methyl 2-(3-(hydroxy-phenyl-methyl)-phenyl)-propionate | 138682-99-2

• 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: methyl 2-(3-(hydroxy-phenyl-methyl)-phenyl)-propionate
• 英文别名: Methyl 2-[3-(phenylhydroxymethyl)phenyl]propionate；methyl 2-[3-[hydroxy(phenyl)methyl]phenyl]propanoate
• CAS: 138682-99-2
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: LFBOBZGAIBKWDK-UHFFFAOYSA-N

物化性质

• 沸点：
  392.3±32.0 °C(Predicted)
• 密度：
  1.139±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  methyl 2-(3-(hydroxy-phenyl-methyl)-phenyl)-propionate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以0.78 g的产率得到二氢酮洛芬
  参考文献：
  名称：

  2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors

  摘要：

  The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNS chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.

  DOI：

  10.1021/jm049082i
• 作为产物：
  描述：

  酮基布洛芬 在 palladium on activated charcoal 硫酸 、 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 methyl 2-(3-(hydroxy-phenyl-methyl)-phenyl)-propionate
  参考文献：
  名称：

  2-Arylpropionic CXC Chemokine Receptor 1 (CXCR1) Ligands as Novel Noncompetitive CXCL8 Inhibitors

  摘要：

  The CXC chemokine CXCL8/IL-8 plays a major role in the activation and recruitment of polymorphonuclear (PMN) cells at inflammatory sites. CXCL8 activates PMNs by binding the seven-transmembrane (7-TM) G-protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2). (R)-Ketoprofen (1) was previously reported to be a potent and specific noncompetitive inhibitor of CXCL8-induced human PMNS chemotaxis. We report here molecular modeling studies showing a putative interaction site of 1 in the TM region of CXCR1. The binding model was confirmed by alanine scanning mutagenesis and photoaffinity labeling experiments. The molecular model driven medicinal chemistry optimization of 1 led to a new class of potent and specific inhibitors of CXCL8 biological activity. Among these, repertaxin (13) was selected as a clinical candidate drug for prevention of post-ischemia reperfusion injury.

  DOI：

  10.1021/jm049082i

文献信息

• Synthesis and Thromboxane A2 Antagonistic Activity of ((1-Aryl(or Benzyl)-1-(benzenesulfonamido)methyl)phenyl)alkanoic Acid Derivatives.
  作者：Shuniciro SAKURAI、Nobuo OGAWA、Tomio SUZUKI、Ken-ichi KATO、Tetsuo OHASHI、Shingo YASUDA、Hideo KATO、Yasuo ITO

  DOI：10.1248/cpb.44.765

  日期：——

  In order to find new antiasthematic and antithrombotic agents, various [[1-aryl(or benzyl)-1-(benzenesulfonamido)methyl]phenyl]alkanoic acids derivatives were synthesized. Evaluation of these compounds for thromboxane A2 (TXA2) antagonistic activities indicated that 4-[4-[(4-chlorobenzenesulfonamido)phenylmethyl]phenyl]butyric acid (6h), 4-[4-[1-(4-chlorobenzenesulfonamido)-2-phenylethyl]butyric acid (6y) and many other compounds have potent inhibitory effects on U-46619-induced guinea-pig platelet aggregation. No significant difference in the inhibitory effect between (+)-6h and its antipode could be detected, although (+)-6y was about 10 times more potent than (-)-6y. The pKb values of 6h and 6y were estimated to be 8.9 and 10, respectively on U-46619-induced contraction of guinea-pig trachea as a pharmacological measure of TXA2 antagonistic activity. These compounds also showed potent inhibitory effects on U-46619-induced bronchoconstriction in guinea-pig after oral administration in vivo. They were also evaluated for other related pharmacological effects involving the arachidonic acid cascade. It ws found that these compounds possess TXA2 synthase inhibitory activity together with TXA2 antagonistic activity, and 6h also possesses weak leukotriene D4 (LTD4) antagonistic acitivity. Structure-activity relationships for TXA2 antagonistic activity of these derivatives are discussed.

