3-(2-三氟甲基-苯氧基)-吡咯烷 | 946760-13-0

• 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)-吡咯烷
• 英文名称: (±)-3-(2-(trifluoromethyl)phenoxy)pyrrolidine
• 英文别名: 3-[2-(Trifluoromethyl)phenoxy]pyrrolidine
• CAS: 946760-13-0
• 化学式: C₁₁H₁₂F₃NO
• 分子量: 231.218
• InChiKey: XNRDRGOBJOHKEX-UHFFFAOYSA-N

物化性质

• 沸点：
  282.4±40.0 °C(Predicted)
• 密度：
  1.231±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 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)-吡咯烷 在 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 32.0h， 生成 (±)-6-methyl-2-(3-(2-(trifluoromethyl)phenoxy)pyrrolidin-1-yl)pyrimidine-4-carboxylic acid
  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
• 作为产物：
  描述：

  1-benzyl-3-(2-(trifluoromethyl)phenoxy)pyrrolidine 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 18.0h， 以83%的产率得到3-(2-三氟甲基-苯氧基)-吡咯烷
  参考文献：
  名称：

  [EN] DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS
  [FR] DÉRIVÉS DE TRIAZINES ET D'URACILES, LEUR PRÉPARATION ET LEURS APPLICATIONS EN THÉRAPEUTIQUE HUMAINE

  摘要：

  本发明涉及一般式I的衍生物，其中： - W代表氮， - R1代表： • 氢或直链或支链C1-C5烷基基团，或者 • 被三氟甲基、腈、羟基、C1-C3烷氧基、C3-C6烷氧基烷氧基、吲哚基、噻吩基、氧硫吩基、C1-C3 N-烷基氨基羰基基团取代的C1-C3烷基基团，或者 • 苯基或吡啶基或萘基，或者选择性地被一个或多个卤素原子、硝基、腈、三氟甲基、乙烯、甲硫基、直链或支链C1-C4烷基、直链或支链C1-C3烷氧基基团取代的噻吩基， • C6 2-氧代环烷基基团 - R2代表甲基或庚基， - m，n等于1， - V代表CH2， - X-Y代表-N- (C=O) -，-CH-O-，- Z代表被一个或多个三氟甲基基团、卤素原子或直链C1-C4烷基基团取代的苯基。

  公开号：

  WO2010006962A1

文献信息

• [EN] NOVEL PHENYL IMIDAZOLES AND PHENYL TRIAZOLES AS GAMMA-SECRETASE MODULATORS<br/>[FR] NOUVEAUX PHÉNYL IMIDAZOLES ET PHÉNYL TRIAZOLES EN TANT QUE MODULATEURS DE LA GAMMA SÉCRÉTASE
  申请人：PFIZER

  公开号：WO2010100606A1

  公开（公告）日：2010-09-10

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受盐已被披露，其中所述化合物具有规范中定义的Formula (I)的结构。相应的药物组合物、治疗方法、合成方法和中间体也已被披露。
• [EN] PHENOXY-PYRROLIDINE DERIVATIVE AND ITS USE AND COMPOSITIONS<br/>[FR] DÉRIVÉ PHÉNOXY-PYRROLIDINE ET SON UTILISATION, ET COMPOSITIONS ASSOCIÉES
  申请人：PFIZER

  公开号：WO2009019566A1

  公开（公告）日：2009-02-12

  The present invention is directed to the compound 2-(4- (hydroxymethyl)phenoxy)-1 -(3-(2-(trifluoromethyl)phenoxy)pyrrolidin-1 -yl)ethanone, its use as an inhibitor of stearoyl CoA desaturase and to pharmaceutical compositions containing this compound.

  本发明涉及化合物2-(4-(羟甲基)苯氧基)-1-(3-(2-(三氟甲基)苯氧基)吡咯烷-1-基)乙酮，其作为硬脂酰辅酶A去饱和酶的抑制剂以及含有该化合物的药物组合物的使用。
• DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS
  申请人：Leroy Isabelle

  公开号：US20110118266A1

  公开（公告）日：2011-05-19

  The present invention relates to derivatives of general formula I wherein: —W represents nitrogen, —R 1 represents: •a hydrogen or a linear or branched C 1 -C 5 alkyl radical or, •a C 1 -C 3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C 1 -C 3 alcoxy, C 3 -C 6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C 1 -C 3 N-alkylcarbamoyl groups or, •a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C 1 -C 4 alkyl, linear or branched C 1 -C 3 alkoxy groups, •a C 6 2-oxocycloalkyl radical—R 2 represents a methyl or heptyl, —m, n are equal to 1, —V represents CH 2 , —X—Y represents —N— (C═O)—, —CH—O—, —Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C 1 -C 4 alkyl groups.

  本发明涉及一般式I的衍生物，其中：-W代表氮，-R1代表：•氢或线性或支链C1-C5烷基基团，或•C1-C3烷基基团，该基团被三氟甲基，腈，羟基，C1-C3烷氧基，C3-C6烷氧基烷氧基，吲哚基，噻吩基，氧代噻吩基，C1-C3N-烷基氨基甲酰基团取代，或•苯基或吡啶基或萘基，或噻吩基，可选地取代一个或多个卤原子，硝基，腈，三氟甲基，乙烯基，甲硫基，线性支链C1-C4烷基，线性或支链C1-C3烷氧基基团，•C62-氧代环烷基基团-R2代表甲基或庚基，-m，n等于1，-V代表CH2，-X-Y代表-N-(C═O)-，-CH-O-，-Z代表一个苯基，该苯基被一个或多个三氟甲基基团，卤原子或线性C1-C4烷基基团取代。
• Derivatives of triazines and uracils, their preparation and their application in human therapeutics
  申请人：Leroy Isabelle

  公开号：US08618287B2

  公开（公告）日：2013-12-31

  The present invention relates to derivatives of general formula I wherein: —W represents nitrogen, —R1 represents: •a hydrogen or a linear or branched C1-C5 alkyl radical or, •a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, •a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, •a C6 2-oxocycloalkyl radical—R2 represents a methyl or heptyl, -m, n are equal to 1, —V represents CH2, —X—Y represents —N— (C═O)—, —CH—O—, —Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.

  本发明涉及一般式I的衍生物，其中：-W代表氮，-R1代表：•氢或线性或支链C1-C5烷基基团，或•C1-C3烷基基团，该基团被取代为三氟甲基、腈、羟基、C1-C3醇基、C3-C6烷氧基、吲哚基、噻吩基、氧代噻吩基、C1-C3 N-烷基氨基羰基基团或•苯基、吡啶基或萘基或噻吩基，或选配有一个或多个卤原子、硝基、腈、三氟甲基、乙烯基、甲基硫基、线性支链C1-C4烷基、线性或支链C1-C3烷氧基基团的基团，•C6 2-氧代环烷基基团-R2代表甲基或庚基，-m，n等于1，-V代表CH2，-X-Y代表—N—（C═O）—，—CH—O—，-Z代表苯基，该苯基被取代为一个或多个三氟甲基基团、卤原子或线性C1-C4烷基基团。
• [EN] BISPECIFIC ANTAGONISTS OF RETINOL-BINDING PROTEIN 4 THAT STABILIZE TRANSTHYRETIN TETRAMERS, THEIR PREPARATION, AND USE IN THE TREATMENT OF COMMON AGE-RELATED COMORBIDITIES<br/>[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
  申请人：UNIV COLUMBIA

  公开号：WO2022020305A3

  公开（公告）日：2022-03-03