tetraethyl 2-hydroxymethyl-1,3-propanebisphosphonate | 796884-26-9

• 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: tetraethyl 2-hydroxymethyl-1,3-propanebisphosphonate
• 英文别名: 2-Hydroxymethyl-1,3-propylene-bisphosphonic acid tetraethylester；3-diethoxyphosphoryl-2-(diethoxyphosphorylmethyl)propan-1-ol
• CAS: 796884-26-9
• 化学式: C₁₂H₂₈O₇P₂
• 分子量: 346.298
• InChiKey: NGNXUGVXEROMCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tetraethyl 2-hydroxymethyl-1,3-propanebisphosphonate 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 [3-(2-iodo-6-methylaminopurin-9-yl)-2-(diethoxyphosphorylmethyl)propyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  P2Y₁ Antagonists:  Combining Receptor-Based Modeling and QSAR for a Quantitative Prediction of the Biological Activity Based on Consensus Scoring

  摘要：

  P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

  DOI：

  10.1021/jm0700971
• 作为产物：
  描述：

  Tetraethyl 2-methylenepropane-1,3-bisphosphonate 在 9-borabicyclo[3.3.1]nonane dimer 、 sodium hydroxide 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以29%的产率得到tetraethyl 2-hydroxymethyl-1,3-propanebisphosphonate
  参考文献：
  名称：

  作为 P2Y 受体拮抗剂的二磷酸腺苷的无环类似物：磷酸盐取代导致抑制血小板聚集的多种途径。

  摘要：

  ADP 激活血小板中的 P2Y(1) 和 P2Y(12) 受体有助于血小板聚集，这些受体亚型的拮抗剂具有抗血栓形成的特性。在较早的出版物中，我们将 SAR 描述为腺嘌呤核苷酸的无环类似物的 P2Y(1) 受体拮抗剂，在对称分支的脂肪链上含有两个磷酸基团，连接在腺嘌呤的 9 位。在这项研究中，我们专注于与 2-氯-N(6)-methyladenine-9-(2-methylpropyl) 支架相关的 P2Y 拮抗剂的抗聚集作用，其中包含不带电荷的磷酸基团取代。对于已知的 P2Y(1) 受体的核苷酸（环状和非环状）二磷酸拮抗剂，3 诱导的聚集抑制之间存在显着相关性。大鼠血小板中的 3 microM ADP 和先前在火鸡红细胞中测定的 P2Y(1) 受体诱导的磷脂酶 C (PLC) 活性的抑制作用。用不可水解的膦酸盐基团取代磷酸盐基团保留了血小板抗聚集活性。用O-酰基取代其中一个磷酸基团大大降低

  DOI：

  10.1021/jm020173u

文献信息

• PHOSPHATE DERIVATIVES AND USE THEREOF
  申请人：ZHU Qing

  公开号：US20210030773A1

  公开（公告）日：2021-02-04

  The present invention discloses a compound with the following formula (I), or a tautomer, mesomer, racemate, enantiomer, and diastereoisomer thereof, or a mixture form thereof, or a pharmaceutically acceptable salt thereof, or a prodrug molecule thereof, wherein D is selected from: The invention further discloses the use of the compound in the preparation of drugs for preventing and/or treating cancers, and the use of the compound in the preparation of drugs for inhibiting cancer metastasis. The compound of the present invention can effectively inhibit the proliferation and metastasis of cancer cells by adjusting the acidity of a tumor microenvironment to achieve a better effect in clinical cancer treatment, and has broad application prospects.

