2-propylthieno[3,2-d]pyrimidin-4(3H)-one | 150113-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2-propylthieno[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 2-propyl-3H-thieno[2,3-e]pyrimidin-4-one；2-Propylthieno[3,2-d]pyrimidin-4(3H)-one；2-propyl-3H-thieno[3,2-d]pyrimidin-4-one
• CAS: 150113-52-3
• 化学式: C₉H₁₀N₂OS
• mdl: MFCD24391223
• 分子量: 194.257
• InChiKey: SPTPGFIELMQWMF-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-propylthieno[3,2-d]pyrimidin-4(3H)-one 在 溴 、 sodium acetate 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 3-benzyl-2-(1-bromopropyl)thieno[2,3-e]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of (+)-N-(3-Aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a Kinesin Spindle Protein Inhibitor and Potential Anticancer Agent

  摘要：

  Structure activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical properties suitable for clinical development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clinical candidate for the treatment of cancer.

  DOI：

  10.1021/jm200629m
• 作为产物：
  描述：

  methyl 3-butyramidothiophene-2-carboxylate 在 ammonium hydroxide 作用下， 以 水 为溶剂， 以58%的产率得到2-propylthieno[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  围绕Thieno [3,2-d] pyrimidin-4（3H）-一个支架的化学空间探索导致了一类新型的高活性艰难梭菌抑制剂。

  摘要：

  艰难梭菌感染（CDI）是美国医疗保健相关感染的主要原因。因此，开发用于CDI的新疗法是当务之急。为了实现这一目标，我们开始体外筛选针对两种致病性艰难梭菌菌株（ATCC BAA 1870和ATCC 43255）的67种化合物的结构多样的内部文库，产生的化合物为2-甲基-8-硝基喹唑啉酮- 4（3 H）-一（2），具有中等效力（MIC = 312/156μM）。2的最优化得到铅化合物6a（2-甲基-7-硝基硫代[3,2 - d ]嘧啶-4（3 H-1）具有增强的效价（MIC = 19/38μM），对正常肠道菌群的选择性，对哺乳动物细胞系的CC 50 s> 606μM ，以及在模拟的胃液和肠液中的可接受的稳定性。在C2-，N3-，C4-和C7位置上对6a的进一步优化导致了针对50多种化合物的文库，其针对艰难梭菌的临床分离株的MIC为3至800μM。化合物8f（MIC = 3/6μM）被确定为进一步优化的有希望的先导。

  DOI：

  10.1021/acs.jmedchem.9b01198

文献信息

• [EN] THIENO- AND FUROPYRIMIDINE DERIVATIVES AS A2A-RECEPTOR ANTAGONISTS<br/>[FR] THIENO- ET DERIVES DE FUROPYRAMIDINES AYANT UNE FONCTION D'ANTAGONISTES DU RECEPTEUR A2A
  申请人：VERNALIS RES LTD

  公开号：WO2001002409A1

  公开（公告）日：2001-01-11

  A compound of formula (I) wherein X is O or S; R1 and R2 are independently selected from hydrogen, alkyl, aryl, hydroxy, alkoxy, aryloxy, cyano, nitro, CO2R7, COR7, OCOR7CONR7R8, CONR7NR8R9, OCONR7R8, NR7R8, NR7COR8, NR7CONR8R9, NR7CO2R8, NR7SO2R8, NR7CONR8NR9R10, NR7NR8CO2R9, NR7NR8CONR9R10, NR7SO2NR8R9, SO2R7, SOR7, SR7 and SO2NR7R8, or R1 and R2 together form a carbonyl group (C=O), an oxime group (C=NOR11), an imine group (C=NR11) or a hydrazone group (C=NNR11R12), or R1 and R2 together form a 5, 6 or 7 membered carbocyclic or heterocyclic ring; R3 is alkyl or aryl; R4, R5 and R6 are independently selected from hydrogen, alkyl, aryl, halogen, hydroxy, nitro, cyano, alkoxy, aryloxy, COR7, OCOR7, CO2R7, SR7, SOR7, SO2R7, SO2NR7R8, CONR7R8, CONR7NR8R9, OCONR7R8, NR7R8, NR7COR8, NR7CONR8R9, NR7CO2R8, NR7SO2R8, CR7=NOR8, NR7CONR8NR9R10, NR7NR8CO2R9, NR7NR8CONR9R10, SO2NR7NR8R9, NR7SO2NR8R9, NR7NR8SO2R9, NR7NR8COR9, NR7NR8R9 and NR7CSNR8R9, or R5 and R6 together form a 5, 6 or 7 membered carbocyclic or heterocyclic ring; and R7, R8, R9, R10, R11 and R12 are independently selected from hydrogen, alkyl and aryl, or a pharmaceutically acceptable salt thereof or prodrug thereof, and the use thereof in therapy, particularly in the therapy of a disorder in which the blocking of purine receptors may be beneficial, such as Parkinson's Disease.

