methyl 3-hydroxy-4-(trifluoromethyl)benzoate | 126541-88-6

• 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: methyl 3-hydroxy-4-(trifluoromethyl)benzoate
• CAS: 126541-88-6
• 化学式: C₉H₇F₃O₃
• 分子量: 220.148
• InChiKey: UJBJCCNJDGUZFA-UHFFFAOYSA-N

物化性质

• 沸点：
  284.6±40.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-hydroxy-4-(trifluoromethyl)benzoate 在 N-乙基吗啉 、 sodium hydroxide 、 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 PPh₃-polystyrene 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 3-[2-(2,4-Dichloro-phenyl)-ethoxy]-N-(3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-4-ylmethyl)-4-trifluoromethyl-benzamide
  参考文献：
  名称：

  Structural Requirements for Factor Xa Inhibition by 3-Oxybenzamides with Neutral P1 Substituents:  Combining X-ray Crystallography, 3D-QSAR, and Tailored Scoring Functions

  摘要：

  The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.

  DOI：

  10.1021/jm049187l
• 作为产物：
  描述：

  4-三氟甲基苯甲酸 在 A-Kohle 、 钯 硫酸 、 氢气 、 硝酸 、 sodium nitrite 作用下， 以 甲醇 、 乙醚 、 溶剂黄146 为溶剂， 反应 3.55h， 生成 methyl 3-hydroxy-4-(trifluoromethyl)benzoate
  参考文献：
  名称：

  Giencke, Astrid; Lackner, Helmut, Liebigs Annalen der Chemie, 1990, # 6, p. 569 - 579

  摘要：

  DOI：

文献信息

• [EN] NOVEL INHIBITORS OF MAP4K1<br/>[FR] NOUVEAUX INHIBITEURS DE MAP4K1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2018215668A1

  公开（公告）日：2018-11-29

  The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.

  本发明涉及新的MAP4K1（HPK1）抑制剂，用于治疗由与MAPK激活相关的信号转导途径失调引起的疾病或病症，包括过度增殖性疾病、免疫系统功能障碍性疾病、炎症性疾病、神经系统疾病和心血管疾病。本发明进一步涉及包含相同抑制剂的药物组合物以及治疗所述疾病和病症的方法。所述抑制剂的结构式为(I)，其中A、D、E、F、R5、R6、R7、Z、环Q、n、x和y的定义如申请中所述。
• [EN] COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR TRAITER DES ÉTATS PATHOLOGIQUES ASSOCIÉS À UNE ACTIVITÉ DE STING
  申请人：IFM DUE INC

  公开号：WO2022015977A1

  公开（公告）日：2022-01-20

  This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

  本公开涉及化学实体（例如，化合物或药物可接受的盐，水合物，共晶体或化合物的药物组合），其抑制（例如，对抗）干扰素基因刺激剂（STING）。这些化学实体是有用的，例如，用于治疗在该主题（例如，人类）中增加（例如，过度）STING激活（例如，STING信号传导）对病理学和/或症状和/或病情进展有贡献的状况，疾病或障碍（例如，癌症）。本公开还涉及包含相同的组合物以及使用和制造相同的方法。
• HETEROARYLAMIDE LOWER CARBOXYLIC ACID DERIVATIVE
  申请人：Machinaga Nobuo

  公开号：US20090324581A1

  公开（公告）日：2009-12-31

  To provide a novel compound which has S1P receptor agonistic activity, exhibits excellent immunosuppressing effect, gives less adverse side effects, and can be orally administered. The invention provides a compound represented by general formula (I) (wherein A is a single bond, —O—, or —CH 2 —; R 1 represents a hydrogen atom or a C 1 -C 6 alkyl group, and V represents any one group selected from among the following groups (1) to (3): (1) -G 1 -, (2) -G 2 -N(R 2 )-G 3 -, and (3) a group represented by formula 2, wherein each of Z 1 and Z 2 represents a hydrogen atom or a C 1 -C 6 alkyl group, Z 3 represents a hydrogen or the like, Q represents —CH 2 —O— or the like, and Y represents a group represented by formula 3, a salt thereof, or a solvate thereof.

  提供一种新型化合物，具有S1P受体激动活性，表现出优异的免疫抑制效果，产生较少的不良副作用，并可口服。本发明提供一种由通式（I）表示的化合物（其中A是单键，-O-或-CH2-；R1表示氢原子或C1-C6烷基基团，V表示从以下组（1）至（3）中选择的任一组：（1）-G1-，（2）-G2-N（R2）-G3-，以及（3）由式2表示的组，其中Z1和Z2分别表示氢原子或C1-C6烷基基团，Z3表示氢或类似物，Q表示-CH2-O-或类似物，Y表示由式3表示的基团，其盐或溶剂化物。
• Partially saturated nitrogen-containing heterocyclic compound
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：US09422240B2

  公开（公告）日：2016-08-23

  There are provided compounds having a superior PHD2 inhibitory effect that are represented by general formula (I′): (in the above-mentioned general formula (I′), W, Y, R2, R3, R4, and Y4 are as described hereinabove), or pharmaceutically acceptable salts thereof.

  提供了具有优越的PHD2抑制效果的化合物，其通式表示为(I'):(在上述通式(I')中，W、Y、R2、R3、R4和Y4如上所述)，或其药学上可接受的盐。
• Intramolecular Hydroarylation of Arenes via Imidazole-Directed C–H Activation in Aqueous Methanol Using Rhodium(III) as the Catalyst and Mechanistic Study
  作者：Nilotpal Sinha、Prasenjit Mistry、Sukanya Das、Tanmoy Datta、Brindaban Roy

  DOI：10.1021/acs.joc.3c00689

  日期：2023.7.7

  A mild and greener approach for intramolecular regioselective hydroarylation is described for the efficient and elegant preparation of a number of dihydrobenzofurans and dihydrobenzo[b]thiophenes using imidazole as a directing group and Rh(III) as a catalyst. Moreover, the protocol may be extended to the formation of indoline and chromane derivatives. Deuterium scrambling experiments and characterization

  描述了一种温和、更环保的分子内区域选择性加氢芳基化方法，使用咪唑作为导向基团和 Rh(III) 作为催化剂，高效、优雅地制备多种二氢苯并呋喃和二氢苯并[b]噻吩。此外，该协议可以扩展到二氢吲哚和苯并二氢吡喃衍生物的形成。探索了氘加扰实验和分离的铑环中间体的表征，以更好地理解该机制。