(1S,2S)-1-ethoxycarbonyl-1,2-bis(hydroxymethyl)cyclopropane | 1427158-39-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (1S,2S)-1-ethoxycarbonyl-1,2-bis(hydroxymethyl)cyclopropane
• 英文别名: (1S,2S)-ethyl 1,2-bis(hydroxymethyl)cyclopropanecarboxylate；ethyl (1S,2S)-1,2-bis(hydroxymethyl)cyclopropanecarboxylate；Ethyl (1S,2S)-1,2-bis(hydroxymethyl)cyclopropane-1-carboxylate
• CAS: 1427158-39-1
• 化学式: C₈H₁₄O₄
• 分子量: 174.197
• InChiKey: QWJMMXIAENUVEY-HTRCEHHLSA-N

物化性质

• 沸点：
  276.4±5.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2S)-1-ethoxycarbonyl-1,2-bis(hydroxymethyl)cyclopropane 在 咪唑 、 盐酸 、 锂硼氢 、 草酰氯 、 四丁基氟化铵 、 四丁基碘化铵 、 sodium hydride 、 戴斯-马丁氧化剂 、 copper(II) sulfate 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 34.67h， 生成 (1R,2S)-1-(benzyloxymethyl)-2-[(1S)-1-tert-butoxycarbonylamino-3-methylbutyl]-1-[trans-2-(ethoxycarbonyl)ethenyl]cyclopropane
  参考文献：
  名称：

  プロレニン受容体リガンド及びアンタゴニスト

  摘要：

  利用环丙烷的结构特征设计、合成β折叠片段类似物，并提供新的（前）肾素受体配体。提供出色的溶解性和稳定性等特性，具有较高的临床应用潜力，提供新型（前）肾素受体抑制剂。解决方案是前肾素受体配体，如式（1）所示。（X1为烷基等；X2为含氮碱性取代基的烷基等；X3和X4为H或与之结合的C形成羰基（C=O）；R1和R2各自独立为H、烷基等）。【选择图】无

  公开号：

  JP2017141185A
• 作为产物：
  描述：

  (1R,5S)-ethyl 2-oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以76%的产率得到(1S,2S)-1-ethoxycarbonyl-1,2-bis(hydroxymethyl)cyclopropane
  参考文献：
  名称：

  プロレニン受容体リガンド及びアンタゴニスト

  摘要：

  利用环丙烷的结构特征设计、合成β折叠片段类似物，并提供新的（前）肾素受体配体。提供出色的溶解性和稳定性等特性，具有较高的临床应用潜力，提供新型（前）肾素受体抑制剂。解决方案是前肾素受体配体，如式（1）所示。（X1为烷基等；X2为含氮碱性取代基的烷基等；X3和X4为H或与之结合的C形成羰基（C=O）；R1和R2各自独立为H、烷基等）。【选择图】无

  公开号：

  JP2017141185A

文献信息

• [EN] SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS mPGES-1 INHIBITORS<br/>[FR] COMPOSÉS À BASE D'HÉTÉROARYLE BICYCLIQUE SUBSTITUÉ CAPABLES D'INHIBER MPGES-1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2013038308A1

  公开（公告）日：2013-03-21

  The present invention relates to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)

  本发明涉及公式（I）的双环化合物或其药用盐，作为mPGES-1抑制剂。这些化合物是微粒体前列腺素E合成酶-1（mPGES-1）酶的抑制剂，因此在治疗多种疾病或症状引起的疼痛和/或炎症方面具有用处，如哮喘、骨关节炎、类风湿关节炎、急性或慢性疼痛和神经退行性疾病。
• [EN] PHTALAZINONE DERIVATIVES AS MPEGS -1 INHIBITORS<br/>[FR] DÉRIVÉS DE PHTALAZINONE EN TANT QU'INHIBITEURS DE MPGES-1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2013072825A1

  公开（公告）日：2013-05-23

  The present patent application is directed to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.

