2-[4-(bromomethyl)phenoxy]-5-(trifluoromethyl)-pyridine | 1160430-95-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-(bromomethyl)phenoxy]-5-(trifluoromethyl)-pyridine
• 英文别名: 2-(4-(Bromomethyl)phenoxy)-5-(trifluoromethyl)pyridine；2-[4-(bromomethyl)phenoxy]-5-(trifluoromethyl)pyridine
• CAS: 1160430-95-4
• 化学式: C₁₃H₉BrF₃NO
• 分子量: 332.12
• InChiKey: HDDZWEWQYBLPCW-UHFFFAOYSA-N

物化性质

• 沸点：
  355.5±42.0 °C(Predicted)
• 密度：
  1.535±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险品运输编号：
  1759
• 危险性描述：
  H302,H315,H318,H335
• 包装等级：
  III
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  2-[4-(bromomethyl)phenoxy]-5-(trifluoromethyl)-pyridine 在 dicyclohexylmethylamine 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 diethyl {2-[(4-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzyl)oxy]phenyl}phosphonate
  参考文献：
  名称：

  鉴定新型硼酸作为有效，选择性和口服活性的激素敏感性脂肪酶抑制剂

  摘要：

  激素敏感性脂肪酶（HSL）是血脂异常的有吸引力的治疗靶标。我们设计并合成了几种化合物，它们是可逆HSL抑制剂，着重于疏水相互作用，被认为对HSL抑制活性有效。在这些努力中，我们鉴定出了具有较强HSL抑制活性的硼化化合物12，IC 50值为7 nM，对胆碱酯酶的选择性很高。此外，化合物12是第一种含硼的HSL抑制剂，在以3 mg / kg的口服剂量给药后，在大鼠中已显示出抗脂解作用。

  DOI：

  10.1016/j.bmc.2016.06.022
• 作为产物：
  描述：

  2-氯-5-三氟甲基吡啶 在 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 18.0h， 生成 2-[4-(bromomethyl)phenoxy]-5-(trifluoromethyl)-pyridine
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)

  摘要：

  Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat.

  DOI：

  10.1021/jm501608q

文献信息

• [EN] 2,6-DISUBSTITUTED PYRIDINES AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS<br/>[FR] PYRIDINES 2,6-DISUBSTITUÉES COMME ACTIVATEURS DE LA GUANYLATE CYCLASE SOLUBLE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009071504A1

  公开（公告）日：2009-06-11

  Disclosed are compounds of formula (I) wherein R1 and R2 are independently selected from hydrogen, halo, CF3, C1-4alkyl and allyl; Y represents (II), (III), (IV) or (V) wherein R3 represents CF3 or C1-4alkyl; and R3a represents CF3 or C1-4alkyl.

  公开的是式（I）的化合物，其中R1和R2分别选自氢、卤素、CF3、C1-4烷基和烯丙基；Y代表（II）、（III）、（IV）或（V），其中R3代表CF3或C1-4烷基；而R3a代表CF3或C1-4烷基。
• [EN] PYRIMIDINE DERIVATIVES AS ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE<br/>[FR] DÉRIVÉS DE PYRIMIDINE COMME ACTIVATEURS DE GUANYLATE CYCLASE SOLUBLE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2010015653A1

  公开（公告）日：2010-02-11

  Disclosed are compounds of formula (I) and or salts thereof which activate soluble guanylate cyclase (sGC), pharmaceutical compositions containing them, their use in the manufacture of a medicament for teating cardiovascular diseases, and processes for their preparation.

  揭示了公式（I）的化合物及其盐，这些化合物激活可溶性鸟苷酸环化酶（sGC），包含它们的药物组合物，它们在制造用于治疗心血管疾病的药物中的应用，以及它们的制备方法。
• Identification of a novel boronic acid as a potent, selective, and orally active hormone sensitive lipase inhibitor
  作者：Tomoko Ogiyama、Mitsuhiro Yamaguchi、Nobuya Kurikawa、Shoko Honzumi、Yuka Yamamoto、Daisuke Sugiyama、Shinichi Inoue

  DOI：10.1016/j.bmc.2016.06.022

  日期：2016.8

  compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC50 value of 7 nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic

  激素敏感性脂肪酶（HSL）是血脂异常的有吸引力的治疗靶标。我们设计并合成了几种化合物，它们是可逆HSL抑制剂，着重于疏水相互作用，被认为对HSL抑制活性有效。在这些努力中，我们鉴定出了具有较强HSL抑制活性的硼化化合物12，IC 50值为7 nM，对胆碱酯酶的选择性很高。此外，化合物12是第一种含硼的HSL抑制剂，在以3 mg / kg的口服剂量给药后，在大鼠中已显示出抗脂解作用。
• Synthesis and Structure–Activity Relationships for Extended Side Chain Analogues of the Antitubercular Drug (6<i>S</i>)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5<i>H</i>-imidazo[2,1-<i>b</i>][1,3]oxazine (PA-824)
  作者：Brian D. Palmer、Hamish S. Sutherland、Adrian Blaser、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、William A. Denny、Andrew M. Thompson

  DOI：10.1021/jm501608q

  日期：2015.4.9

  Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat.