3-(4-benzylpiperazin-1-yl)propan-1-ol | 23253-99-8

• 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: 3-(4-benzylpiperazin-1-yl)propan-1-ol
• 英文别名: 1-benzyl-4-(3-hydroxypropyl)piperazine
• CAS: 23253-99-8
• 化学式: C₁₄H₂₂N₂O
• mdl: MFCD11613840
• 分子量: 234.341
• InChiKey: BKRJTLPVSARANE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-benzylpiperazin-1-yl)propan-1-ol 在 盐酸 、 硝酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 氯仿 、 溶剂黄146 为溶剂， 反应 2.0h， 生成 1-benzyl-4-[3-(4-hydroxy-3-nitrocoumarin-7-yloxy)propyl]piperazine
  参考文献：
  名称：

  N-Benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties

  摘要：

  In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.

  DOI：

  10.1021/jm00377a013
• 作为产物：
  描述：

  1-(ethylcarboxy)-4-benzylpiperazine 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙二醇乙醚 、 丁酮 为溶剂， 反应 21.0h， 生成 3-(4-benzylpiperazin-1-yl)propan-1-ol
  参考文献：
  名称：

  N-Benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties

  摘要：

  In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.

  DOI：

  10.1021/jm00377a013

文献信息

• N-Alkylated 1,4-Dihydropyridines: New Agents to Overcome Multidrug Resistance.
  作者：Koji OHSUMI、Kazuo OHISHI、Yoshihiro MORINAGA、Ryusuke NAKAGAWA、Yasuyo SUGA、Takaaki SEKIYAMA、Yukio AKIYAMA、Takashi TSUJI、Takashi TSURUO

  DOI：10.1248/cpb.43.818

  日期：——

  New N-alkylated 1, 4-dihydropyridine derivatives were synthesized and their ability to overcome multidrug resistance was examined in vincristine-resistant P388 cells (P388/VCR cells). Compounds that possessed an arylalkyl substituent on the dihydropyridine ring nitrogen were more potent than verapamil in potentiating the cytotoxicity of vincristine against P388/VCR cells. However, neither drug effectively enhanced the antitumor activity of vincristine in tumor-bearing mice. Introduction of basic nitrogen-containing substituents on the side chain of 1, 4-dihydropyridines gave improved activity in vitro and in vivo. The piperazine derivative 12c and 12o were more than 10 times as potent as verapamil in vitro. Four compounds selected for in vivo testing showed superior antitumor activity in P388/VCR-bearing mice in combination with vincristine. The structure-activity relationships of the compounds are discussed.

  新合成的N-烷基化1,4-二氢吡啶衍生物，在长春新碱耐药的P388细胞（P388/VCR细胞）中检测了其克服多药耐药的能力。在二氢吡啶环氮上带有芳烷基取代基的化合物，比维拉帕米更能增强长春新碱对P388/VCR细胞的细胞毒性。然而，这两种药物均未有效地增强长春新碱在携带肿瘤的小鼠中的抗肿瘤活性。在1,4-二氢吡啶的侧链上引入含有碱性氮的取代基，在体外和体内均能提高活性。哌嗪衍生物12c和12o在体外比维拉帕米强10倍以上。选出四种化合物进行体内测试，它们与长春新碱联合使用时，在携带P388/VCR的肿瘤小鼠中显示出优越的抗肿瘤活性。讨论了化合物的构效关系。
• 5-memberd heteroaryl substituted 1,4-dihydropyridine compounds as bradykinin antagonists
  申请人：——

  公开号：US20010046993A1

  公开（公告）日：2001-11-29

  This invention provides a compound of the formula (I): 1 or the pharmaceutically acceptable salts thereof wherein A is independently halo; Y 1 is —(CH 2 ) m —, C(O) or S(O); Y 2 is N or CH; R 1 and R 2 are independently C 1-4 alkyl; R 3 is selected from the following: (a) optionally substituted —(CH 2 ) p —C 3-7 cycloalkyl; (b) optionally substituted —C 5-7 alkyl; and (c) substituted —C 1-4 alkyl; and (d) optionally substituted C 7- bicycloalkyl; R 4 is optionally substituted thiazolyl, imidazolyl or oxazolyl; X is S, —NH, —N—C 1-4 alkyl or O; R 5 is hydrogen or C 1-4 alkyl; R 6 is C 1-4 alkyl or halo; m is 0, 1 or 2; n is 0, 1, 2, 3, 4 or S; and p is 0, 1, 2, 3, 4, 5 or 6. These compounds are useful for the treatment of medical conditions caused by bradykinin such as inflammation, cardiovascular disease, pain, etc. This invention also provides a pharmaceutical composition comprising the above compound.

