(S)-[1-(3-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester | 266369-42-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (S)-[1-(3-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester
• 英文别名: (S)-tert-butyl 1-(3-hydroxyphenyl)ethylcarbamate；tert-butyl (1S)-1-(3-hydroxyphenyl)ethylcarbamate；[(S)-1-(3-hydroxyphenyl)ethyl]carbamic acid, 1,1-dimethylethyl ester；Tert-butyl [(1S)-1-(3-hydroxyphenyl)ethyl]carbamate；tert-butyl N-[(1S)-1-(3-hydroxyphenyl)ethyl]carbamate
• CAS: 266369-42-0
• 化学式: C₁₃H₁₉NO₃
• 分子量: 237.299
• InChiKey: WOFCTRSNCBCJCV-VIFPVBQESA-N

物化性质

• 沸点：
  387.3±25.0 °C(Predicted)
• 密度：
  1.096±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-[1-(3-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester 在 盐酸 、 4-二甲氨基吡啶 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 2-(二叔丁基膦)联苯 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 36.5h， 生成 (E)-3-(2,5-difluorophenyl)-N-[(1S)-1-(3-morpholin-4-ylphenyl)ethyl]prop-2-enamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Acrylamides as KCNQ2 Potassium Channel Openers

  摘要：

  A new class of acrylamides was synthesized, and the effects of these analogues on outward potassium current were evaluated by using two electrode voltage clamp recordings from Xenopus laevis oocytes expressing cloned mKCNQ2 channels. SAR studies indicated that the pharmacophore of the acrylamide series includes the (S) absolute configuration at the (1-phenyl)ethyl moiety and the alpha,beta-unsaturated acrylamide functionality with a free NH. This study identified (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide ((S)-1) and (S)-N-[1-(4-fluoro-3morpholin-4-yl-phenyl)-ethyl]-3-(4-fluoro-phenyl)-acrylamide ((S)-2) as KCNQ2 openers for further electrophysiological evaluations. These two acrylamides demonstrated significant activity in the cortical spreading depression model of migraine as we reported previously.

  DOI：

  10.1021/jm0305826
• 作为产物：
  描述：

  [(1S)-1-(3-甲氧基苯基)乙基]氨基甲酸叔丁酯 在 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-[1-(3-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain

  摘要：

  Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.092

文献信息

• [EN] 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES AS INHIBITORS OF MUTANT IDH<br/>[FR] 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES COMME INHIBITEURS D'IDH MUTANTE
  申请人：NOVARTIS AG

  公开号：WO2014141104A1

  公开（公告）日：2014-09-18

  The invention is directed to a formula (I), or a pharmamceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

  这项发明涉及一种式(I)的配方，或其药用可接受的盐，其中R1、R2a、R2b和R3-R7在此处。该发明还涉及含有式(I)化合物的组合物，以及在抑制具有新型活性的突变IDH蛋白中使用这种化合物的用途。该发明还涉及在治疗与这种突变IDH蛋白相关的疾病或紊乱中使用式(I)化合物，包括但不限于细胞增殖紊乱，如癌症。
• 3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES AS INHIBITORS OF MUTANT IDH
  申请人：VESTAS WIND SYSTEMS A/S

  公开号：US20140235620A1

  公开（公告）日：2014-08-21

  The invention is directed to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 -R 6 are defined herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

  该发明涉及公式（I）的化合物或其药用盐，其中R1-R6在此处定义。该发明还涉及含有公式（I）化合物的组合物，以及利用这些化合物抑制具有新型活性的突变IDH蛋白。该发明还涉及利用公式（I）的化合物治疗与这些突变IDH蛋白相关的疾病或紊乱，包括但不限于细胞增殖紊乱，如癌症。
• Cinnamide derivatives as KCNQ potassium channel modulators
  申请人：——

