1-(4-氨基-1-哌啶基)-2,2,2-三氟乙烷酮 | 497177-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-(4-氨基-1-哌啶基)-2,2,2-三氟乙烷酮
• 英文名称: 1-(4-aminopiperidin-1-yl)-2,2,2-trifluoroethanone
• CAS: 497177-66-9
• 化学式: C₇H₁₁F₃N₂O
• 分子量: 196.172
• InChiKey: IMIRFQOBCRHHFT-UHFFFAOYSA-N

物化性质

• 沸点：
  288.2±40.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H302,H319

反应信息

• 作为反应物：
  描述：

  1-(4-氨基-1-哌啶基)-2,2,2-三氟乙烷酮 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 生成 tert-butyl (3-(pyrazin-2-yl)-2-propyn-1-yl)(1-(trifluoroacetyl)piperidin-4-yl)carbamate
  参考文献：
  名称：

  NOVEL HETEROCYCLIC COMPOUND OR SALT THEREOF AND INTERMEDIATE THEREOF

  摘要：

  公开号：

  EP2022793B1
• 作为产物：
  描述：

  4-(N-苄氧羰基)-氨基哌啶 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 22.0h， 生成 1-(4-氨基-1-哌啶基)-2,2,2-三氟乙烷酮
  参考文献：
  名称：

  Discovery of 2-substituted 1 H -benzo[ d ]immidazole-4-carboxamide derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors with in vivo anti-tumor activity

  摘要：

  Novel 1H-benzo[d]immidazole-4-carboxamide derivatives bearing five-membered or six-membered N-heterocyclic moieties at the 2-position were designed and synthesized as PARP-1 inhibitors. Structure activity relationships were conducted and led to a number of potent PARP-1 inhibitors having IC50 values in the single or double digit nanomolar level. Some potent PARP-1 inhibitors also had similar inhibitory activities against PARP-2. Among all the synthesized compounds, compound 10a and 11e displayed strong potentiation effects on temozolomide (TMZ) in MX-1 cells (PF50 = 7.10, PF50 = 4.17). In vivo tumor growth inhibition was investigated using compound 10a in combination with TMZ, and it was demonstrated that compound 10a could strongly potentiate the cytotoxicity of TMZ in MX-1 xenograft tumor model. Two co-crystal structures of compounds 11b and 15e complexed with PARP-1 were achieved and demonstrated a unique binding mode of these benzo-imidazole derivatives. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.013

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET UTILISATION DE CES COMPOSÉS
  申请人：NATIONAL HEALTH RES INST

  公开号：WO2018132326A1

  公开（公告）日：2018-07-19

  Heterocyclic compounds of Formula (I) shown herein. Also disclosed is a pharmaceutical composition containing one of the heterocyclic compounds. Further disclosed are methods of using one of the heterocyclic compounds for mobilizing hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation, and for treating tissue injury, cancer, inflammatory disease, and autoimmune disease.

  本文所示的式(I)的杂环化合物。还公开了含有其中一种杂环化合物的药物组合物。进一步公开了使用其中一种杂环化合物将造血干细胞和内皮祖细胞转移到外周循环，并用于治疗组织损伤、癌症、炎症性疾病和自身免疫疾病的方法。
• A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment
  作者：Jen-Shin Song、Chih-Chun Chang、Chien-Huang Wu、Trinh Kieu Dinh、Jiing-Jyh Jan、Kuan-Wei Huang、Ming-Chen Chou、Ting-Yun Shiue、Kai-Chia Yeh、Yi-Yu Ke、Teng-Kuang Yeh、Yen-Nhi Ngoc Ta、Chia-Jui Lee、Jing-Kai Huang、Yun-Chieh Sung、Kak-Shan Shia、Yunching Chen

  DOI：10.1073/pnas.2015433118

  日期：2021.3.30

  The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded

  CXC 趋化因子受体 4 (CXCR4) 受体及其配体 CXCL12 在各种癌症中过度表达，并介导肿瘤进展和缺氧介导的癌症治疗耐药性。虽然 CXCR4 拮抗剂与常规抗癌药物联合使用时具有潜在的抗癌作用，但它们对 CXCL12/CXCR4 下游信号通路的弱效力和全身毒性已排除了临床应用。在此，BPRCX807 被称为安全、选择性和有效的 CXCR4 拮抗剂，已被设计并通过实验实现。在体外和体内肝细胞癌小鼠模型中，它可以通过减少肿瘤相关巨噬细胞 (TAM) 的浸润，显着抑制原发性肿瘤生长，防止远处转移/细胞迁移，减少血管生成，并使免疫抑制性肿瘤微环境正常化，将 TAM 重编程为免疫刺激表型并促进细胞毒性 T 细胞浸润到肿瘤中。尽管单独使用 BPRCX807 治疗与已上市的索拉非尼和抗 PD-1 一样有效地延长了总生存期，但它可以在联合治疗中与它们中的任何一种协同作用，以进一步延长预期寿命并更显着地抑制远处转移。
• HETEROCYCLIC COMPOUNDS AND USE THEREOF
  申请人：National Health Research Institutes

  公开号：US20160083369A1

  公开（公告）日：2016-03-24

  Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds.

