2-cyclopentylidenemalonic acid diethyl ester | 41589-42-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-cyclopentylidenemalonic acid diethyl ester
• 英文别名: cyclopentylidene-malonic acid diethyl ester；Cyclopentyliden-malonsaeure-diaethylester；cyclopentylidene-propanedioic acid, diethyl ester；Diethyl 2-cyclopentylidenepropanedioate
• CAS: 41589-42-8
• 化学式: C₁₂H₁₈O₄
• 分子量: 226.273
• InChiKey: LAVZDVNJFVRYRZ-UHFFFAOYSA-N

物化性质

• 沸点：
  327.88°C (rough estimate)
• 密度：
  1.0616

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyclopentylidenemalonic acid diethyl ester 在 potassium cyanide 、 乙醇 作用下， 生成 1-(羧甲基)环戊烷-1-羧酸
  参考文献：
  名称：

  Kon; Speight, Journal of the Chemical Society, 1926, p. 2733

  摘要：

  DOI：
• 作为产物：
  描述：

  cyclopentyl tosylate 在 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 27.0h， 生成 2-cyclopentylidenemalonic acid diethyl ester
  参考文献：
  名称：

  Stepwise Introduction of π-Electron Cross-Conjugation:  A Possible Access to [5]Radialenes?

  摘要：

  As starting points to the stepwise access to the corresponding [5]radialene, the unsaturated esters 14a and 18a have been prepared. These compounds have been isolated along with their isomers 14b and 18b, resulting from an intracyclic double-bond migration. Moreover a subsequent base-catalyzed process mediated the total isomerization of these mixtures to the latter more stable compounds 14b and 18b. The energy contents of the various compounds, and the corresponding tri- and tetrasubstituted higher homologues 19 and 20, have been calculated at the ab initio level, using several minimal as well as extended basis sets, and the observed experimental results rationalized.

  DOI：

  10.1021/jo970107d

文献信息

• Synthesis of Novel Potent Dipeptidyl Peptidase IV Inhibitors with Enhanced Chemical Stability:  Interplay between the N-Terminal Amino Acid Alkyl Side Chain and the Cyclopropyl Group of α-Aminoacyl-<scp>l</scp>-<i>cis</i>-4,5-methanoprolinenitrile-Based Inhibitors
  作者：David R. Magnin、Jeffrey A. Robl、Richard B. Sulsky、David J. Augeri、Yanting Huang、Ligaya M. Simpkins、Prakash C. Taunk、David A. Betebenner、James G. Robertson、Benoni E. Abboa-Offei、Aiying Wang、Michael Cap、Li Xin、Li Tao、Doree F. Sitkoff、Mary F. Malley、Jack Z. Gougoutas、Ashish Khanna、Qi Huang、Song-Ping Han、Rex A. Parker、Lawrence G. Hamann

  DOI：10.1021/jm049924d

  日期：2004.5.1

  inhibitors to date suffer from chemical instability stemming from an amine to nitrile intramolecular cyclization. Installation of a cyclopropyl moiety at either the 3,4- or 4,5-position of traditional 2-cyanopyrrolidide proline mimetics led to compounds with potent inhibitory activity against the enzyme. Additionally, cis-4,5-methanoprolinenitriles with beta-branching in the N-terminal amino acid provided enhanced

  合成了一系列含甲氧脯氨酸腈的二肽模拟物，并将其作为N端序列特异性丝氨酸蛋白酶二肽基肽酶IV（DPP-IV）的抑制剂进行了分析。DPP-IV的催化作用是降解胰高血糖素样肽1的主要手段，胰高血糖素样肽1是葡萄糖刺激的胰岛素分泌的关键介质，而DPP-IV的抑制显示出作为治疗2型糖尿病的新机制的临床益处。但是，迄今为止，许多可逆性抑制剂都具有从胺到腈分子内环化的化学不稳定性。在传统的2-氰基吡咯啉脯氨酸模拟物的3,4-或4,5-位上安装环丙基部分会导致产生对该酶具有强抑制活性的化合物。此外，顺式4 N末端氨基酸带有β支链的5-甲基脯氨酸腈提供了增强的化学稳定性和高抑制力。这类抑制剂还显示了在雄性Zucker大鼠口服葡萄糖激发后抑制餐后葡萄糖升高的能力。
• Brønsted Base-Modulated Regioselective Pd-Catalyzed Intramolecular Aerobic Oxidative Amination of Alkenes: Formation of Seven-Membered Amides and Evidence for Allylic C−H Activation
  作者：Liang Wu、Shuifa Qiu、Guosheng Liu

  DOI：10.1021/ol900941t

  日期：2009.6.18

  A novel palladium-catalyzed intramolecular aerobic oxidative allylic C−H amination of olefins has been developed. Brønsted base can modulate the regioselectivity, favoring the formation of 7-membered rings. Mechanistic studies using deuterium-labeled substrates as probes support a rate-determining allylic C−H activation/irreversible reductive elimination pathway.

