3-(4-苯基哌嗪-1-基)丙酸 | 124078-87-1

• 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: 3-(4-苯基哌嗪-1-基)丙酸
• 英文名称: 3-(4-phenylpiperazin-1-yl)propanoic acid
• 英文别名: 3‐(4‐phenylpiperazin‐1‐yl)propanoic acid；3-(4-phenyl-1-piperazinyl)-propionic acid；3-(4-Phenylpiperazin-1-ium-1-yl)propanoate
• CAS: 124078-87-1
• 化学式: C₁₃H₁₈N₂O₂
• mdl: MFCD05668055
• 分子量: 234.298
• InChiKey: JUXGOBSASOVDKO-UHFFFAOYSA-N

物化性质

• 熔点：
  187.6-188.6 °C(Solv: water (7732-18-5))
• 沸点：
  412.7±40.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  3-(4-苯基哌嗪-1-基)丙酸 在 磷酸 、 三氯化磷 作用下， 以 氯苯 为溶剂， 反应 3.0h， 以17%的产率得到3-(4-phenylpiperazinyl)-1-hydroxy-propane-1,1-diphosphonic acid
  参考文献：
  名称：

  Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa)

  摘要：

  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.

  DOI：

  10.1021/jm020819i
• 作为产物：
  描述：

  1-(4-甲氧基苯基)哌嗪 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 3-(4-苯基哌嗪-1-基)丙酸
  参考文献：
  名称：

  新型多恶唑苯并恶唑酮/苯并噻唑酮衍生物的设计，合成和生物学评价

  摘要：

  在这项研究中，设计，合成和评估了具有苯并恶唑酮和苯并噻唑酮核心的四个系列化合物，作为对抗阿尔茨海默氏病（AD）的多功能药物。另外，为了阐明苯并恶唑酮/苯并噻唑酮的羰基的作用，还合成并评价了含苯并恶唑/苯并噻唑的类似物。测试了所有最终化合物对胆碱酯酶的抑制能力及其抗氧化活性。随后，还对所选化合物进行了抗炎活性，细胞毒性，细胞凋亡和Aβ聚集抑制试验。结果表明，化合物11c，具有苯并噻唑酮核心的戊酰胺衍生物和14b，具有苯并噻唑酮核心的酮衍生物，被认为是有希望的针对AD的进一步研究的多功能药物。还对具有最高AChE 14b（ee AChE IC 50  = 0.34μM，hu AChE IC 50  = 0.46μM）和BChE 11c（eq BChE IC 50  = 2.98μM，hu BChE ）的化合物进行了可逆性，动力学和分子对接研究IC 50  = 2.56μM）抑制活性。

  DOI：

  10.1016/j.ejmech.2020.113124

文献信息

• Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in-vitro acetylcholinesterase and butyrylcholinesterase
  作者：Burcu Kilic、Hayrettin O. Gulcan、Fatma Aksakal、Tugba Ercetin、Nihan Oruklu、E. Umit Bagriacik、Deniz S. Dogruer

  DOI：10.1016/j.bioorg.2018.05.006

  日期：2018.9

  A series of new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring were designed, synthesized and evaluated for their ability to inhibit both cholinesterase enzymes. In addition, a series of carboxamide and propanamide derivatives bearing biphenyl instead of phenylpyridazine were also synthesized to examine the inhibitory effect of pyridazine moiety on both cholinesterase

  设计，合成并评估了一系列以苯基哒嗪为核心环的新的羧酰胺和丙酰胺衍生物，以抑制它们同时抑制胆碱酯酶的能力。另外，还合成了一系列带有联苯而不是苯基哒嗪的羧酰胺和丙酰胺衍生物，以检验哒嗪部分对两种胆碱酯酶的抑制作用。抑制活性结果表明，化合物5b，5f，5h，5j，5l哒嗪-3-甲酰胺衍生物表现出选择性乙酰胆碱酯酶（AChE）抑制作用，IC 50值为0.11至2.69 µM。其中，化合物5h是活性最高的化合物（IC 50 = 0.11 µM），且其有效浓度对AChE无细胞毒性作用。此外，哒嗪-3-甲酰胺衍生物5d（AChE的IC 50 = 0.16 µM，BChE的IC 50 = 9.80 µM）和联苯-4-羧酰胺衍生物6d（AChE的IC 50 = 0.59 µM，BChE的IC 50 = 1.48 µM ）显示出双重胆碱酯酶抑制活性。此外，还测试了活性化合物抑制Aβ聚集的能力。化合物的理论理化
• Novel quinazolinone derivatives as 5-HT7 receptor ligands
  作者：Yong Ho Na、Sung Ho Hong、Jung Hyang Lee、Woo-Kyu Park、Du-Jong Baek、Hun Yeong Koh、Yong Seo Cho、Hyunah Choo、Ae Nim Pae

