4-fluoro-3-methanesulfonylbenzene-1-sulfonyl chloride | 1188525-46-3

• 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: 4-fluoro-3-methanesulfonylbenzene-1-sulfonyl chloride
• 英文别名: 4-fluoro-3-methylsulfonylbenzenesulfonyl chloride
• CAS: 1188525-46-3
• 化学式: C₇H₆ClFO₄S₂
• mdl: MFCD12913017
• 分子量: 272.706
• InChiKey: RLXOANSRXCHLPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  85
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-3-methanesulfonylbenzene-1-sulfonyl chloride 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.0h， 以945 mg的产率得到4-fluoro-3-(methylsulfonyl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins

  摘要：

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

  DOI：

  10.1021/jm800669s
• 作为产物：
  描述：

  2-氟苯基甲基砜 在 氯磺酸 作用下， 反应 15.0h， 生成 4-fluoro-3-methanesulfonylbenzene-1-sulfonyl chloride
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins

  摘要：

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

  DOI：

  10.1021/jm800669s

文献信息

• BENZOCYCLOHEPTENE ACETIC ACIDS
  申请人：Firooznia Fariborz

  公开号：US20120309796A1

  公开（公告）日：2012-12-06

  Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of inflammatory diseases and disorders such as, for example, asthma and COPD.

  本文提供的是化合物的公式(I)以及其药用盐，其中取代基如规范中所披露的那样。这些化合物及含有它们的药物组合物对于治疗炎症性疾病和紊乱，如哮喘和慢性阻塞性肺病等，具有用处。
• SULFONAMIDE COMPOUND OR SALT THEREOF
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP3466934A1

  公开（公告）日：2019-04-10

  The present invention provides a novel sulfonamide compound having a ribonucleotide reductase inhibitory activity or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient. A compound represented by Formula (I) [wherein, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents -NH-; X4 represents a hydrogen atom or the like; R1 represents -C(R11)(R12)- or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof.

  本发明提供了一种具有核糖核苷酸还原酶抑制活性的新型磺酰胺化合物或其盐，以及含有该化合物作为活性成分的药物组合物。 由式(I)代表的化合物[其中，X1代表氧原子或类似物；X2代表氧原子；X3代表-NH-；X4代表氢原子或类似物；R1代表-C(R11)(R12)-或类似物；R11和R12相同或不同且各自代表氢原子或类似物；R2代表任选取代的C6-C14芳烃基团或类似物；R3代表任选取代的C6-C14芳烃基团或类似物；R4代表氢原子或类似物]或其盐。
• ANTITUMOR AGENT
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：EP3718545A1

  公开（公告）日：2020-10-07

  The present invention provides a method of enhancing an antitumor effect by a compound strongly inhibiting ribonucleotide reductase (RNR) or a salt thereof. A combination formulation involving combined administration of a sulfonamide compound represented by Formula (I) [In the formula, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents -NH-; X4 represents a hydrogen atom or the like; R1 represents -C(R11) (R12)- or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof, having RNR inhibitory activity, and other antitumor agent(s).

  本发明提供了一种通过强抑制核糖核苷酸还原酶（RNR）的化合物或其盐增强抗肿瘤效果的方法。 一种组合制剂涉及联合给药由式(I)代表的磺酰胺化合物[式中，X1代表氧原子或类似物；X2代表氧原子；X3代表-NH-；X4代表氢原子或类似物；R1代表-C(R11)(R12)-或类似物；R11和R12相同或不同，各自代表氢原子或类似物；R2代表任选取代的C6-C14芳烃基团或类似物；R3代表任选取代的C6-C14芳烃基团或类似物；R4代表氢原子或类似物]或其盐，具有RNR抑制活性，以及其他抗肿瘤剂。
• Sulfonamide compound or salt thereof
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：US10889555B2

  公开（公告）日：2021-01-12

  The present invention provides a novel sulfonamide compound having a ribonucleotide reductase inhibitory activity or a salt thereof, and a pharmaceutical composition containing the same as an active ingredient. A compound represented by Formula (I) [wherein, X1 represents an oxygen atom or the like; X2 represents an oxygen atom; X3 represents —NH—; X4 represents a hydrogen atom or the like; R1 represents —C(R11)(R12)— or the like; R11 and R12 are the same or different and each represents a hydrogen atom or the like; R2 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R3 represents an optionally substituted C6-C14 aromatic hydrocarbon group or the like; R4 represents a hydrogen atom or the like] or a salt thereof.

  本发明提供了一种具有核糖核苷酸还原酶抑制活性的新型磺酰胺化合物或其盐，以及含有该化合物作为活性成分的药物组合物。 由式(I)代表的化合物[其中，X1代表氧原子或类似物；X2代表氧原子；X3代表-NH-；X4代表氢原子或类似物；R1代表-C(R11)(R12)-或类似物；R11和R12相同或不同且各自代表氢原子或类似物；R2代表任选取代的C6-C14芳烃基团或类似物；R3代表任选取代的C6-C14芳烃基团或类似物；R4代表氢原子或类似物]或其盐。
• EP3466934
  申请人：——

  公开号：——

  公开（公告）日：——