噻吩-2,3-二羧酸 | 71189-23-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 噻吩类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 噻吩-2,3-二羧酸
• 中文别名: 2-噻唑异氰酸酯；噻吩-2,3-二甲酸
• 英文名称: Thiazol-2-ylisocyanate
• 英文别名: 2-Isocyanato-Thiazole；2-isocyanato-1,3-thiazole
• CAS: 71189-23-6
• 化学式: C₄H₂N₂OS
• mdl: MFCD08460108
• 分子量: 126.139
• InChiKey: MXJQJCACXRHPOV-UHFFFAOYSA-N

物化性质

• 沸点：
  216 ºC
• 密度：
  1.41
• 闪点：
  85 ºC

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  噻吩-2,3-二羧酸 、 3-氨基苯硼酸频哪醇酯 以 二氯甲烷 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach

  摘要：

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.045
• 作为产物：
  描述：

  2-氨基噻唑 、 三光气 在 三乙胺 作用下， 以 甲苯 为溶剂， 生成 噻吩-2,3-二羧酸
  参考文献：
  名称：

  Inhibitors of protein isoprenyl transferases

  摘要：

  具有以下化学式或其药学上可接受的盐的化合物，其中R1为(a)氢，(b)低烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤素烷基，(h)芳基-L2-，以及(i)杂环-L2-; R2选自(b)-C(O)NH-CH(R14)-C(O)OR15，(d)-C(O)NH-CH(R14)-C(O)NHSO2R16，(e)-C(O)NH-CH(R14)-四唑基，(f)-C(O)NH-杂环，以及(g)-C(O)NH-CH(R14)-C(O)NR17R18; R3为杂环，芳基，取代或未取代的环烷基; R4为氢，低烷基，卤素烷基，卤素，芳基，芳基烷基，杂环或(杂环)烷基; L1不存在或选自(a)-L4-N(R5)-L5-，(b)-L4-O-L5-，(c)-L4-S(O)n-L5-，(d)-L4-L6-C(W)-N(R5)-L5-，(e)-L4-L6-S(O)m-N(R5)-L5-，(f)-L4-N(R5)-C(W)-L7-L5-，(g)-L4-N(R5)-S(O)p-L7-L5-，(h)可选取代的烷基，(i)可选取代的烯基，以及(j)可选取代的炔基是蛋白质异戊烷基转移酶的抑制剂。还公开了蛋白质异戊烷基转移酶抑制剂组合物和一种抑制蛋白质异戊烷基转移酶的方法。

  公开号：

  US06204293B1

文献信息

• Inhibitors of protein isoprenyl transferases
  申请人：University of Pittsburgh

  公开号：US20020193596A1

  公开（公告）日：2002-12-19

  Compounds having the formula 1 or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 —, and (i) heterocyclic-L 2 —; R 2 is selected from (a) 2 (b) —C(O)NH—CH(R 14 )—C(O)OR 15 , (c) 3 (d) —C(O)NH—CH(R 14 )—C(O)NHSO 2 R 16 (e) —C(O)NH—CH(R 14 )-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R 14 )—C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) —L 4 —N(R 5 )—L 5 —, (b) —L 4 —O—L 5 —, (c) —L 4 —S(O) n —L 5 — (d) —L 4 -L 6 —C(W)—N(R 5 )—L 5 —, (e) —L 4 -L 6 —S(O) m —N(R 5 )—L 5 —, (f) —L 4 —N(R 5 )—C(W)—L 7 -L 5 —, (g) —L 4 —N(R 5 )—S(O) p —L 7 —L 5 —, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

