N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide | 791012-39-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide
• 英文别名: 4-(N-2,4-dichlorobenzylcarbamoyl)piperidine；N-[(2,4-dichlorophenyl)methyl]piperidine-4-carboxamide
• CAS: 791012-39-0
• 化学式: C₁₃H₁₆Cl₂N₂O
• 分子量: 287.189
• InChiKey: QNYVIVMXMZNMLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-三氟甲基苯磺酰氯 、 N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 N-[(2,4-dichlorophenyl)methyl]-1-[2-(trifluoromethyl)phenyl]sulfonylpiperidine-4-carboxamide
  参考文献：
  名称：

  Discovery of potent non-urea inhibitors of soluble epoxide hydrolase

  摘要：

  Soluble epoxide hydrolase (sEH) is a novel target for the treatment of hypertension and vascular inflammation. A new class of potent non-urea sEH inhibitors was identified via high throughput screening (HTS) and chemical modification. IC(50)s of the most potent compounds range from micromolar to low nanomolar. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.066
• 作为产物：
  描述：

  1-Cbz-4-哌啶甲酸甲酯 在 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 N-[(2,4-dichlorophenyl)methyl]-4-piperidinecarboxamide
  参考文献：
  名称：

  POTENT NON-UREA INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE

  摘要：

  本发明涉及通过抑制可溶性环氧合酶（sEH）的活性而具有血管舒张和抗炎效果的化合物。本发明还涉及识别此类化合物的方法，以及使用此类化合物治疗与血管舒张、炎症和/或内皮细胞功能障碍相关的疾病。特别是非限制性实施例中，发明的组成成分可用于治疗高血压。

  公开号：

  US20160052883A1

文献信息

• [EN] NOVEL sEH INHIBITORS AND THEIR USE<br/>[FR] NOUVEAUX INHIBITEURS DE sEH ET LEUR UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009097475A1

  公开（公告）日：2009-08-06

  The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula I:(I) wherein R1, R2, R3, R5, R6, R13, A, B, Y, Z, x, and m are defined herein, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及新型sEH抑制剂及其在通过sEH酶介导的疾病治疗中的应用。具体而言，该发明涉及符合以下式(I)的化合物：(I)其中R1、R2、R3、R5、R6、R13、A、B、Y、Z、x和m在此处定义，并其药学上可接受的盐。该发明的化合物是sEH抑制剂，可用于治疗通过sEH酶介导的疾病，如高血压。因此，该发明进一步涉及包括该发明的化合物的药物组合物。该发明还进一步涉及使用该发明的化合物或包含该发明的化合物的药物组合物来抑制sEH和治疗与之相关的疾病的方法。
• [EN] NOVEL SEH INHIBITORS AND THEIR USE<br/>[FR] NOUVEAUX INHIBITEURS DE SEH ET LEUR UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009097474A1

  公开（公告）日：2009-08-06

  The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula (I): wherein R1, R2, R3, R5a, R6a, A, B, K, L, M, Y, Z, x, and m are defined herein, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及新型sEH抑制剂及其在治疗由sEH酶介导的疾病中的应用。具体而言，该发明涉及符合以下式（I）的化合物：其中R1、R2、R3、R5a、R6a、A、B、K、L、M、Y、Z、x和m在此处定义，并且其药用盐。该发明的化合物是sEH抑制剂，可用于治疗由sEH酶介导的疾病，如高血压。因此，该发明还涉及包含该发明化合物的药物组合物。该发明还涉及使用该发明化合物或包含该发明化合物的药物组合物抑制sEH和治疗与之相关的疾病的方法。
• [EN] NOVEL SEH INHIBITORS AND THEIR USE<br/>[FR] INHIBITEURS INÉDITS DE LA SEH ET LEUR UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009049165A1

  公开（公告）日：2009-04-16

  The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R5a, R6a A, B, Y, x, and m are defined below, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及新颖的sEH抑制剂及其在通过sEH酶介导的疾病治疗中的应用。具体而言，该发明涉及符合以下式I的化合物：(I) 其中R1、R2、R3、R5a、R6a、A、B、Y、x和m的定义如下，并且其药用盐。该发明的化合物是sEH抑制剂，可用于治疗通过sEH酶介导的疾病，如高血压。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制sEH和治疗与之相关的疾病的方法。
• 4-Amino-2-piperidino-quinazolines
  申请人：Pfizer Inc.

  公开号：US04243666A1

  公开（公告）日：1981-01-06

  Regulators of the cardiovascular system and, in particular, in the treatment of hypertension having the formula ##STR1## wherein R is lower alkyl; X, is a 3- or 4-position substituent and is --(CH.sub.2).sub.n CONR.sup.1 R.sup.2, --O(CH.sub.2).sub.n CONR.sup.1 R.sup.2 or ##STR2## wherein n is 0, 1 or 2; R.sup.1 is hydrogen or lower alkyl, and R.sup.2 is lower alkyl; lower alkenyl, lower alkynyl, phenyl, substituted phenyl, C.sub.3 -C.sub.7 cycloalkyl; lower alkyl substituted by phenyl, substituted phenyl, C.sub.3 -C.sub.7 cycloalkyl, halogen, trifluoromethyl, hydroxy, lower alkoxy, lower alkoxycarbonyl, phenoxy, substituted phenoxy or --NR.sup.3 R.sup.4 wherein R.sup.3 and R.sup.4 each represent hydrogen, lower alkyl, lower alkanoyl or lower alkylsulfonyl; with the proviso that any O, N or halogen atom in R.sup.2 is separated by at least 2 carbon atoms from the nitrogen atom to which R.sup.2 is attached; or R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached form a morpholino group optionally substituted by one or two lower alkyl groups, or a 1,2,3,4-tetrahydroisoquinolyl group optionally substituted on the benzene ring portion by one or two lower alkoxy groups; the pharmaceutically acceptable bioprecursors therefor, and the pharmaceutically acceptable acid addition salts thereof.

  心血管系统的调节剂，尤其是治疗高血压的化合物的公式为##STR1##其中R是较低的烷基；X是3-或4-位取代基，为--(CH.sub.2).sub.n CONR.sup.1 R.sup.2，--O(CH.sub.2).sub.n CONR.sup.1 R.sup.2或##STR2##其中n为0、1或2；R.sup.1为氢或较低的烷基，而R.sup.2为较低的烷基；较低的烯基，较低的炔基，苯基，取代苯基，C.sub.3-C.sub.7环烷基；较低的烷基被苯基，取代苯基，C.sub.3-C.sub.7环烷基，卤素，三氟甲基，羟基，较低的烷氧基，较低的烷氧羰基，苯氧基，取代苯氧基或--NR.sup.3 R.sup.4取代的；其中R.sup.3和R.sup.4分别表示氢，较低的烷基，较低的烷酰基或较低的烷基磺酰基；但R.sup.2中的任何O、N或卤原子与R.sup.2连接的氮原子至少相隔2个碳原子；或R.sup.1和R.sup.2与它们连接的氮原子一起形成一个吗啡基，该吗啡基可以选择地被一个或两个较低的烷基取代，或者一个1,2,3,4-四氢异喹啉基，该基可以选择地在苯环部分被一个或两个较低的烷氧基取代；其药用上可接受的生物前体，以及其药用上可接受的酸加盐。
• Inhibitors of monomine uptake
  申请人：Barry Clark Peter

  公开号：US20060079554A1

  公开（公告）日：2006-04-13

  N,N-disubstituted 4-amino-piperidines of the general Formula (I) are inhibitors of the uptake of serotonin and/or norepinephrine and/or dopamine. As such, they may be useful for the treatment of disorders of the central and/or peripheral nervous system.

  通式为（I）的N,N-二取代4-氨基哌啶是血清素和/或去甲肾上腺素和/或多巴胺摄取抑制剂。因此，它们可能对中枢和/或周围神经系统的疾病治疗有用。