1-(2-methoxyphenyl)-2-methylbutan-1-one | 1196852-29-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-methoxyphenyl)-2-methylbutan-1-one
• CAS: 1196852-29-5
• 化学式: C₁₂H₁₆O₂
• 分子量: 192.258
• InChiKey: WJHUYMISWHPUSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-氯甲基呋喃并[2,3-d]嘧啶-2,4-二胺 、 1-(2-methoxyphenyl)-2-methylbutan-1-one 在 三丁基膦 、 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 3.0h， 生成 5-[(Z)-2-(2'-methoxyphenyl)-3-methylpent-1-en-1-yl]-furo[2,3-d]pyrimidine-2,4-diamine 、 5-[(E)-2-(2'-methoxyphenyl)-3-methylpent-1-en-1-yl]-furo[2,3-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors

  摘要：

  To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase ( DHFR) inhibition, the E-and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 and 1.4 angstrom, respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5 angstrom) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7 and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.044
• 作为产物：
  描述：

  仲丁基锂 、 邻甲氧基苯甲酸 在 水 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 以25%的产率得到2-(sec-butyl)benzoic acid
  参考文献：
  名称：

  未保护的苯甲酸通过硅T俩的未催化CO2Li介导的SNAr反应

  摘要：

  所述烷基和芳基锂亲核芳香取代（S ñ从氟或甲氧基的AR）位移未受保护的2-氟/甲氧基羧酸进行了讨论。已经发现，位于羧基邻位C6-位的TMS基团有效地屏蔽了羧酸盐以防止亲核攻击，从而显着减少了酮的形成，并使亲核取代重新定向至C2-位。与氟取代的底物7的反应有效地进行。与此相反，使用甲氧基-官能化的苯甲酸8个得到中等产率与小号-BuLi和PhLi。这种未催化的偶联反应可直接进入联芳基化合物，大概是通过共振稳定的五价硅内酯-迈森海默络合物的中间形成，通过加成-消除序列进行的。

  DOI：

  10.1071/ch15398

文献信息

• [EN] NEW COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS RELATING THERETO<br/>[FR] NOUVEAUX COMPOSÉS, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉS CORRESPONDANTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010149684A1

  公开（公告）日：2010-12-29

  New compounds are disclosed which have utility in the treatment of a variety of metabolic related conditions in a patient. The compounds of this invention have the structure (I): wherein R1, R2, R3, n, p, q, and Ar are as defined herein, including stereoisomers, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising a compound of this invention, as well as methods relating to the use thereof in a patient in need thereof.

  本发明公开了具有结构(I)的新化合物，其在患者中治疗各种与代谢相关的病症具有实用性：其中R1、R2、R3、n、p、q和Ar如本文所定义，包括立体异构体、溶剂合物和药学上可接受的盐。还公开了包含本发明化合物的药物组合物，以及关于其在有需要的患者中使用的方法。
• BICYCLIC PYRROLE DERIVATIVES
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP1829877A1

  公开（公告）日：2007-09-05

  Compounds represented by the general formula (I), prodrugs thereof, or pharmaceutically acceptable salts of both are provided as compounds which have high DPP-IV inhibiting activity and are improved in safety, toxicity and so on: (I) wherein the solid line and dotted line between A1 and A2 represents a double bond (A1=A2) or the like; A1 is C(R4) or the like; A2 is nitrogen atom or the like; R1 is hydrogen atom, optionally substituted alkly group, or the like; R2 is hydrogen atom, optionally substituted alkyl group, or the like; R3 is hydrogen atom, halogen atom, or the like; R4 is hydrogen atom, hydroxyl, halogen atom, or the like; and Y is a group represented by the general formula (A) or the like; (A) [wherein m1 is 0, 1, 2 or 3; and the group (A) may be freed from R6 or substituted with one or two R6's which are each independently halogen atom or the like.]

  通式(I)代表的化合物、其原药或二者的药学上可接受的盐类具有较高的 DPP-IV 抑制活性，并在安全性、毒性等方面有所改善：(I) 其中 A1 和 A2 之间的实线和虚线代表双键（A1=A2）或类似物；A1 是 C(R4)或类似物；A2 是氮原子或类似物；R1 是氢原子、任选取代的烷基或类似物；R2 是氢原子、任选取代的烷基或类似物；R3 是氢原子、卤素原子或类似物；R4 是氢原子、羟基、卤素原子或类似物；Y 是通式（A）所代表的基团或类似物； (A) [其中 m1 是 0、1、2 或 3；基团 (A) 可以不含 R6，也可以被一个或两个各自独立为卤素原子或类似物的 R6 取代。］