N-[3-(3-benzoyl-thioureido)-4-methoxy-phenyl]-acetamide | 722550-78-9

• 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: N-[3-(3-benzoyl-thioureido)-4-methoxy-phenyl]-acetamide
• 英文别名: N-[(5-acetamido-2-methoxyphenyl)carbamothioyl]benzamide
• CAS: 722550-78-9
• 化学式: C₁₇H₁₇N₃O₃S
• 分子量: 343.406
• InChiKey: QNPPFYSTSXPBHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[3-(3-benzoyl-thioureido)-4-methoxy-phenyl]-acetamide 在 氢溴酸 、 二甲基亚砜 作用下， 以 溶剂黄146 为溶剂， 反应 2.5h， 以86%的产率得到N-(7-acetylamino-4-methoxy-benzothiazol-2-yl)-benzamide
  参考文献：
  名称：

  Cyclization process for substituted benzothiazole derivatives

  摘要：

  本发明涉及一种制备式I1的氨基取代苯并噻唑衍生物的方法，其中R1、R2和R3分别独立地为氢、低烷基、低烷氧基或卤素；R4为氢、低烷基、低烷氧基、卤素，或为未取代或取代的五元或六元非芳香杂环基，取代基为低烷基或氧代基，或为—NR5R6，其中R5和R6独立地为氢、低烷基、—C（O）-低烷基、—（CH2）nO-低烷基或苄基，可选地取代为低烷基，或为五元或六元杂环芳基基团；R1和R2或R2和R3可与相应的碳原子一起形成含有—O—CH2—O—或—CH═CH—CH═CH—的环；R为氢或—C（O）R′；R′为五元或六元非芳香杂环基、五元或六元杂环芳基基团或为芳基，这些环可以被从低烷基、卤素-低烷基、低烷氧基、氰基、硝基、—C（O）H、—C（O）OH或吡咯烷-1-基甲基中选择的基取代；n为1至4；或其药学上可接受的盐，其中通过使用硫醇氧化物/HBr/溶剂处理式2的化合物进行环化反应，从而得到所需的式I的产物，其中R为氢（式Ia）或R为—C（O）R′（式Ib）3。

  公开号：

  US20040138465A1
• 作为产物：
  描述：

  3-氨基-4-甲氧基乙酰苯胺 、 苯甲酰基异硫氰酸酯 以 丙酮 为溶剂， 以69%的产率得到N-[3-(3-benzoyl-thioureido)-4-methoxy-phenyl]-acetamide
  参考文献：
  名称：

  4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: Drug-like and non-xanthine based A2B adenosine receptor antagonists

  摘要：

  7-N-Acetamide-4-methoxy-2-aminobenzothiazole 4-fluorobenzamide (compound 1) was chosen as a drug-like and non-xanthine based starting point for the discovery of A(2B) receptor antagonists because of its slight selectivity against A(1) and A(2A) receptors and modest A(2B) potency. SAR exploration of compound 1 described herein included modi. cations to the 7-N-acetamide group, substitution of the 4-methoxy group by halogens as well as replacement of the p-flouro-benzamide side chain. This work culminated in the identification of compound 37 with excellent A(2B) potency, modest selectivity versus A(2A) and A(1) receptors, and good rodent PK properties. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.056

文献信息

• CYCLIZATION PROCESS FOR SUBSTITUTED BENZOTHIAZOLE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1583752A2

  公开（公告）日：2005-10-12
• US7087761B2
  申请人：——

  公开号：US7087761B2

  公开（公告）日：2006-08-08
• [EN] CYCLIZATION PROCESS FOR SUBSTITUTED BENZOTHIAZOLE DERIVATIVES<br/>[FR] PROCEDE DE CYCLISATION POUR DES DERIVES DE BENZOTHIAZOLE SUBSTITUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004060879A2

  公开（公告）日：2004-07-22

  The present invention relates to a process for preparation of amino substituted benzothiazole derivatives of formula (I), wherein R1, R2 and R3 are independently from each other hydrogen, lower alkyl, lower alkoxy or halogen; R4 is hydrogen, lower alkyl, lower alkyloxy, halogen, or is a five or six membered non aromatic heterocyclyl group, unsubstituted or substituted by lower alkyl or an oxo-group, or is -NR5R6 wherein R5 and R6 are independently from each other hydrogen, lower alkyl, -C(O)-lower alkyl, -(CH2)nO-lower alkyl or benzyl, opionally substituted by lower alkyl, or is an five or six membered heteroaryl group; R1 and R2 or R2 and R3 may form together with the corresponding carbon atoms a ring containing -O-CH2-O- or -CH=CH-CH=CH-; R is hydrogen or -C(O)R'; R' is a five or six membered non aromatic heterocyclyl group, five or six membered heteroaryl group or is aryl, which rings may be substituted by the groups, selected from lower alkyl, halogen-lower alkyl, lower alkoxy, cyano, nitro, -C(O)H, -C(O)OH or by pyrrolidin-1-yl-methyl; n is 1 to 4; and to their pharmaceutically acceptable salts, wherein the cyclization is carried out by the treatment of a compound of formula with sulphoxide/HBr/solvent to give the desired products of formula (I) for R is hydrogen (formula IA) and for R is -C(O)R’ (formula IB).
• Cyclization process for substituted benzothiazole derivatives
  申请人：——

