ethyl 4-(diethoxyphosphorylmethyl)benzoate | 71441-08-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(diethoxyphosphorylmethyl)benzoate
• 英文别名: Diethyl (4-carbethoxybenzyl)phosphonate
• CAS: 71441-08-2
• 化学式: C₁₄H₂₁O₅P
• 分子量: 300.292
• InChiKey: OFUCEQWVGVURAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-(diethoxyphosphorylmethyl)benzoate 生成 ethyl 4-[(E)-2-bicyclo[2.2.1]heptanylidenemethyl]benzoate
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  对甲基苯甲酸乙酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 6.0h， 生成 ethyl 4-(diethoxyphosphorylmethyl)benzoate
  参考文献：
  名称：

  合成氨基甲基单烷基次膦酸酯的简便方法

  摘要：

  从易于获得的4-甲基苯甲酸（一种制备4-（氨基甲基）苄基（甲基）次膦酸乙酯的有效方法）开始（1），在该通报中报道了一种新型的氨基甲基单烷基次膦酸酯。重要的步骤涉及通过POCl 3对膦酸酯进行选择性单氯化并形成膦酰氯，然后将CH 3 MgBr亲核加成到酰氯中间体中。

  DOI：

  10.1002/cjoc.201200123

文献信息

• [EN] COMPOUNDS AND THEIR USE TO TREAT HISTAMINE H3 RELATED DISORDERS<br/>[FR] COMPOSÉS ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS AU RÉCEPTEUR H3 DE L'HISTAMINE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013027001A1

  公开（公告）日：2013-02-28

  The present invention provides compounds of formula (1) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, m, n, p, q, Q1, Q2, Q3, Q4, Q5, Q6, X1, X2, X3, X4, A1 and L1, are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（1）的化合物及其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17、R18、R19、R20、m、n、p、q、Q1、Q2、Q3、Q4、Q5、Q6、X1、X2、X3、X4、A1和L1如规范中所定义，其制备方法，含有它们的药物组合物以及它们在治疗中的用途。
• 4-(Pyrrolidinyl)methoxybenzoic Acid Derivatives as a Potent, Orally Active VLA-4 Antagonist
  作者：Jun Chiba、Shin Iimura、Yoshiyuki Yoneda、Yuichi Sugimoto、Takao Horiuchi、Fumito Muro、Yuichi Ochiai、Tomomi Ogasawara、Masao Tsubokawa、Yutaka Iigou、Gensuke Takayama、Tomoe Taira、Yoshimi Takata、Mika Yokoyama、Tohru Takashi、Atsushi Nakayama、Nobuo Machinaga

  DOI：10.1248/cpb.54.1515

  日期：——

  A novel series of benzoic acid derivatives as VLA-4 antagonists were synthesized. Optimization, focusing on activity and lipophilicity needed for cell permeability, resulted in the identification of 15b and 15e with good activity (IC50=1.6 nM each) and moderate lipophilicity (Log D=2.0, 1.8). Furthermore, 15e demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg.

  合成了一系列苯甲酸衍生物作为VLA-4拮抗剂。优化侧重于活性和细胞通透性所需的亲脂性，最终鉴定出活性良好（IC50分别为1.6纳摩尔）和适度亲脂性（Log D=2.0，1.8）的化合物15b和15e。此外，化合物15e在30毫克/千克口服剂量下对小鼠哮喘模型显示出疗效。
• VLA-4 inhibitor compounds
  申请人：Daiichi Pharmaceutical Co., LTD.

  公开号：US20030078249A1

  公开（公告）日：2003-04-24

  Compounds that selectively inhibit the binding of ligands to &agr;4&bgr;1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: 1 As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.

  本发明公开了选择性抑制配体与α4β1整合素（VLA-4）结合的化合物及其制备方法。在一个实施例中，本发明的化合物由式I表示： 1 作为VLA-4介导的细胞粘附的选择性抑制剂，本发明的化合物可用于治疗与该粘附相关的疾病，包括但不限于炎症和自身免疫反应、糖尿病、哮喘、银屑病、炎症性肠病、移植排斥和肿瘤转移。还公开了包含式I化合物的药物组合物、抑制VLA-4介导的细胞粘附的方法以及治疗与VLA-4介导的细胞粘附相关疾病的方法。
• New carboxamide compounds having melanin concentrating hormone antagonistic activity, pharmaceutical preparations comprising these compounds and process for their manufacture
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20040242572A1

  公开（公告）日：2004-12-02

  The present invention relates to carboxamide compounds of general formula I 1 wherein the groups and residues A, B, W, X, Y, Z, R 1 , R 2 , R 3 and k have the meanings given in claim 1. Moreover the invention relates to process for preparing the above mentioned carboxamides as well as pharmaceutical compositions containing at least one carboxamide according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及具有通式I的羧酰胺化合物 1 其中，A、B、W、X、Y、Z、R 1 、R 2 、R 3 和k的含义如权利要求1中所述。此外，本发明还涉及制备上述羧酰胺的方法以及含有至少一种根据本发明的羧酰胺的药物组合物。由于它们对MCH受体的拮抗活性，根据本发明的药物组合物适合用于治疗代谢紊乱和/或饮食紊乱，特别是肥胖症、厌食症、暴食症、糖尿病。
• Method of treatment with compounds having retinoid-like activity and
  申请人：Allergan, Inc.

  公开号：US05324840A1

  公开（公告）日：1994-06-28

  Compounds that provide non-teratogenic effects and lack irritation to the skin are shown in the formula below where the partially drawn ring signifies an aromatic ring which may be carbocyclic or heteroaromatic, 6-membered or 5-membered, and may be condensed with another ring. R.sub.1 is lower alkyl, Cl, Br, or I, R.sub.2 is H, lower alkyl, Cl, Br, or I, and R.sub.3 is lower alkyl, Cl, Br, I, or is an ether, thioether, ester, thioester, amine or substituted amine group. ##STR1##

  提供不致畸变作用且不刺激皮肤的化合物如下式所示，其中部分绘制的环表示可能是碳环或杂环，6元环或5元环，并且可能与另一个环融合。R.sub.1为较低的烷基、Cl、Br或I，R.sub.2为H、较低的烷基、Cl、Br或I，R.sub.3为较低的烷基、Cl、Br、I，或者是醚、硫醚、酯、硫酯、胺或取代胺基团。