3-cyclopentyloxy-N'-hydroxy-4-methoxybenzenecarboximidamide | 874485-04-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-cyclopentyloxy-N'-hydroxy-4-methoxybenzenecarboximidamide
• CAS: 874485-04-8
• 化学式: C₁₃H₁₈N₂O₃
• mdl: MFCD00830999
• 分子量: 250.298
• InChiKey: IXCVJUBFNZUOPG-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：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  77.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-cyclopentyloxy-N'-hydroxy-4-methoxybenzenecarboximidamide 在 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 ethyl 4-(3-(3-cyclopentyloxy-4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2

  摘要：

  A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.

  DOI：

  10.1111/j.1747-0285.2011.01304.x
• 作为产物：
  描述：

  3-羟基-4-甲氧基苯腈 在 盐酸羟胺 、 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-cyclopentyloxy-N'-hydroxy-4-methoxybenzenecarboximidamide
  参考文献：
  名称：

  Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2

  摘要：

  A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.

  DOI：

  10.1111/j.1747-0285.2011.01304.x

文献信息

• [EN] DIMERIC PIPERIDINE DERIVATIVES<br/>[FR] DERIVES DE PIPERIDINE DIMERES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006008260A1

  公开（公告）日：2006-01-26

  The compounds of the following formula (I) : the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, useful in the treatment of neurodegenerative mediated disorders.

  以下公式（I）的化合物：N-氧化物形式，药用可接受的添加盐及其立体异构形式，在治疗神经退行性媒介紊乱中具有用途。
• Synthesis of novel 1,2,4-oxadiazoles and analogues as potential anticancer agents
  作者：Dalip Kumar、Gautam Patel、Angela K. Chavers、Kuei-Hua Chang、Kavita Shah

  DOI：10.1016/j.ejmech.2011.03.031

  日期：2011.7

  A library of 3,5-disubstituted-1,2,4-oxadiazoles 7–9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of oxadiazoles 7–9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres

  合成了3,5-二取代-1,2,4-恶二唑7–9及其生物等效物1,3,4-恶二唑14和1,3,4-噻二唑16的文库，并对其体外抗癌性进行了评估。对一组六种人类癌细胞系的潜力。合成恶二唑7–9的关键步骤包括将of胺肟6与适当的羧酸偶联，然后进行热环化。由常见的前体二酰基肼13的反应制备生物甾体1,3,4-恶二唑14和1,3,4-噻二唑16分别使用亚硫酰氯和Lawesson试剂。对合成化合物的抗癌研究表明，在C-3芳基环上存在环戊氧基或正丁氧基，在1,2,4-恶二唑的C-5位置上存在哌啶-4-基或三氯甲基是必不可少的。活动。尤其是1,2,4-恶二唑7i和类似物1,3,4-噻二唑16分别显示出对DU145（IC 50：9.3μM）和MDA-MB-231（IC 50：9.2μM）细胞系的显着活性。。
• Synthesis and anticancer activities of novel 3,5-disubstituted-1,2,4-oxadiazoles
  作者：Dalip Kumar、Gautam Patel、Emmanuel O. Johnson、Kavita Shah

  DOI：10.1016/j.bmcl.2009.03.158

  日期：2009.5

  A series of 3,5-disubstituted-1,2,4-oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Formation of 1,2,4-oxadiazole ring was accomplished by the reaction of amidoxime with carboxylic acids. The in vitro cytotoxic effects of 3,5-disubstituted-1,2,4-oxadiazoles have been demonstrated across a wide array of tumor cell types and

  合成了一系列3,5-二取代-1,2,4-恶二唑，并评估了它们对各种癌细胞的体外抗增殖活性。1,2,4-恶二唑环的形成是通过of胺肟与羧酸的反应完成的。已在多种肿瘤细胞类型中证明了3,5-二取代-1,2,4-恶二唑的体外细胞毒性作用，一些化合物对胰腺（3f，3h，3j和3k）和前列腺具有特异性（3n）癌细胞。在制备的3,5-二取代-1,2,4-恶二唑中，化合物3n的选择性最高（> 450倍），化合物3p 对前列腺癌细胞系具有最大的细胞毒性（10 nM）。
• Dimeric Piperidine Derivatives
  申请人：Cik Miroslav