  这项发明提供了以下式(I)的化合物或其药学上可接受的盐，其中A独立地是卤素；Y1是—(CH2)m—、C(O)或S(O)；Y2是N或CH；R1和R2独立地是C1-4烷基；R3从以下选项中选择：(a) 可选地取代的—(CH2)p—C3-7环烷基；(b) 可选地取代的—C5-7烷基；以及(c) 取代的—C1-4烷基；和(d) 可选地取代的C7双环烷基；R4是可选地取代的噻唑基、咪唑基或噁唑基；X是S、—NH、—N—C1-4烷基或O；R5是氢或C1-4烷基；R6是C1-4烷基或卤素；m是0、1或2；n是0、1、2、3、4或S；p是0、1、2、3、4、5或6。这些化合物可用于治疗由激肽酶引起的医疗状况，如炎症、心血管疾病、疼痛等。该发明还提供了包含上述化合物的药物组合物。
• Search for new multi-target compounds against Alzheimer’s disease among histamine H3 receptor ligands
  作者：Marek Bajda、Dorota Łażewska、Justyna Godyń、Paula Zaręba、Kamil Kuder、Stefanie Hagenow、Kamil Łątka、Ewelina Stawarska、Holger Stark、Katarzyna Kieć-Kononowicz、Barbara Malawska

  DOI：10.1016/j.ejmech.2019.111785

  日期：2020.1

  Multi-target-directed ligands seem to be an interesting approach to the treatment of complex disorders such as Alzheimer's disease. The aim of the present study was to find novel multifunctional compounds in a non-imidazole histamine H3 receptor ligand library. Docking-based virtual screening was applied for selection of twenty-six hits which were subsequently evaluated in Ellman's assay for the inhibitory

  靶向多靶标的配体似乎是治疗复杂疾病（例如阿尔茨海默氏病）的有趣方法。本研究的目的是在非咪唑组胺H3受体配体库中发现新型多功能化合物。基于对接的虚拟筛选用于选择26个命中，随后在Ellman分析中评估了对乙酰基（AChE）和丁酰胆碱酯酶（BuChE）的抑制能力。具有高成功率的虚拟筛选能够选择多靶标定向的配体。根据对接结果，所有选定的配体均能够结合AChE和BuChE的催化位点和外围位点。最有前途的衍生物通过六个碳原子接头将黄酮部分与杂环部分（例如氮杂环庚烷）结合在一起，哌啶或3-甲基哌啶。他们显示出对胆碱酯酶的最高抑制活性，以及​​对H3R和这两种酶的均衡功效。选择了两个导数-5（IC50 = 0.46μM（AChE）; 0.44μM（BuChE）; Ki = 159.8 nM（H3R））和17（IC50 = 0.50μM（AChE）; 0.76μM（BuChE）; Ki = 228.2 nM
• Heterocyclic coumarin derivatives
  申请人：Beecham Group Limited

  公开号：US04263299A1

  公开（公告）日：1981-04-21

  A compound of formula (I): ##STR1## and pharmaceutically acceptable salts thereof, wherein R is hydrogen or an alkyl group containing up to 6 carbon atoms; X is a bond or oxygen; Y is --(CH.sub.2).sub.n -- where n is 0 or an integer from 1 to 5 wherein one carbon atom not bound to the nitrogen atom may be optionally substituted with a hydroxy group; and Z is hydrogen or halogen; may be used in the prophylaxis and treatment of diseases whose symptoms are controlled by the mediators of the allergic response, for example asthma, hay-fever, rhinitis and allergic eczema.

  化合物的结构式（I）：##STR1##及其药学上可接受的盐，其中R是氢或含有最多6个碳原子的烷基基团；X是键或氧；Y是--(CH.sub.2).sub.n--，其中n为0或1至5的整数，其中一个未与氮原子结合的碳原子可以选择性地被羟基取代；Z是氢或卤素；可用于预防和治疗由过敏反应介质控制症状的疾病，例如哮喘、花粉症、鼻炎和过敏性湿疹。
• 6-phenyltetrahydro-1,3-oxazin-2-one derivative and pharmaceutical composition containing the same
  申请人：Nikken Chemicals Co., LTD

  公开号：US06251897B1

  公开（公告）日：2001-06-26

  A 6-phenyltetrahydro-1,3-oxazin-2-one derivative having the formula (I): wherein, R1 is an unsubstituted or substituted C1 to C8 alkyl group; an unsubstituted or substituted C3 to C7 cycloalkyl group;, etc., R2 is a C1 to C4 alkyl group, R3 is H; an unsubstituted or substituted C1 to C5 alkyl group; etc., R4 is H; an unsubstituted or substituted C1 to C6 alkyl group, and R5 and R6 are independently a hydrogen atom; an unsubstituted or substituted C1 to C5 alkyl group; etc. an optical isomer thereof, or a pharmacologically acceptable salt thereof, or a hydrate or a solvate thereof and pharmaceutical compositions containing the same, in particular a drug for the prevention or treatment of inflammatory diseases and a drug for asthma. The above 6-phenyltetrahydro-1,3-oxazin-2-one derivative has a strong type IV PDE inhibitory activity and has a bronchiodilator and antiinflammatory effects.

  具有以下结构式（I）的6-苯基四氢-1,3-噁嗪-2-酮衍生物：其中，R1是未取代或取代的C1至C8烷基基团；未取代或取代的C3至C7环烷基基团；等等，R2是C1至C4烷基基团，R3是H；未取代或取代的C1至C5烷基基团；等等，R4是H；未取代或取代的C1至C6烷基基团，R5和R6独立地是氢原子；未取代或取代的C1至C5烷基基团；等等。其光学异构体，或其药理学上可接受的盐，或其水合物或溶剂合物，以及含有它们的药物组合物，特别是用于预防或治疗炎症性疾病和哮喘的药物。上述6-苯基四氢-1,3-噁嗪-2-酮衍生物具有强烈的Ⅳ型磷酸二酯酶抑制活性，并具有支气管扩张剂和抗炎作用。