2-(4-Chlorophenyl)-3-methoxybenzoic acid | 215115-15-4

• 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-Chlorophenyl)-3-methoxybenzoic acid
• CAS: 215115-15-4
• 化学式: C₁₄H₁₁ClO₃
• 分子量: 262.693
• InChiKey: IPVCHWJLAAYFRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-Chlorophenyl)-3-methoxybenzoic acid 在 叠氮磷酸二苯酯 、 对甲苯磺酸 、 三乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 二苯醚 、 苯 为溶剂， 生成 8-(4-chlorophenyl)-7-methoxy-2-methyl-N,N-dipropylquinolin-4-amine
  参考文献：
  名称：

  Synthesis and SAR of 8-Arylquinolines as potent corticotropin-Releasing factor1 (CRF1) receptor antagonists

  摘要：

  A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF1 receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[l,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF1 antagonists with lower lipophilicity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00684-x
• 作为产物：
  描述：

  2-溴-3-甲氧基苯甲酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium hydroxide 、 potassium phosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 2-(4-Chlorophenyl)-3-methoxybenzoic acid
  参考文献：
  名称：

  Diaminoindanes as Microsomal Triglyceride Transfer Protein Inhibitors

  摘要：

  The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC50 values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

  DOI：

  10.1021/jm010294e

文献信息

• [EN] CRF ANTAGONISTIC QUINO- AND QUINAZOLINES<br/>[FR] QUINO- ET QUINAZOLINES ANTAGONISTES CRF
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1998047874A1

  公开（公告）日：1998-10-29

  (EN) This invention concerns compounds of formula (I), including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R1 is C1-6alkyl, NR6R7, OR6 or SR7; R2 is hydrogen, C1-6alkyl, C1-6alkyloxy or C1-6alkylthio; R3 is Ar1 or Het1; R4 and R5 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, cyano, nitro, amino, and mono- or di(C1-6alkyl)amino; R6 is hydrogen, C1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfoxy or C1-6alkylthio; R7 is hydrogen, C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxy-C1-6alkyl or C1-6alkyloxyC1-6alkyl; R6 is C1-8alkyl, mono- or di(C3-6cycloalkyl)-methyl, Ar2CH2, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, C3-6alkenyl, thienylmethyl, furanylmethyl, C1-6alkylthioC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, C1-6alkylcarbonylC1-6alkyl; or R6 and R7 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C1-6alkyl or C1-6alkyloxyC1-6alkyl; and Ar1 and Ar2 are each optionally substituted phenyl; and Het1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).(FR) La présente invention concerne des composés représentés par la formule (I) comprenant des stéréoisomères et les formes de sels d'addition acides pharmaceutiquement acceptables de ceux-ci, dans laquelle R1 représente C1-6alkyle, NR6R7, OR6 ou SR7; R2 représente hydrogène, C1-6alkyle, C1-6alkyloxy ou C1-6alkylthio; R3 représente Ar1 or Het1; R4 et R5 sont chacun sélectionnés indépendamment dans le groupe hydrogène, halo, C1-6alkyle, C1-6alkyloxy, trifluorométhyl, cyano, nitro, amino, et mono- ou di(C1-6alkyle)amino; R6 représente hydrogène, C1-6alkyle, C1-6alkylsulfonyl, C1-6alkylsulfoxy ou C1-6alkylthio; R7 représente hydrogène, C1-8alkyle, mono- ou di(C3-6cyclo-alkyle)méthyl, C3-6cycloalkyl, C3-6alcényl, hydroxyC1-6alkyle, C1-6alkylcarbonyloxyC1-6alkyle ou C1-6alkyloxyC1-6alkyle; R6 représente C1-8alkyle, mono- ou di(C3-6cycloalkyl)-méthyl, Ar2CH2, C1-6alkyloxyC1-6alkyle, hydroxyC1-6alkyle, C3-6alcényle, thiénylméthyl, furanylméthyl, C1-6alkylthioC1-6alkyle, mono ou di(C1-6alkyle)aminoC1-6alkyle, di(C1-6alkyle)amino, C1-6alkylcarbonylC1-6alkyle; ou R6 et R7 pris ensemble avec l'atome d'azote auquel ils sont liés peuvent former un pyrrolidinyl, un pipéridinyl, un homopipéridinyl ou un groupe morpholinyl, éventuellement substitué avec C1-6alkyle ou C1-6alkyloxyC1-6alkyle; et Ar1 et Ar2 représentent chacun un phényl éventuellement substitué; Het1 représente un pyridinyl éventuellement substitué; présentant des propriétés antagonistes de récepteur CFR. La présente invention concerne également des compositions pharmaceutiques contenant lesdits composés comme ingrédients actifs ainsi que des procédés de traitement d'affections liées à l'hypersécrétion de CRF telles que la dépression, l'anxiété, l'abus de substance, en administrant une quantité efficace d'un composé représenté par la formule (I).

