1-(4-三氟甲基嘧啶-2-基)哌嗪 | 179756-91-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(4-三氟甲基嘧啶-2-基)哌嗪
• 中文别名: 2-哌嗪-YL-4-(三氟代甲基)嘧啶；1-[2-(4-三氟甲基嘧啶基)]哌嗪
• 英文名称: 2-(piperazin-1-yl)-4-(trifluoromethyl)pyrimidine
• 英文别名: 2-piperazin-1-yl-4-(trifluoromethyl)pyrimidine；2-piperazin-1-yl-4-trifluoromethyl-pyrimidine；2-piperazin-1-yl-4-trifluoromethylpyrimidine
• CAS: 179756-91-3
• 化学式: C₉H₁₁F₃N₄
• mdl: MFCD00203912
• 分子量: 232.208
• InChiKey: WBJVPAABGFBMJQ-UHFFFAOYSA-N

物化性质

• 熔点：
  50-52°C
• 沸点：
  331.3±52.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  1-(4-三氟甲基嘧啶-2-基)哌嗪 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (1R,3S)-3-Isopropyl-3-({4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}carbonyl)cyclopentanamine
  参考文献：
  名称：

  Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist

  摘要：

  We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.015
• 作为产物：
  描述：

  tert-Butyl [(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]carbamate 以 solution 、 盐酸 、 1,4-二氧六环 为溶剂， 反应 1.0h， 以to give 270 mg of desired product的产率得到1-(4-三氟甲基嘧啶-2-基)哌嗪
  参考文献：
  名称：

  3-Aminocyclopentanecarboxamides as modulators of chemokine receptors

  摘要：

  本发明涉及化合物I式：它们是趋化因子受体调节剂。该发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。

  公开号：

  US20060004018A1
• 作为试剂：
  描述：

  2-氯-4-三氟甲基嘧啶 、 potassium carbonate 、 哌嗪 在 1-(4-三氟甲基嘧啶-2-基)哌嗪 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以to give the title compound as yellow oil (1.25 g, 75%)的产率得到1-(4-三氟甲基嘧啶-2-基)哌嗪
  参考文献：
  名称：

  SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF

  摘要：

  本文提供了新颖的杂环芳基化合物、药学上可接受的盐和药物配方，用于选择性抑制血清素再摄取和/或作为5-HT1A受体激动剂。本文还提供了包含这些杂环芳基化合物的制药组合物以及使用这些制药组合物治疗哺乳动物，特别是人类中枢神经系统（CNS）功能障碍的方法。

  公开号：

  US20160083370A1

文献信息

• Melanocortin-4 receptor binding compounds and methods of use thereof
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040082779A1

  公开（公告）日：2004-04-29

  Provided are MC4-R binding compounds of the formula XVII: 1 wherein L 2 is a linker group, and P 1 , P 2 , P 3 , P 4 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , t, s, and R are as described in the specification. Methods of using the compounds to treat MC4-R associated disorders, such as disorders associated with weight loss, are also provided.

  提供了具有以下化学式XVII的MC4-R结合化合物： 其中L2是连接基团，P1、P2、P3、P4、Z1、Z2、Z3、Z4、Z5、t、s和R如规范中所述。还提供了使用这些化合物治疗与MC4-R相关疾病的方法，例如与体重减轻相关的疾病。
• Aminopyrimidine Kinase Inhibitors
  申请人：Baldino Carmen M.

  公开号：US20110152235A1

  公开（公告）日：2011-06-23

  Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of casein kinase 1 (e.g., CK1γ), casein kinase 2 (CK2), Pim 1, Pim2, Pim3, the TGFβ pathway, the Wnt pathway, the JAK/STAT pathway, and/or the mTOR pathway. Uses are also disclosed for the treatment or prevention of a range of therapeutic indications due at least in part to aberrant physiological activity of casein kinase 1 (e.g., CK1γ), casein kinase 2 (CK2), Pim 1, Pim2, Pim3, the TGFβ pathway, the Wnt pathway, the JAK/STAT pathway, and/or the mTOR pathway.

  揭示了化合物、含有这些化合物的药物组合物，以及这些化合物和组合物作为酪蛋白激酶1（例如CK1γ）、酪蛋白激酶2（CK2）、Pim 1、Pim2、Pim3、TGFβ途径、Wnt途径、JAK/STAT途径和/或mTOR途径调节剂的用途。还揭示了用于治疗或预防一系列治疗适应症的用途，至少部分原因是由于酪蛋白激酶1（例如CK1γ）、酪蛋白激酶2（CK2）、Pim 1、Pim2、Pim3、TGFβ途径、Wnt途径、JAK/STAT途径和/或mTOR途径的异常生理活性。
• Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme
  申请人：Link T. James

  公开号：US20050277647A1

  公开（公告）日：2005-12-15

  The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and other diseases and conditions that are mediated by excessive glucocorticoid action.

