(2S,3R)-1-benzhydryl-2-methylazetidin-3-ol | 164906-64-3

• 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: (2S,3R)-1-benzhydryl-2-methylazetidin-3-ol
• 英文别名: (2s,3r)-1-(Diphenylmethyl)-2-methylazetidin-3-ol
• CAS: 164906-64-3
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: RVJIUWJMJDLQIP-XJKSGUPXSA-N

物化性质

• 沸点：
  361.2±42.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-benzhydryl-2-methylazetidin-3-ol 在 盐酸 、 20% palladium hydroxide-activated charcoal 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 40.0h， 以89%的产率得到(2S,3R)-2-methylazetidin-3-ol
  参考文献：
  名称：

  Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose

  摘要：

  Increased fructose consumption and its subsequent metabolism have been implicated in metabolic disorders such as nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance. Ketohexokinase (KHK) converts fructose to fructose-1-phosphate (F1P) in the first step of the metabolic cascade. Herein we report the discovery of a first-in-class KHK inhibitor, PF-06835919 (8), currently in phase 2 clinical trials. The discovery of 8 was built upon our originally reported, fragment-derived lead 1 and the recognition of an alternative, rotated binding mode upon changing the ribose-pocket binding moiety from a pyrrolidinyl to an azetidinyl ring system. This new binding mode enabled efficient exploration of the vector directed at the Arg-108 residue, leading to the identification of highly potent 3-azabicyclo[3.1.0]hexane acetic acid-based KHK inhibitors by combined use of parallel medicinal chemistry and structure-based drug design.

  DOI：

  10.1021/acs.jmedchem.0c00944
• 作为产物：
  描述：

  1-benzhydryl-2-methylazetidin-3-ol 在 二甲基十二/十四烷基叔胺 作用下， 以 甲醇 、 乙醇 、 二氧化碳 为溶剂， 以19.2 g的产率得到(2S,3R)-1-benzhydryl-2-methylazetidin-3-ol
  参考文献：
  名称：

  DISUBSTITUTED PYRAZOLE COMPOUNDS

  摘要：

  本发明提供了一种I式化合物或其药学上可接受的盐，并且利用I式化合物治疗代谢性疾病，如2型糖尿病、心力衰竭、糖尿病肾病和非酒精性脂肪肝炎。

  公开号：

  US20200392118A1

文献信息

• [EN] TETRAHYDROPYRIDO-PYRIDINE AND TETRAHYDROPYRIDO-PYRIMIDINE COMPOUNDS AND USE THEREOF AS C5A RECEPTOR MODULATORS<br/>[FR] COMPOSÉS DE TÉTRAHYDROPYRIDOPYRIDINE ET TÉTRAHYDROPYRIDOPYRIMIDINE ET UTILISATION DE CEUX-CI EN TANT QUE MODULATEURS DE RÉCEPTEUR C5A
  申请人：NOVARTIS AG

  公开号：WO2013016197A1

  公开（公告）日：2013-01-31

  The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种化合物I的化合物：(I)本发明的化合物的制备方法及其治疗用途。本发明还提供了一种药理活性剂的组合和药物组合物。
• 7-Azetidinylquinolones as Antibacterial Agents. 3. Synthesis, Properties and Structure-Activity Relationships of the Stereoisomers Containing a 7-(3-Amino-2-methyl-1-azetidinyl) Moiety
  作者：Jordi Frigola、David Vano、Antoni Torrens、Angels Gomez-Gomar、Edmundo Ortega、Santiago Garcia-Granda

  DOI：10.1021/jm00007a017

  日期：1995.3

  de]-1,4-benzoxazine-6-carboxylic acids was synthesized to study the effect of the azetidine moiety on tricyclic quinolone antibacterial agents. A series of amino acid prodrugs of chiral naphthyridines 24a and 24b and quinolone 33a (cetefloxacin) was prepared and evaluated for antibacterial activity, solubility, and pharmacokinetic behavior. The absolute configuration of the new azetidinylquinolones

  一系列立体化学纯的7-（3-氨基-2-甲基-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸制备了位于1、5和8位的取代基，以确定手性相对于外消旋混合物的效价和体内功效的影响（第2部分，参见：J. Med.Chem。1994，37， 4195-4210）。一系列手性9-氟-2,3-二氢-3-甲基-7-氧-10-（取代的1-氮杂环丁烷基）-7H-吡啶[1,2,3-de] -1,4-苯并恶嗪合成-6-羧酸以研究氮杂环丁烷部分对三环喹诺酮抗菌剂的作用。制备了一系列手性萘啶24a和24b以及喹诺酮33a（cetefloxacin）的氨基酸前药，并评估了其抗菌活性，溶解度和药代动力学行为。通过对拆分的氮杂环丁醇（15）和化合物25a（E-4767）的一种非对映异构盐进行X射线分析，可以确定新的氮杂环丁烷基喹诺酮类化合物的绝对构型，该化合物在体外和体内的总体情况最佳。
• SUBSTITUTED 3-AZABICYCLO[3.1.0]HEXANES AS KETOHEXOKINASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20170183328A1

  公开（公告）日：2017-06-29

  Provided herein are substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

  本文提供了替代3-氮杂双环[3.1.0]己烷作为酮己糖激酶抑制剂，制备该类化合物的方法，以及包括向需要的哺乳动物施用该类化合物的方法。
• Substituted Azetidine compounds, their preparation and use as medicaments
  申请人：Cuberes Altisen Rosa

  公开号：US20050187208A1

  公开（公告）日：2005-08-25

  The present invention relates to substituted Azetidine compounds of general formula (I), methods for their preparation, medicaments comprising these compounds as well as their use for the preparation of a medicament for the treatment of humans and animals.

  本发明涉及通式（I）的取代氮杂环丙烷化合物，其制备方法，包含这些化合物的药物以及它们用于制备治疗人类和动物的药物的用途。
• Substituted 1-diphenylmethyl azetidines
  申请人：Laboratorios Del Dr. Esteve, S.A.

  公开号：US05073646A1

  公开（公告）日：1991-12-17

  New azetidines, characterized in that they correspond to the general formula (I) ##STR1## in which R.sub.3 represents an amino radical, an alkylamino radical, a dialkylamino radical, a cycloalkylamino radical, an acylamino radical, an alkylacylamino radical, an aminomethyl radical, an alkylaminomethyl radical, an acylaminomethyl radical or an alkylacylaminomethyl radical, in which radicals each acyl fragment may be substituted with one or more halogen, especially fluorine, atoms; and R.sub.1, R.sub.2, R.sub.4, R.sub.5 and R.sub.6 represent a hydrogen atom or a lower alkyl radical, with the proviso that at least one of them represents a lower alkyl radical, and also their salts.

  新的氮杂环化合物，其特征在于它们符合通式（I）##STR1## 其中R.sub.3代表氨基基团、烷基氨基基团、二烷基氨基基团、环烷基氨基基团、酰胺基团、烷基酰胺基团、氨甲基基团、烷基氨甲基基团、酰胺基甲基基团或烷基酰胺基甲基基团，其中每个酰基片段可以被一个或多个卤素，特别是氟原子取代;而R.sub.1、R.sub.2、R.sub.4、R.sub.5和R.sub.6代表氢原子或较低的烷基基团，但至少其中之一代表较低的烷基基团，同时还包括它们的盐。