  本发明涉及化合物(I)的公式，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1为C1-6烷基，NR6R7，OR6或SR7; R2为氢，C1-6烷基，C1-6烷氧基或C1-6烷硫基; R3为Ar1或Het1; R4和R5各自独立地选择自氢，卤素，C1-6烷基，C1-6烷氧基，三氟甲基，氰基，硝基，氨基和单个或双(C1-6烷基)氨基; R6为氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷氧基或C1-6烷硫基; R7为氢，C1-8烷基，单个或双(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基; R6为C1-8烷基，单个或双(C3-6环烷基)-甲基，Ar2CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩基甲基，呋喃基甲基，C1-6烷硫基C1-6烷基，单个或双(C1-6烷基)氨基C1-6烷基，双(C1-6烷基)氨基，C1-6烷基羰基C1-6烷基; 或R6和R7与它们连接的氮原子一起可以形成一个吡咯烷基，哌嗪基，同源哌嗪基或吗啡啉基，可选地取代C1-6烷基或C1-6烷氧基C1-6烷基; Ar1和Ar2各自为可选取代的苯基; Het1为可选取代的吡啶基; 具有CRF受体拮抗作用; 包含这样的化合物作为活性成分的药物组合物; 通过给予公式(I)化合物的有效量来治疗与CRF过度分泌相关的疾病，如抑郁症、焦虑症、物质滥用的方法。
• CRF antagonistic quino- and quinazolines
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20040121998A1

  公开（公告）日：2004-06-24

  This invention concerns compounds of formula 1 including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R 1 is C 1-6 alkyl, NR 6 R 7 , OR 6 or SR 7 ; R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkyloxy or C 1-6 alkylthio; R 3 is Ar 1 or Het 1 ; R 4 and R 5 are each independently selected from hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, cyano, nitro, amino, and mono- or di(C 1-6 alkyl)amino; R 6 is hydrogen, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfoxy or C 1-6 alkylthio; R 7 is hydrogen, C 1-8 alkyl, mono- or di(C 3-6 cyclo-alkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxy-C 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; R 6 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)-methyl, Ar 2 CH 2 , C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 alkenyl, thienylmethyl, furanylmethyl, C 1-6 alkylthioC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylC 1-6 alkyl; or R 6 and R 7 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; and Ar 1 and Ar 2 are each optionally substituted phenyl; and Het 1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及式1的化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是C1-6烷基，NR6R7，OR6或SR7; R2是氢，C1-6烷基，C1-6烷氧基或C1-6烷基硫基; R3是Ar1或Het1; R4和R5各自独立地选自氢，卤素，C1-6烷基，C1-6烷氧基，三氟甲基，氰基，硝基，氨基，和单烷基或双烷基（C1-6）氨基; R6是氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷基亚磺酰基或C1-6烷基硫基; R7是氢，C1-8烷基，单烷基或双（C3-6）环烷基甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基; R6是C1-8烷基，单烷基或双（C3-6）环烷基甲基，Ar2CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩甲基，呋喃甲基，C1-6烷基硫基C1-6烷基，单烷基或双（C1-6）氨基C1-6烷基，双（C1-6）氨基，C1-6烷基羧酰基C1-6烷基; 或R6和R7与它们连接的氮原子一起可以形成吡咯烷基，哌啶基，同型哌啶基或吗啉基，可选地取代C1-6烷基或C1-6烷氧基C1-6烷基; Ar1和Ar2各自是可选地取代的苯基; Het1是可选地取代的吡啶基; 具有CRF受体拮抗性能的制剂，包含这样的化合物作为活性成分; 通过给予式（I）化合物的有效量来治疗与CRF的过度分泌相关的疾病，例如抑郁症，焦虑症，物质滥用等的方法。
• CRF antagonistic quino-and quinazolines
  申请人：——

