3-[2-(三氟甲基)苯氧基]氮杂环丁烷盐酸盐 | 82622-46-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-[2-(三氟甲基)苯氧基]氮杂环丁烷盐酸盐
• 英文名称: 3-(2-(trifluoromethyl)phenoxy)azetidine hydrochloride
• 英文别名: 3-[2-(Trifluoromethyl)phenoxy]azetidine Hydrochloride；3-[2-(trifluoromethyl)phenoxy]azetidine;hydrochloride
• CAS: 82622-46-6
• 化学式: C₁₀H₁₀F₃NO*ClH
• 分子量: 253.652
• InChiKey: ALYCFCGEABMLRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  21.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[2-(三氟甲基)苯氧基]氮杂环丁烷盐酸盐 、 6-氯哒嗪-3-甲酸甲酯 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 以50%的产率得到methyl 6-{3-[2-(trifluoromethyl)phenoxy]azetidin-1-yl}pyridazine-3-carboxylate
  参考文献：
  名称：

  Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitors

  摘要：

  Potent and orally bioavailable SCD inhibitors built on an azetidinyl pyridazine scaffold were identified. In a one-month gDIO mouse model of obesity, we demonstrated that there was no therapeutic index even at low doses; efficacy in preventing weight gain tracked closely with skin and eye adverse events. This was attributed to the local SCD inhibition in these tissues as a consequence of the broad tissue distribution observed in mice for this class of compounds. The search for new structural scaffolds which may display a different tissue distribution was initiated. In preparation for an HTS campaign, a radiolabeled azetidinyl pyridazine displaying low non-specific binding in the scintillation proximity assay was prepared. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.107
• 作为产物：
  描述：

  oxalic acid;1-(1-phenylethyl)-3-[2-(trifluoromethyl)phenoxy]azetidine 生成 3-[2-(三氟甲基)苯氧基]氮杂环丁烷盐酸盐
  参考文献：
  名称：

  CALE, A. D.

  摘要：

  DOI：

文献信息

• [EN] DERIVATIVES OF 2H PYRIDAZIN- 3 -ONES, THEIR PREPARATION AND THEIR USE AS SCD-1 INHIBITORS<br/>[FR] DÉRIVÉS DE 2H-PYRIDAZIN-3-ONES, LEUR PRÉPARATION ET LEUR UTILISATION COMME INHIBITEURS DE LA SCD-1
  申请人：PF MEDICAMENT

  公开号：WO2011015629A1

  公开（公告）日：2011-02-10

  The present invention concerns compounds of general formula (I) characterized in that (formula 1) wherein, in particular: -R1 represents one or more groups such as: trif luoromethyl, halogen such as F, C1, -when n=m=1, W represents CH then Y represents oxygen, -U represents: • either - (C=O) CH2NH- and is branched at position 4 of pyridazinone, then R2 represents H, • or -(C=O)NH- and U is branched at positions (4), (5) or (6) of pyridazinone, then R2 represents H, - R3 represents a hydrogen or methyl and the addition salts with pharmaceutically acceptable bases and acids and the different isomers, and their mixtures in any proportion for use as SCD-1 enyzme inhibitors for the treatment of obesitz, tzpe-2 diabetes and lipid disorders.

  本发明涉及一般式(I)的化合物，其特征在于（式1），其中，特别是： -R1代表三氟甲基、氟、C1等一种或多种基团， -当n=m=1时，W代表CH，Y代表氧， -U代表： • 要么是-(C=O)CH2NH-并且在吡啶并酮的4位分支，然后R2代表H， • 要么是-(C=O)NH-并且U在吡啶并酮的(4)、(5)或(6)位分支，然后R2代表H， -R3代表氢或甲基，以及与药用可接受的碱和酸形成的加合物，以及不同的异构体，以及它们在任何比例下的混合物，用作SCD-1酶抑制剂，用于治疗肥胖症、2型糖尿病和脂质紊乱。
• DERIVATIVES OF 2H PYRIDAZIN- 3 -ONES, THEIR PREPARATION AND THEIR USE AS SCD-1 INHIBITORS
  申请人：Dupont-Passelaigue Elisabeth

  公开号：US20120178678A1

  公开（公告）日：2012-07-12

  The present invention concerns compounds of general formula (I) characterized in that (formula 1) wherein, in particular: —R 1 represents one or more groups such as: trifluoromethyl, halogen such as F, Cl, —when n=m=1, W represents CH then Y represents oxygen, —U represents: either —(C═O)CH 2 NH— and is branched at position 4 of pyridazinone, then R2 represents H, or —(C═O)NH— and U is branched at positions (4), (5) or (6) of pyridazinone, then R2 represents H, —R3 represents a hydrogen or methyl and the addition salts with pharmaceutically acceptable bases and acids and the different isomers, and their mixtures in any proportion for use as SCD-1 enzyme inhibitors for the treatment of obesity, type-2 diabetes and lipid disorders.

  本发明涉及一般式(I)的化合物，其特征在于（公式1），其中特别地： - R1表示三氟甲基、卤素（如F、Cl）等一个或多个基团； - 当n=m=1时，W表示CH，Y表示氧； - U表示：要么是(C═O)CH2NH，且在吡嗪酮的位置4处分支，此时R2表示H；要么是(C═O)NH，且U在吡嗪酮的位置(4)、(5)或(6)处分支，此时R2表示H； - R3表示氢或甲基； - 以及它们与药用可接受的酸和碱形成的加合物和不同的异构体，以及它们在任意比例下混合，作为SCD-1酶抑制剂，用于治疗肥胖症、2型糖尿病和脂质代谢紊乱。
• Azetidine Derivatives as Inhibitors of Stearoyl-Coenzyme a Delta-9 Desaturase
  申请人：Isabel Elise

  公开号：US20090170828A1

  公开（公告）日：2009-07-02

  Azetidine derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease; atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; liver steatosis; and non-alcoholic steatohepatitis. (I)

  结构式I的氮杂环丙烷衍生物是选择性抑制硬脂酰辅酶A delta-9去饱和酶(SCD1)的化合物，相对于其他已知的硬脂酰辅酶A去饱和酶。本发明的化合物可用于预防和治疗与异常脂质合成和代谢相关的疾病，包括心血管疾病；动脉粥样硬化；肥胖症；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；肝脂肪变性和非酒精性脂肪性肝炎。
• WO2007/143823
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Evaluation of Nonretinoid Retinol Binding Protein 4 Antagonists for the Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease
  作者：Christopher L. Cioffi、Nicoleta Dobri、Emily E. Freeman、Michael P. Conlon、Ping Chen、Douglas G. Stafford、Daniel M. C. Schwarz、Kathy C. Golden、Lei Zhu、Douglas B. Kitchen、Keith D. Barnes、Boglarka Racz、Qiong Qin、Enrique Michelotti、Charles L. Cywin、William H. Martin、Paul G. Pearson、Graham Johnson、Konstantin Petrukhin

  DOI：10.1021/jm5010013

  日期：2014.9.25

  Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-). mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.