diethyl (3-oxopropyl)phosphonate | 3986-95-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl (3-oxopropyl)phosphonate
• 英文别名: 3-oxopropylphosphonic acid diethyl ester；3-(Diethoxyphosphinyl)propanal；3-diethoxyphosphorylpropanal
• CAS: 3986-95-6
• 化学式: C₇H₁₅O₄P
• 分子量: 194.167
• InChiKey: FUBLLKKWKHVTTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  12
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl (3-oxopropyl)phosphonate 在 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以68%的产率得到(3-氨丙基)磷酸二乙酯
  参考文献：
  名称：

  Collignon, N.; Fabre, G.; Varlet, J. M., Phosphorus and Sulfur and the Related Elements, 1981, vol. 10, p. 81 - 86

  摘要：

  DOI：
• 作为产物：
  描述：

  diethyl 3-bromo-prop-2-enyl-1-phosphonate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 diethyl (3-oxopropyl)phosphonate
  参考文献：
  名称：

  Lavielle,G. et al., Bulletin de la Societe Chimique de France, 1967, p. 4186 - 4194

  摘要：

  DOI：

文献信息

• [EN] PHOSPHORIBOSYLTRANSFERASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE PHOSPHORIBOSYLTRANSFÉRASES ET LEURS UTILISATIONS
  申请人：IND RES LTD

  公开号：WO2012150866A1

  公开（公告）日：2012-11-08

  The invention relates to compounds of formula (I) that are inhibitors of hypoxanthine and/or guanine purine phosphoribosyltransferases and to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and methods of treating diseases or conditions in which it is desirable to inhibit hypoxanthine and/or guanine purine phosphoribosyltransferases. Such diseases include malaria.

  这项发明涉及到式（I）的化合物，这些化合物是次黄嘌呤和/或鸟嘌呤磷酸核糖转移酶的抑制剂，以及含有这些化合物的药物组合物、制备这些化合物的方法，以及治疗希望抑制次黄嘌呤和/或鸟嘌呤磷酸核糖转移酶的疾病或症状的方法。这些疾病包括疟疾。
• [EN] NOVEL CYCLIC BENZIMIDAZOLE DERIVATIVES USEFUL ANTI-DIABETIC AGENTS<br/>[FR] NOUVEAUX AGENTS ANTIDIABÉTIQUES UTILES AVEC DES DÉRIVÉS DE BENZIMIDAZOLE CYCLIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2010051206A1

  公开（公告）日：2010-05-06

  Novel compounds of the structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK- activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

  结构式（I）的新化合物是AMP-蛋白激酶的激活剂，并且在治疗、预防和抑制由AMPK激活的蛋白激酶介导的疾病方面非常有用。本发明的化合物在治疗2型糖尿病、高血糖、代谢综合征、肥胖、高胆固醇血症和高血压方面非常有用。
• [EN] COMPOUNDS FOR INHIBITING 1- DEOXY-D-XYLULOSE- 5 - PHOSPHATE REDUCTOISOMERASE<br/>[FR] COMPOSÉS DESTINÉS À INHIBER LA 1-DÉSOXY-D-XYLULOSE-5-PHOSPHATE RÉDUCTOISOMÉRASE
  申请人：UNIV GEORGE WASHINGTON

  公开号：WO2013006444A1

  公开（公告）日：2013-01-10

  [0082] In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits l-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).

  特别是，该化合物能有效抑制结核分枝杆菌（Mtb）中的Dxr。本发明涉及具有通式（I）的化合物，其中X是酸性基团，如羧酸盐、膦酸盐、硫酸盐和四唑基；Ar是取代或未取代的芳香或杂环芳基团；n为0、1、2、3或4，优选为2、3或4。这些化合物抑制l-脱氧-D-木糖-5-磷酸还原异构酶（Dxr），特别是结核分枝杆菌（Mtb）中的Dxr。
• Compounds for inhibiting 1-deoxy-D-xylulose-5-phosphate reductoisomerase
  申请人：Boshoff Helena I.

  公开号：US09593136B2

  公开（公告）日：2017-03-14

  In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or (II) where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).

  特别是，该化合物能有效抑制结核分枝杆菌（Mtb）中的Dxr。本发明涉及具有一般式（I）或（II）的化合物 其中X是酸性基团，如羧酸盐、膦酸盐、硫酸盐和四唑基；Ar是取代或未取代的芳香或杂芳基团；n为0、1、2、3或4，优选为2、3或4。这些化合物抑制1-脱氧-D-木糖-5-磷酸还原异构酶（Dxr），特别是结核分枝杆菌（Mtb）中的Dxr。
• Design of potential bisubstrate inhibitors against Mycobacterium tuberculosis (Mtb) 1-deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr)—evidence of a novel binding mode
  作者：Géraldine San Jose、Emily R. Jackson、Eugene Uh、Chinchu Johny、Amanda Haymond、Lindsay Lundberg、Chelsea Pinkham、Kylene Kehn-Hall、Helena I. Boshoff、Robin D. Couch、Cynthia S. Dowd

  DOI：10.1039/c3md00085k

  日期：——

  In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity. Our goal was to use the Mtb Dxr-fosmidomycin co-crystal structure to design bisubstrate ligands to bind to both the DXP and NADPH sites. Such compounds would be expected to demonstrate improved whole cell activity due to increased lipophilicity. Two series of compounds were designed and synthesized. Compounds from both series inhibited Mtb Dxr. The most potent compound (8) has an IC50 of 17.8 μM. Analysis shows 8 binds to Mtb Dxr via a novel, non-bisubstrate mechanism. Further, the diethyl ester of 8 inhibits Mtb growth making this class of compounds interesting lead molecules in the search for new antitubercular agents.

  在大多数细菌中，非梅瓦隆酸途径用于合成异构烯单位。该途径的第二步是Dxr，它催化NADPH依赖的1-脱氧-D-木酮糖-5-磷酸（DXP）转化为2-C-甲基-D-赤藓糖-4-磷酸（MEP）的还原异构化反应。Dxr受到天然产品fosmidomycin和FR900098的抑制，这些化合物与DXP结合位点结合。这些化合物虽然是Dxr的强效抑制剂，但由于其极性，缺乏对结核分枝杆菌（Mtb）的全细胞活性。我们的目标是利用Mtb Dxr-fosmidomycin共晶结构设计双底物配体，以同时结合DXP和NADPH位点。这类化合物预计由于其增强的疏水性而表现出更好的全细胞活性。设计并合成了两系列化合物。两系列中的化合物均抑制Mtb Dxr。最强效的化合物（8）的IC50为17.8 µM。分析表明，化合物8通过一种新颖的非双底物机制与Mtb Dxr结合。此外，化合物8的二乙酯抑制了Mtb的生长，这使得这一类化合物成为寻找新抗结核药物的有趣领先分子。