tert-butyl (S)-(1-hydroxy-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate | 944470-71-7

• 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: tert-butyl (S)-(1-hydroxy-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate
• 英文别名: tert-butyl N-[(2S)-1-hydroxy-3-[4-(trifluoromethyl)phenyl]propan-2-yl]carbamate
• CAS: 944470-71-7
• 化学式: C₁₅H₂₀F₃NO₃
• 分子量: 319.324
• InChiKey: UILYFAHOMMFALF-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(1-hydroxy-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate 在 氯化亚砜 、 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以85%的产率得到(R,S)-tert-butyl-(S)-4-(4-trifluoromethylbenzyl)-1,2,3-oxathiazolidine-3-carboxylate-2-oxide
  参考文献：
  名称：

  [EN] HETEROCYCLIC MODULATORS OF PKB
  [FR] MODULATEURS HÉTÉROCYCLIQUES DE PKB

  摘要：

  公开号：

  WO2009011880A3
• 作为产物：
  描述：

  BOC-L-4-三氟甲基苯丙氨酸 在 N-甲基吗啉 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.5h， 生成 tert-butyl (S)-(1-hydroxy-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate
  参考文献：
  名称：

  强效四唑游离脂肪酸受体 2 拮抗剂的发现

  摘要：

  游离脂肪酸受体 2 (FFA2)，也称为 GPR43，介导短链脂肪酸的作用，作为治疗各种代谢和炎症疾病的潜在靶点而引起人们的兴趣。在此，我们报告了已建立的 FFA2 拮抗剂 CATPB 的羧酸基团的生物等排取代结果以及围绕这些化合物的 SAR 研究，从而发现了第一个高效 FFA2 拮抗剂，其中优选化合物 TUG-2304 ( 16l )在 cAMP 和 GTPγS 测定中IC 50值为 3-4 nM，具有良好的理化和药代动力学特性，并且能够完全抑制丙酸诱导的中性粒细胞迁移和呼吸爆发。

  DOI：

  10.1021/acs.jmedchem.2c01935

文献信息

• [EN] SUBSTITUTED AMINO TRIAZOLES USEFUL AS CHITINASE INHIBITORS<br/>[FR] AMINOTRIAZOLES SUBSTITUÉS UTILES EN TANT QU'INHIBITEURS DE CHITINASE
  申请人：ONCOARENDI THERAPEUTICS SA

  公开号：WO2021009209A1

  公开（公告）日：2021-01-21

  Disclosed are amino triazole compounds of formula (I). These compounds are inhibitors of acidic mammalian chitinase and chitotriosidase. Also disclosed are methods of using the compounds to treat asthma reactions caused by allergens, as well as acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer.

  公开了化学式（I）的氨基三唑化合物。这些化合物是酸性哺乳动物几丁质酶和几丁三糖酶的抑制剂。还公开了使用这些化合物治疗由过敏原引起的哮喘反应，以及急性和慢性炎症性疾病、自身免疫疾病、牙科疾病、神经系统疾病、代谢性疾病、肝脏疾病、多囊卵巢综合征、子宫内膜异位症和癌症的方法。
• Heterocyclic modulators of PKB
  申请人：ZENG Qingping

  公开号：US20090275592A1

  公开（公告）日：2009-11-05

  The invention relates to heterocyclic compounds of Formula I and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种公式I的杂环化合物及其组合物，其中变量具有本文所提供的定义，其在治疗由蛋白激酶B（PKB）介导的疾病方面具有用途。本发明还涉及这种化合物和组合物在治疗与异常细胞生长、癌症、炎症和代谢紊乱相关的疾病状态方面的治疗用途。
• Thiadiazole modulators of PKB
  申请人：Zeng Qingping

  公开号：US20090298836A1

  公开（公告）日：2009-12-03

  The invention relates to thiazole compounds of Formula I and Formula II and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种化合物，其为公式I和公式II的噻唑化合物，以及其组合物，可用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有本文中提供的定义。本发明还涉及在治疗异常细胞生长、癌症、炎症和代谢紊乱等疾病状态中使用这种噻唑化合物和其组合物的治疗用途。
• [EN] THIADIAZOLE MODULATORS OF PKB<br/>[FR] THIADIAZOLES MODULATEURS DE L'ACTIVITÉ DE PKB
  申请人：AMGEN INC

  公开号：WO2009011871A3

  公开（公告）日：2009-04-30
• Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension
  作者：Gui-Dong Zhu、Viraj B. Gandhi、Jianchun Gong、Sheela Thomas、Keith W. Woods、Xiaohong Song、Tongmei Li、R. Bruce Diebold、Yan Luo、Xuesong Liu、Ran Guan、Vered Klinghofer、Eric F. Johnson、Jennifer Bouska、Amanda Olson、Kennan C. Marsh、Vincent S. Stoll、Mulugeta Mamo、James Polakowski、Thomas J. Campbell、Ruth L. Martin、Gary A. Gintant、Thomas D. Penning、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1021/jm0701019

  日期：2007.6.1

  Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.