2-bromo-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone | 141333-65-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-bromo-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone
• 英文别名: 2-Bromo-1-[3-(cyclopentyloxy)-4-methoxyphenyl]ethanone；2-bromo-1-(3-cyclopentoxy-4-methoxyphenyl)ethanone；2-Bromo-1-[3-(cyclopentyloxy)-4-methoxyphenyl]ethan-1-one；2-bromo-1-(3-cyclopentyloxy-4-methoxyphenyl)ethanone
• CAS: 141333-65-5
• 化学式: C₁₄H₁₇BrO₃
• 分子量: 313.191
• InChiKey: WMKVGHONISCRRI-UHFFFAOYSA-N

物化性质

• 沸点：
  397.9±27.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone 、 4-amino-5-(3-methoxyphenyl)-4H-[1,2,4]triazole-3-thiol 以 乙醇 为溶剂， 以87%的产率得到6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(3-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
  参考文献：
  名称：

  Safety and Efficacy of New 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine Analogs as Potential Phosphodiesterase-4 Inhibitors in NIH-3T3 Mouse Fibroblastic Cells

  摘要：

  A novel series of potential phosphodiesterase‐4 (PDE‐4) inhibitors, 6‐(3‐(cyclopentyloxy)‐4‐methoxyphenyl)‐3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH‐3T3 cells to determine their safety and efficacy in NIH‐3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE‐4 inhibitor. The viability of cells was determined by (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐di‐phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme‐linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC50 of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE‐4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE‐4 enzyme.

  DOI：

  10.1111/j.1747-0285.2011.01167.x
• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 manganese(IV) oxide 、 copper(ll) bromide 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 反应 8.5h， 生成 2-bromo-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone
  参考文献：
  名称：

  Safety and Efficacy of New 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine Analogs as Potential Phosphodiesterase-4 Inhibitors in NIH-3T3 Mouse Fibroblastic Cells

  摘要：

  A novel series of potential phosphodiesterase‐4 (PDE‐4) inhibitors, 6‐(3‐(cyclopentyloxy)‐4‐methoxyphenyl)‐3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH‐3T3 cells to determine their safety and efficacy in NIH‐3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE‐4 inhibitor. The viability of cells was determined by (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐di‐phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme‐linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC50 of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE‐4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE‐4 enzyme.

  DOI：

  10.1111/j.1747-0285.2011.01167.x

文献信息

• Highly cis-Diastereoselective Synthesis of Coumarin-Based 2,3-Disubstituted Dihydrobenzothiazines by Organocatalysis
  作者：Mehdi Khoobi、Ali Ramazani、Alireza Foroumadi、Saeed Emami、Farnaz Jafarpour、Amir Mahyari、Katarzyna Ślepokura、Tadeusz Lis、Abbas Shafiee

  DOI：10.1002/hlca.201100357

  日期：2012.4

  organocatalyzed asymmetric reaction of phenacyl halides with coumarin‐based dihydrobenzothiazoles was developed to afford cis‐2,3‐disubstituted 3,4‐dihydro‐2H‐benzothiazines. This method provides a one‐step and highly diastereoselective route to a wide variety of coumarin‐based 3,4‐dihydro‐2H‐benzothiazines using the cheap and commercially available Cinchona alkaloid quinine hydrochloride.

  与香豆素系dihydrobenzothiazoles苯甲酰甲基卤化物的有效和organocatalyzed不对称反应物展开，获得顺式- 2,3-二取代的3,4-二氢-2- ħ -benzothiazines。该方法使用便宜的市售Cinchona生物碱奎宁盐酸盐为多种基于香豆素的3,4-二氢-2 H-苯并噻嗪提供了一步式且高度非对映选择性的途径。
• Pyrrolopyridazinone Compound
  申请人：Hagihara Masahiko

  公开号：US20090036453A1

  公开（公告）日：2009-02-05

  The present invention discloses a pyrrolopyridazinone compound represented by the formula (1): wherein R 1 represents C 1 -C 2 alkyl group or halogeno C 1 -C 2 alkyl group, R 2 repersents C 3 -C 5 cycloalkyl group, (C 3 -C 5 cycloalkyl)C 1 -C 2 alkyl group or C 1 -C 3 alkyl group, R 3 represents hydrogen atom, or methylene group or cis-vinylene group for forming substituted oxygen-containing hetero ring in combination with group —O—R 2 , R 4 represents hydrogen atom, halogen atom, C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, hydroxy C 3 -C 6 alkenyl group, hydroxy C 3 -C 6 alkynyl group, C 1 -C 6 alkyl group substituted by substituent(s) selected from Substituent group (a), C 3 -C 6 cycloalkyl group which may be substituted by substituent(s) selected from Substituent group (b), “C 1 -C 3 alkyl group which is substituted by C 3 -C 6 cycloalkyl group which may be substituted by substituent(s) selected from Substituent group (b), and which may be substituted by a hydroxy group”, an aromatic ring group or heteroaromatic ring group each of which may be substituted by a substituent(s) selected from Substituent group (c) or “C 1 -C 2 alkyl group which is substituted by aromatic ring group or heteroaromatic ring group each of which may be substituted by group(s) selected from Substituent group (c), and which may be substituted by a hydroxy group”, Substituent group (a) represents a halogen atom, hydroxy group, cyano group, carboxy group, C 1 -C 5 alkoxy group, halogeno C 1 -C 4 alkoxy group, C 3 -C 6 cycloalkoxy group, (C 3 -C 6 cycloalkyl)C 1 -C 2 alkoxy group, C 1 -C 4 alkoxycarbonyl group, C 2 -C 4 alkanoyl group, C 2 -C 4 alkanoyloxy group or C 1 -C 4 alkyl-substituted amino group, Substituent group (b) represents a hydroxy group or a halogen atom, Substituent group (c) represents a halogen atom, a hydroxy group, a cyano group, a nitro group, a carboxy group, C 1 -C 5 alkoxy group, C 1 -C 4 alkoxycarbonyl group, C 2 -C 4 alkanoyloxy group, C 1 -C 4 alkyl-substituted amino group or a C 1 -C 4 alkyl group which may be substituted by a substituent(s) selected from the group consisting of (a halogen atom, a hydroxy group and a carboxy group), or a pharmaceutically acceptable salt thereof.