  DOI：10.1016/j.bmc.2007.11.049

  日期：2008.3

  the 5-HT(7) receptor of the quinazolinone library 1, which was designed with various substituents (X, Y, R(1), and R(2)) on the aromatic rings and different carbon chain length. Total 85 compounds of the quinazolinone library 1 were synthesized and the binding affinities of all the synthesized compounds were obtained by radioligand binding assay for the 5-HT(7) receptor. Among the 85 compounds, 24

  5-HT（7）受体拮抗剂在动物模型中产生了抗抑郁样作用，并且5-HT（7）受体参与了其他病理生理机制，例如温度调节，学习和记忆以及睡眠，这一点已被各种研究重点介绍。作为我们发现新型5-HT（7）受体拮抗剂的工作之一，我们在此报告喹唑啉酮文库1的5-HT（7）受体的合成和结合亲和力，该库设计有各种取代基（X，Y，R（1）和R（2））在芳香环上和不同的碳链长度。合成了喹唑啉酮文库1的总共85种化合物，并通过放射性配体结合测定法对5-HT（7）受体获得了所有合成化合物的结合亲和力。在85种化合物中，24种化合物显示出非常好的结合亲和力，IC（50）值低于100 nM。IC（50）值低于100 nM的化合物主要具有o-OMe或o-OEt作为R（2）取代基。具有最佳结合亲和力的化合物为1-68，其中IC（50）值为12 nM。在体内动物研究中，某些合成的化合物在小鼠的强迫游泳试验中确实具有抗抑郁活性。
• COLCHICINE DERIVATIVES
  申请人：——

  公开号：US20040204370A1

  公开（公告）日：2004-10-14

  Certain N-deacetylcolchicine and N-deacetylthiocolchine derivatives are described wherein the 7-N position on the B ring is substituted with the group —C(O)—(CHR 4 ) m -AR, wherein m is an integer of 0-10, A is S, O, N or a covalent bond; R 1 is substituted phenyl or substituted benzoyl; optionally substituted cycloalkyl of 3-7 carbons; optionally substituted naphtyl; an optionally substituted imide ring; an optionally substituted 5 or 6 member heterocycle with at least one N, S, or O in the ring; or an optionally substituted fused heterocyclic or fused carboxyclic ring system; R 2 (at the 2 -position of the A ring) is methoxy, hydroxy, or methylenedioxy when taken together with R 3 ; R 3 (at the 3 -position of the A ring) is methoxy, hydroxy, a monosaccharide radical, or is methylenedioxy when taken together with R 2 ; and R 4 is H or is H or methyl when m is 1. Also dimers of such compounds are disclosed. When combined with suitable pharmaceutical excipients, these compounds are useful for treating various types of cancer.

  描述了某些N-去乙酰基秋水仙碱和N-去乙酰基硫秋水仙碱衍生物，其中B环上的7-N位置被取代为基团—C(O)—(CHR4)m-AR，其中m为0-10的整数，A为S、O、N或共价键；R1为取代苯基或取代苯甲酰基；可选择取代的含有3-7个碳原子的环烷基；可选择取代的萘基；可选择取代的亚胺环；可选择取代的含有至少一个N、S或O的5或6元杂环；或可选择取代的融合杂环或融合环戊二酸环系统；R2（在A环的2位）为甲氧基、羟基或与R3一起时为亚甲二氧基；R3（在A环的3位）为甲氧基、羟基、单糖基团，或与R2一起时为亚甲二氧基；R4为H或在m为1时为H或甲基。此外，还公开了这些化合物的二聚体。与适当的药用辅料结合时，这些化合物可用于治疗各种类型的癌症。
• [EN] NITROGEN-BASED HOMO-CAMPTOTHECIN DERIVATIVES<br/>[FR] DERIVES AZOTES D'HOMO-CAMPTOTHECINE
  申请人：CALIFORNIA PACIFIC MED CENTER

  公开号：WO2003101998A1

  公开（公告）日：2003-12-11

  (20) esters of camptothecin analogs are provided. The compounds are (20) esters of an aminoalkanoic acid or an imidoalkanoic acid and homocamptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the homocamptothecin ring. The compounds are useful for treating cancer.

  提供了一种紧张素类似物的(20)酯。这些化合物是氨基烷酸或亚胺基烷酸与同伽蓝紧张素的(20)酯，该同伽蓝紧张素在7、9、10、11和12位置可能被取代。这些化合物可用于治疗癌症。
• Nitrogen-based camptothecin derivatives
  申请人：——

  公开号：US20030032624A1

  公开（公告）日：2003-02-13

  (20S) esters of camptothecin analogs are provided. The compounds are (20S) esters of an aminoalkanoic acid or an imidoalkanoic acid and camptothecin, which is optionally substituted at the 7, 9, 10, 11, and 12 positions of the camptothecin ring. The compounds are useful for treating cancer.

  提供了一种紫杉醇类似物的（20S）酯类。这些化合物是氨基烷基酸或亚胺基烷基酸和紫杉醇的（20S）酯，在紫杉醇环的第7、9、10、11和12位置可选择性地被取代。这些化合物可用于治疗癌症。