  本发明涉及抑制11-β-羟基类固醇脱氢酶1型酶的化合物。本发明还涉及利用11-β-羟基类固醇脱氢酶1型酶的抑制剂治疗非胰岛素依赖型2型糖尿病、胰岛素抵抗、肥胖、脂质紊乱、代谢综合征以及其他由过度糖皮质激素作用介导的疾病和症状。
• Discovery of potent 2,4-difluoro-linker poly(ADP-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy
  作者：Wen-hua Chen、Shan-shan Song、Ming-hui Qi、Xia-juan Huan、Ying-qing Wang、Hualiang Jiang、Jian Ding、Guo-bin Ren、Ze-hong Miao、Jian Li

  DOI：10.1038/aps.2017.104

  日期：2017.11

  Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, we identified a series of 2,4-difluorophenyl-linker analogs (15–55) derived from olaparib as novel PARP1 inhibitors. Four potent analogs 17, 43, 47, and 50 (IC50=2.2–4.4 nmol/L) effectively inhibited the proliferation of Chinese hamster lung fibroblast V-C8 cells (IC50=3.2–37.6 nmol/L) in vitro, and showed specificity toward BRCA-deficient cells (SI=40–510). The corresponding hydrochloride salts 56 and 57 (based on 43 and 47) were highly water soluble in pH=1.0 buffered salt solutions (1628.2 μg/mL, 2652.5 μg/mL). In a BRCA1-mutated xenograft model, oral administration of compound 56 (30 mg·kg-1·d-1, for 21 d) exhibited more prominent tumor growth inhibition (96.6%) compared with the same dose of olaparib (56.3%); in a BRCA2-mutated xenograft model, oral administration of analog 43 (10 mg·kg-1·d-1, for 28 d) significantly inhibited tumor growth (69.0%) and had no negative effects on the body weights. Additionally, compound 56 exhibited good oral bioavailability (F=32.2%), similar to that of olaparib (F=45.4%). Furthermore, the free base 43 of the hydrochloride salt 56 exhibited minimal hERG inhibition activity (IC50=6.64 μmol/L). Collectively, these data demonstrate that compound 56 may be an excellent drug candidate for the treatment of cancer, particularly BRCA-deficient tumors.

  聚(ADP-核糖)聚合酶1(PARP1)在一系列癌症中过度表达,尤其是在乳腺癌和卵巢癌中;而缺乏乳腺癌基因1/2(BRCA1/2)的肿瘤细胞对PARP1抑制高度敏感。本研究以奥拉帕利为先导物,设计合成了一系列对2-氟-4-氟苯基连结体结构进行改造的PARP1抑制剂15-55,其中活性较好的4个化合物17、43、47、50(IC50=2.2-4.4 nmol/L)对仓鼠肺成纤维细胞V-C8的增殖具有较高抑制活性(IC50=3.2-37.6 nmol/L),并且对BRCA缺陷细胞更具选择性,选择性指数(SI)高达40-510。其中43、47经盐酸成盐后的化合物56、57在pH=1.0的盐溶液中具有非常好的溶解性(分别为1628.2 μg/mL和2652.5 μg/mL)。在BRCA1突变的异种移植瘤模型中,经口给予56(30 mg·kg-1·d-1,21 d)显示了较奥拉帕利(56.3%)更显著(96.6%)的肿瘤生长抑制作用;在BRCA2突变异种移植瘤模型中,43(10 mg·kg-1·d-1,28 d)显著抑制肿瘤生长(69.0%)且对小鼠体质量无负面影响。此外,56具有良好的口服生物利用度(32.2%),与奥拉帕利相当。此外,56的游离碱43表现出最小的hERG抑制活性。综上所述,56可能是治疗癌症,特别是BRCA缺陷型肿瘤的优秀候选药物。
• Substituted acylpiperazine derivatives
  申请人：Alberati-Giani Daniela

  公开号：US20050059668A1

  公开（公告）日：2005-03-17

  The invention relates to compounds of formula wherein the substituents are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The invention further relates to methods for the treatment of psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  该发明涉及以下式中的化合物，其中取代基如规范中定义，并且其药用可接受的酸盐。该发明还涉及治疗精神病、疼痛、记忆和学习中的神经退行性功能障碍、精神分裂症、痴呆症以及其他认知过程受损的疾病的方法，如注意力缺陷障碍或阿尔茨海默病。