ethyl 5,6-dihydro-2-(isothiocyanato)-4H-cyclopenta[4,5]thiophene-3-carboxylate | 257610-90-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: ethyl 5,6-dihydro-2-(isothiocyanato)-4H-cyclopenta[4,5]thiophene-3-carboxylate
• 英文别名: ethyl 2-isothiocyanato-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylate
• CAS: 257610-90-5
• 化学式: C₁₁H₁₁NO₂S₂
• 分子量: 253.346
• InChiKey: CCKDXTHWGJHOFV-UHFFFAOYSA-N

物化性质

• 熔点：
  55-56 °C
• 沸点：
  434.1±45.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  99
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5,6-dihydro-2-(isothiocyanato)-4H-cyclopenta[4,5]thiophene-3-carboxylate 在 sodium hydroxide 、 PPA 、 mercury(II) oxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 54.66h， 生成 10-(Diethylamino)-11-oxa-7-thia-9-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6),9-trien-12-one
  参考文献：
  名称：

  2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.

  DOI：

  10.1021/jm991108w
• 作为产物：
  描述：

  氰乙酸乙酯 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 二乙胺 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 ethyl 5,6-dihydro-2-(isothiocyanato)-4H-cyclopenta[4,5]thiophene-3-carboxylate
  参考文献：
  名称：

  Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors

  摘要：

  Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50 = 160 nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-kappa B activation to trigger the downstream cytokines, such as TNF-alpha and secreted alkaline phosphatase (SEAP). (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.067

文献信息

• 2-氨基-环戊烯并[b]噻吩-3-羧酸酯衍生物及其制备方法和用途
  申请人：广州辉睿生物科技有限公司

  公开号：CN112079828A

  公开（公告）日：2020-12-15

  本发明涉及2‑氨基‑环戊烯并[b]噻吩‑3‑羧酸酯骨架类衍生物的制备方法及用途。本发明的化合物的特点在于能够有效的激活TLR1/2受体以及对炎症因子也有激活作用，其中具体公开了式I所示化合物11个，并公开阐述化合物在制备TLR2受体激动剂的方法及应用为免疫佐剂、抗炎、抗肿瘤等方面的应用。其结构如下式所示：式I。
• Aromatic 2-(Thio)ureidocarboxylic Acids As a New Family of Modulators of Multidrug Resistance-Associated Protein 1: Synthesis, Biological Evaluation, and Structure−Activity Relationships
  作者：Hans-Georg Häcker、Stefan Leyers、Jeanette Wiendlocha、Michael Gütschow、Michael Wiese

  DOI：10.1021/jm900688v

  日期：2009.8.13

  Four series of aromatic carboxylic acids were prepared with a urea or thiourea moiety at the neighboring position to the carboxyl group and benzene or thiophene as aromatic scaffold. Using a calcein AM assay, these compounds were evaluated as inhibitors of multidrug resistance-associated protein I (MRP1) and selected compounds were examined toward P-glycoprotein (P-gp) as well as breast cancer resistance protein (BCRP) to assess selectivity for MRP1. Two 2-thioureidobenzo[b]-thiophene-3-carboxylic acids (48, 49) were identified as particularly potent inhibitors of MRP1, with IC50 values of around 1 mu M. The structural features of this new family or nontoxic MRP1 inhibitors include a (thio)urea disubstituted with preferentially two alkyl groups at the terminal nitrogen and an additional fused aromatic ring.
• High potent and selective arylpiperazine derivatives as ligands for the 5-HT 1A receptor
  作者：Maria Modica、Maria Santagati、Andrea Santagati、Filippo Russo、Alfredo Cagnotto、Mara Goegan、Tiziana Mennini

  DOI：10.1016/s0960-894x(00)00165-7

  日期：2000.5

  This paper reports the synthesis and affinities on the 5HT(1A) versus the alpha(1)A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16-24. Arylpiperazines 16-23 show affinities values in the nanomolar range for the 5HT(1A) receptor. The compound 16 is highly potent (K-i 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (K-i 9.40 and 5.06 nM, selectivity 207 and 73, respectively). (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis of urea analogues bearing N-alkyl-N'-(thiophen-2-yl) scaffold and evaluation of their innate immune response to toll-like receptors
  作者：Zhipeng Chen、Xiaohong Cen、Junjie Yang、Zhiman Lin、Meihuan Liu、Kui Cheng

  DOI：10.1016/j.ejmech.2019.02.067

  日期：2019.5

  Previous high throughput virtual screening of 10 million-compound and following cell based validation led to the discovery of a novel, nonlipopeptide-like chemotype ZINC 6662436, as toll-like receptor 2 (TLR2) agonists. In this report, compounds belonging to four areas of structural modification of ZINC6662436 were evaluated for biological activity using human HEK-Blue TLR2 reporter cells, and human THP-1 monocytic cells, yield SMU-C13 as an optimized, direct and high potent (EC50 = 160 nM) agonist of human TLR2. Moreover, preliminary mechanism studies indicated that SMU-C13 through activates TLR1 and TLR2 then stimulates the NF-kappa B activation to trigger the downstream cytokines, such as TNF-alpha and secreted alkaline phosphatase (SEAP). (C) 2019 Elsevier Masson SAS. All rights reserved.
• 2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase
  作者：Michael Gütschow、Lars Kuerschner、Ulf Neumann、Markus Pietsch、Reik Löser、Norman Koglin、Kurt Eger

  DOI：10.1021/jm991108w

  日期：1999.12.1

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.