  公开号：US20030166650A1

  公开（公告）日：2003-09-04

  There is provided novel cinnamide derivatives of Formula I 1 wherein R is C 1-4 alkyl or trifluoromethyl; R 1 is selected from the group consisting of pyridinyl, quinolinyl, thienyl, furanyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, chromanyl, indanyl, biphenylyl, phenyl and substituted phenyl in which said substituted phenyl is substituted with one or two substituents each independently selected-from the group consisting of halogen, C 1-4 alkyl, C 1-4 alkoxy, trifluoromethyl, trifluoromethoxy and nitro; R 2 and R 3 are each independently selected from the group consisting of hydrogen, C 1-4 alkyl, and halogen; R 4 is selected from the group consisting of di(C 1-4 alkyl)amino, trifluoromethoxy and optionally substituted morpholin-4-yl, pyridinyl, pyrimidinyl, piperazinyl, and pyrazinyl with one or two substituents in which said substituent is independently selected from the group consisting of C 1-4 alkyl, aminomethyl, hydroxymethyl, chloro or fluoro; R 5 is hydrogen, chloro or fluoro; or R 4 and R 5 taken together are —CH═CH—CH═CH— or —X(CH 2 ) m Y— in which X and Y are each independently selected from the group consisting of CH 2 , (CH 2 ) n N(R 9 )— and O, wherein m is 1 or 2; n is 0 or 1; and R 6 , R 7 , and R 8 are each independently selected from hydrogen, chloro and fluoro; and R 9 is selected from the group consisting of hydrogen, C 1-4 alkyl, hydroxyethyl, C 1-4 alkoxyethyl, cyclopropylmethyl, —CO 2 (C 1-4 alkyl), and —CH 2 CH 2 NR 10 R 11 in which R 10 and R 11 are each independently hydrogen or C 1-4 alkyl, which are openers of the KCNQ potassium channels and are useful in the treatment of disorders which are responsive to the opening of the KCNQ potassium channels.

  提供了一种新型的 Formula I1 中的肉桂酰胺衍生物，其中 R 为 C1-4 烷基或三氟甲基；R1 选自吡啶基、喹啉基、噻吩基、呋喃基、1,4-苯并二氧杂基、1,3-苯并二氧杂基、色基、茚基、联苯基、苯基和取代苯基，其中所述取代苯基取代有一个或两个取代基，每个取代基独立地选自卤素、C1-4 烷基、C1-4 烷氧基、三氟甲基、三氟甲氧基和硝基；R2 和 R3 各自独立地选自氢、C1-4 烷基和卤素；R4 选自二(C1-4 烷基)氨基、三氟甲氧基和可选取代的吗啉-4-基、吡啶基、嘧啶基、哌嗪基和吡嗪基，其中所述基带有一个或两个取代基，所述取代基独立地选自 C1-4 烷基、氨甲基、羟甲基、氯或氟；R5 为氢、氯或氟；或者 R4 和 R5 结合成 —CH═CH—CH═CH— 或 —X(CH2)mY—，其中 X 和 Y 各自独立地选自 、( )nN(R9)— 和 O，其中 m 为 1 或 2；n 为 0 或 1；R6、R7 和 R8 各自独立地选自氢、氯和氟；R9 选自氢、C1-4 烷基、羟乙基、C1-4 烷氧乙基、环丙基甲基、—CO2(C1-4 烷基) 和 — NR10R11，其中 R10 和 R11 各自独立地为氢或 C1-4 烷基，这些化合物是 KCNQ 钾通道的开放剂，可用于治疗对 KCNQ 钾通道的开放有反应的疾病。
• Pyridinyl, pyrimidinyl and pyrazinyl amides as potassium channel openers
  申请人：——

  公开号：US20040102449A1

  公开（公告）日：2004-05-27

  The present invention provides novel heterocyclic amides and related derivatives having the general Formula I 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A, B and Z are as defined in the specification, or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof which are openers or activators of KCNQ potassium channels. The present invention also provides pharmaceutical compositions comprising said heterocyclic amides and to the method of treatment of disorders sensitive to KCNQ potassium channel opening activity such as migraine or a migraine attack, bipolar disorders, epilepsy, acute and chronic pain and anxiety.

