N4-(2'-chlorophenyl)-N2-(4'-carbamoylphenyl)-5-fluoropyrimidine-2,4-diamine | 1395886-20-0

• 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: N4-(2'-chlorophenyl)-N2-(4'-carbamoylphenyl)-5-fluoropyrimidine-2,4-diamine
• 英文别名: Bisanilinopyrimidine, 9m；4-[[4-(2-chloroanilino)-5-fluoropyrimidin-2-yl]amino]benzamide
• CAS: 1395886-20-0
• 化学式: C₁₇H₁₃ClFN₅O
• 分子量: 357.775
• InChiKey: XSPXJYVALVHTAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  邻氯苯胺 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 126.0h， 生成 N4-(2'-chlorophenyl)-N2-(4'-carbamoylphenyl)-5-fluoropyrimidine-2,4-diamine
  参考文献：
  名称：

  [EN] AURORA KINASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
  [FR] INHIBITEURS DE KINASE AURORA ET PROCÉDÉS POUR LES FABRIQUER ET LES UTILISER

  摘要：

  公开号：

  WO2012135641A3

文献信息

• [EN] AURORA KINASE AND JANUS KINASE INHIBITORS FOR PREVENTION OF GRAFT VERSUS HOST DISEASE<br/>[FR] INHIBITEURS DES KINASES AURORA ET DES JANUS KINASES POUR LA PRÉVENTION DE LA MALADIE DU GREFFON CONTRE L'HÔTE
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2017156527A1

  公开（公告）日：2017-09-14

  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.

  本文披露了一种化合物和方法，用于降低受试者发展、预防或治疗移植物抗宿主病（GVHD）的风险。这些化合物可以同时阻断Aurora激酶A和JAK2信号传导，从而协同抑制体外异体反应性人T细胞，预防异种移植物抗宿主病而不影响抗肿瘤反应，并促进CD39+诱导性Treg的发展和抑制效能。在某些方面，本文披露了Formula I-V的化合物。
• 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。
• Development of <i>o</i>-Chlorophenyl Substituted Pyrimidines as Exceptionally Potent Aurora Kinase Inhibitors
  作者：Harshani R. Lawrence、Mathew P. Martin、Yunting Luo、Roberta Pireddu、Hua Yang、Harsukh Gevariya、Sevil Ozcan、Jin-Yi Zhu、Robert Kendig、Mercedes Rodriguez、Roy Elias、Jin Q. Cheng、Saïd M. Sebti、Ernst Schonbrunn、Nicholas J. Lawrence

  DOI：10.1021/jm300334d

  日期：2012.9.13

  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.
• 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.