3-(benzyloxy)cyclopentyl methanesulfonate | 905961-63-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(benzyloxy)cyclopentyl methanesulfonate
• 英文别名: (3-Phenylmethoxycyclopentyl) methanesulfonate；(3-phenylmethoxycyclopentyl) methanesulfonate
• CAS: 905961-63-9
• 化学式: C₁₃H₁₈O₄S
• 分子量: 270.35
• InChiKey: WCQIJAWKFGPAGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)cyclopentyl methanesulfonate 、 3-[[4-(trifluoromethyl)-2-pyridyl]oxy]-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis

  摘要：

  Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo[3,4-d]pyrimidine-4-amine (PP) compounds that are bulky ATP mimetics. Here we rationally designed, synthesized, and tested a series of novel PP analogs that were evaluated for inhibition of CDPK1 enzyme activity in vitro and parasite growth in cell culture. Optimal substitution on the PP scaffold included 2-pyridyl ethers directed into the hydrophobic pocket and small carbocyclic rings accessing the ribose-binding pocket. Further optimization of the series led to identification of the lead compound 3a that displayed excellent potency, selectivity, safety profile, and efficacy in vivo. The results of these studies provide a foundation for further work to optimize CDPK1 inhibitors for the treatment of acute and chronic toxoplasmosis.

  DOI：

  10.1021/acs.jmedchem.0c00419
• 作为产物：
  描述：

  1,3-环戊二醇 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 3-(benzyloxy)cyclopentyl methanesulfonate
  参考文献：
  名称：

  Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis

  摘要：

  Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo[3,4-d]pyrimidine-4-amine (PP) compounds that are bulky ATP mimetics. Here we rationally designed, synthesized, and tested a series of novel PP analogs that were evaluated for inhibition of CDPK1 enzyme activity in vitro and parasite growth in cell culture. Optimal substitution on the PP scaffold included 2-pyridyl ethers directed into the hydrophobic pocket and small carbocyclic rings accessing the ribose-binding pocket. Further optimization of the series led to identification of the lead compound 3a that displayed excellent potency, selectivity, safety profile, and efficacy in vivo. The results of these studies provide a foundation for further work to optimize CDPK1 inhibitors for the treatment of acute and chronic toxoplasmosis.

  DOI：

  10.1021/acs.jmedchem.0c00419

文献信息

• CONDENSED ISOXALINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASE TYPE - IV
  申请人：Palle Venkata P.

  公开号：US20090048247A1

  公开（公告）日：2009-02-19

  The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.

  本发明涉及异噁唑啉衍生物，可用作选择性磷酸二酯酶（PDE）IV型抑制剂。特别地，本文所披露的化合物可用于治疗艾滋病、哮喘、关节炎、支气管炎、慢性阻塞性肺疾病（COPD）、银屑病、过敏性鼻炎、休克、特应性皮炎、克罗恩病、成人呼吸窘迫综合症（ARDS）、嗜酸性肉芽肿、过敏性结膜炎、骨关节炎、溃疡性结肠炎和其他炎症性疾病的患者，特别是人类。本发明还涉及所披露的化合物的制备方法，以及其作为磷酸二酯酶（PDE）IV型抑制剂的药物组合物及其应用。
• CONDENSED ISOXALINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASE TYPE-IV
  申请人：Ranbaxy Laboratories Limited

  公开号：EP1869054A2

  公开（公告）日：2007-12-26
• [EN] INHIBITORS OF PHOSPHODIESTERASE TYPE-IV<br/>[FR] INHIBITEURS DE LA PHOSPHODIESTERASE DE TYPE IV
  申请人：RANBAXY LAB LTD

  公开号：WO2006085212A2

  公开（公告）日：2006-08-17

  [EN] The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.
  [FR] Cette invention concerne des dérivés isoxazoline, qui peuvent être utilisés comme inhibiteurs sélectifs de la phosphodiestérase (PDE) de type IV. Les composés de cette invention peuvent en particulier être utilisés pour traiter le SIDA, l'asthme, l'arthrite, la bronchite, la bronchopneumopathie chronique obstructive (BPCO), le psoriasis, la rhinite allergique, un choc, la dermatite atopique, la maladie de Crohn, le syndrome de détresse respiratoire aiguë de l'adulte (SDRA), le granulome à éosinophiles, la conjonctivite allergique, l'ostéoarthrite, la colite ulcéreuse et autres maladies inflammatoires chez un patient, en particulier chez des êtres humains. Cette invention concerne également des procédés de préparation des composés de cette invention, des compositions pharmaceutiques renfermant ces composés ainsi que leur utilisation comme inhibiteurs de la phosphodiestérase (PDE) de type IV.
• Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis
  作者：James W. Janetka、Allen T. Hopper、Ziping Yang、Jennifer Barks、Mary Savari Dhason、Qiuling Wang、L. David Sibley

  DOI：10.1021/acs.jmedchem.0c00419

  日期：2020.6.11

  Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo[3,4-d]pyrimidine-4-amine (PP) compounds that are bulky ATP mimetics. Here we rationally designed, synthesized, and tested a series of novel PP analogs that were evaluated for inhibition of CDPK1 enzyme activity in vitro and parasite growth in cell culture. Optimal substitution on the PP scaffold included 2-pyridyl ethers directed into the hydrophobic pocket and small carbocyclic rings accessing the ribose-binding pocket. Further optimization of the series led to identification of the lead compound 3a that displayed excellent potency, selectivity, safety profile, and efficacy in vivo. The results of these studies provide a foundation for further work to optimize CDPK1 inhibitors for the treatment of acute and chronic toxoplasmosis.