  为了寻找新的抗静血和抗血栓药物，人们合成了各种[[1-芳基（或苄基）-1-（苯磺酰胺基）甲基]苯基]烷酸衍生物。对这些化合物的血栓素 A2（TXA2）拮抗活性评估表明，4-[4-[(4-氯苯磺酰胺基)苯基甲基]苯基]丁酸（6h）、4-[4-[1-(4-氯苯磺酰胺基)-2-苯基乙基]丁酸（6y）和许多其他化合物对 U-46619 诱导的豚鼠血小板聚集具有强效抑制作用。尽管(+)-6y 的抑制作用是(-)-6y 的 10 倍左右，但(+)-6h 与其反式之间的抑制作用并无明显差异。在 U-46619 诱导的豚鼠气管收缩中，作为 TXA2 拮抗活性的药理学指标，6h 和 6y 的 pKb 值分别为 8.9 和 10。这些化合物在体内口服后，对 U-46619 诱导的豚鼠支气管收缩也有很强的抑制作用。还对涉及花生四烯酸级联的其他相关药理作用进行了评估。结果发现，这些化合物具有 TXA2 合酶抑制活性和 TXA2 拮抗活性，6h 还具有微弱的白三烯 D4（LTD4）拮抗活性。本文讨论了这些衍生物 TXA2 拮抗活性的结构-活性关系。
• Substituted diphenylmethane derivatives as analgesic or
  申请人：Sociedad Espanola de Especialidades Farmaco-Terapeuticas S.A.

  公开号：US05204365A1

  公开（公告）日：1993-04-20

  A compound of formula I or a pharmaceutically acceptable salt thereof ##STR1## where --R.sub.1 is hydrogen or methyl; --X-- is --CO-- or --CH.sub.2 --; --Y-- is >CH--A or its vinylogous group >C.dbd.CH--CH.sub.2 --A, wherein --A is a --NR.sub.4 R.sub.5 group, where each R.sub.4 and R.sub.5, equal or different between them, is C.sub.1 -C.sub.4 -alkyl or a phenyl-substituted C.sub.1 -C.sub.4 -alkyl; or --A is the N-radical of a 5- or 6-membered, uncharged (i.e. neither quaternary nor zwitterionic) monocyclic ring, either aromatic or non-aromatic, said ring containing one N atom, two N atoms, three N atoms or an N/O pair of atoms, all other atoms in the ring being carbon, and said ring being optionally mono- or di-substituted by groups selected from C.sub.1 -C.sub.4 -alkyl, benzyl, 2-furanylmethyl and 2-thienylmethyl; --R.sub.2 is hydrogen or a radical C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, di-(C.sub.1 -C.sub.4 -alkyl)amino, nitro or halogen, said radical being attached at the 2, 3 or 4 substitution positions of the phenyl ring; --R.sub.3 is hydrogen, phenyl, C.sub.1 -C.sub.10 -alkyl, a C.sub.3 -C.sub.10 -alkenyl or alkynyl group with the double or triple bond non-adjacent to the O--C bond, --(CH.sub.2 CH.sub.2 O).sub.n --H with n=1, 2 or 3, --(CHOH).sub.m --H with m=2, 3 or 4, or --when X is CO-- the radical I-bis where Y is defined as above-useful as analgesic or anti-inflammatory agents.

