3-methylsalicylchlorophosphane | 192752-93-5

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 3-methylsalicylchlorophosphane
• 英文别名: 2-Chloro-8-methyl-2H,4H-1,3,2-benzodioxaphosphinine；2-chloro-8-methyl-4H-1,3,2-benzodioxaphosphinine
• CAS: 192752-93-5
• 化学式: C₈H₈ClO₂P
• 分子量: 202.577
• InChiKey: MLOZFJWYOHVQQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methylsalicylchlorophosphane 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 作用下， 生成 cyclo-3-methylsaligenyl 3'-azido-2',3'-dideoxythymidine monophosphate
  参考文献：
  名称：

  Interaction of cycloSal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship

  摘要：

  A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K-i/K-m: similar to2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.

  DOI：

  10.1021/jm031032a
• 作为产物：
  描述：

  3-甲基水杨酸 在 吡啶 、 lithium aluminium tetrahydride 、 三氯化磷 作用下， 以 乙醚 为溶剂， 反应 15.5h， 生成 3-methylsalicylchlorophosphane
  参考文献：
  名称：

  Nucleotide Delivery fromcycloSaligenyl-3′-azido-3′-deoxythymidine Monophosphates (cycloSal-AZTMP)

  摘要：

  DOI：

  10.1002/(sici)1099-0690(199805)1998:5<837::aid-ejoc837>3.0.co;2-7

文献信息

• SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
  申请人：Alios BioPharma, Inc.

  公开号：US20130165400A1

  公开（公告）日：2013-06-27

  Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

  本文披露了核苷、核苷酸及其类似物，包括一个或多个核苷、核苷酸及其类似物的药物组合物，以及它们的合成方法。本文还披露了使用核苷、核苷酸和其类似物来改善和/或治疗疾病和/或病况的方法，包括使用核苷、核苷酸和其类似物来治疗副粘病毒和/或正粘病毒感染的方法。
• [EN] SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF<br/>[FR] NUCLÉOSIDES, NUCLÉOTIDES SUBSTITUÉS ET LEURS ANALOGUES
  申请人：ALIOS BIOPHARMA INC

  公开号：WO2014209979A1

  公开（公告）日：2014-12-31

  Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a norovirus, with a nucleoside, a nucleotide and an analog thereof.

  本文揭示了核苷、核苷酸及其类似物，包括一个或多个核苷、核苷酸及其类似物的药物组合物，以及它们的合成方法。本文还揭示了利用核苷、核苷酸及其类似物改善和/或治疗疾病和/或病况的方法，包括使用核苷、核苷酸和其类似物治疗诺如病毒感染的方法。
• Stereoselective Synthesis of<scp>D</scp>- and<scp>L</scp>-Carbocyclic Nucleosides by Enzymatically Catalyzed Kinetic Resolution
  作者：Miriam Mahler、Bastian Reichardt、Philip Hartjen、Jan van Lunzen、Chris Meier

  DOI：10.1002/chem.201200733

  日期：2012.8.27

  the starting materials for the syntheses of carbocyclic D‐ and L‐nucleoside analogues were readily accessible. 3′,4′‐Unsaturated D‐ or L‐carbocyclic nucleosides were obtained from the condensation of various nucleobases with (S)‐ or (R)‐cyclopentenol. Functionalization of the double bond in 3′‐deoxy‐3′,4′‐didehydro‐carba‐D‐thymidine led to a variety of new nucleoside analogues. By using the cycloSal

  通过应用酶催化动力学拆分方法开发了（S）-或（R）-3-（苄氧基甲基）环戊-3-烯醇的有效合成方法。该方法允许合成具有高光学纯度（> 98％ee）的对映体结构单元（S）-和（R）-环戊烯醇。与以前的方法相比，此方法的主要优势在于，可在仅包含一个立体生成中心的对映异构体水平上进行拆分。由于该特征，可以将对映异构体彼此化学转化。通过这种途径，合成碳环D-和L的原料核苷类似物很容易获得。3'，4'-不饱和D-或L-碳环核苷是通过各种核碱基与（S）-或（R）-环戊烯醇的缩合获得的。3'-脱氧-3'，4'-二氢-卡巴-D-胸苷中双键的功能化导致了许多新的核苷类似物。通过使用环Sal方法，可以轻松获得其相应的磷酸化代谢产物。此外，碳环2'-脱氧核苷组成的新的合成路线被开发，从而导致d -和大号-卡巴-dT。d -卡巴-dT是为测试抗病毒活性对多药耐药的HIV-1菌株和E2-2相对于已知的抗病毒剂的d4T，以及大号-卡巴-dT。虽然发现L
• Nucleoside Mono- and Diphosphate Prodrugs of 2′,3′-Dideoxyuridine and 2′,3′-Dideoxy-2′,3′-didehydrouridine
  作者：Florian Pertenbreiter、Jan Balzarini、Chris Meier

