methyl 4-(thioureidomethyl)benzoate | 540737-38-0

• 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 4-(thioureidomethyl)benzoate
• 英文别名: 1-(4-methoxycarbonylbenzyl)-2-thiourea；methyl 4-[(carbamothioylamino)methyl]benzoate
• CAS: 540737-38-0
• 化学式: C₁₀H₁₂N₂O₂S
• 分子量: 224.283
• InChiKey: VMMOTGMKOGNJSQ-UHFFFAOYSA-N

物化性质

• 熔点：
  131-133 °C
• 沸点：
  384.8±52.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-(thioureidomethyl)benzoate 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.0h， 生成 methyl 4-((N-(4-phenylthiazol-2-yl)morpholine-4-carboxamido)methyl)benzoate
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS FOR SELECTIVE HISTONE DEACETYLASE INHIBITORS, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  [FR] NOUVEAUX COMPOSÉS POUR INHIBITEURS SÉLECTIFS D'HISTONE DÉSACÉTYLASES ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT

  摘要：

  本发明涉及新型尿素衍生物，更特别地涉及具有组蛋白去乙酰化酶（HDAC）抑制活性的新型尿素衍生物，其异构体，其药学上可接受的盐，它们用于制备包含相同成分的药物的用途，包含相同成分的药物组合物，使用该组合物的治疗方法，以及制备新型尿素衍生物的方法。作为选择性组蛋白去乙酰化酶（HDAC）抑制剂的新型尿素衍生物对于治疗组蛋白去乙酰化酶介导的疾病，如恶性肿瘤、炎症性疾病、类风湿性关节炎、神经退行性疾病等非常有效。

  公开号：

  WO2014178606A1
• 作为产物：
  描述：

  4-氨甲基苯甲酸甲酯盐酸盐 在 三乙胺 、 N,N'-硫羰基二咪唑 、 氨 作用下， 以 氯仿 、 甲醇 、 水 为溶剂， 反应 3.0h， 以91.3%的产率得到methyl 4-(thioureidomethyl)benzoate
  参考文献：
  名称：

  EP1452530

  摘要：

  公开号：

文献信息

• Azole compound and medicinal use thereof
  申请人：Inaba Takashi

  公开号：US20050065196A1

  公开（公告）日：2005-03-24

  The present invention relates to an azole compound represented by the formula [I] wherein W is S or O; R is —COOR 7 , —X 1 -A 1 -COOR 7 (R 7 is H, alkyl) or tetrazolyl; R 1 , R 2 , R 3 and R 4 are H and the like; A is —(CH 2 ) m —X— (X is —N(R 8 )—, —C(R 9 )(R 10 )—, —CO— or —CO—N(R 8 )—); B is aryl or aromatic heterocyclic group; R 5 is H and the like; R 6 is —(Y) s1 -(A 2 ) s -Z (Y is —O—, —S(O) t —, —N(R 13 )—, —N(R 14 )—CO—, —N(R 14 )—SO 2 —, —SO 2 —N(R 14 )— and the like, A 2 is alkylene, and Z is cycloalkyl, aryl, aromatic heterocyclic group, indanyl, piperazinyl, a prodrug thereof or a pharmaceutically acceptable salt thereof. The compound [I] of the present invention has a protein tyrosine phosphatase 1B inhibitory activity, and is useful as a therapeutic agent for diabetes, a therapeutic drug for diabetic complications or a therapeutic drug for hyperlipidemia.

  本发明涉及一种由式[I]表示的唑类化合物，其中W为S或O；R为—COOR7，—X1-A1-COOR7（R7为H，烷基）或四唑基；R1、R2、R3和R4为H等；A为—（CH2）m—X—（X为—N（R8）—、—C（R9）（R10）—、—CO—或—CO—N（R8）—）；B为芳基或芳香杂环基；R5为H等；R6为—（Y）s1-（A2）s-Z（Y为—O—、—S（O）t—、—N（R13）—、—N（R14）—CO—、—N（R14）—SO2—、—SO2—N（R14）—等，A2为烷基，Z为环烷基，芳基，芳香杂环基，茚基，哌嗪基，其前体药物或其药学上可接受的盐。本发明的化合物[I]具有蛋白酪氨酸磷酸酶1B抑制活性，并且可用作糖尿病治疗剂、糖尿病并发症治疗药物或高脂血症治疗药物。
• NOVEL COMPOUNDS FOR SELECTIVE HISTONE DEACETYLASE INHIBITORS, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：CHONG KUN DANG PHARMACEUTICAL CORP.

  公开号：US20160083354A1

  公开（公告）日：2016-03-24

  The present invention relates to novel urea derivatives and, more particularly, to novel urea derivatives with histone deacetylase (HDAC) inhibitory activity, isomers thereof, pharmaceutically acceptable salts thereof, their use for the preparation of a medicaments comprising the same, a pharmaceutical composition comprising the same, a treatment method using the composition, and a method for preparing novel urea derivatives. The novel urea derivatives as selective histone deacetylase (HDAC) inhibitors are effective for the treatment of histone deacetylase-mediated diseases such as malignant tumors, inflammatory diseases, rheumatoid arthritis, neurodegeneration, etc.

