2-(4-chlorobenzoyl)-5-methoxy-benzoic acid | 934265-01-7

• 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: 2-(4-chlorobenzoyl)-5-methoxy-benzoic acid
• 英文别名: 2-(4-Chlorobenzoyl)-5-methoxybenzoic acid
• CAS: 934265-01-7
• 化学式: C₁₅H₁₁ClO₄
• 分子量: 290.703
• InChiKey: MGTMWVXZOVLVDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-chlorobenzoyl)-5-methoxy-benzoic acid 在 sodium hydride 、 sodium carbonate 、 一水合肼 、 sodium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 4-(4-chlorophenyl)-7-methoxy-2-[3-[4-[3-(acetylamino)phenyl]piperidin-1-yl]propyl]phthalazin-1(2H)-one
  参考文献：
  名称：

  4-Arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1)

  摘要：

  A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC50 = 1 nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.111
• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以63%的产率得到2-(4-chlorobenzoyl)-5-methoxy-benzoic acid
  参考文献：
  名称：

  4-Arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1)

  摘要：

  A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC50 = 1 nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.111

文献信息

• 1-AMINO-PHTHALAZINE DERIVATIVES, THE PREPARATION AND THE THERAPEUTIC USE THEREOF
  申请人：Augereau Michel Jean

  公开号：US20070099895A1

  公开（公告）日：2007-05-03

  A 1-amino-phthalazine derivative of general formula (I) wherein the substituents are as defined herein. Also disclosed are a method for preparing such compounds, intermediates for use in such method and medical treatments using the compounds of formula (I).

  通用式（I）的1-氨基邻苯二酮衍生物，其中取代基如本文所定义。还披露了制备这类化合物的方法，用于该方法的中间体以及使用式（I）化合物进行医疗治疗的方法。
• 1-amino-phthalazine derivatives, the preparation and the therapeutic use thereof
  申请人：Sanofi-Aventis

  公开号：US07423030B2

  公开（公告）日：2008-09-09

  A 1-amino-phthalazine derivative of general formula (I) wherein the substituents are as defined herein. Also disclosed are a method for preparing such compounds, intermediates for use in such method and medical treatments using the compounds of formula (I).

  本发明涉及一种一般式(I)的1-氨基菲嗪衍生物，其中取代基如本文所定义。本发明还公开了制备这种化合物的方法，用于该方法的中间体以及利用式(I)化合物进行的医学治疗。
• US7423030B2
  申请人：——

  公开号：US7423030B2

  公开（公告）日：2008-09-09
• [EN] DERIVATIVES OF 1-AMINO-ISOQUINOLINE, PREPARATION METHOD THEREOF AND USE OF SAME IN THERAPEUTICS IN THE TREATMENT OF A DYSFUNCTION ASSOCIATED WITH MCH RECEPTOR 1<br/>[FR] DERIVES DE LA 1-AMINO-ISOQUINOLINE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE DANS LE TRAITEMENT D' UN DYSFONCTIONNEMENT LIE AU RECEPTEUR 1 DE LA MCH
  申请人：SANOFI AVENTIS