  本发明公开了一种由式（1）表示的吡咯吡啶二酮化合物：其中，R1代表C1-C2烷基或卤代C1-C2烷基，R2代表C3-C5环烷基、（C3-C5环烷基）C1-C2烷基或C1-C3烷基，R3代表氢原子，或与基团-O-R2结合形成取代含氧杂环的亚甲基或顺式乙烯基，R4代表氢原子、卤素原子、C1-C8烷基、C2-C6烯基、C2-C6炔基、羟基C3-C6烯基、羟基C3-C6炔基、由从取代基团（a）中选择的取代基团取代的C1-C6烷基，可由从取代基团（b）中选择的取代基团取代的C3-C6环烷基，可由从取代基团（b）中选择的取代基团取代的C1-C3烷基，且可由羟基取代，芳香环基或杂芳香环基，每个都可由从取代基团（c）中选择的取代基团取代或由取代基团（c）选择的基团取代的C1-C2烷基，且可由羟基取代，取代基团（a）表示卤素原子、羟基、氰基、羧基、C1-C5烷氧基、卤代C1-C4烷氧基、C3-C6环烷氧基、（C3-C6环烷基）C1-C2烷氧基、C1-C4烷氧羰基、C2-C4酰基、C2-C4酰氧基或C1-C4烷基取代的氨基基团，取代基团（b）表示羟基或卤素原子，取代基团（c）表示卤素原子、羟基、氰基、硝基、羧基、C1-C5烷氧基、C1-C4烷氧羰基、C2-C4酰氧基、C1-C4烷基取代的氨基基团或可由从由卤素原子、羟基和羧基组成的基团中选择的取代基团取代的C1-C4烷基，或其药学上可接受的盐。
• Pyrrolopyridazinone compound
  申请人：Hagihara Masahiko

  公开号：US08450319B2

  公开（公告）日：2013-05-28

  The present invention discloses a pyrrolopyridazinone compound represented by the formula (1): useful, for example, as an anti-inflammatory agent or an inhibitor of respiratory tract contraction.

  本发明公开了一种由式(1)表示的吡咯吡啶并噻唑酮化合物：可用作抗炎剂或呼吸道收缩抑制剂。
• [DE] THIAZOL-DERIVATE ALS SELEKTIVE INHIBITOREN DER PDE-IV<br/>[EN] THIAZOLE DERIVATIVES USEFUL AS SELECTIVE INHIBITORS OF PDE-IV<br/>[FR] NOUVEAUX DERIVES DE THIAZOL S'UTILISANT COMME INHIBITEURS SELECTIFS DE LA PDE-IV
  申请人：BYK GULDEN LOMBERG CHEMISCHE FABRIK GMBH

  公开号：WO1998008844A1

  公开（公告）日：1998-03-05

  (DE) Verbindungen der Formel (I), worin R1, R2, R3, R4 und n die in der Beschreibung angegebenen Bedeutungen haben, sind neue wirksame Bronchialtherapeutika.(EN) Compounds having the formula (I), in which R1, R2, R3, R4 and n have the meanings given in the description, are new effective bronchotherapeutic agents.(FR) L'invention concerne des composés de la formule (I) dans laquelle R1, R2, R3, R4 et n ont la signification mentionnée dans la description. Ces composés sont de nouveaux agents thérapeutiques bronchiques actifs.

  将以下英文文本翻译成中文：仅返回翻译后的中文文本， （DE）Verbindungen der Formel (I), worin R1, R2, R3, R4 und n die in der Beschreibung angegebenen Bedeutungen haben, sind neue wirksame Bronchialtherapeutika. (EN) Compounds having the formula (I), in which R1, R2, R3, R4 and n have the meanings given in the description, are new effective bronchotherapeutic agents. (FR) L'invention concerne des composés de la formule (I) dans laquelle R1, R2, R3, R4 et n ont la signification mentionnée dans la description. Ces composés sont de nouveaux agents thérapeutiques bronchiques actifs.
• Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors
  作者：Amanda P. Skoumbourdis、Christopher A. LeClair、Eduard Stefan、Adrian G. Turjanski、William Maguire、Steven A. Titus、Ruili Huang、Douglas S. Auld、James Inglese、Christopher P. Austin、Stephen W. Michnick、Menghang Xia、Craig J. Thomas

  DOI：10.1016/j.bmcl.2009.01.057

  日期：2009.7

  An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively. (C) 2009 Published by Elsevier Ltd.