2-cyano-1-hydroxymethylcyclopropane | 39891-85-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-cyano-1-hydroxymethylcyclopropane
• 英文别名: racemic trans-2-(hydroxymethyl)cyclopropanecarbonitrile；trans-2-(hydroxymethyl)cyclopropane-1-carbonitrile；trans-2-Hydroxymethylcyclopropancarbonitril；trans-2-(hydroxymethyl)cyclopropanecarbonitrile；(1R,2R)-2-(hydroxymethyl)cyclopropane-1-carbonitrile
• CAS: 39891-85-5
• 化学式: C₅H₇NO
• 分子量: 97.1167
• InChiKey: YRFBEHLXLHSHMV-WHFBIAKZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-cyano-1-hydroxymethylcyclopropane 在 三乙烯二胺 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 racemic trans-2-(aminomethyl)cyclopropanecarbonitrile
  参考文献：
  名称：

  [EN] 5-(7H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)-5-AZASPIRO[2.5]OCTANE-8-CARBOXYLIC ACID DERIVATIVES AS NOVEL JAK KINASE INHIBITORS
  [FR] DÉRIVÉS D'ACIDE 5-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-5-AZASPIRO[2,5] OCTANE-8-CARBOXYLIQUE EN TANT QUE NOUVEAUX INHIBITEURS DE KINASE JAK

  摘要：

  本发明涉及一种符合式(I)的化合物，其中X代表NH或O；n是从1到3选择的整数；Y代表键，-C(O)O- *，-C(O)OR3- *或-C(O)NHR3- *；W选自苯基，吡啶基，(C3-C7)环烷基和4-6成员杂环烷基的组；或其药学上可接受的盐，水合物或溶剂合物。本发明进一步涉及所述化合物在治疗中的用途，包括含有所述化合物的药物组合物，用所述化合物治疗疾病的方法，以及所述化合物用于制造药品的用途。

  公开号：

  WO2018141842A1
• 作为产物：
  描述：

  (1S,2R)-2-Hydroxymethyl-cyclopropanecarbonitrile 在 三氟乙酸 作用下， 以 氘代氯仿 为溶剂， 反应 48.0h， 生成 2-cyano-1-hydroxymethylcyclopropane
  参考文献：
  名称：

  经由开环机理对取代的（顺式）-受体-供体环丙烷进行酸性异构化

  摘要：

  在中酸性条件下，合成了许多带有1-吸电子基团和2-羟基亚甲基的（顺式）-环丙烷，并使其异构化，得到了相应的反式异构体。报告了该机制。

  DOI：

  10.1016/s0040-4039(00)73037-1

文献信息

• Cyclopropane-Containing Polyamine Analogues Are Efficient Growth Inhibitors of a Human Prostate Tumor Xenograft in Nude Mice
  作者：Benjamin Frydman、Andrei V. Blokhin、Sara Brummel、George Wilding、Yulia Maxuitenko、Aparajita Sarkar、Subhra Bhattacharya、Dawn Church、Venodhar K. Reddy、John A. Kink、Laurence J. Marton、Aldonia Valasinas、Hirak S. Basu

  DOI：10.1021/jm030175u

  日期：2003.10.1

  Polyamine analogues 7, 10, 18, 27, and 32 containing cyclopropane rings were obtained by chemical synthesis. Their antineoplastic activities were assessed against the cultured human prostate tumor cell lines DU-145, DuPro, and PC-3. Decamines 32 and 27 exhibited variable levels of cytotoxicity against all three cell lines, while 7, 10, and 18 were efficacious against DU-145 and DuPro. Maximum tolerated doses (MTD) for all five compounds in a NCr-nu mouse model were determined at dosing schedules of q1d x 5 (ip) in two cycles with a break of 10 days between cycles. Their antitumor efficacies were then tested against DU-145 tumor xenografts in mice treated with all five agents at their respective MTDs. In addition, the efficacies of 7 and 10 against the same tumor xenograft were assessed at doses below their respective MTDs. In all experiments, administration began two weeks after tumor implantation. All compounds efficiently inhibited tumor growth for up to 50 days postimplantation, with negligible animal body weight loss. Tetramine 10 and hexamine 18 were the most efficient among the five analogues in arresting tumor growth. Tetramine 10 containing two cyclopropane rings had the lowest systemic toxicity as reflected in animal body weight loss. It was further assessed at a weekly administration regimen of (q1w x 4) in two cycles with a four-week break between the cycles. At this dosing schedule, 10 again efficiently arrested tumor growth with negligible effect on animal body weight. Tetramine 10 also arrested the growth of large tumors (ca. 2000 mm(3)) treated 66 days postimplantation. Studies on the metabolism of 10 showed that it accumulates in tumor within 6 h after the end of administration and reached a maximum level 72 h after cessation of dosing. Intracellular concentrations of 10 in liver and kidney were much smaller when compared to those in the tumor when measured 72 h after cessation of dosing. In liver and kidney, the deethyl metabolites of 10 accumulated over a 96 h period after cessation of dosing.
• Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor
  作者：Antonia F. Stepan、Chakrapani Subramanyam、Ivan V. Efremov、Jason K. Dutra、Theresa J. O’Sullivan、Kenneth J. DiRico、W. Scott McDonald、Annie Won、Peter H. Dorff、Charles E. Nolan、Stacey L. Becker、Leslie R. Pustilnik、David R. Riddell、Gregory W. Kauffman、Bethany L. Kormos、Liming Zhang、Yasong Lu、Steven H. Capetta、Michael E. Green、Kapil Karki、Evelyn Sibley、Kevin P. Atchison、Andrew J. Hallgren、Christine E. Oborski、Ashley E. Robshaw、Blossom Sneed、Christopher J. O’Donnell