  公开号：US20030119818A1

  公开（公告）日：2003-06-26

  This invention concerns compounds of formula 1 including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, wherein R 1 is C 1-6 alkyl, NR 6 R 7 , OR 6 or SR 7 ; R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkyloxy or C 1-6 alkylthio; R 3 is Ar 1 or Het 1 ; R 4 and R 5 are each independently selected from hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, cyano, nitro, amino, and mono- or di(C 1-6 alkyl)amino; R 6 is hydrogen, C 1-6 alkyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfoxy or C 1-6 alkylthio; R 7 is hydrogen, C 1-8 alkyl, mono- or di(C 3-6 cyclo-alkyl)methyl, C 3-6 cycloalkyl, C 3-6 alkenyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyloxy-C 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; R 6 is C 1-8 alkyl, mono- or di(C 3-6 cycloalkyl)-methyl, Ar 2 CH 2 , C 1-6 alkyloxyC 1-6 alkyl, hydroxyC 1-6 alkyl, C 3-6 alkenyl, thienylmethyl, furanylmethyl, C 1-6 alkylthioC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)amino, C 1-6 alkylcarbonylC 1-6 alkyl; or R 6 and R 7 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C 1-6 alkyl or C 1-6 alkyloxyC 1-6 alkyl; and Ar 1 and Ar 2 are each optionally substituted phenyl; and Het 1 is optionally substituted pyridinyl; having CRF receptor antagonistic properties; pharmaceutical compositions containing such compounds as active ingredients; methods of treating disorders related to hypersecretion of CRF such as depression, anxiety, substance abuse, by administering an effective amount of a compound of formula (I).

  本发明涉及公式1的化合物，包括其立体异构体和药学上可接受的酸加成盐形式，其中R1是C1-6烷基，NR6R7，OR6或SR7；R2是氢，C1-6烷基，C1-6烷氧基或C1-6烷硫基；R3是Ar1或Het1；R4和R5各自独立地选自氢，卤素，C1-6烷基，C1-6烷氧基，三氟甲基，氰基，硝基，氨基，以及单烷基或二烷基氨基的C1-6；R6是氢，C1-6烷基，C1-6烷基磺酰基，C1-6烷基磺酸氧基或C1-6烷基硫基；R7是氢，C1-8烷基，单烷基或二(C3-6环烷基)甲基，C3-6环烷基，C3-6烯基，羟基C1-6烷基，C1-6烷基羧酸酯-C1-6烷基或C1-6烷氧基C1-6烷基；R6是C1-8烷基，单烷基或二(C3-6环烷基)-甲基，Ar2CH2，C1-6烷氧基C1-6烷基，羟基C1-6烷基，C3-6烯基，噻吩基甲基，呋喃基甲基，C1-6烷硫基C1-6烷基，单烷基或二烷基氨基C1-6烷基，二烷基氨基，C1-6烷基羧酰基C1-6烷基；或R6和R7连同它们所连接的氮原子可以形成吡咯烷基，哌啶基，同型哌啶基或吗啉基，可选择地用C1-6烷基或C1-6烷氧基C1-6烷基取代；Ar1和Ar2各自是可选择地取代的苯基；Het1是可选择地取代的吡啶基；具有CRF受体拮抗作用；含有这种化合物作为活性成分的药物组合物；通过给予公式(I)化合物的有效量治疗与CRF过度分泌相关的疾病，例如抑郁症，焦虑症，物质滥用。
• Amide compounds
  申请人：——

  公开号：US20040157866A1

  公开（公告）日：2004-08-12

  The present invention relates to compounds of the formula (I) wherein X 1 is wherein R 1 , R 2 and R 10 are independently hydrogen or a suitable substituent; R 11 and R 12 are independently hydrogen or a suitable substituent; R is unsaturated 5 to 6-membered heteromonocyclic group; A is direct bond or —NH—; X 2 is monocyclic arylene, unsaturated 5 to 6-membered heteromonocyclic group or cycloalkenylene; Y is bivalent group selected from ethylene, trimethylene and vinylene, wherein CH 2 is optionally replaced by NH or O, and CH is optionally replaced by N; and Z is —(CH 2 ) n —, —CO—(CH 2 ) m —, —CH═CH— or —CO—NH—, wherein n is 1, 2 or 3 and m is 1 or 2, or a salt thereof. The compounds of the present invention inhibit apolipoprotein B (Apo B) secretion and are useful as a medicament for prophylactic and treatment of diseases or conditions resulting from elevated circulating levels of Apo B. 1

  本发明涉及公式（I）的化合物，其中X1为R1，R2和R10分别为氢原子或适当的取代基；R11和R12分别为氢原子或适当的取代基；R为不饱和的5至6元杂环单环基；A为直接键或—NH—；X2为单环芳烃，不饱和的5至6元杂环单环基或环烯基；Y为乙烯基，三亚甲基或乙烯基中选择的双价基团，其中CH2可以被NH或O替代，CH可以被N替代；Z为—（CH2）n—，—CO—（CH2）m—，—CH=CH—或—CO—NH—，其中n为1、2或3，m为1或2，或其盐。本发明的化合物抑制载脂蛋白B（Apo B）的分泌，并可用作预防和治疗由于Apo B循环水平升高而导致的疾病或病症的药物。
• CRF ANTAGONISTIC QUINO- AND QUINAZOLINES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0977737A1

  公开（公告）日：2000-02-09