  公开号：US20040138465A1

  公开（公告）日：2004-07-15

  The present invention relates to a process for preparation of amino substituted benzothiazole derivatives of formula I 1 wherein R 1 , R 2 and R 3 are independently from each other hydrogen, lower alkyl, lower alkoxy or halogen; R 4 is hydrogen, lower alkyl, lower alkyloxy, halogen, or is a five or six membered non aromatic heterocyclyl group, unsubstituted or substituted by lower alkyl or an oxo-group, or is —NR 5 R 6 , wherein R 5 and R 5 are independently from each other hydrogen, lower alkyl, —C(O)-lower alkyl, —(CH 2 ) n O-lower alkyl or benzyl, opionally substituted by lower alkyl, or is an five or six membered heteroaryl group; R 1 and R 2 or R 2 and R 3 may form together with the corresponding carbon atoms a ring containing —O—CH 2 —O— or —CH═CH—CH═CH—; R is hydrogen or —C(O)R′; R′ is a five or six membered non aromatic heterocyclyl group, five or six membered heteroaryl group or is aryl, which rings may be substituted by the groups, selected from lower alkyl, halogen-lower alkyl, lower alkoxy, cyano, nitro, —C(O)H, —C(O)OH or by pyrrolidin- 1 -yl-methyl; n is 1 to 4; or a pharmaceutically acceptable salt thereof, wherein the cyclization is carried out by the treatment of a compound of formula 2 with sulphoxide/HBr/solvent to give the desired products of formula I for R is hydrogen (formula IA) or for R is —C(O)R′ (formula IB) 3

  本发明涉及一种制备式I1的氨基取代苯并噻唑衍生物的方法，其中R1、R2和R3分别独立地为氢、低烷基、低烷氧基或卤素；R4为氢、低烷基、低烷氧基、卤素，或为未取代或取代的五元或六元非芳香杂环基，取代基为低烷基或氧代基，或为—NR5R6，其中R5和R6独立地为氢、低烷基、—C（O）-低烷基、—（CH2）nO-低烷基或苄基，可选地取代为低烷基，或为五元或六元杂环芳基基团；R1和R2或R2和R3可与相应的碳原子一起形成含有—O—CH2—O—或—CH═CH—CH═CH—的环；R为氢或—C（O）R′；R′为五元或六元非芳香杂环基、五元或六元杂环芳基基团或为芳基，这些环可以被从低烷基、卤素-低烷基、低烷氧基、氰基、硝基、—C（O）H、—C（O）OH或吡咯烷-1-基甲基中选择的基取代；n为1至4；或其药学上可接受的盐，其中通过使用硫醇氧化物/HBr/溶剂处理式2的化合物进行环化反应，从而得到所需的式I的产物，其中R为氢（式Ia）或R为—C（O）R′（式Ib）3。
• 4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: Drug-like and non-xanthine based A2B adenosine receptor antagonists
  作者：Adrian Wai-Hing Cheung、John Brinkman、Fariborz Firooznia、Alexander Flohr、Joseph Grimsby、Mary Lou Gubler、Kevin Guertin、Rachid Hamid、Nicholas Marcopulos、Roger D. Norcross、Lida Qi、Gwendolyn Ramsey、Jenny Tan、Yang Wen、Ramakanth Sarabu

  DOI：10.1016/j.bmcl.2010.05.056

  日期：2010.7

  7-N-Acetamide-4-methoxy-2-aminobenzothiazole 4-fluorobenzamide (compound 1) was chosen as a drug-like and non-xanthine based starting point for the discovery of A(2B) receptor antagonists because of its slight selectivity against A(1) and A(2A) receptors and modest A(2B) potency. SAR exploration of compound 1 described herein included modi. cations to the 7-N-acetamide group, substitution of the 4-methoxy group by halogens as well as replacement of the p-flouro-benzamide side chain. This work culminated in the identification of compound 37 with excellent A(2B) potency, modest selectivity versus A(2A) and A(1) receptors, and good rodent PK properties. (C) 2010 Elsevier Ltd. All rights reserved.