3-amino-1,1,1-trifluoro-4-phenyl-2-butanol | 124044-49-1

• 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: 3-amino-1,1,1-trifluoro-4-phenyl-2-butanol
• 英文别名: 1,1,1-trifluoro-3-amino-4-phenyl-2-butanol；3-Amino-1,1,1-trifluoro-4-phenylbutan-2-ol
• CAS: 124044-49-1
• 化学式: C₁₀H₁₂F₃NO
• 分子量: 219.207
• InChiKey: OCZXOWATVOYDFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-1,1,1-trifluoro-4-phenyl-2-butanol 在 二氯乙酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 2-[5-benzyloxycarbonylamino-6-oxo-2-(p-tolyl)-1,6-dihydro-1-pyrimidyl]-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-acetamide
  参考文献：
  名称：

  Non-Peptidic inhibitors of human chymase. Synthesis, structure–activity relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6-dihydropyrimidine-containing trifluoromethyl ketones

  摘要：

  Chymase possesses a wide variety of actions, including promotion of angiotensin II production and histamine release from mast cells. However, due to a lack of effective inhibitors featuring both high inhibitory activity and high metabolic stability, the pathophysiological role of chymase has not been fully elucidated. We designed non-peptidic inhibitors based on the predicted binding mode of the peptidic chymase inhibitor Val-Pro-Phe-CF3 and demonstrated that the Val-Pro unit is replaceable with a (5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl)acetyl moiety. Structure-activity relationship studies revealed that phenyl substitution at the 2-position of the pyrimidinone ring is indispensable for high activity. The most potent compound 1h (K-i = 0.0506 muM) is superior in potency to the parent peptidic inhibitor Val-Pro-Phe-CF3 and has good selectivity for chymase over other proteases. The related analogue 1e was orally absorbed and maintained high plasma levels for at least 2 h. These results suggest that the derivatives reported here could be developed as agents for treatment of chymase-induced disease. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00244-3
• 作为产物：
  描述：

  3-硝基-4-苯基-1,1,1-三氟丁烷-2-醇 在 镍 氢气 作用下， 以 乙醇 、 水 为溶剂， 23.0 ℃ 、101.33 kPa 条件下， 反应 14.0h， 以95%的产率得到3-amino-1,1,1-trifluoro-4-phenyl-2-butanol
  参考文献：
  名称：

  Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease

  摘要：

  A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2-P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a K-i value of 0.3 mu M after 4 h incubation. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.02.040

文献信息

• Heterocyclic amide compounds and pharmaceutical use of the same
  申请人：The Green Cross Corporation

  公开号：US05948785A1

  公开（公告）日：1999-09-07

  Heterocyclic amide compounds of the formula (I) ##STR1## wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.

  式(I)的杂环酰胺化合物##STR1##，其中每个符号如规范中定义的那样，其药理学上可接受的盐，其药物组合物和其药用。本发明的杂环酰胺化合物及其药理学上可接受的盐对哺乳动物包括人类的胰蛋白酶组具有优越的抑制活性，并可经口或经肠外途径给药。因此，它们可用作胰蛋白酶抑制剂，并可有效预防和治疗由胰蛋白酶引起的各种疾病，如由II型血管紧张素引起的疾病。
• HETEROCYCLIC AMIDE COMPOUNDS AND MEDICINAL USE OF THE SAME
  申请人：THE GREEN CROSS CORPORATION

  公开号：EP0826671A1

  公开（公告）日：1998-03-04

  Heterocyclic amide compounds of the formula (I) wherein each symbol is as defined in the specification, pharmacologically acceptable salts thereof, pharmaceutical compositions thereof and pharmaceutical use thereof. The heterocyclic amide compounds and pharmacologically acceptable salts thereof of the present invention have superior inhibitory activity against chymase groups in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be effective for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.

  式 (I) 的杂环酰胺化合物 其中各符号如说明书中所定义，其药理上可接受的盐、其药物组合物和其药物用途。本发明的杂环酰胺化合物及其药理学上可接受的盐类对哺乳动物（包括人类）的糜蛋白酶基团具有优异的抑制活性，并且可以口服或肠外给药。因此，它们可作为糜蛋白酶抑制剂，有效预防和治疗由糜蛋白酶引起的各种疾病，如血管紧张素 II 引起的疾病。
• Peptidyl human heart chymase inhibitors. 1. Synthesis and inhibitory activity of difluoromethylene ketone derivatives bearing P′ binding subsites
  作者：Masahiro Eda、Atsuyuki Ashimori、Fumihiko Akahoshi、Takuya Yoshimura、Yoshihisa Inoue、Chikara Fukaya、Masahide Nakajima、Hajime Fukuyama、Teruaki Imada、Norifumi Nakamura

  DOI：10.1016/s0960-894x(98)00131-0

  日期：1998.4

  Peptidyl difluoromethylene ketone derivatives were designed to take advantage of probable additional interactions with the S' subsite of human heart chymase. They showed potent inhibitory activities against human heart chymase and were more efficient than bovine chymotrypsin. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G
  作者：Norton P. Peet、Joseph P. Burkhart、Michael R. Angelastro、Eugene L. Giroux、Shujaath Mehdi、Philippe Bey、Michael Kolb、Bernhard Neises、Daniel Schirlin

  DOI：10.1021/jm00163a063

  日期：1990.1

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.
• INHIBITORS OF BETA-AMYLOID PROTEIN PRODUCTION
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0721449B1

  公开（公告）日：2001-12-19