  本发明涉及新型尿素衍生物，更具体地涉及具有组蛋白去乙酰化酶（HDAC）抑制活性的新型尿素衍生物、其异构体、其药学上可接受的盐、用于制备包括它们的药物的使用、包括它们的制药组合物、使用该组合物的治疗方法和制备新型尿素衍生物的方法。这些新型尿素衍生物作为选择性组蛋白去乙酰化酶（HDAC）抑制剂对组蛋白去乙酰化酶介导的疾病，如恶性肿瘤、炎症性疾病、类风湿性关节炎、神经退行性疾病等具有治疗作用。
• AZOLE COMPOUND AND MEDICINAL USE THEREOF
  申请人：Japan Tobacco Inc.

  公开号：EP1452530A1

  公开（公告）日：2004-09-01

  The present invention relates to an azole compound represented by the formula [I] wherein W is S or O; R is -COOR7, -X1-A1-COOR7 (R7 is H, alkyl) or tetrazolyl; R1, R2, R3 and R4 are H and the like; A is -(CH2)m-X- (X is -N(R8)-, -C(R9)(R10)-, -CO- or -CO-N(R8)-); B is aryl or aromatic heterocyclic group; R5 is H and the like; R6 is -(Y)s1-(A2)s-Z (Y is -O-, -S(O)t-, -N(R13)-, -N(R14)-CO-, -N(R14)-SO2-, -SO2-N(R14)- and the like, A2 is alkylene, and Z is cycloalkyl, aryl, aromatic heterocyclic group, indanyl, piperazinyl, a prodrug thereof or a pharmaceutically acceptable salt thereof. The compound [I] of the present invention has a protein tyrosine phosphatase 1B inhibitory activity, and is useful as a therapeutic agent for diabetes, a therapeutic drug for diabetic complications or a therapeutic drug for hyperlipidemia.

  本发明涉及一种由式[I]表示的唑化合物 其中W是S或O；R是-COOR7、-X1-A1-COOR7（R7是H、烷基）或四唑基；R1、R2、R3和R4是H等；A是-(CH2)m-X-（X是-N(R8)-、-C(R9)(R10)-、-CO-或-CO-N(R8)-）；B是芳基或芳香杂环基团；R5是H等；R6是-(Y)s1-(A2)s-Z（Y是-O-、-S(O)t-、-N(R13)-、-N(R14)-CO-、-N(R14)-SO2-、-SO2-N(R14)-等，A2是亚烷基，Z是环烷基、芳基、芳香杂环基、茚基、哌嗪基、其原药或其药学上可接受的盐。本发明的化合物[I]具有蛋白酪氨酸磷酸酶 1B 抑制活性，可作为糖尿病治疗剂、糖尿病并发症治疗药物或高脂血症治疗药物。
• Synthesis of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas and evaluation as modulators of the isoforms of nitric oxide synthase
  作者：C Goodyer

  DOI：10.1016/s0968-0896(03)00451-6

  日期：2003.9.15

  Inhibition of the isoforms of nitric oxide synthase (NOS) has important applications in therapy of several diseases, including cancer. Using 1400W [N-(3-aminomethylbenzyl)acetamidme], thiocitrulline and N-delta-(4,5-dihydrothiazol-2-yl)ornithine as lead compounds, series of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas were designed as inhibitors of NOS. Ring-substituted benzyl and phenyl isothiocyanates were synthesised by condensation of the corresponding amines with thiophosgene and addition of ammonia gave the corresponding thioureas in high yields. The substituted 2-amino-4,5-dihydrothiazoles were approached by two routes. Treatment of simple benzylamines with 2-methylthio-4,5-dihydrothiazole at 180degreesC afforded the corresponding 2-benzylamino-4,5-dihydrothiazoles. For less nucleophilic amines and those carrying more thermally labile substituents, the 4,5-dihydrothiazoles were approached by acid-catalysed cyclisation of N-(2-hydroxyethyl)thioureas. This cyclisation was shown to proceed by an S(N)2-like process. Modest inhibitory activity was shown by most of the thioureas and 4,5-dihydrothiazoles, with N-(3-aminomethylphenyl)thiourea (IC50 = 13 muM vs rat neuronal NOS and IC50 = 23 muM vs rat inducible NOS) and 2-(3-aminomethylphenylamino)-4,5-dihydrothiazole (IC50 - 13 muM vs rat neuronal NOS and IC50 = 19 muM vs human inducible NOS) being the most potent. Several thioureas and 4,5-dihydrothiazoles were found to stimulate the activity of human inducible NOS in a time-dependent manner. (C) 2003 Elsevier Ltd. All rights reserved.
• US7163952B2
  申请人：——

  公开号：US7163952B2

  公开（公告）日：2007-01-16