4-(4-isopropyl-piperazin-1-yl)-benzoic acid | 354813-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-isopropyl-piperazin-1-yl)-benzoic acid
• 英文别名: 4-(4-Propan-2-ylpiperazin-4-ium-1-yl)benzoate
• CAS: 354813-24-4
• 化学式: C₁₄H₂₀N₂O₂
• mdl: MFCD06742240
• 分子量: 248.325
• InChiKey: TVFABCRYJXZFKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-isopropyl-piperazin-1-yl)-benzoic acid 生成 4-(4-isopropylpiperazin-1-yl)-N-((S)-1-((3aS,6R,6aS)-6-methoxy-3-oxodihydro-2H-furo[3,2-b]pyrrol-4(5H,6H,6aH)-yl)-4,4-dimethyl-1-oxopentan-2-yl)benzamide
  参考文献：
  名称：

  WO2008/7114

  摘要：

  公开号：
• 作为产物：
  描述：

  1-异丙基哌嗪 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 生成 4-(4-isopropyl-piperazin-1-yl)-benzoic acid
  参考文献：
  名称：

  通过基于片段的虚拟筛选，设计和合成新型1H-1,2,4-三唑，苯并噻唑和吲唑基衍生物，作为有效的FGFR1抑制剂。

  摘要：

  成纤维细胞生长因子受体（FGFR）是癌症治疗的潜在靶标。通过基于片段的虚拟筛选，我们设计了三种新型的带有吲唑，苯并噻唑和1H-1,2,4-三唑支架的FGFR1抑制剂。在体外评估所有新合成的化合物对FGFR1的抑制活性。首先将带有吲唑支架的化合物9d鉴定为具有优良激酶抑制活性（IC50 = 15.0 nM）和适度的抗增殖活性（IC50 = 785.8 nM）的命中化合物。通过两轮优化，吲唑衍生物9 u是最强的FGFR1抑制剂，具有最佳的酶抑制活性（IC50 = 3.3 nM）和细胞活性（IC50 = 468.2 nM）。此外，9 u还表现出良好的激酶选择性。此外，

  DOI：

  10.1080/14756366.2019.1673745

文献信息

• Benzamide nitriles
  申请人：——

  公开号：US20040248949A1

  公开（公告）日：2004-12-09

  Compounds of the formula (I) 1 wherein m, n, A, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as described herein, together with methods for making the compounds and using the compounds for treatment of diseases or conditions mediated by Cathepsin K.

  式（I）的化合物 其中m，n，A，R1，R2，R3，R4，R5和R6如本文所述，以及制备这些化合物的方法以及利用这些化合物治疗由Cathepsin K介导的疾病或症状。
• Furo[3,2-B] pyrrol -3-one derivatives and their use as cysteinyl porteinase inhibitors
  申请人：Quibell Martin

  公开号：US20100010009A1

  公开（公告）日：2010-01-14

  The present invention relates to compounds of formula (1), and pharmaceutically acceptable salts thereof, A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof (I), wherein: one of R 1 and R 2 is H, and the other is selected from F and Cl, or R 1 and R 2 are both F; R 3 is selected from cyclopentyl and cyclohexyl; R 4 is an optionally substituted 5- or 6-membered monocyclic or an 8- to 10-membered bicyclic aryl or heteroaryl ring which includes up to four heteroatoms. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及式（1）的化合物及其药学上可接受的盐，式（I）的化合物或药学上可接受的盐、水合物、配合物或前药，其中：R1和R2中的一个为H，另一个为F和Cl中的一种，或R1和R2均为F；R3选自环戊基和环己基；R4为可选取代的5-或6-成员单环或8-到10-成员的双环芳基或杂环芳基环，其中包含最多四个杂原子。本发明还涉及包括式（I）的化合物的制药组合物，并且在治疗骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病以及骨癌疾病如骨转移和相关疼痛中使用这种化合物的用途。
• VLA-4 inhibitor compounds
  申请人：Baldwin J. John

  公开号：US20070054909A1

  公开（公告）日：2007-03-08

  Compounds that selectively inhibit the binding of ligands to α4β1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion.

  本发明揭示了选择性抑制配体与α4β1整合素（VLA-4）结合的化合物以及它们的制备方法。在一种实施例中，本发明的化合物由式I表示：作为VLA-4介导的细胞黏附的选择性抑制剂，本发明的化合物可用于治疗与此类黏附相关的疾病，包括但不限于炎症和自身免疫反应、糖尿病、哮喘、牛皮癣、炎症性肠病、移植排斥和肿瘤转移等疾病。本发明还揭示了抑制VLA-4介导的细胞黏附的方法以及治疗与VLA-4介导的细胞黏附相关的疾病的方法。
• FURO[3. 2-B] PYRROL DERIVATIVES
  申请人：Quibell Martin

  公开号：US20100216811A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R 3 is tert-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R 4 is optionally substituted C 1-8 alkyl or optionally substituted C 3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及式（I）的化合物及其药学上可接受的盐，其中：R3是叔丁基甲基、仲丁基或叔丁基；X是CH或N；R4是可选取代的C1-8烷基或可选取代的C3-8环烷基。本发明还涉及包含式（I）的化合物的药物组合物，以及将这些化合物用于治疗从骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病，以及骨癌疾病，如骨转移和相关疼痛。
• Tetrahydrofuro[3,2-B] pyrrol-3-ones as cathepsin K inhibitors
  申请人：Amura Therapeutics Limited

  公开号：US07803803B2

  公开（公告）日：2010-09-28

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl, or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; and R8 is C1-8-alkyl or C3-8-cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及公式(I)的化合物及其药学上可接受的盐，其中：X为CH或N；R1和R2中的一个为H，另一个选择自OR6、SR6、NR6R7、N3、Me、Et、CF3、SOR8和SO2R8；R3选择自叔丁基甲基、异丙基甲基、仲丁基、叔丁基、环戊基和环己基；R4为可选择性取代的C1-8烷基或可选择性取代的C3-8环烷基；R6和R7各自独立地选择自H、C1-8烷基和C3-8环烷基，或R6和R7与它们所附着的氮一起形成一个环状基团；R8为C1-8烷基或C3-8环烷基。本发明还涉及包含公式(I)化合物的药物组合物，以及在治疗骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病以及骨癌疾病如骨转移和相关疼痛中使用这种化合物的用途。