3-amino-5-chlorobenzo[b]thiophene-2-carboxylic acid methyl ester | 1026241-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 3-amino-5-chlorobenzo[b]thiophene-2-carboxylic acid methyl ester
• 英文别名: methyl 3-amino-5-chlorobenzo[b]thiophene-2-carboxylate；methyl 3-amino-5-chlorobenzothiophene-2-carboxylate；methyl 3-amino-5-chloro-1-benzothiophene-2-carboxylate
• CAS: 1026241-99-5
• 化学式: C₁₀H₈ClNO₂S
• 分子量: 241.698
• InChiKey: CFYACBCHHBWDOO-UHFFFAOYSA-N

物化性质

• 沸点：
  395.1±37.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-amino-5-chlorobenzo[b]thiophene-2-carboxylic acid methyl ester 在 四丁基氯化铵 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 二乙二醇二甲醚 、 乙腈 为溶剂， 生成 8-Chloro-4-(4-methylpiperazin-1-yl)-[1]benzothiolo[3,2-d]pyrimidin-2-amine
  参考文献：
  名称：

  Tricyclic aminopyrimidine histamine H4 receptor antagonists

  摘要：

  This report discloses the development of a series of tricyclic histamine H-4 receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H-4 receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.014
• 作为产物：
  描述：

  巯基乙酸甲酯 、 5-氯-2-氟苯腈 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.18h， 以92%的产率得到3-amino-5-chlorobenzo[b]thiophene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  微波辅助合成3-氨基苯并[ b ]噻吩支架以制备激酶抑制剂†

  摘要：

  在三乙胺存在下，在130°C的条件下，在三乙胺的存在下对2-卤代苄腈和巯基乙酸甲酯进行微波辐射，可以快速获得3-氨基苯并[ b ]噻吩，产率58-96％。此转化已应用于LIMK1抑制剂噻吩并[2,3- b ]吡啶核心基序，苯并[4,5]噻吩并[3,2- e ] [1,4] diazepin-5（2）的合成中H）-一个MK2抑制剂的支架和PIM激酶的苯并[4,5]噻吩并[3,2 - d ]嘧啶-4-酮抑制剂。

  DOI：

  10.1039/c5ob00819k

文献信息

• PIM KINASE INHIBITORS AS CANCER CHEMOTHERAPEUTICS
  申请人：Penning Thomas D.

  公开号：US20080161559A1

  公开（公告）日：2008-07-03

  Inhibitors of Pim kinases, ways to make them and methods of treating patients using them are disclosed.

  抑制Pim激酶的抑制剂，制备方法以及利用它们治疗患者的方法被披露。
• Conversion of 2-Thioxo-2,3-dihydroquinazolin-4(1H)-ones to N(3)-Unsubstituted 2-(Het)Arylquinazolin-4(3H)-ones by Copper-Mediated Pd-Catalysed Cross-Coupling Reactions
  作者：Algirdas Šačkus、Vilija Kriščiūnienė、Gita Matulevičiūtė、Osvaldas Paliulis

  DOI：10.3987/com-15-s(t)12

  日期：——

  With the purpose of searching for new heterocyclic building blocks, a new method to access N(3)-unsubstituted 2-(het)arylquinazolin-4(3H)-ones from 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives was developed. The synthetic protocol was based on the copper-mediated palladium-catalysed cross-coupling reactions of 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones with (het)arylstannanes or their S-benzylated derivatives with (het)arylboronic acids, using CuBr center dot Me2S and CuMeSal as promoters, respectively. A similar transformation was applied for the preparation of 2-aryl[ 1]benzothieno[3,2-d]pyrimidin-4(3H)-ones.
• Syntheses of substituted 2,4-dioxo-thienopyrimidin-1-acetic acids and their evaluation as aldose reductase inhibitors
  作者：K Ogawva、I Yamawaki、YI Matsusita、N Nomura、PF Kador、JH Kinoshita

  DOI：10.1016/0223-5234(93)90112-r

  日期：1993.1

  A series of 2,4-dioxo-thieno[2,3-d], [3,2-d] and [3,4-d]pyrimidin-1-acetic acids (2) with a benzyl moiety at the N-3 position were prepared and tested in vitro for aldose reductase inhibitory activity against partially purified enzyme from rat lens. Some of these compounds were also evaluated for inhibition of sorbitol accumulation in the sciatic nerve or lens of streptozotocin-induced diabetic rats in vivo. Among the synthesized compounds, several showed potent aldose reductase inhibitory activity with IC50s in the 10(-8) M range. Particularly, the potencies of non-substituted thieno- (2a and 2aa), 5-methylthieno- (2c), 5,6-dimethylthieno-(2g), 6-isopropylthieno- (2j and 2k), 6-chlorothienopyrimidine (2q) and benzothienopyrimidine (2ac) analogs were approximately equipotent to FK-366 (1A) and Ponalrestat (1B) as references. Although most compounds were inactive in vivo, 2 compounds, 2k and 2q, possessed moderate in vivo activity.
• Discovery of 3<i>H</i>-Benzo[4,5]thieno[3,2-<i>d</i>]pyrimidin-4-ones as Potent, Highly Selective, and Orally Bioavailable Inhibitors of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM) Kinases
  作者：Zhi-Fu Tao、Lisa A. Hasvold、Joel D. Leverson、Edward K. Han、Ran Guan、Eric F. Johnson、Vincent S. Stoll、Kent D. Stewart、Geoff Stamper、Nirupama Soni、Jennifer J. Bouska、Yan Luo、Thomas J. Sowin、Nan-Horng Lin、Vincent S. Giranda、Saul H. Rosenberg、Thomas D. Penning

  DOI：10.1021/jm900943h

  日期：2009.11.12

  Pim-1, Pim-2, and Pim-3 are a family of serine/threonine kinases which have been Found to be overexpressed in a variety of hematopoietic malignancies and solid tumors. Benzothienopyrimidinones were discovered as a novel class of Pim inhibitors that potently inhibit all three Pim kinases with subnanomolar to low single-digit nanomolar K-i values and exhibit excellent selectivity against a panel of diverse kinases. Protein crystal structures of the bound Pim-1 complexes of benzothienopyrimidinones 3b (PDB code 3JYA), 6e (PDB code 3JYO), and 12b (PDB code 3JXW) were determined and used to guide SAR studies. Multiple compounds exhibited potent antiproliferative activity in K562 and MV4-11 cells with submicromolar EC50 values. For example, compound 14j inhibited the growth of K562 cells with an EC50 value of 1.7 mu M and showed K-i values of 2, 3, and 0.5 nM against Pim-1, Pim-2, and Pim-3, respectively. These novel Pim kinase inhibitors efficiently interrupted the phosphorylation of Bad in both K562 and LnCaP-Bad cell lines, indicating that their potent biological activities are mechanism-based. The pharmacokinetics of 14j was studied in CD-1 mice and shown to exhibit bioavailability of 76% after oral dosing. ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein bin-ling, and no CYP inhibition below 20 mu M concentration.
• Ogawva K., Yamawaki I., Matsusita Y. I., Nomura N., Kador P. F., Kinoshit+, Eur. I. Med. Chem, 28 (1993) N 10, S 769-781
  作者：Ogawva K., Yamawaki I., Matsusita Y. I., Nomura N., Kador P. F., Kinoshit+

  DOI：——

  日期：——