Foselutoclax | 2271269-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: Foselutoclax
• 英文别名: 5-(4-chlorophenyl)-2-methyl-4-[3-[4-[4-[[4-[[(2R)-1-phenylsulfanyl-4-(4-phosphonooxypiperidin-1-yl)butan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylamino]phenyl]piperazin-1-yl]phenyl]-1-propan-2-ylpyrrole-3-carboxylic acid
• CAS: 2271269-01-1
• 化学式: C₅₃H₅₉ClF₃N₆O₁₀PS₃
• 分子量: 1159.7
• InChiKey: FSZILRQCEAUYPL-VQJSHJPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  77
• 可旋转键数：
  20
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  253
• 氢给体数：
  5
• 氢受体数：
  19

文献信息

• Acyl sulfonamides that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
  申请人：Unity Biotechnology, Inc.

  公开号：US10717722B2

  公开（公告）日：2020-07-21

  The aryl sulfonamide compounds of this invention have powerful and cell-type specific Bcl inhibitory activity. Compounds of this invention include compounds according to formula (I): Selected compounds in this class promote apoptosis in senescent cells, and are being developed for treating senescent-related conditions. Selected compounds in this class promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

  本发明的芳基磺酰胺化合物具有强大的细胞类型特异性 Bcl 抑制活性。本发明的化合物包括符合式（I）的化合物： 这类化合物可促进衰老细胞的凋亡，目前正被开发用于治疗与衰老相关的疾病。这类化合物中的某些化合物能促进癌细胞凋亡，可开发为化疗药物。
• Methods of inhibiting pathological angiogenesis
  申请人：Unity Biotechnology, Inc.

  公开号：US11129838B2

  公开（公告）日：2021-09-28

  This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology—such as neovascularization and vaso-obliteration—that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.

  本发明基于以下发现：许多与衰老相关的眼部疾病至少部分是由具有衰老表型的细胞介导的。衰老细胞随着年龄的增长而积聚，并表达有助于老年相关疾病病理生理学的因子。数据显示，在年龄匹配的患者中，年龄相关疾病的严重程度与衰老细胞的数量相关，清除衰老细胞有助于缓解病情。清除眼部受影响组织中衰老细胞的小分子药物在治疗眼科疾病方面具有特殊疗效。它们不仅能抑制疾病的发展，还能逆转一些导致视力下降的病理生理学现象，如新生血管和血管闭塞。这些衰老溶解剂具有适当的剂量和特异性特征，可以有效地用于以前难以治愈的眼科疾病的临床治疗。
• Methods of Inhibiting Pathological Angiogenesis
  申请人：Unity Biotechnology, Inc.

  公开号：US20200253991A1

  公开（公告）日：2020-08-13

  This invention is based on the discovery that many eye conditions associated with aging are mediated at least in part by cells bearing a senescent phenotype. Senescent cells accumulate with age, and express factors that contribute to the pathophysiology of age related conditions. The data show that in age-matched patients, the severity of age-related conditions correlates with the abundance of senescent cells, and that clearing senescent cells can help abrogate the condition. Small molecule drugs that remove senescent cells from affected tissue in the eye are provided that have special efficacy in treating ophthalmic conditions. They not only inhibit progression of the disease, they can also reverse some of the pathophysiology—such as neovascularization and vaso-obliteration—that lead to vision loss. These senolytic agents have an appropriate dose and specificity profile to be effective in the clinical management of previously intractable ophthalmic conditions.
• Acyl Sulfonamides that are BCL Family Antagonists for Use in Clinical Management of Conditions Caused or Mediated by Senescent Cells and for Treating Cancer
  申请人：Unity Biotechnology, Inc.

  公开号：US20200317640A1

  公开（公告）日：2020-10-08

  The aryl sulfonamide compounds of this invention have powerful and cell-type specific Bcl inhibitory activity. Selected compounds in this class promote apoptosis in senescent cells, and are being developed for treating senescent-related conditions. Selected compounds in this class promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.
• Killing Senescent Cells And Treating Senescence-Associated Conditions Using A Bcl Inhibitor And An Mcl-1 Inhibitor
  申请人：Unity Biotechnology, Inc.

  公开号：US20210379078A1

  公开（公告）日：2021-12-09

  This invention is based on the discovery that inhibiting more than one pathway in senescent cells leading to apoptosis has a profound effect: namely, increasing the potency or the cell specificity of the therapy. Combining a Bcl inhibitor with an Mcl 1 inhibitor increases the ability of the Bcl inhibitor to remove senescent cells from the site of an adverse condition synergistically. This increases the types of senescent cells that can be targeted, broadens the therapeutic range, and allows the user to tailor a particular combination of agents by adjusting the molar ratio for the patient being treated. Suitable indications for treatment may include any condition thought to be mediated at least in part by senescent cells, such as ophthalmic conditions, pulmonary conditions, and atherosclerosis.