(S)-2-(4-fluorophenylsulfonamido)-4-methylpentanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-(4-fluorophenylsulfonamido)-4-methylpentanoic acid
• 英文别名: (S)-2-(4-fluoro-benzenesulfonylamino)-4-methyl-pentanoic acid；(2S)-2-[(4-fluorophenyl)sulfonylamino]-4-methylpentanoic acid
• 化学式: C₁₂H₁₆FNO₄S
• mdl: MFCD02555822
• 分子量: 289.328
• InChiKey: QBRGIJYBQSSWND-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-(4-fluorophenylsulfonamido)-4-methylpentanoic acid 生成 (S)-4-Methyl-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonylamino]-pentanoic acid
  参考文献：
  名称：

  Sulfonamide inhibitors of matrix metalloproteinases

  摘要：

  描述了磺胺类化合物，它们是基质金属蛋白酶的抑制剂，特别是基质金属蛋白酶-1和明胶酶A（72kD明胶酶）的抑制剂。还描述了使用这些化合物治疗多发性硬化症、动脉粥样硬化斑块破裂、主动脉瘤、心力衰竭、再狭窄、牙周病、角膜溃疡、烧伤、褥疮、慢性溃疡或创伤、癌症转移、肿瘤血管生成、关节炎或其他依赖白细胞组织入侵的自身免疫或炎症性疾病的方法。

  公开号：

  US05977141A1
• 作为产物：
  描述：

  L-亮氨酸 、 4-氟苯磺酰氯 在 sodium hydroxide 作用下， 以 水 为溶剂， 以43%的产率得到(S)-2-(4-fluorophenylsulfonamido)-4-methylpentanoic acid
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy

  摘要：

  AIMP2-DX2, a splicing variant of AIMP2, is up-regulated in lung cancer, possesses oncogenic activity, and results in tumorigenesis. Specifically inhibiting the interaction between AIMP2-DX2 and HSP70 to suppress AIMP2-DX2-dependent cancers with small molecules is considered a promising avenue for cancer therapeutics. Optimization of hit BC-DXI-04 (IC50 = 40.1 mu M) provided new potent sulfonamide based AIMP2-DX2 inhibitors. Among these, BC-DXI-843 showed improved inhibition against AIMP2-DX2 (IC50 = 0.92 mu M) with more than 100-fold selectivity over AIMP2 in a luciferase assay. Several binding assays indicated that this compound effectively induces cancer cell apoptosis by specifically interrupting the interaction between DX2 and HSP70, which leads to the degradation of DX2 via Siah1-mediated ubiquitination. More importantly, BC-DXI-843 demonstrated in vivo efficacy in a tumor xenograft mouse model (H460 cells) at a dosage of 50 mg/kg, suggesting it as a promising lead for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

  DOI：

  10.1021/acs.jmedchem.9b01961

文献信息

• SULFONAMIDE INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0874836A1

  公开（公告）日：1998-11-04
• US5977141A
  申请人：——

  公开号：US5977141A

  公开（公告）日：1999-11-02
• US6153612A
  申请人：——

  公开号：US6153612A

  公开（公告）日：2000-11-28
• US6297247B1
  申请人：——

  公开号：US6297247B1

  公开（公告）日：2001-10-02
• [EN] SULFONAMIDE INHIBITORS OF MATRIX METALLOPROTEINASES<br/>[FR] INHIBITEURS DE METALLOPROTINEASES MATRICIELLES A BASE DE SULFAMIDE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1997019068A1

  公开（公告）日：1997-05-29

  (EN) Sulfonamide compounds are described which are inhibitors of matrix metalloproteinases, particularly stromelysin-1 and gelatinase A (72 kD gelatinase). Also described are methods for the treatment of multiple sclerosis, atherosclerotic plaque rupture, aortic aneurism, heart failure, restenosis, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthritis, or other autoimmune or inflammatory disorders dependent upon tissue invasion by leukocytes using the compounds.(FR) L'invention a trait à des composés de sulfamide, inhibiteurs de métalloprotinéases matricielles, notamment la stromélysine-1 et la gélatinase A (gélatinase de 72 kD). Elle concerne également des méthodes faisant appel à ces composés pour le traitement de la sclérose en plaques, de la rupture de la plaque athéroscléreuse, de l'anévrisme aortique, de l'insuffisance cardiaque, de la resténose, de la parodontopathie, de l'ulcération cornéenne, des brûlures, des ulcères du décubitus, d'ulcères chroniques ou de lésions, de métastases cancéreuses, de l'angiogénèse tumorale, de l'arthrite ou d'autres affections auto-immunes ou inflammatoires liées à une invasion leucocytaire des tissus.