  DOI：10.1021/jm300094u

  日期：2012.4.12

  Replacement of the central, para-substituted fluorophenyl ring in the gamma-secretase inhibitor 1 (BMS-708,163) with the bic-yclo[1.1.1]pentane motif led to the discovery of compound 3, an equipotent enzyme inhibitor with significant improvements in passive permeability and aqueous solubility. The modified biopharmaceutical properties of 3 translated into excellent oral absorption characteristics (similar to 4-fold up arrow C-max and AUC values relative to 1) in a mouse model of gamma-secretase inhibition. In addition, SAR studies into other fluorophenyl replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane moiety over conventional phenyl ring replacements with respect to achieving an optimal balance of properties (e.g., gamma-secretase inhibition, aqueous solubility/permeability, in vitro metabolic stability). Overall, this work enhances the scope of the [1.1.1]-bicycle beyond that of a mere "spacer" unit and presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.
• [EN] CDK2 INHIBITORS<br/>[FR] INHIBITEURS DE CDK2
  申请人：[en]BLUEPRINT MEDICINES CORPORATION

  公开号：WO2023278326A1

  公开（公告）日：2023-01-05

  The present disclosure provides a compound represented by structural Formula (I): or a pharmaceutically acceptable salt thereof useful for treating a cancer.
• [EN] 5-(7H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)-5-AZASPIRO[2.5]OCTANE-8-CARBOXYLIC ACID DERIVATIVES AS NOVEL JAK KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE 5-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-5-AZASPIRO[2,5] OCTANE-8-CARBOXYLIQUE EN TANT QUE NOUVEAUX INHIBITEURS DE KINASE JAK
  申请人：LEO PHARMA AS

  公开号：WO2018141842A1

  公开（公告）日：2018-08-09

  The present invention relates to a compound according to formula (I), wherein X represents NH or O; n is an integer selected from 1-3; Y represents a bond, -C(O)O-*, -C(O)OR3-* or –C(O)NHR3-*; W is selected from the group consisting of phenyl, pyridyl, (C3-C7)cycloalkyl and 4-6 membered heterocycloalkyl; or pharmaceutically acceptable salts, hydrates, or solvates thereof. The invention relates further to said compounds for use in therapy, to pharmaceutical compositions comprising said compounds, to methods of treating diseases, with said compounds, and to the use of said compounds in the manufacture of medicaments.

  本发明涉及一种符合式(I)的化合物，其中X代表NH或O；n是从1到3选择的整数；Y代表键，-C(O)O- *，-C(O)OR3- *或-C(O)NHR3- *；W选自苯基，吡啶基，(C3-C7)环烷基和4-6成员杂环烷基的组；或其药学上可接受的盐，水合物或溶剂合物。本发明进一步涉及所述化合物在治疗中的用途，包括含有所述化合物的药物组合物，用所述化合物治疗疾病的方法，以及所述化合物用于制造药品的用途。
• Acidic isomerization of vicinally substituted (cis)-acceptor-donor cyclopropanes via an open ring mechanism
  作者：Luc Dechoux、Eric Doris

  DOI：10.1016/s0040-4039(00)73037-1

  日期：1994.3

  Many (cis)-cyclopropanes bearing 1-electronwithdrawing and 2-hydroxymethylene groups were synthetised and isomerized under midl acidic conditions to afford the corresponding trans isomers. The mechanism is reported.

  在中酸性条件下，合成了许多带有1-吸电子基团和2-羟基亚甲基的（顺式）-环丙烷，并使其异构化，得到了相应的反式异构体。报告了该机制。