3-(2-三氟甲基苯氧基)氮杂丁烷 | 76263-24-6

• 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)氮杂丁烷
• 英文名称: 3-[2-(trifluoromethyl)phenoxy]azetidine
• 英文别名: 3-(2-(trifluoromethyl)phenoxy)azetidine；3-[2-(trifluoromethyl)phenoxy)azetidine；3-(2-trifluoromethylphenoxy) azetidine
• CAS: 76263-24-6
• 化学式: C₁₀H₁₀F₃NO
• 分子量: 217.191
• InChiKey: UMRYPVYCXBBOJV-UHFFFAOYSA-N

物化性质

• 沸点：
  263℃
• 密度：
  1.277
• 闪点：
  113℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 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：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3-(2-三氟甲基苯氧基)氮杂丁烷 在 水 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 32.0h， 生成 6-methyl-2-(3-(2-(trifluoromethyl)phenoxy)azetidin-1-yl)pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  [EN] BISPECIFIC ANTAGONISTS OF RETINOL-BINDING PROTEIN 4 THAT STABILIZE TRANSTHYRETIN TETRAMERS, THEIR PREPARATION, AND USE IN THE TREATMENT OF COMMON AGE-RELATED COMORBIDITIES
  [FR] ANTAGONISTES BISPÉCIFIQUES DE LA PROTÉINE 4 DE LIAISON AU RÉTINOL QUI STABILISENT LES TÉTRAMÈRES DE LA TRANSTHYRÉTINE, LEUR PRÉPARATION ET LEUR UTILISATION DANS LE TRAITEMENT DE COMORBIDITÉS COMMUNE ASSOCIÉES À L'ÂGE

  摘要：

  公开号：

  WO2022020305A3
• 作为产物：
  描述：

  邻三氟甲基苯酚 在 caesium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 3-(2-三氟甲基苯氧基)氮杂丁烷
  参考文献：
  名称：

  Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities

  摘要：

  Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol (1) delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analogue (+/-)-44 possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding.

  DOI：

  10.1021/acs.jmedchem.0c00996

文献信息

• 3-(2-chloro-4-(trifluoromethyl)phenoxy)-1-azetidine carboxamides having
  申请人：A. H. Robins Company, Incorporated

  公开号：US05095014A1

  公开（公告）日：1992-03-10

  The present invention relates to novel 3-(2-chlor-4-trifluoromethylphenoxy)-1-azetidine carboxamides having the formula: ##STR1## wherein R1 and R2, same or different, are selected from hydrogen, C.sub.1 -C.sub.4 alkyl, and allyl. In a series of 3-(substitutedphenoxy)-1-azetidinecarboxamides, introduction of a chlorine atom at the 2-position of the phenoxy group of the corresponding 4-trifluoromethylphenoxy-1-azetidinecarboxamides resulted in unexpected increased potency in anticonvulsant pharmacological tests.

  本发明涉及具有以下结构式的新型3-(2-氯-4-三氟甲基苯氧基)-1-氮杂环戊酰胺：##STR1##其中R1和R2，相同或不同，选自氢、C.sub.1-C.sub.4烷基和烯丙基。在一系列3-(取代苯氧基)-1-氮杂环戊酰胺中，在相应的4-三氟甲基苯氧基-1-氮杂环戊酰胺的苯氧基的2-位引入氯原子导致在抗惊厥药理试验中出现意外增强的效力。
• Method of treating muscular tension, muscle spasticity and anxiety with
  申请人：A. H. Robins Company, Incorporated

  公开号：US05183902A1

  公开（公告）日：1993-02-02

  A method of treating animals to obtain muscle relaxation and/or to relieve anxiety is disclosed utilizing novel and known 3-aryloxy and 3-arylthioazetidinecarboxamides having the formula: ##STR1## wherein Z is oxygen or sulfur; B is oxygen or sulfur; Ar is pyridyl or halo substituted pyridyl, phenyl or substituted phenyl; R.sup.1 and R.sup.2 are hydrogen, loweralkyl, aryl, allyl groups, propargyl, cycloalkyl, loweralkylcycloalkyl, cycloalkylloweralkyl, arylloweralkyl and diloweralkylaminoalkyl, and R.sup.1 and R.sup.2 when taken together with the adjacent nitrogen atom may form a heterocyclic amine radical; R.sup.3 is hydrogen, loweralkyl, aryl or arylloweralkyl, and the geometrical isomers thereof and pharmaceutical salts thereof and hydrates thereof when they are possible.

  披露了一种利用具有以下结构式的新型和已知的3-芳氧基和3-芳硫基氮杂环丙酰胺来治疗动物以获得肌肉松弛和/或缓解焦虑的方法：##STR1## 其中Z为氧或硫；B为氧或硫；Ar为吡啶基或卤代吡啶基，苯基或取代苯基；R.sup.1和R.sup.2为氢、较低烷基、芳基、烯丙基、丙炔基、环烷基、较低烷基环烷基、环烷基较低烷基、芳基较低烷基和二较低烷氨基烷基，当R.sup.1和R.sup.2与相邻的氮原子一起时，可能形成杂环胺基；R.sup.3为氢、较低烷基、芳基或芳基较低烷基，以及它们的几何异构体和药用盐以及可能的水合物。
• N-Lower-alkyl 3-phenoxy-1-azetidinecarboxamides
  申请人：A. H. Robins Company, Inc.

  公开号：US04226861A1

  公开（公告）日：1980-10-07

  N-Lower-alkyl 3-phenoxy-1-azetidinecarboxamides having the formula: ##STR1## wherein R is alkyl and R.sup.1 is hydrogen, aminocarbonyl and trifluoromethyl having central nervous system activity particularly anti-convulsant activity, are disclosed.

  N-较低烷基3-苯氧基-1-氮杂环丙烷羧酰胺的化学式为：##STR1##其中R为烷基，R.sup.1为氢，氨基甲酰基和三氟甲基，具有中枢神经系统活性，特别是抗惊厥活性。
• [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。