  公开号：US20080015225A1

  公开（公告）日：2008-01-17

  the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; R 2 represents hydroxy; —X— represents C 2-4 alkynyl, C 1-12 alkyl optionally substituted with hydroxy or X represents a divalent radical of the formula wherein; —X 1 — represents C 1-12 alkyl, phenyl or a divalent radical selected from the group consisting of —X 2 — represents C 1-12 alkyl, C 1-4 alkyloxyC 1-4 alkyl, phenyl or a divalent radical of formula —X 3 — represents phenyl or a divalent radical selected from the group consisting of R 1 independently represents hydrogen, C 1-4 alkyl, C 1-4 alkyloxy-, Ar 1 , Ar 2 -carbonyl, Het 1 -C 1-4 alkyl, Het 2 , NR 3 R 4 —C 1-4 alkyl, Ar 3 -C 1-4 alkyloxy- or Het 4 -oxy-; R 3 and R 4 each independently represents hydrogen, C 1-4 alkyl, C 1-4 alkyloxy-, or Het 3 ; Het 1 represents a heterocycle selected from pyridinyl, indolinyl, indolyl, benzimidazolyl, benzthiazolyl, benzisoxazolyl, thiazolyl, pyridinyl, or thiadiazolyl wherein said Het 1 is optionally substituted with one or where possible two or more substituents selected from the group consisting of hydroxy, halo, C 1-4 alkyloxycarbonyl-, C 1-4 alkyl-, C 1-4 alkyloxy- and C 1-4 alkyloxy-substituted with halo; in particular Het 1 represents a heterocycle selected from indolyl or pyridinyl; Het 2 represents a heterocycle selected from indolyl, benzisoxazolyl or oxodiazolyl wherein said Het 2 is optionally substituted with one or where possible two or more substituents selected from the group consisting of hydroxy, halo, C 1-6 alkyl- and C 1-4 alkyloxy-; Het 3 represents a heterocycle selected from benzimidazolyl, benzisoxazolyl or benzthiazolyl wherein said Het 3 is optionally substituted with one or where possible two or more substituents selected from the group consisting of hydroxy, halo, C 1-6 alkyl- and C 1-4 alkyloxy-; in particular Het 3 represents benzthiazolyl substituted with C 1-4 alkyloxy-; Het 4 represents a heterocycle selected from benzimidazolyl, benzisoxazolyl or benzthiazolyl wherein said Het 4 is optionally substituted with one or where possible two or more substituents selected from the group consisting of hydroxy, halo, C 1-6 alkyl- and C 1-4 alkyloxy-; in particular Het 4 represents benzthiazolyl; Ar 1 represents phenyl optionally substituted with halo, C 1-4 alkyl or C 1-4 alkyl substituted with one, two or three halo substituents; Ar 2 represents phenyl optionally substituted with halo, C 1-4 alkyl or C 1-4 alkyl substituted with one, two or three halo substituents; in particular Ar 2 represents phenyl substituted with halo or trifluromethyl; Ar 3 represents phenyl optionally substituted with halo, C 1-4 alkyl or C 1-4 alkyloxy-.
• Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2
  作者：Dalip Kumar、Gautam Patel、Lalitha Vijayakrishnan、Sunanda G. Dastidar、Abhijit Ray

  DOI：10.1111/j.1747-0285.2011.01304.x

  日期：2012.5

  A series of 3,5‐disubstituted‐1,2,4‐oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5‐disubstituted‐1,2,4‐oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50 = 5.28 μm). Structure–activity relationship studies of 3,5‐disubstituted‐1,2,4‐oxadiazoles revealed that substituents 3‐cyclopentyloxy‐4‐methoxyphenyl group at 3‐position and cyclic ring bearing heteroatoms at 5‐position are important for activity. Molecular modeling study of the 3,5‐disubstituted‐1,2,4‐oxadiazoles with PDE4B has shown similar interactions of 3‐cyclopentyloxy‐4‐methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3‐(3‐Cyclopentyloxy‐4‐methoxyphenyl)‐5‐(piperidin‐4‐yl)‐1,2,4‐oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin‐induced pain in mice and carrageenan‐induced paw edema model in rat.