  公开号：WO2007042668A1

  公开（公告）日：2007-04-19

  [EN] The invention relates to derivatives of 1-amino-isoquinoline, having general formula (I) wherein: R = H, C_1-5-alkyl, C_1-3-fluoroalkyl, C_3-6-cycloalkyl, C_1-3-alkylene-C_3-6-cycloalkyl, -C(O)-C_1-5-alkyl, -CH₂-C=CH, C_2-4-alkylene-NR_aR_b, C_1-3-alkylene-X-C_1-3-alkyl, in which X =O or SO₂; R₁ = aryl or heteroaryl which are optionally substituted; R₂ = H or group C_1-5-alkyl; R₄ = H, C_1-5-alkyl, C_1-3-fluoroalkyl, C_3-6-cycloalkyl, C_1-3-alkylene-C_3-6-cycloalkyl, C_1-3-alkylene-O-C_1-3-alkyl, C_1-3-alkylene-(OH), C_1-3-alkylene-X-C_1-3-alkyl, in which X = S, SO or SO₂, or R₄ = C_1-3-alkylene-NR_aR_b, aryl, C_1-3-alkylene-aryl, C_1-3-alkylene-O-aryl, C_1-3-alkylene-O-C_1-3-alkylene-aryl, heteroaryl or C_1-3-alkylene-heteroaryl which are optionally substituted, or R₄ = heterocycle which is optionally substituted by a group C_1-3-alkyl, -C(O)-C_1-5-alkyl, -C(O)-C_1-5-fluoroalkyl, C_1-3-alkylene-C_3-6-cycloalkyl, C_1-3-alkylene-aryl, C_1-3-alkylene-heteroaryl which are optionally substituted; R₇ = H, halogen, C_1-5-alkyl, C_1-3-fluoroalkyl, C_1-5-alkoxy, C_1-3-fluoroalkoxy, C_1-3-alkylene-(OH), -CN, -COOH, -C(O)O-C_1-3-alkyl, - NO_2, -X-C_1-3-alkyl, in which X = S, SO or SO₂, or R₇ = -NR_aR_b,_{C1-3-alkylene-NRaRb,- C(O)-NRaRb,-C(O)-C1-3-alkyl, aryl, -O-aryl or heteroaryl which are optionally substituted; Rp and R'p = H, C1-5-alkyl, or Rp and R'p together form a single bond or C1-4-alkylene; in the form of a base, an acid addition salt, a hydrate or a solvate. The invention also relates to the method of preparing said derivatives and to the use of same in therapeutics.
  [FR] L'invention concerne des dérivés de Ia 1-amino-isoquinoline de formule générale (I) dans laquelle, R = H, C1-5-alkyle, C1-3-fluoroalkyle, C3.6-cycloalkyle, C1-3-alkylene-C3.6- cycloalkyle, -C(O)-C1-5-alkyle, -CH2-C=CH, C2-4-alkylène-NRaRb, C1-3-alkylène-X-C1-3- alkyle où X =O ou SO2 ; R1 = aryle ou hétéroaryle éventuellement substitués ; R2 =H ou groupe C1-5-alkyle ; R4 = H, C1-5-alkyle, C1-3-fluoroalkyle, C3-6-cycloalkyle, C1-3- alkylène-C3-6-cycloalkyle, C1-3-alkylène-O-C1-3-alkyle, C1-3-alkylène-(OH), C1-3-alkylène- X-C1-3-alkyle où X = S, SO ou SO2, ou bien R4 = C1-3-alkylène-NRaRb, aryle, C1-3- alkylène-aryle, C1-3-alkylène-O-aryle, C1-3-alkylène-O-C1-3-alkylène-aryle, hétéroaryle ou C1-3-alkylène-hétéroaryle éventuellement substitués, ou bien R4 = hétérocycle éventuellement substitué par un groupe C1-3-alkyle, -C(O)-C1-5-alkyle, - C(0)-C1-5-fluoroalkyle, C1-3-alkylène-C3-6-cycloalkyle, C1-3-alkylène-aryle, C1-3-alkylène- hétéroaryle éventuellement substitués ; R7 = H, halogène, C1-5-alkyle, C1-3-fluoroalkyle, C1-5-alcoxy, C1-3-fluoroalcoxy, C1-3-alkylène-(OH), -CN, -COOH, -C(O)O-C1-3-alkyle, - NO2, -X-C1-3-alkyle où X = S, SO ou SO2, ou bien R7 = -NRaRb, C1-3-alkylène-NRaRb, - C(O)-NRaRb, -C(O)-C1-3-alkyle, aryle, -O-aryle ou hétéroaryle éventuellement substitués ; Rp et R'p = H, C1-5-alkyle, ou bien Rp et R'p forment ensemble une liaison simple ou C1-4-alkylène ; à l'état de base ou de sel d'addition à un acide, ainsi qu'à l'état d'hydrate ou de solvat. Procédé de préparation et application en thérapeutique.}
• 4-Arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1)
  作者：Chae Jo Lim、Soo Hee Kim、Byung Ho Lee、Kwang-Seok Oh、Kyu Yang Yi

  DOI：10.1016/j.bmcl.2011.10.111

  日期：2012.1

  A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC50 = 1 nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.