  化合物的化学式为（I），其中X为O或S；R1和R2分别选自氢，烷基，芳基，羟基，烷氧基，芳氧基，氰基，硝基，CO2R7，COR7，OCOR7CONR7R8，CONR7NR8R9，OCONR7R8，NR7R8，NR7COR8，NR7CONR8R9，NR7CO2R8，NR7SO2R8，NR7CONR8NR9R10，NR7NR8CO2R9，NR7NR8CONR9R10，NR7SO2NR8R9，SO2R7，SOR7，SR7和SO2NR7R8，或R1和R2共同形成一个羰基（C=O），肟基（C=NOR11），亚胺基（C=NR11）或肼基（C=NNR11R12），或R1和R2共同形成一个5、6或7元环的碳环或杂环；R3为烷基或芳基；R4、R5和R6分别选自氢，烷基，芳基，卤素，羟基，硝基，氰基，烷氧基，芳氧基，COR7，OCOR7，CO2R7，SR7，SOR7，SO2R7，SO2NR7R8，CONR7R8，CONR7NR8R9，OCONR7R8，NR7R8，NR7COR8，NR7CONR8R9，NR7CO2R8，NR7SO2R8，CR7=NOR8，NR7CONR8NR9R10，NR7NR8CO2R9，NR7NR8CONR9R10，SO2NR7NR8R9，NR7SO2NR8R9，NR7NR8SO2R9，NR7NR8COR9，NR7NR8R9和NR7CSNR8R9，或R5和R6共同形成一个5、6或7元环的碳环或杂环；R7、R8、R9、R10、R11和R12分别选自氢，烷基和芳基，或其药学上可接受的盐或前药，以及在治疗中的使用，特别是在阻断嘌呤受体可能有益的疾病，如帕金森病的治疗中的使用。
• THIENO- AND FUROPYRIMIDINE DERIVATIVES AS A2A-RECEPTOR ANTAGONISTS
  申请人：VERNALIS RESEARCH LIMITED

  公开号：EP1192164A1

  公开（公告）日：2002-04-03
• US6787541B1
  申请人：——

  公开号：US6787541B1

  公开（公告）日：2004-09-07
• Chemical Space Exploration around Thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one Scaffold Led to a Novel Class of Highly Active <i>Clostridium difficile</i> Inhibitors
  作者：Xuwei Shao、Ahmed AbdelKhalek、Nader S. Abutaleb、Uday Kiran Velagapudi、Sabesan Yoganathan、Mohamed N. Seleem、Tanaji T. Talele

  DOI：10.1021/acs.jmedchem.9b01198

  日期：2019.11.14

  treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 μM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one)

  艰难梭菌感染（CDI）是美国医疗保健相关感染的主要原因。因此，开发用于CDI的新疗法是当务之急。为了实现这一目标，我们开始体外筛选针对两种致病性艰难梭菌菌株（ATCC BAA 1870和ATCC 43255）的67种化合物的结构多样的内部文库，产生的化合物为2-甲基-8-硝基喹唑啉酮- 4（3 H）-一（2），具有中等效力（MIC = 312/156μM）。2的最优化得到铅化合物6a（2-甲基-7-硝基硫代[3,2 - d ]嘧啶-4（3 H-1）具有增强的效价（MIC = 19/38μM），对正常肠道菌群的选择性，对哺乳动物细胞系的CC 50 s> 606μM ，以及在模拟的胃液和肠液中的可接受的稳定性。在C2-，N3-，C4-和C7位置上对6a的进一步优化导致了针对50多种化合物的文库，其针对艰难梭菌的临床分离株的MIC为3至800μM。化合物8f（MIC = 3/6μM）被确定为进一步优化的有希望的先导。
• Discovery of (+)-<i>N</i>-(3-Aminopropyl)-<i>N</i>-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-<i>d</i>]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a Kinesin Spindle Protein Inhibitor and Potential Anticancer Agent
  作者：Maria-Elena Theoclitou、Brian Aquila、Michael H. Block、Patrick J. Brassil、Lillian Castriotta、Erin Code、Michael P. Collins、Audrey M. Davies、Tracy Deegan、Jayachandran Ezhuthachan、Sandra Filla、Ellen Freed、Haiqing Hu、Dennis Huszar、Muthusamy Jayaraman、Deborah Lawson、Paula M Lewis、Murali V. P. Nadella、Vibha Oza、Maniyan Padmanilayam、Timothy Pontz、Lucienne Ronco、Daniel Russell、David Whitston、Xiaolan Zheng

  DOI：10.1021/jm200629m

  日期：2011.10.13

  Structure activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical properties suitable for clinical development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clinical candidate for the treatment of cancer.