  本文显示的式（I）的杂环化合物。还公开了含有这些杂环化合物的药物组合物以及使用这些杂环化合物将造血干细胞和内皮祖细胞转移到外周循环的方法。此外，还提供了使用这些杂环化合物治疗组织损伤、癌症、炎症性疾病和自身免疫疾病的方法。
• CONFORMATIONALLY RESTRICTED UREA INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE
  申请人：Hammock D. Bruce

  公开号：US20070225283A1

  公开（公告）日：2007-09-27

  Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases.

  提供了可抑制可溶性环氧化物水解酶（sEH）的抑制剂，这些抑制剂结合了多种药效团，并且在治疗疾病方面具有用途。
• 1h-Indazole-3-carboxamide compounds as cyclin dependent kinase (cdk) inhibitors
  申请人：Berdino Valerio

  公开号：US20060135589A1

  公开（公告）日：2006-06-22

  The invention provides a compound of the formula (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase: wherein A is a group R 2 or CH 2 —R 2 where R 2 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; B is a bond or an acyclic linker group having a linking chain length of up to 3 atoms selected from C, N, S and O; R 1 is hydrogen or a group selected from SO 2 R b , SO 2 NR 7 R 8 , CONR 7 R 8 , NR 7 R 9 and carbocyclic and heterocyclic groups having from 3 to 7 ring members; R 3 , R 4 , R 5 and R 6 are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group R a —R b wherein R a is a bond, O, CO, X 1 C(X 2 ), C(X 2 )X 1 , X 1 C(X 2 )X 1 , S, SO, SO 2 , NR c , SO 2 NR c or NR c SO 2 ; and R b is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ; R c is hydrogen or C 1-4 hydrocarbyl; X 1 is O, S or NR c and X 2 is ═O, ═S or ═NR c ; R 7 is selected from hydrogen and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ; R 8 is selected from R 7 and carbocyclic and heterocyclic groups having from 3 to 12 ring members; R 9 is selected from R 8 , COR 8 and SO 2 R 8 ; or NR 7 R 8 or NR 7 R 9 may each form a heterocyclic group having from 5 to 12 ring members; but excluding the compounds N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide and N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide.

  该发明提供了化合物(I)的使用，用于预防或治疗由细胞周期依赖性激酶介导的疾病状态或病情：其中A是R2基团或CH2-R2基团，其中R2是具有3到12个环成员的碳环或杂环基团；B是键或具有链长高达3个C、N、S和O中选择的原子的非环状连接基团；R1是氢或从SO2Rb、SO2NR7R8、CONR7R8、NR7R9和具有3到7个环成员的碳环或杂环基团中选择的基团；R3、R4、R5和R6相同或不同，且每个都从氢、卤素、羟基、三氟甲基、氰基、硝基、羧基、氨基、具有3到12个环成员的碳环或杂环基团中选择；Ra-Rb基团其中Ra是键、O、CO、X1C(X2)、C(X2)X1、X1C(X2)X1、S、SO、SO2、NRc、SO2NRc或NRcSO2；Rb从具有3到12个环成员的碳环或杂环基团和C1-8烃基组中选择，可选地被一个或多个从羟基、氧代、卤素、氰基、硝基、氨基、单个或双个C1-4烃基氨基、具有3到12个环成员的碳环或杂环基团中选择的取代基所取代，其中C1-8烃基组的一个或多个碳原子可选择被O、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1所取代；Rc是氢或C1-4烃基；X1是O、S或NRc，X2是═O、═S或═NRc；R7从氢和可选地被一个或多个从羟基、氧代、卤素、氰基、硝基、氨基、单个或双个C1-4烃基氨基、具有3到12个环成员的碳环或杂环基团中选择的取代基所取代的C1-8烃基中选择，其中C1-8烃基的一个或多个碳原子可选择被O、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1所取代；R8从R7和具有3到12个环成员的碳环或杂环基团中选择；R9从R8、COR8和SO2R8中选择；或NR7R8或NR7R9各自可以形成具有5到12个环成员的杂环基团；但不包括化合物N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide和N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide]。