Meraxin | 849776-05-2

• 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: Meraxin
• 英文别名: R-(-)-2-[(4^'-trifluoromethanesulfonyloxy)phenyl]-N-methanesulfonyl propionamide；(R)-(-)-2-[(4'-trifluoromethanesulfonyloxy)phenyl]-N-methanesulfonyl propionamide；R(-)-2-[(4'-trifluoromethanesulfonyloxy)phenyl]-N-methanesulfonyl propionamide；ladarixin；DF2156A；[4-[(2R)-1-(methanesulfonamido)-1-oxopropan-2-yl]phenyl] trifluoromethanesulfonate
• CAS: 849776-05-2
• 化学式: C₁₁H₁₂F₃NO₆S₂
• 分子量: 375.347
• InChiKey: DDLPYOCJHQSVSZ-SSDOTTSWSA-N

物化性质

• 溶解度：
  DMSO：100 mg/mL（266.43 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  9

制备方法与用途

一种新型的别构非竞争性双重CXCR1/2抑制剂，在体外能够以半数有效浓度（IC50）为0.7纳摩尔抑制人多形核中性粒细胞向CXCL8迁移。

反应信息

• 作为反应物：
  描述：

  Meraxin 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 生成 DF 2156A
  参考文献：
  名称：

  [EN] 2-PHENYLPROPIONIC ACID DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  [FR] DERIVES DE L'ACIDE 2-PHENYLPROPIONIQUE ET COMPOSITIONS PHARMACEUTIQUES CONTENANT LESDITS DERIVES

  摘要：

  公开号：

  WO2005090295A3
• 作为产物：
  描述：

  (R)-2-(4-hydroxyphenyl)propionic acid methyl ester 在 盐酸 、 溶剂黄146 、 二异丙胺 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 23.5h， 生成 Meraxin
  参考文献：
  名称：

  Predicting Human Serum Albumin Affinity of Interleukin-8 (CXCL8) Inhibitors by 3D-QSPR Approach

  摘要：

  A novel class of 2-(R)-phenylpropionamides has been recently reported to inhibit in vitro and in vivo interleukin-8 (CXCL8)-induced biological activities, These CXCL8 inhibitors are derivatives of phenylpropionic nonsteroidal antiinflammatory drugs (NSAIDs), high-affinity ligands for site II of human serum albumin (HSA). Up to date, only a limited number of in silico models for the prediction of albumin protein binding are available. A three-dimensional quantitative structure-property relationship (3D-QSPR) approach was used to model the experimental affinity constant (K-i) to plasma proteins of 37 structurally related molecules, using physicochemical. and 3D-pharmacophoric descriptors. Molecular docking studies highlighted that training set molecules preferentially bind site II of HSA. The obtained model shows satisfactory statistical parameters both in fitting and predicting validation. External validation confirmed the statistical significance of the chemometric model, which is a powerful tool for the prediction of HSA binding in virtual libraries of structurally related compounds.

  DOI：

  10.1021/jm049227l

文献信息

• 2-phenylpropionic acid derivatives and pharmaceutical compositions containing them
  申请人：——

  公开号：US08039656B2

  公开（公告）日：2011-10-18

  4-(trifluoromethanesulfonyloxyphenyl)propionic acid derivatives and pharmaceutical composition containing such compounds are useful in inhibiting the chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from said activation. Notably, these metabolites are devoid of cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrophil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.

  4-(三氟甲磺酰氧基苯基)丙酸衍生物及含有此类化合物的药物组合物可用于抑制由白细胞介素-8（IL-8）与CXCR1和CXCR2膜受体相互作用引起的中性粒细胞（PMN白细胞）趋化活化。这些化合物用于预防和治疗由该活化引起的病理情况。值得注意的是，这些代谢物不具有环氧化酶抑制活性，特别适用于治疗中性粒细胞依赖性病理情况，例如银屑病、溃疡性结肠炎、黑色素瘤、慢性阻塞性肺病（COPD）、大疱性类天疱疮、类风湿性关节炎、特发性纤维化、肾小球肾炎以及预防和治疗缺血再灌注引起的损伤。
• 2-aryl-propionic acids and pharmaceutical compositions containing them
  申请人：Dompe PHA.R.MA S.p.A.

  公开号：US08063242B2

  公开（公告）日：2011-11-22

  (R) and (S) 2-Aryl-propionic acids, and pharmaceutical compositions that contain them, are useful in inhibiting chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The acids are used for the prevention and treatment of pathologies deriving from said activation. In particular, the (R) enantiomers of said acids are lacking cyclo-oxygenase inhibition activity and are particularly useful in the treatment of neutrofil-dependent pathologies such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bollous pemphigo, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.

  (R)和(S) 2-芳基丙酸以及含有它们的制药组合物，对于抑制由Interleukin-8 (IL-8)与CXCR1和CXCR2膜受体相互作用引起的中性粒细胞（PMN白细胞）趋化激活非常有用。这些酸被用于预防和治疗由该激活引起的病理。特别是，这些酸的(R)对映体缺乏环氧化酶抑制活性，特别适用于治疗依赖于中性粒细胞的病理，例如银屑病、溃疡性结肠炎、黑色素瘤、慢性阻塞性肺疾病（COPD）、大疱性天疱疮、类风湿性关节炎、特发性纤维化、肾小球肾炎以及缺血再灌注引起的损害的预防和治疗。
• IL-8 INHIBITORS FOR USE IN THE TREATMENT OF CERTAIN UROLOGICAL DISORDERS
  申请人：Dompé farmaceutici s.p.a.

  公开号：EP3117835A1

  公开（公告）日：2017-01-18

  The present invention relates to IL-8 inhibitor compounds, preferably dual CXCR1/CXCR2 receptor inhibitors, useful in the treatment and/or prevention of interstitial cystitis / painful bladder syndrome (IC/PBS) and/or over active bladder (OAB), also including IC/PBS and/or OAB induced by anticancer therapy. Methods of treatment and/or prevention, combinations and kits comprising said IL-8 inhibitors are also covered therein.

  本发明涉及IL-8抑制剂化合物，最好是CXCR1/CXCR2双重受体抑制剂，可用于治疗和/或预防间质性膀胱炎/膀胱疼痛综合征（IC/PBS）和/或膀胱过度活动症（OAB），也包括抗癌治疗诱发的IC/PBS和/或OAB。 其中还包括由所述IL-8抑制剂组成的治疗和/或预防方法、组合物和试剂盒。
• IL-8 INIHIBITORS FOR USE IN THE TREATMENT OF SOME UROLOGICAL DISORDERS
  申请人：Dompé farmaceutici S.p.A.

  公开号：EP3342407A1

  公开（公告）日：2018-07-04

  The present invention relates to IL-8 inhibitor compounds for use in the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia.

  本发明涉及用于治疗慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）和良性前列腺增生的IL-8抑制剂化合物。
• Method for treating cancer using dual antagonists of CXCR1 and CXCR2
  申请人：Syntrix Biosystems, Inc.

  公开号：US10561676B2

  公开（公告）日：2020-02-18

  What is described is a method for treating cancer in a patient in need of such treatment through the use of a dual CXCR1/2 antagonist by administering a therapeutically effective amount of a dual CXCR1/2 antagonist, or pharmaceutical compositions thereof, either alone as monotherapy, or in combination with at least one other anticancer therapy.

  所描述的是一种通过使用双重CXCR1/2拮抗剂治疗需要这种治疗的患者癌症的方法，其方法是施用治疗有效量的双重CXCR1/2拮抗剂或其药物组合物，既可以单独作为单一疗法，也可以与至少一种其他抗癌疗法联合使用。