  本发明公开了具有以下式（I）的化合物，或其互变异构体、共振异构体、外消旋体、对映体和非对映异构体，或其混合形式，或其药学上可接受的盐，或其前药分子，其中D从以下中选择： 该发明还公开了该化合物在制备用于预防和/或治疗癌症的药物中的用途，以及该化合物在制备用于抑制癌症转移的药物中的用途。本发明的化合物可以通过调节肿瘤微环境的酸度来有效抑制癌细胞的增殖和转移，从而在临床癌症治疗中取得更好的效果，并具有广阔的应用前景。
• Dental Materials on the Basis of Highly Acidic Polymerizable Bisphosphonic Acids
  申请人：IVOCLAR VIVADENT AG

  公开号：US20140296364A1

  公开（公告）日：2014-10-02

  The invention relates to a dental material which comprises a polymerizable bisphosphonic acid of Formula I: The invention also relates to the use of a polymerizable bisphosphonic acid of Formula I for the preparation of a dental material and in particular for the preparation of an adhesive, cement or composite.

  这项发明涉及一种包括化学式I的可聚合双膦酸的牙科材料。该发明还涉及使用化学式I的可聚合双膦酸制备牙科材料，特别是用于制备粘合剂、水泥或复合材料。
• Dental materials on the basis of highly acidic polymerizable bisphosphonic acids
  申请人：Ivoclar Vivadent AG

  公开号：US09040602B2

  公开（公告）日：2015-05-26

  The invention relates to a dental material which comprises a polymerizable bisphosphonic acid of Formula I: The invention also relates to the use of a polymerizable bisphosphonic acid of Formula I for the preparation of a dental material and in particular for the preparation of an adhesive, cement or composite.

  本发明涉及一种含有Formula I的可聚合双磷酸的牙科材料。本发明还涉及使用Formula I的可聚合双磷酸来制备牙科材料，特别是用于制备粘接剂、水泥或复合材料。
• [EN] PHOSPHATE DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS DE PHOSPHATE ET UTILISATION ASSOCIÉE<br/>[ZH] 磷酸盐类衍生物及其用途
  申请人：ZHU QING

  公开号：WO2019184866A1

  公开（公告）日：2019-10-03

  本发明公开了一种具有下述通式(I)的化合物，或其互变异构体、内消旋体、外消旋体、对映异构体、非对映异构体、或其混合物形式、或其可药用盐、或其前药分子，其中D选自：(II)。本发明还公开了上述化合物在制备预防和/或治疗癌症药物中的用途。本发明还公开了上述化合物在制备抑制癌症转移的药物中的用途。本发明的化合物，能通过调整肿瘤微环境的酸性，有效抑制癌细胞的增殖与转移，使临床癌症治疗取得更好效果，具有广阔的应用前景。
• Antiaggregatory activity in human platelets of potent antagonists of the P2Y1 receptor
  作者：Marco Cattaneo、Anna Lecchi、Michihiro Ohno、Bhalchandra V. Joshi、Pedro Besada、Susanna Tchilibon、Rossana Lombardi、Norbert Bischofberger、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1016/j.bcp.2004.06.026

  日期：2004.11

  Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500 (2-iodo-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate) was introduced as a highly potent and selective antagonist for this receptor. We have studied the actions of MRS2500 in human platelets and compared these effects with the effects of two acyclic nucleotide analogues, a bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y(1) receptor antagonists, although less potently than MRS2500. Improved synthetic methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to be more stable in general in biological systems than phosphate antagonists due to the non-hydrolyzable C-P bond. MRS2500 inhibited the ADP-induced aggregation of human platelets with an IC50 value of 0.95 nM. MRS2298 and MRS2496 also both inhibited the ADP-induced aggregation of human platelets with IC50 values of 62.8 nM and 1.5 muM, respectively. A similar order of potency was observed for the three antagonists in binding to the recombinant human P2Y(1) receptor and in inhibition of ADP-induced shape change and ADP-induced rise in intracellular Ca2+. No substantial antagonism of the pathway linked to the inhibition of cyclic AMP was observed for the nucleotide derivatives, indicating no interaction of these three P2Y(1) receptor antagonists with the proaggregatory P2Y(12) receptor, which is also activated by ADP. Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and MRS2500 is the most potent such antagonist yet reported. (C) 2004 Elsevier Inc. All rights reserved.