(+/-)-methyl-N-(1,1,1-trifluoro-3-phenylprop-2-yl)carbamate | 245126-04-9

• 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: (+/-)-methyl-N-(1,1,1-trifluoro-3-phenylprop-2-yl)carbamate
• 英文别名: methyl (1,1,1-trifluoro-3-phenylpropan-2-yl)carbamate；methyl N-(1,1,1-trifluoro-3-phenylpropan-2-yl)carbamate
• CAS: 245126-04-9
• 化学式: C₁₁H₁₂F₃NO₂
• 分子量: 247.217
• InChiKey: MFRMWVGLGDFFPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl-N-(1,1,1-trifluoro-3-phenylprop-2-yl)carbamate 在 盐酸 、 platinum(IV) oxide 、 硼烷四氢呋喃络合物 、 硫酸 、 氢气 、 四氯化锡 、 potassium nitrate 、 sodium nitrite 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (R)-7-chloro-3-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Inhibitors of phenylethanolamine N-methyltransferase devoid of α2-adrenoceptor affinity

  摘要：

  A series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines was synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although their PNMT inhibitory potency decreased compared with corresponding 3-methyl-, 3-hydroxymethyl- or 3-unsubstituted-THIQs, some of them showed good selectivity due to their extremely low a2-adrenoceptor affinity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.033
• 作为产物：
  描述：

  2-氨基-3-苯基-1,1,1-三氟丙烷 、 氯甲酸甲酯 在 吡啶 作用下， 以 氯仿 为溶剂， 反应 18.0h， 以81%的产率得到(+/-)-methyl-N-(1,1,1-trifluoro-3-phenylprop-2-yl)carbamate
  参考文献：
  名称：

  [EN] BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS
  [FR] COMPOSÉS BENZOLACTAMES UTILISÉS EN TANT QU'INHIBITEURS DE PROTÉINE KINASE

  摘要：

  该发明提供了一个化合物，其化学式为(0)：或其药学上可接受的盐、N-氧化物或互变异构体。这些化合物是ERK 1/2激酶的抑制剂，并将在治疗ERKl/2介导的疾病中发挥作用。因此，这些化合物在治疗中特别是在癌症治疗中是有用的。

  公开号：

  WO2017068412A1

文献信息

• Synthesis and Evaluation of 3-Trifluoromethyl-7-substituted- 1,2,3,4-tetrahydroisoquinolines as Selective Inhibitors of Phenylethanolamine <i>N</i>-Methyltransferase versus the α₂-Adrenoceptor
  作者：Gary L. Grunewald、Timothy M. Caldwell、Qifang Li、Kevin R. Criscione

  DOI：10.1021/jm980734a

  日期：1999.8.1

  compared to previously studied THIQ-type inhibitors, except for 16 which was found to have good affinity for PNMT (PNMT K(i) = 0.52 microM). Compounds 14 and 16 proved to be the most selective inhibitors in this small series of compounds and are some of the most selective inhibitors of PNMT known (14, selectivity alpha(2) K(i)/PNMT K(i) = 700; 16, selectivity alpha(2) K(i)/PNMT K(i) > 1900). Compounds

  合成了一系列的3-三氟甲基-1,2,3,4-四氢异喹啉，并作为苯基乙醇胺N-甲基转移酶（PNMT）的抑制剂和可乐定在α（2）-肾上腺素受体上的结合抑制剂进行了评估。发现这些化合物是PNMT的选择性抑制剂，因为它们与α（2）-肾上腺素受体的亲和力降低，这归因于1,2,3,4-四氢异喹啉（THIQ）3位附近的空间体积不耐受性α-（2）-肾上腺素能受体和由于3-三氟甲基部分导致的THIQ胺的pK（a）降低。总体而言，与之前研究的THIQ型抑制剂相比，这些化合物对PNMT的亲和力较小，只有16种对PNMT具有良好的亲和力（PNMT K（i）= 0.52 microM）。事实证明，化合物14和16是这一小系列化合物中最具选择性的抑制剂，并且是某些已知的PNMT最具选择性的抑制剂（14，选择性alpha（2）K（i）/ PNMT K（i）= 700; 16 ，选择性alpha（2）K（i）/ PNMT
• Benzolactam compounds as protein kinase inhibitors
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：US10457669B2

  公开（公告）日：2019-10-29

  The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof. The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.

  本发明提供了一种式 (0) 的化合物： 或其药学上可接受的盐、N-氧化物或同系物；其中 n 是 1 或 2 X 是 CH 或 N Y 选自 CH 和 C-F Z 选自 C-Rz 和 N； R1 选自 -(Alk1)t-Cyc1；其中 t 为 0 或 1； 任选取代的 C1-6 无环烃基团 R2 选自氢、卤素和任选被一个或多个氟原子取代的 C1-3 烃基； R3 是氢或基团 L1-R7； R4 选自氢、甲氧基和任选被取代的 C1-3 烷基；以及 R4a 选自氢和 C1-3 烷基； 其中 Rz、Alk1、Cyc1、L1 和 R7 在本文中定义； 只要该化合物不是 6-苄基-3-2-[(2-甲基嘧啶-4-基)氨基]吡啶-4-基}-7,8-二氢-1,6-萘啶-5(6H)-酮和 3-2-[(2-甲基嘧啶-4-基)氨基]吡啶-4-基}-7,8-二氢-1,6-萘啶-5(6H)-酮及其盐和它们的同系物。 这些化合物是 ERK1/2 激酶的抑制剂，可用于治疗 ERK1/2 介导的疾病。因此，这些化合物可用于治疗，特别是治疗癌症。
• BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：US20190047990A1

  公开（公告）日：2019-02-14

  The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—R z and N; R 1 is selected from: -(Alk 1 ) t -Cyc 1 ; wherein t is 0 or 1; Optionally substituted C 1-6 acyclic hydrocarbon groups R 2 is selected from hydrogen; halogen; and C 1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R 3 is hydrogen or a group L 1 -R 7 ; R 4 is selected from hydrogen; methoxy; and optionally substituted C 1-3 alkyl; and R 4a is selected from hydrogen and a C 1-3 alkyl group; wherein R z , Alk 1 , Cyc 1 , L 1 and R 7 are defined herein; provided that the compound is other than 6-benzyl-3-2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof. The compounds are inhibitors of ERK1/2 kinases and will be useful in the treatment of ERK1/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.