17,17'-[1,4-Phenylenebis(methylene)]bis[3,6,14,17, 23,24-hexaazatricyclo[17.3.1.1<8,12>]tetracosa-1(23),8,10,12(24),19,21-hexaene]

• 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: 17,17'-[1,4-Phenylenebis(methylene)]bis[3,6,14,17, 23,24-hexaazatricyclo[17.3.1.1<8,12>]tetracosa-1(23),8,10,12(24),19,21-hexaene]
• 英文别名: 3-[[4-(3,6,14,17,23,24-hexazatricyclo[17.3.1.18,12]tetracosa-1(22),8,10,12(24),19(23),20-hexaen-3-ylmethyl)phenyl]methyl]-3,6,14,17,23,24-hexazatricyclo[17.3.1.18,12]tetracosa-1(22),8,10,12(24),19(23),20-hexaene
• 化学式: C₄₄H₅₈N₁₂
• 分子量: 755.0
• InChiKey: WFEUKKAYFIIJEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  56
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  130
• 氢给体数：
  6
• 氢受体数：
  12

文献信息

• Chemokine combinations to mobilize progenitor/stem cells
  申请人：Bridger J. Gary

  公开号：US20060035829A1

  公开（公告）日：2006-02-16

  Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 in combination with the CXCR2 chemokine GROβ, including its modified forms, are disclosed.

  使用与趋化因子受体CXCR4结合的化合物与CXCR2趋化因子GROβ及其改良形式结合，揭示了提高动物主体中祖细胞和干细胞数量的方法。
• Methods to mobilize progenitor/stem cells
  申请人：Bridger Gary

  公开号：US20050043367A1

  公开（公告）日：2005-02-24

  Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′  (1) or pharmaceutically acceptable salt thereof wherein Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ is of the formula —Ar(Y) j ; wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3; and “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

  本文揭示了利用与趋化因子受体CXCR4结合的化合物来提高动物主体和干细胞计数的方法。这些化合物的优选实施方式为式Z-连接-Z' (1)或其药用盐，其中Z的式为其中A包括至少含有一个N的单环或双环融合环系统，B为H或含有1-20个原子的有机基团，Z'的式为-Ar(Y)j；其中Ar为芳香或杂芳基团，每个Y独立地表示非干扰取代基，j为0-3；“连接物”代表键，烷基（1-6C）或可能包含芳基，融合芳基，含有在烷基链中的氧原子，或可能含有酮基团或氮或硫原子。
• METHODS TO MOBILIZE PROGENITOR/STEM CELLS
  申请人：Genzyme Global S.à.r.l.

  公开号：EP3632425A1

  公开（公告）日：2020-04-08

  Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z' (1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system; or Z is of formula (a), wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z' may be embodied in a form as defined by Z above, or alternatively may be of the formula -N(R)-(CR2)n-X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; "linker" represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulphur atoms.

  本研究公开了使用与趋化因子受体 CXCR4 结合的化合物提高动物体内祖细胞和干细胞数量的方法。此类化合物的优选实施方案为式 Z-linker-Z' (1) 或其药学上可接受的盐，其中 Z 是环状多胺，包含 9-32 个环成员，其中 3-8 个为氮原子，所述氮原子之间至少相隔 2 个碳原子，所述杂环除氮原子外还可选择包含其他杂原子和/或可与其他环系统融合；或 Z 为式(a)，其中 A 包含单环或双环融合环系统，至少含有一个 N，B 为 H 或 1-20 个原子的有机分子，Z'可以如上文 Z 所定义的形式体现，或者可以为式-N(R)-(CR2)n-X，其中每个 R 独立地为 H 或直链、支链或环状烷基（1-6C），n 为 1 或 2，X 为芳香环，包括杂芳香环，或者为硫醇；"连接剂 "代表键、亚烷基（1-6C），或可包括芳基、融合芳基、亚烷基链中包含的氧原子，或可包含酮基或氮或硫原子。
• Dosing regimens for the mobilization of hematopoietic stem cells
  申请人：Magenta Therapeutics Inc.

  公开号：US10058573B1

  公开（公告）日：2018-08-28

  Described herein are compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a subject, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the composition and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

  本文描述的组合物和方法可用于动员受试者体内的造血干细胞和祖细胞群，以及确定动员细胞样本是否适合释放用于体外扩增和/或治疗用途。根据本文所述的组合物和方法，动员的造血干细胞和祖细胞可从供体中提取并施用给患者，用于治疗各种疾病，包括造血疾病、代谢性疾病、癌症和自身免疫性疾病等。
• Mobilizing agents and uses therefor
  申请人：The University of Queensland

  公开号：US10933049B2

  公开（公告）日：2021-03-02

  The present invention discloses the use of a complement 3a receptor (C3aR) antagonist and a mobilizer of hematopoietic stem cells and/or progenitor cells in methods and compositions for stimulating or enhancing the development, mobilization, proliferation and/or differentiation of a neutrophil-containing leukocyte population that inhibits growth and/or spread of a tumor and for treating or preventing a hyperproliferative cell disorder.

  本发明公开了补体3a受体（C3aR）拮抗剂和造血干细胞和/或祖细胞动员剂在刺激或增强含中性粒细胞的白细胞群的发育、动员、增殖和/或分化的方法和组合物中的应用，该方法和组合物能抑制肿瘤的生长和/或扩散，并能治疗或预防细胞过度增殖症。