  具有以下公式的化合物或其药学上可接受的盐，其中R1为(a)氢，(b)较低的烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤代烷基，(h)芳基-L2—，以及(i)杂环-L2—；R2从(a)中选择，(b) -C(O)NH-CH(R14)-C(O)OR15，(c)中选择，(d) -C(O)NH-CH(R14)-C(O)NHSO2R16，(e) -C(O)NH-CH(R14)-四唑基，(f) -C(O)NH-杂环，以及(g) -C(O)NH-CH(R14)-C(O)NR17R18；R3为杂环，芳基，取代或未取代的环烷基；R4为氢，较低烷基，卤代烷基，卤素，芳基，芳基烷基，杂环基，或(杂环)烷基；L1为空缺或从(a) -L4-N(R5)-L5-，(b) -L4-O-L5-，(c) -L4-S(O)n-L5-，(d) -L4-L6-C(W)-N(R5)-L5-，(e) -L4-L6-S(O)m-N(R5)-L5-，(f) -L4-N(R5)-C(W)-L7-L5-，(g) -L4-N(R5)-S(O)p-L7-L5-，(h)可选择取代的烷基，(i)可选择取代的烯基，以及(j)可选择取代的炔基是蛋白异戊二烯转移酶的抑制剂。还公开了蛋白异戊二烯转移酶抑制组合物和抑制蛋白异戊二烯转移酶的方法。
• A facile synthesis of unsymmetrical ureas
  作者：Andrey V. Bogolubsky、Sergey V. Ryabukhin、Sergey E. Pipko、Oleg Lukin、Alexander Shivanyuk、Dmytro Mykytenko、Andrey Tolmachev

  DOI：10.1016/j.tet.2011.03.101

  日期：2011.5

  versatile method for the synthesis of unsymmetrical ureas from readily available reagents is reported. In the first step trifluoroethylchloroformate is reacted with a stoichiometric amount of a primary amine to give an intermediate trifluoroethyl carbamate. The addition of a second amine (primary or secondary) to the trifluoroethyl carbamate furnishes corresponding unsymmetrical ureas in 75–85% yield. A

  报道了一种由容易获得的试剂合成不对称脲的简便而通用的方法。在第一步中，使三氟乙基氯甲酸酯与化学计算量的伯胺反应，得到中间体三氟乙基氨基甲酸酯。在氨基甲酸三氟乙酯中添加第二种胺（伯胺或仲胺）可提供相应的不对称脲，产率为75-85％。简单的后处理程序，获得的高收率和分离产物的纯度适用于具有高结构和功能多样性的不对称脲组合库的平行合成。
• Discovery of potent and selective thienopyrimidine inhibitors of Aurora kinases
  作者：William J. McClellan、Yujia Dai、Cele Abad-Zapatero、Daniel H. Albert、Jennifer J. Bouska、Keith B. Glaser、Terry J. Magoc、Patrick A. Marcotte、Donald J. Osterling、Kent D. Stewart、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1016/j.bmcl.2011.06.041

  日期：2011.9

  In an effort to discover Aurora kinase inhibitors, an HTS hit revealed an amide containing pyrrolopyrimidine compound. Replacement of the pyrrolopyrimidine residue with a thienopyrimidine moiety led to a series of potent and selective Aurora inhibitors.

  为了发现Aurora激酶抑制剂，HTS命中发现含有酰胺的吡咯并嘧啶化合物。用噻吩并嘧啶部分取代吡咯并嘧啶残基导致一系列有效的和选择性的Aurora抑制剂。
• Potent hFPRL1 (ALXR) agonists as potential anti-inflammatory agents
  作者：Roland W. Bürli、Han Xu、Xiaoming Zou、Kristine Muller、Jennifer Golden、Mike Frohn、Matthew Adlam、Matthew H. Plant、Min Wong、Michele McElvain、Kelly Regal、Vellarkad N. Viswanadhan、Philip Tagari、Randall Hungate

  DOI：10.1016/j.bmcl.2006.04.068

  日期：2006.7

  We report the discovery of potent agonists for the human formyl-peptide-like 1 receptor (hFPRL1). These compounds did not act at a closely related receptor denoted human formyl peptide receptor (hFPR) up to 10 mu M concentration. Recent studies have indicated that agonizing this receptor may promote resolution of inflammation. In an exploratory study, a novel hFPRL1 agonist showed efficacy in a mouse ear inflammation model following oral administration. (c) 2006 Elsevier Ltd. All rights reserved.
• Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach
  作者：Yuanyuan Shan、Hongping Gao、Xiaowei Shao、Jinfeng Wang、Xiaoyan Pan、Jie Zhang

  DOI：10.1016/j.ejmech.2015.08.045

  日期：2015.10

  Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization. (C) 2015 Elsevier Masson SAS. All rights reserved.