2-(5-Chloro-pentanoylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl ester | 304898-28-0

• 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: 2-(5-Chloro-pentanoylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 2-(5-chloropentanoylamino)-4,5-dimethylthiophene-3-carboxylate
• CAS: 304898-28-0
• 化学式: C₁₄H₂₀ClNO₃S
• 分子量: 317.837
• InChiKey: NFOGBESNXZYIEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5-Chloro-pentanoylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl ester 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 3-Amino-2-{4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-butyl}-5,6-dimethyl-3H-thieno[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

  摘要：

  In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT1AR. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT1A Ki 1 499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00175-6
• 作为产物：
  描述：

  5-氯代戊酰氯 、 2-氨基-4,5-二甲基噻吩-3-羧酸乙酯 以 氯仿 为溶剂， 反应 4.0h， 以34%的产率得到2-(5-Chloro-pentanoylamino)-4,5-dimethyl-thiophene-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

  摘要：

  In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT1AR. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT1A Ki 1 499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00175-6

文献信息

• Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4 receptor ligands
  作者：Maria Modica、Maria Santagati、Salvatore Guccione、Filippo Russo、Alfredo Cagnotto、Mara Goegan、Tiziana Mennini

  DOI：10.1016/s0223-5234(01)01216-8

  日期：2001.3

  the 5-HT3 and 5-HT4 receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one derivative 28 showed the highest affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki=3.92 nM, 5-HT4 not active)

  这项工作报告了新的噻吩并嘧啶并哌嗪和哌嗪基糖基氨基二甲基噻吩衍生物的5-HT3和5-HT4受体的合成和结合试验，以便确定每种受体的有效和选择性配体。3-氨基-2-（4-苄基-1-哌嗪基）-5,6-二甲基-噻吩并[2,3-d]嘧啶-4（3H）-一衍生物28对5的亲和力和选择性最高-HT3超过5-HT4受体（5-HT3 Ki = 3.92 nM，5-HT4无效），而2- [4- [4-（2-嘧啶基）-1-哌嗪基]丁酰基氨基] -4,5 -5-二甲基-3-噻吩羧酸乙酯（41）对5-HT4的亲和力和选择性高于5-HT3受体（5-HT4 Ki = 81.3 nM，5-HT3不活泼）。以化合物41为模板，对哌嗪基糖基氨基二甲基噻吩系列（39-42）的化合物进行构象分析。