N⁴-(2-chlorophenyl)-N²-[4-(2H-tetrazol-5-yl)phenyl]-5-chloropyrimidine-2,4-diamine hydrochloride | 1395918-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N⁴-(2-chlorophenyl)-N²-[4-(2H-tetrazol-5-yl)phenyl]-5-chloropyrimidine-2,4-diamine hydrochloride
• 英文别名: Bisanilinopyrimidine, 12d；5-chloro-4-N-(2-chlorophenyl)-2-N-[4-(2H-tetrazol-5-yl)phenyl]pyrimidine-2,4-diamine
• CAS: 1395918-36-1
• 化学式: C₁₇H₁₂Cl₂N₈
• 分子量: 399.242
• InChiKey: YQQWGLNBSUZDRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-(4-硝基苯基)-1H-四唑 在 盐酸 、 10% Pd/C 、 氢气 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 14.67h， 生成 N⁴-(2-chlorophenyl)-N²-[4-(2H-tetrazol-5-yl)phenyl]-5-chloropyrimidine-2,4-diamine hydrochloride
  参考文献：
  名称：

  Development of o-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors

  摘要：

  The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC50 = 6.1 +/- 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallography studies revealed that compound 1 is a type I inhibitor that binds the Aurora kinase active site in a DFG-in conformation. Structure-activity guided replacement of the A-ring carboxylic acid with halogens and incorporation of fluorine at the pyrimidine 5-position led to highly potent inhibitors of Aurora A that bind in a DFG-out conformation. B-Ring modifications were undertaken to improve the solubility and cell permeability. Compounds such as 9m with water-solubilizing moieties at the para position of the B-ring inhibited the autophosphorylation of Aurora A in MDA-MB-468 breast cancer cells.

  DOI：

  10.1021/jm300334d

文献信息

• AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Sebti Said M.

  公开号：US20140057913A1

  公开（公告）日：2014-02-27

  Described herein are inhibitors of Aurora kinase and their use in the treatment of cancer. Methods of screening for selective inhibitors of Aurora kinases are also disclosed.

  本文描述了Aurora激酶的抑制剂及其在癌症治疗中的应用。还公开了筛选选择性抑制Aurora激酶的方法。
• Aurora kinase and Janus kinase inhibitors for prevention of graft versus host disease
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US11203576B2

  公开（公告）日：2021-12-21

  Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft-versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible Treg. In certain aspects, disclosed are compounds of Formula I-V.

  本文公开了用于降低受试者发生、预防或治疗移植物抗宿主疾病（GVHD）风险的化合物和方法。这些化合物可同时阻断极光激酶 A 和 JAK2 的信号转导，从而协同抑制体外异基因活性人 T 细胞，预防异基因移植物抗宿主疾病而不损害抗肿瘤反应，并促进 CD39+ 诱导性 Treg 的发育和抑制效力。在某些方面，公开了式 I-V 的化合物。
• AURORA KINASE AND JANUS KINASE INHIBITORS FOR PREVENTION OF GRAFT VERSUS HOST DISEASE
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20190127335A1

  公开（公告）日：2019-05-02

  Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft-versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible T reg . In certain aspects, disclosed are compounds of Formula I-V.
• US9249124B2
  申请人：——

  公开号：US9249124B2

  公开（公告）日：2016-02-02
• US9597329B2
  申请人：——

  公开号：US9597329B2

  公开（公告）日：2017-03-21