peptide substance, an organic acid and a biocompatible organic solvent, and provides a pharmaceutical solution wherein a physiologically active non-peptide substance is dissolved at a high concentration.

  本发明涉及一种含有生理活性非肽物质、有机酸和生物相容性有机溶剂的药物溶液，并提供了一种药物溶液，其中生理活性非肽物质以高浓度溶解。
• Medicinal solutions
  申请人：——

  公开号：US20040116522A1

  公开（公告）日：2004-06-17

  The present invention relates to a pharmaceutical solution containing a physiologically active non-peptide substance, an organic acid and a biocompatible organic solvent, and provides a pharmaceutical solution wherein a physiologically active non-peptide substance is dissolved at a high concentration.

  本发明涉及一种含有生理活性非肽物质、有机酸和生物相容性有机溶剂的药物溶液，并提供了一种药物溶液，其中生理活性非肽物质以高浓度溶解。
• PREVENTIVES/REMEDIES FOR ALZHEIMER'S DISEASE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1393747A1

  公开（公告）日：2004-03-03

  The present invention provides an agent for the prophylaxis or treatment of Alzheimer's disease. The agent for the prophylaxis or treatment of Alzheimer's disease of the present invention containing a compound having a GnRH antagonistic action shows low toxicity and has a superior preventive and therapeutic effect on Alzheimer's disease.

  本发明提供了一种预防或治疗阿尔茨海默病的制剂。本发明的预防或治疗阿尔茨海默病的制剂含有一种具有 GnRH 拮抗作用的化合物，毒性低，对阿尔茨海默病有很好的预防和治疗效果。