  化合物I式或其药学上可接受的盐的公式如下：##STR1## 其中，-R.sub.1为氢或甲基；-X-为-CO-或-CH.sub.2-；-Y-为>CH-A或其乙烯基类>C.dbd.CH-CH.sub.2-A，其中-A为-NR.sub.4R.sub.5基团，其中每个R.sub.4和R.sub.5，相等或不同，为C.sub.1-C.sub.4-烷基或苯基取代的C.sub.1-C.sub.4-烷基；或-A为5-或6-成员的、未带电的（即既非季铵盐也非离子缔合物）单环芳香族或非芳香族环的N-基团，该环含有一个N原子、两个N原子、三个N原子或一个N/O原子对，环中的其他原子均为碳，并且该环可选地被来自C.sub.1-C.sub.4-烷基、苯甲基、2-呋喃甲基和2-噻吩甲基的基团单取代或双取代；-R.sub.2为氢或基团C.sub.1-C.sub.4-烷基、C.sub.1-C.sub.4-烷氧基、二（C.sub.1-C.sub.4-烷基）氨基、硝基或卤素，该基团附加在苯环的2、3或4位取代位置；-R.sub.3为氢、苯基、C.sub.1-C.sub.10-烷基、双键或三键与O-C键不相邻的C.sub.3-C.sub.10-烯基或炔基，-(CH.sub.2CH.sub.2O).sub.n-H，其中n=1、2或3，-(CHOH).sub.m-H，其中m=2、3或4，或当X为CO-时，基团I-bis，其中Y如上所定义-作为镇痛剂或抗炎药物有用。
• Substituted diphenylmethane derivatives as analgesic or anti-inflammatory agents
  申请人：SOCIEDAD ESPANOLA DE ESPECIALIDADES FARMACO-TERAPEUTICAS, S.A.

  公开号：EP0458160A2

  公开（公告）日：1991-11-27

  A compound of formula I or a pharmaceutically acceptable salt thereof where -R₁ is hydrogen or methyl; -X- is -CO- or -CH₂-; -Y- is >CH-A or its vinylogous group >C=CH-CH₂-A, wherein -A is a -NR₄R₅ group, where each R₄ and R₅, equal or different between them, is C₁-C₄-alkyl or a phenyl-substituted C₁-C₄-alkyl; or -A is the N-radical of a 5- or 6-membered, uncharged (i.e. neither quaternary nor zwitterionic) monocyclic ring, either aromatic or non-aromatic, said ring containing one N atom, two N atoms, three N atoms or an N/O pair of atoms, all other atoms in the ring being carbon, and said ring being optionally mono- or di-substituted by groups selected from C₁-C₄-alkyl, benzyl, 2-furanylmethyl and 2-thienylmethyl; -R₂ is hydrogen or a radical C₁-C₄-alkyl, C₁-C₄-alkoxy, di-(C₁-C₄-alkyl)amino, nitro or halogen, said radical being attached at the 2, 3 or 4 substitution positions of the phenyl ring; -R₃ is hydrogen, phenyl, C₁-C₁₀-alkyl, a C₃-C₁₀-alkenyl or alkynyl group with the double or triple bond non-adjacent to the O-C bond, -(CH₂CH₂O)n-H with n = 1, 2 or 3, -(CHOH)m-H with m = 2, 3 or 4, or -when X is CO-the radical I-bis where Y is defined as above.

  式 I 的化合物或其药学上可接受的盐 其中 -R₁是氢或甲基； -X-是-CO-或-CH₂-； -Y-是 >CH-A 或其乙烯基 >C=CH-CH₂-A、 其中-A 是-NR₄R₅基团，其中每个 R₄ 和 R₅ 之间，无论相等或不同，都是 C₁-C₄ 烷基或苯基取代的 C₁-C₄ 烷基；或-A 是 5 或 6 元、不带电（即所述环含有一个 N 原子、两个 N 原子、三个 N 原子或一对 N/O 原子，环中所有其他原子均为碳原子，所述环可任选被选自 C₁-C₄-烷基、苄基、2-呋喃基甲基和 2-噻吩基甲基的基团单取代或二取代； -R₂是氢或 C₁-C₄-烷基、C₁-C₄-烷氧基、二(C₁-C₄-烷基)氨基、硝基或卤素基，所述基连接在苯基环的 2、3 或 4 个取代位置上； -R₃是氢、苯基、C₁-C₁₀-烷基、C₃-C₁₀-烯基或炔基，其双键或三键与 O-C 键不相邻、-(CH₂CH₂O)n-H，n = 1、2 或 3；-(CHOH)m-H，m = 2、3 或 4；或-当 X 为 CO 时-基 I-双，其中 Y 定义如上。
• 2-Arylpropensäuren und ihre Verwendung bei der Herstellung von S-Ketoprofen
  申请人：BAYER AG

  公开号：EP0529444B1

  公开（公告）日：1997-04-16
• US5204365A
  申请人：——

  公开号：US5204365A

  公开（公告）日：1993-04-20