  本发明提供了具有一般式I1的新型杂环酰胺和相关衍生物，其中R1、R2、R3、R4、R5、R6、A、B和Z如规范中所定义，或其无毒药学上可接受的盐、溶剂或水合物，它们是KCNQ钾通道的开放剂或激活剂。本发明还提供了包括上述杂环酰胺的药物组合物以及对于对KCNQ钾通道开放活性敏感的疾病的治疗方法，如偏头痛或偏头痛发作、双相障碍、癫痫、急性和慢性疼痛和焦虑。
• Aromatic amine derivatives, their production and use
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07160887B1

  公开（公告）日：2007-01-09

  Compounds of a formula: wherein Ring A represents an optionally-substituted aromatic ring; Ring B represents an optionally-substituted cyclic hydrocarbon group; Z represents an optionally-substituted cyclic group; R1 represents a hydrogen atom, an optionally-substituted hydrocarbon group, an optionally-substituted heterocyclic group, or an acyl group; R2 represents an optionally-substituted amino group; D represents a chemical bond or a divalent group; E represents —CO—, —CON(Ra)—, COO—, N(Ra)CON(Rb)—, —N(Ra)COO—, —N(Ra)SO2—, N(Ra)—, —O—, —S—, —SO— or —SO2— (in which Ra and Rb each independently represent a hydrogen atom or an optionally-substituted hydrocarbon group); G represents a chemical bond or a divalent group; L represents (1) a chemical bond or (2) a divalent hydrocarbon group optionally having from 1 to 5 substituents selected from; (i) a C1-6 alkyl group, (ii) a halogeno-C1-6 alkyl group, (iii) a phenyl group, (iv) a benzyl group, (v) an optionally-substituted amino group, (vi) an optionally-substituted hydroxy group, and (vii) a carbamoyl or thiocarbamoyl group optionally substituted by: <1> a C1-6 alkyl group, <2> an optionally-substituted phenyl group, or <3> an optionally-substituted heterocyclic group, and optionally interrupted by —O— or —S—; X represents an oxygen atom, an optionally-oxidized sulfur atom, an optionally-substituted nitrogen atom, or an optionally-substituted divalent hydrocarbon group; Y represents two hydrogen atoms, an oxygen atom or a sulfur atom; . . . means that R2 may be bonded to the atom on Ring B to form a ring, or their salts, and a method for producing them.

  公式化合物：其中环A代表可选取代芳香环；环B代表可选取代的环烃基团；Z代表可选取代的环基团；R1代表氢原子、可选取代的烃基团、可选取代的杂环基团或酰基；R2代表可选取代的氨基团；D代表化学键或二价基团；E代表-CO-、-CON（Ra）-、COO-、N（Ra）CON（Rb）-、-N（Ra）COO-、-N（Ra）SO2-、N（Ra）-、-O-、-S-、-SO-或-SO2-（其中Ra和Rb各自独立地代表氢原子或可选取代的烃基团）；G代表化学键或二价基团；L代表（1）化学键或（2）二价烃基团，可选取1到5个取代基，所选取代基包括：（i）C1-6烷基，（ii）卤代C1-6烷基，（iii）苯基，（iv）苄基，（v）可选取代的氨基团，（vi）可选取代的羟基和（vii）可选取代的羰基或硫代羰基，可选取代基被- O-或-S-中断，其中： <1> C1-6烷基，<2> 可选取代的苯基或<3> 可选取代的杂环基团；X代表氧原子、可选氧化的硫原子、可选取代的氮原子或可选取代的二价烃基团；Y代表两个氢原子、一个氧原子或一个硫原子；...表示R2可以与环B上的原子结合形成环，或其盐，以及制备它们的方法。