(R)-3-[1-(1-丙烯酰哌啶-3-基)-4-氨基-1H-吡唑并[3,4-d]嘧啶-3-基]-N-(4-异丙基-5-甲基苯基)苯甲酰胺 | 1407966-77-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (R)-3-[1-(1-丙烯酰哌啶-3-基)-4-氨基-1H-吡唑并[3,4-d]嘧啶-3-基]-N-(4-异丙基-5-甲基苯基)苯甲酰胺
• 中文别名: (R)-3-(1-(1-丙烯酰基哌啶-3-基)-4-氨基-1H-吡唑并[3,4-d]嘧啶-3-基)-N-(3-甲基-4-(1-甲基乙基))苯甲酰胺
• 英文名称: PF-06465469
• 英文别名: (R)-3-(1-(1-acryloylpiperidin-3-yl)-4-amino-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-(4-isopropyl-3-methylphenyl)benzamide；Discontinued See A191400；3-[4-amino-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]pyrazolo[3,4-d]pyrimidin-3-yl]-N-(3-methyl-4-propan-2-ylphenyl)benzamide
• CAS: 1407966-77-1
• 化学式: C₃₀H₃₃N₇O₂
• 分子量: 523.638
• InChiKey: CGJVMKJGKFEHTL-HSZRJFAPSA-N

物化性质

• 熔点：
  209-212°C
• 沸点：
  730.2±60.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶，5mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

反应信息

• 作为产物：
  描述：

  (S)-1-叔丁氧羰基-3-羟基哌啶 在 盐酸 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 偶氮二甲酸二异丙酯 、 水 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 (R)-3-[1-(1-丙烯酰哌啶-3-基)-4-氨基-1H-吡唑并[3,4-d]嘧啶-3-基]-N-(4-异丙基-5-甲基苯基)苯甲酰胺
  参考文献：
  名称：

  Covalent Inhibitors of Interleukin-2 Inducible T Cell Kinase (Itk) with Nanomolar Potency in a Whole-Blood Assay

  摘要：

  We wish to report a strategy that targets interleukin-2 inducible T cell kinase (Itk) with covalent inhibitors. Thus far, covalent inhibition of Itk has not been disclosed in the literature. Structure-based drug design was utilized to achieve low nanomolar potency of the disclosed series even at high ATP concentrations. Kinetic measurements confirmed an irreversible binding mode with off-rate half-lives exceeding 24 h and moderate on-rates. The analogues are highly potent in a cellular IP1 assay as well as in a human whole-blood (hWB) assay. Despite a half-life of approximately 2 h in resting primary T cells, the covalent inhibition of Itk resulted in functional silencing of the TCR pathway for more than 24 h. This prolonged effect indicates that covalent inhibition is a viable strategy to target the inactivation of Itk.

  DOI：

  10.1021/jm301190s

文献信息

• EXPANSION OF TUMOR INFILTRATING LYMPHOCYTES FROM LIQUID TUMORS AND THERAPEUTIC USES THEREOF
  申请人：Iovance Biotherapeutics, Inc.

  公开号：US20200224161A1

  公开（公告）日：2020-07-16

  Methods of expanding tumor infiltrating lymphocytes (TILs), including peripheral blood lymphocytes and marrow infiltrating lymphocytes, from blood and/or bone marrow of patients with hematological malignancies, such as liquid tumors, including lymphomas and leukemias, and uses of such expanded TILs in the treatment of diseases such as cancers and hematological malignancies are disclosed herein.
• Expansion Of Peripheral Blood Lymphocytes (PBLS) From Peripheral Blood
  申请人：Iovance Biotherapeutics, Inc.

  公开号：US20200347350A1

  公开（公告）日：2020-11-05

  Methods of expanding tumor infiltrating lymphocytes (TILs), including peripheral blood lymphocytes (PBLs) and marrow infiltrating lymphocytes (MILs), from blood and/or bone marrow of patients with hematological malignancies, such as liquid tumors, including lymphomas and leukemias, and genetic modifications of expanded TILs, PBLs, and MILs to incorporate chimeric antigen receptors, genetically modified T-cell receptors, and other genetic modifications, and uses of such expanded and/or modified TILs, PBLs, and MILs in the treatment of diseases such as cancers and hematological malignancies are disclosed herein.
• PROCESSES FOR PRODUCTION OF TUMOR INFILTRATING LYMPHOCYTES AND USES OF SAME IN IMMUNOTHERAPY
  申请人：Iovance Biotherapeutics, Inc.

  公开号：US20220118011A1

  公开（公告）日：2022-04-21

  The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.
• Expansion of Tumor Infiltrating Lymphocytes From Liquid Tumors and Therapeutic Uses Thereof
  申请人：Iovance Biotherapeutics, Inc.

  公开号：US20220133795A1

  公开（公告）日：2022-05-05

  Methods of expanding peripheral blood lymphocytes (PBLs) from blood of patients with hematological malignancies, including lymphomas and leukemias, genetic modifications of expanded PBLs to incorporate chimeric antigen receptors, genetically modified T cell receptors, and other genetic modifications, and uses of such expanded and/or modified PBLs in the treatment of diseases such as cancers and hematological malignancies are disclosed herein.
• Covalent Inhibitors of Interleukin-2 Inducible T Cell Kinase (Itk) with Nanomolar Potency in a Whole-Blood Assay
  作者：Christoph W. Zapf、Brian S. Gerstenberger、Li Xing、David C. Limburg、David R. Anderson、Nicole Caspers、Seungil Han、Ann Aulabaugh、Ravi Kurumbail、Subarna Shakya、Xin Li、Vikki Spaulding、Robert M. Czerwinski、Nilufer Seth、Quintus G. Medley

  DOI：10.1021/jm301190s

  日期：2012.11.26

  We wish to report a strategy that targets interleukin-2 inducible T cell kinase (Itk) with covalent inhibitors. Thus far, covalent inhibition of Itk has not been disclosed in the literature. Structure-based drug design was utilized to achieve low nanomolar potency of the disclosed series even at high ATP concentrations. Kinetic measurements confirmed an irreversible binding mode with off-rate half-lives exceeding 24 h and moderate on-rates. The analogues are highly potent in a cellular IP1 assay as well as in a human whole-blood (hWB) assay. Despite a half-life of approximately 2 h in resting primary T cells, the covalent inhibition of Itk resulted in functional silencing of the TCR pathway for more than 24 h. This prolonged effect indicates that covalent inhibition is a viable strategy to target the inactivation of Itk.