  本专利申请涉及公式(I)的双环化合物或其药用盐，作为mPGES-1抑制剂。这些化合物是微粒体前列腺素E合成酶-1（mPGES-1）酶的抑制剂，因此在治疗多种疾病或情况引起的疼痛和/或炎症方面非常有用，如哮喘、骨关节炎、类风湿性关节炎、急性或慢性疼痛和神经退行性疾病。
• Synthesis and Antiviral Activity of Novel Acyclic Nucleosides:  Discovery of a Cyclopropyl Nucleoside with Potent Inhibitory Activity against Herpesviruses
  作者：Takaaki Sekiyama、Satoshi Hatsuya、Yasuhiro Tanaka、Mamoru Uchiyama、Nobukazu Ono、Satoshi Iwayama、Miki Oikawa、Katsuya Suzuki、Masahiko Okunishi、Takashi Tsuji

  DOI：10.1021/jm9705869

  日期：1998.4.1

  A series of acyclic nucleosides with two hydroxymethyl groups mimicking the 3'- and 5'-hydroxyl groups of the 2'-deoxyribose moiety were prepared and evaluated for their antiherpetic activity. Among those, 9-[[cis-1',2'-bis(hydroxymethyl)cycloprop-1'yl]methyl]guanine (3) showed extremely potent antiviral activity against herpes simplex virus type-1 (HSV-1) with good selectivity. Both enantiomers of 3 were synthesized stal ting from chiral epichlorohydrins, and only one of the enantiomers with 1'S,2'R-configuration (3a) exhibited strong antiherpetic activity (IC50 of 0.020 mu g/mL against HSV-1 Tomioka vs 0.81 mu g/mL for acyclovir). Enantiomer 3a was also more inhibitory than acyclovir against varicella-zoster virus (VZV) but ineffective against human immunodeficiency virus (HIV). Compound 3a is phosphorylated by HSV-1 thymidine kinase (TK) very efficiently. The relationship between conformation and antiherpetic activity in this series of compounds is discussed.
• Discovery of benzo[d]imidazo[5,1-b]thiazole as a new class of phosphodiesterase 10A inhibitors
  作者：Abhisek Banerjee、Lakshminarayana Narayana、Firoj A. Raje、Dnyandeo V. Pisal、Pradip A. Kadam、Srinivas Gullapalli、Hemant Kumar、Sandeep V. More、Malini Bajpai、Ramachandra Rao Sangana、Satyawan Jadhav、Girish S. Gudi、Neelima Khairatkar-Joshi、Ravi R.T. Merugu、Sreedhara R. Voleti、Laxmikant A. Gharat

  DOI：10.1016/j.bmcl.2013.10.027

  日期：2013.12

  The design, synthesis and structure activity relationship studies of a series of compounds from benzo[d]imidazo[5,1-b]thiazole scaffold as phosphodiesterase 10A (PDE10A) inhibitors are discussed. Several potent analogs with heteroaromatic substitutions (9a-d) were identified. The anticipated binding mode of these analogs was confirmed by performing the in silico docking experiments. Later, the heteroaromatics were substituted with saturated heteroalkyl groups which provided a tool compound 9e with excellent PDE10A activity, PDE selectivity, CNS penetrability and with favorable pharmacokinetic profile in rats. Furthermore, the compound 9e was shown to be efficacious in the MK-801 induced psychosis model and in the CAR model of psychosis. (C) 2013 Elsevier Ltd. All rights reserved.
• Three-Dimensional Structural Diversity-Oriented Peptidomimetics Based on the Cyclopropylic Strain
  作者：Akira Mizuno、Shiho Miura、Mizuki Watanabe、Yoshihiko Ito、Shizuo Yamada、Takenao Odagami、Yuji Kogami、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1021/ol400469w

  日期：2013.4.5

  Conformationally restricted peptidomimetics comprising eight stereoisomeric scaffolds with three-dimensional structural diversity were designed based on the structural features of cyclopropane, that is, cyclopropylic strain, which mimic wide-ranging tetrapeptide conformations covering beta-turns through beta-strands. Stereoselective synthesis of the designed peptidomimetics led to the identification of nonpeptidic melanocortin-4 receptor ligands.