1-[(4-dimethylaminophenyl)carbonyl]piperazine | 610802-19-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[(4-dimethylaminophenyl)carbonyl]piperazine
• 英文别名: DAPPZ；N,N-Dimethyl-4-(piperazine-1-carbonyl)aniline；[4-(dimethylamino)phenyl]-piperazin-1-ylmethanone
• CAS: 610802-19-2
• 化学式: C₁₃H₁₉N₃O
• mdl: MFCD09934596
• 分子量: 233.313
• InChiKey: XNELEOAVITVYRL-UHFFFAOYSA-N

物化性质

• 沸点：
  415.5±40.0 °C(Predicted)
• 密度：
  1.118±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[(4-dimethylaminophenyl)carbonyl]piperazine 在 四(三苯基膦)钯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 caesium carbonate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.33h， 生成 (4-(4-(3-amino-1H-indazol-6-yl)benzoyl)piperazin-1-yl)(4-(dimethylamino)phenyl)methanone
  参考文献：
  名称：

  Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety

  摘要：

  As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-Abl(wT) and Bcr-Abl(T3151) in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-Abl(wT) and Bcr-Abl(T3151) kinases with IC50 of 0.043 mu M and 0.17 mu M, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 mu M and 5.42 mu M, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.091
• 作为产物：
  描述：

  哌啶 、 4-二甲氨基苯甲酸 在 三甲基乙酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 3.0h， 生成 1-[(4-dimethylaminophenyl)carbonyl]piperazine
  参考文献：
  名称：

  Discovery of novel Bcr-AblT315I inhibitors with flexible linker. Part 1: Confirmation optimization of phenyl-1H-indazol-3-amine as hinge binding moiety

  摘要：

  As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-Abl(wT) and Bcr-Abl(T3151) in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-Abl(wT) and Bcr-Abl(T3151) kinases with IC50 of 0.043 mu M and 0.17 mu M, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 mu M and 5.42 mu M, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.091

文献信息

• [EN] CARBAMIC ACID COMPOUNDS COMPRISING A PIPERAZINE LINKAGE AS HDAC INHIBITORS<br/>[FR] COMPOSES D'ACIDE CARBAMIQUE COMPRENANT UN CHAINON DE PIPERAZINE TELS QUE LES INHIBITEURS HDAC
  申请人：PROLIFIX LTD

  公开号：WO2003082288A1

  公开（公告）日：2003-10-09

  This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula:[Insert formula]wherein: Cy is independently a cyclyl group; Q1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J1 is independently a covalent bond or -C(=O)- ; J2 is independently -C(=O)- or -S(=O)2- ; Q2 is independently an acid leader group; wherein: Cy is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is independently: a covalent bond; C1-7alkylene; or C1-7alkylene-X-C1-7alkylene, -X-C1-7alkylene, or C1-7alkylene-X-, wherein X is -O- or -S-; and is optionally substituted; Q2 is independently: C4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q2 is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or, C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及一些碳酰胺化合物，其抑制以下式的HDAC（组蛋白去乙酰化酶）活性：[插入式]其中：Cy独立地是环烷基团；Q1独立地是共价键或环烷基团；哌嗪-1,4-二基基团可选地被取代；J1独立地是共价键或-C（=O）-；J2独立地是-C（=O）-或-S（=O）2-；Q2独立地是酸基团；其中：Cy独立地是C3-20碳环烷基、C3-20杂环烷基或C5-20芳基；并可选地被取代；Q1独立地是：共价键；C1-7烷基；或C1-7烷基-X-C1-7烷基、-X-C1-7烷基或C1-7烷基-X-，其中X是-O-或-S-；并可选地被取代；Q2独立地是：C4-8烷基；并可选地被取代；并且具有至少4个原子的骨架长度；或：Q2独立地是：C5-20芳基；C5-20芳基-C1-7烷基；C1-7烷基-C5-20芳基；或C1-7烷基-C5-20芳基-C1-7烷基；并可选地被取代；并且具有至少4个原子的骨架长度；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及包含这种化合物的制药组合物，以及这种化合物和组合物的使用，无论是体外还是体内，用于抑制HDAC，并用于治疗由HDAC介导的疾病，如癌症、增殖性疾病、牛皮癣等。
• CARBAMIC ACID COMPOUNDS COMPRISING A PIPERAZINE LINKAGE AS HDAC INHIBITORS
  申请人：WATKINS Clare J.

  公开号：US20080269237A1

  公开（公告）日：2008-10-30

  This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及以下化学式中抑制HDAC（组蛋白去乙酰化酶）活性的某些碳酰胺类化合物：同时，本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物的使用，无论是在体内还是体外，以抑制HDAC，并用于治疗由HDAC介导的疾病，如癌症、增殖性疾病、银屑病等。
• POLY (ADP-RIBOSE) POLYMERASE INHIBITOR
  申请人：Chengdu Di'ao Pharmaceutical Group Co., Ltd.

  公开号：EP2799435B1

  公开（公告）日：2018-03-28
• Synthesis and structure–activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor
  作者：Ga Eun Lee、Bhalchandra V. Joshi、Wangzhong Chen、Lak Shin Jeong、Hyung Ryong Moon、Kenneth A. Jacobson、Yong-Chul Kim

  DOI：10.1016/j.bmcl.2007.11.077

  日期：2008.1

  Analogues of the P2X(7) receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X(7) receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1 beta release in differentiated THP-1 cells. Substitution of the arylsulfonyl, moiety with a nitro group increased antagonistic potency relative to methyl substitution, such that compound 21 was slightly more potent than KN-62. Substitution with D-tyrosine in 36 and sterically bulky tyrosyl 3,5-dimethyl groups in 9 enhanced antagonistic potency. (c) 2007 Elsevier Ltd. All rights reserved.
• Unconjugated bile acids in rat brain: Analytical method based on LC/ESI-MS/MS with chemical derivatization and estimation of their origin by comparison to serum levels
  作者：Tatsuya Higashi、Shui Watanabe、Koki Tomaru、Wataru Yamazaki、Kazumi Yoshizawa、Shoujiro Ogawa、Hidenori Nagao、Kouichi Minato、Masamitsu Maekawa、Nariyasu Mano

  DOI：10.1016/j.steroids.2017.07.001

  日期：2017.9

  Although some studies have revealed the implication of bile acids (BAs) and neurological diseases, the levels and origin of the BAs in the brain are not fully understood. In this study, we first developed and validated a sensitive and specific method for the determination of three unconjugated BAs [cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)] in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry combined with chemical derivatization. The measured brain concentrations (mean +/- standard deviation, n = 10) of normal rats were 58.7 +/- 48.8, 14.2 +/- 11.7 and 13.2 +/- 8.7 ng/g tissue for CA, CDCA and DCA, respectively. For their origin, we developed the hypothesis that they might be mostly derived from the periphery. To test this hypothesis, the brain BA levels were compared with the serum levels. The brain levels had high correlations with the serum levels, and were always lower than the serum levels for the three unconjugated BAs. Furthermore, the higher brain-to-serum concentration ratios were found for the BAs with higher logD values (higher lipophilicity). Moreover, the brains of the rats intraperitoneally administered with deuterium-labeled CA and CDCA were also analyzed; the deuterium-labeled BAs were detected in the brain of the rats administered with these compounds. Based on all the results, we concluded that the BAs found in the brain are mostly derived from the periphery and the major mechanism for the transportation of the unconjugated BAs to the brain is by passive diffusion.