  DOI：10.1002/cmdc.201402295

  日期：2015.1

  Despite their close structural similarity to nucleoside analogues such as the anti‐HIV drugs AZT and d4T, 2′,3′‐dideoxyuridine (ddU) and 2′,3′‐dideoxy‐2′,3′‐didehydrouridine (d4U) are entirely inactive against HIV in their nucleoside form. However, it has been shown that the corresponding triphosphates of these two nucleosides can effectively block HIV reverse transcriptase. Herein we report on two

  尽管它们与核苷类似物（如抗HIV药物AZT和d4T）具有相似的结构相似性，但2'，3'-二脱氧尿苷（ddU）和2'，3'-二脱氧-2'，3'-二氢尿苷（d4U）完全相同对核苷形式的艾滋病毒无活性。然而，已经显示这两个核苷的相应三磷酸可以有效地阻断HIV逆转录酶。在此，我们报道了ddU和d4U的两种核苷酸前药（环Sal和Di PP ro核苷酸），以研究其克服细胞内磷酸化不足的能力，这可能是其抗HIV活性低的原因。通过在磷酸盐缓冲液（pH 7.3）和人CD中的水解研究证明了从这些化合物中释放出相应的单磷酸酯和二磷酸酯4 + T淋巴细胞CEM细胞提取物。然而，令人惊讶的是，这些化合物在人CD 4 + T淋巴细胞CEM细胞的测试中显示出低或没有抗HIV活性。核苷二磷酸激酶（NDPK）将ddUDP和d4UDP转化为三磷酸代谢物的研究表明，两种磷酸酯均几乎没有转化，这可能是细胞内三磷酸水平低导致抗病毒活性降低的原因。
• <i>cyclo</i>Sal-Pronucleotides of 2‘,3‘-Dideoxyadenosine and 2‘,3‘-Dideoxy-2‘,3‘-didehydroadenosine:  Synthesis and Antiviral Evaluation of a Highly Efficient Nucleotide Delivery System
  作者：Chris Meier、Tina Knispel、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm981096z

  日期：1999.5.1

  nucleosides ddA (2) and d4A (3) as judged by their log P values. In hydrolysis studies, 9 and 10 decomposed under mild aqueous basic conditions releasing solely ddAMP (7) and d4AMP (8), as well as the diols 14. Further hydrolysis studies under acidic conditions showed a marked increase in stability with respect to the acid-catalyzed cleavage of the glycosyl bond. Phosphotriesters 9 and 10 exhibited antiviral

  抗病毒嘌呤双脱氧核苷类似物2'，3'-双脱氧腺苷（ddA）（2）和报道了2′，3′-二脱氧-2′，3′-二氢腺苷（d4A）（3）。这些潜在的前核苷酸通过受控的化学诱导的串联反应选择性地释放ddAMP（7）或d4AMP（8）。使用我们先前报道的磷（III）方法，从取代的水杨醇14a-h开始以高收率合成所有新化合物9和10a-d。相对于在磷中心的构型，以立体化学优选为2：1获得了磷酸三酯9和10。在1-辛醇/水混合物中，磷酸三酯9和10的亲脂性比其亲本核苷ddA（2）和d4A（3）高出7-43倍，这可通过它们的log P值来判断。在水解研究中，9和10在温和的碱性水溶液中分解，仅释放ddAMP（7）和d4AMP（8）以及二醇14。进一步的水解研究表明，在酸性条件下，相对于酸-稳定性显着提高。催化的糖基键裂解。磷酸三酸酯9和10对人T淋巴细胞（CEM / O）细胞中的野生型HIV-1和HIV-2