  已经开发了一种新型的钯催化的烯烃分子内需氧氧化烯丙基CH胺化反应。布朗斯台德碱可以调节区域选择性，有利于7元环的形成。使用氘标记的底物作为探针的机理研究支持决定速率的烯丙基CH活化/不可逆还原消除途径。
• [EN] TRICYCLIC COMPOUNDS AS VASOPRESSIN V1A RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS TRICYCLIQUES UTILISÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR DE LA VASOPRESSINE V1A
  申请人：RICHTER GEDEON NYRT

  公开号：WO2019116325A1

  公开（公告）日：2019-06-20

  The present invention relates to 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine derivatives of general formula (I) and/or salts thereof and/or geometric isomers thereof and/or stereoisomers thereof and/or enantiomers thereof and/or racemates thereof and/or diastereomers thereof and/or biologically active metabolites thereof and/or prodrugs thereof and/or solvates thereof and/or hydrates thereof and/or polymorphs thereof which are centrally and/or peripherally acting V1a receptor modulators, particularly V1a receptor antagonists. Additional subject of the present invention is the process for the preparation of the compounds and the intermediates of the preparation process as well. The invention also relates to the pharmaceutical compositions containing the compounds or together with one or more other active substances, as well as to the use in the treatment and/or prophylaxis of a disease or condition associated with V1a receptor function.

  本发明涉及通式（I）的5,6-二氢-4H-[1,2,4]三唑[4,3-a][1]苯并蒽啉衍生物和/或其盐和/或其几何异构体和/或其立体异构体和/或其对映异构体和/或其消旋体和/或其二对映异构体和/或其生物活性代谢物和/或其前药和/或其溶剂化合物和/或其水合物和/或其多晶型，这些化合物是中枢和/或外周作用V1a受体调节剂，特别是V1a受体拮抗剂。本发明的另一个主题是化合物的制备方法以及制备过程的中间体。该发明还涉及含有这些化合物或与一个或多个其他活性物质一起的药物组合物，以及在治疗和/或预防与V1a受体功能相关的疾病或症状中的使用。
• Knoevenagel-kondensationen mit TiCl4/base—III
  作者：W. Lehnert

  DOI：10.1016/0040-4020(73)85007-0

  日期：1973.1

  In the presence of titanium tetrachloride and pyridine in THF, diethyl malonate undergoes condensation with aliphatic and aromatic ketones. The yields of the resulting α,β-unsaturated compounds are good even in cases, where other condensation methods are unsuccessful. Products, resulting from α-mono-, α,α-, α,α′-di- and α,α,α-trihalogeno ketones are probably of special interest as useful intermediates

  在THF中存在四氯化钛和吡啶的情况下，丙二酸二乙酯与脂肪族和芳香族酮缩合。即使在其他缩合方法不成功的情况下，所得的α，β-不饱和化合物的收率也良好。由α-单-，α，α-，α，α'-二-和α，α，α-三卤代酮制得的产物可能作为制备杂环的有用中间体特别受关注。
• Azepanone-based inhibitors of human cathepsin S: Optimization of selectivity via the P2 substituent
  作者：Jeffrey K. Kerns、Hong Nie、William Bondinell、Katherine L. Widdowson、Dennis S. Yamashita、Attiq Rahman、Patricia L. Podolin、Donald C. Carpenter、Qi Jin、Benoit Riflade、Xiaoyang Dong、Neysa Nevins、Paul M. Keller、Laura Mitchell、Thaddeus Tomaszek

  DOI：10.1016/j.bmcl.2011.06.045

  日期：2011.8

  A series of azepanone inhibitors of cathepsin S is described. Selectivity over both cathepsin K and cathepsin L was achieved by varying the P2 substituent. Ultimately, a balanced potency and selectivity profile was achieved in compound 39 possessing a 1-methylcyclohexyl alanine at P2 and nicotinamide as the P′ substituent. The cellular potency of selected analogs is also described.

  描述了一系列组织蛋白酶S的氮杂环庚烷抑制剂。通过改变P2取代基，可以实现对组织蛋白酶K和组织蛋白酶L的选择性。最终，在具有在P2处具有1-甲基环己基丙氨酸和作为P'取代基的烟酰胺的化合物39中实现了平衡的效能和选择性。还描述了所选类似物的细胞效力。