3-[3-(2-Chloro-ethyl)-ureido]-benzofuran-2-carboxylic acid ethyl ester | 152032-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3-[3-(2-Chloro-ethyl)-ureido]-benzofuran-2-carboxylic acid ethyl ester
• 英文别名: 3-[[[(2-Chloroethyl)amino]carbonyl]amino]-2-benzofurancarboxylic acid ethyl ester；ethyl 3-(2-chloroethylcarbamoylamino)-1-benzofuran-2-carboxylate
• CAS: 152032-93-4
• 化学式: C₁₄H₁₅ClN₂O₄
• 分子量: 310.737
• InChiKey: NAUVZVYQPWOLMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  438.7±45.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苯基)哌嗪 、 3-[3-(2-Chloro-ethyl)-ureido]-benzofuran-2-carboxylic acid ethyl ester 反应 3.0h， 以59%的产率得到3-{2-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-ethyl}-1H-benzo[4,5]furo[3,2-d]pyrimidine-2,4-dione
  参考文献：
  名称：

  Pyrimido[5,4-b]benzofuran and pyrimido[5,4-b]benzothiophene derivatives Ligands for α1-and 5HT1A-receptors

  摘要：

  A number of 3-phenylpiperazinylethyl pyrimido[5,4-b]benzofuran-2,4-dione and pyrimido[5,4-b]benzothiophene-2,4-dione derivatives 5-15 were designed as bioisosters of the previously reported pyrimido[5,4-b]indole-2,4-diones and synthesized starting from the 3-amino-2-carboxybenzofuran and benzothiophene ethyl and methyl esters respectively. They were evaluated for their in vitro alpha1-adrenoceptor and 5HT1A-receptor affinities by radioligand receptor binding assays. All target compounds showed good to excellent affinities for the alpha1-adrenoceptor with K(i) values in the subnanomolar range. Some compounds were also good ligands for the 5HT1A-receptor with K(i) values in the nanomolar range. 3-[2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl pyrimido[5,4-b]benzothiophen-2,4-dione 15 was the most active derivative in displacing [H-3]-8-OH-DPAT from rat hippocampal membranes. There is evidence suggesting that the N1 methyl group of the tricyclic moiety of the title compounds is probably able to undergo a Van der Waals interaction at the 5HT1A-receptor binding site but not at the alpha1-adrenoceptor active site.

  DOI：

  10.1016/0223-5234(93)90017-9
• 作为产物：
  描述：

  氯乙基异氰酸酯 、 3-氨基苯并呋喃-2-甲酸乙酯 以 甲苯 为溶剂， 反应 1.0h， 以69%的产率得到3-[3-(2-Chloro-ethyl)-ureido]-benzofuran-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Pyrimido[5,4-b]benzofuran and pyrimido[5,4-b]benzothiophene derivatives Ligands for α1-and 5HT1A-receptors

  摘要：

  A number of 3-phenylpiperazinylethyl pyrimido[5,4-b]benzofuran-2,4-dione and pyrimido[5,4-b]benzothiophene-2,4-dione derivatives 5-15 were designed as bioisosters of the previously reported pyrimido[5,4-b]indole-2,4-diones and synthesized starting from the 3-amino-2-carboxybenzofuran and benzothiophene ethyl and methyl esters respectively. They were evaluated for their in vitro alpha1-adrenoceptor and 5HT1A-receptor affinities by radioligand receptor binding assays. All target compounds showed good to excellent affinities for the alpha1-adrenoceptor with K(i) values in the subnanomolar range. Some compounds were also good ligands for the 5HT1A-receptor with K(i) values in the nanomolar range. 3-[2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl pyrimido[5,4-b]benzothiophen-2,4-dione 15 was the most active derivative in displacing [H-3]-8-OH-DPAT from rat hippocampal membranes. There is evidence suggesting that the N1 methyl group of the tricyclic moiety of the title compounds is probably able to undergo a Van der Waals interaction at the 5HT1A-receptor binding site but not at the alpha1-adrenoceptor active site.

  DOI：

  10.1016/0223-5234(93)90017-9

文献信息

• Structure−Activity Studies for a Novel Series of Tricyclic Substituted Hexahydrobenz[<i>e</i>]isoindole α_1A Adrenoceptor Antagonists as Potential Agents for the Symptomatic Treatment of Benign Prostatic Hyperplasia (BPH)
  作者：Michael D. Meyer、Robert J. Altenbach、Fatima Z. Basha、William A. Carroll、Stephen Condon、Steven W. Elmore、James F. Kerwin、Kevin B. Sippy、Karin Tietje、Michael D. Wendt、Arthur A. Hancock、Michael E. Brune、Steven A. Buckner、Irene Drizin

  DOI：10.1021/jm990567u

  日期：2000.4.1

  In search of a uroselective agent that exhibits a high level of selectivity for the alpha(1A) receptor, a novel series of tricyclic hexahydrobenz[e]isoindoles was synthesized. A generic pharmacophoric model was developed requiring the presence of a basic amine core and a fused heterocyclic side chain separated by an alkyl chain. It was shown that the 6-OMe substitution with R, R stereochemistry of the ring junction of the benz[e]isoindole and a two-carbon spacer chain were optimal. In contrast to the highly specific requirements for the benz[e]isoindole portion and linker chain, a wide variety of tricyclic fused heterocyclic attachments were tolerated with retention of potency and selectivity. In vitro functional assays for the alpha(1) adrenoceptor subtypes were used to further characterize these compounds, and in vivo models of vascular vs prostatic tone were used to assess uroselectivity.
• Pyrimido[5,4-b]benzofuran and pyrimido[5,4-b]benzothiophene derivatives Ligands for α1-and 5HT1A-receptors
  作者：G Romeo、G Ambrosini、S Guccione、A De Blasi、F Russo

  DOI：10.1016/0223-5234(93)90017-9

  日期：1993.1

  A number of 3-phenylpiperazinylethyl pyrimido[5,4-b]benzofuran-2,4-dione and pyrimido[5,4-b]benzothiophene-2,4-dione derivatives 5-15 were designed as bioisosters of the previously reported pyrimido[5,4-b]indole-2,4-diones and synthesized starting from the 3-amino-2-carboxybenzofuran and benzothiophene ethyl and methyl esters respectively. They were evaluated for their in vitro alpha1-adrenoceptor and 5HT1A-receptor affinities by radioligand receptor binding assays. All target compounds showed good to excellent affinities for the alpha1-adrenoceptor with K(i) values in the subnanomolar range. Some compounds were also good ligands for the 5HT1A-receptor with K(i) values in the nanomolar range. 3-[2-[4-(2-Methoxyphenyl)piperazin-1-yl]ethyl]-1-methyl pyrimido[5,4-b]benzothiophen-2,4-dione 15 was the most active derivative in displacing [H-3]-8-OH-DPAT from rat hippocampal membranes. There is evidence suggesting that the N1 methyl group of the tricyclic moiety of the title compounds is probably able to undergo a Van der Waals interaction at the 5HT1A-receptor binding site but not at the alpha1-adrenoceptor active site.