1-二甲基磷酰氧基-2-甲基-丙烷 | 61820-17-5

• 分子结构分类: 有机化合物 - 有机磷化合物 - 有机膦酸及其衍生物
• 中文名称: 1-二甲基磷酰氧基-2-甲基-丙烷
• 英文名称: isobutyl P,P-dimethyl-phosphinate
• 英文别名: isobutyl dimethylphosphinate；isobutyl, P,P-dimethyl-phosphinate；1-dimethylphosphoryloxy-2-methylpropane
• CAS: 61820-17-5
• 化学式: C₆H₁₅O₂P
• mdl: MFCD01630846
• 分子量: 150.158
• InChiKey: XAZJFCQCYNQNBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  1-(4-氯苯基)-2-硝基乙烯 、 1-二甲基磷酰氧基-2-甲基-丙烷 在 lithium diisopropyl amide 作用下， 生成 次膦酸,[2-(4-氯苯基)-3-硝基丙基]甲基-,2-甲基丙基酯
  参考文献：
  名称：

  Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists

  摘要：

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

  DOI：

  10.1021/jm00017a016
• 作为产物：
  描述：

  甲基亚膦酸异丁酯 、 碘甲烷 在 sodium hydride 作用下， 生成 1-二甲基磷酰氧基-2-甲基-丙烷
  参考文献：
  名称：

  Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists

  摘要：

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

  DOI：

  10.1021/jm00017a016

文献信息

• LXR AGONISTS AND USES THEREOF
  申请人：Martinez Eduardo J.

  公开号：US20170066791A1

  公开（公告）日：2017-03-09

  This invention features compounds that modulate the activity of liver X receptors, pharmaceutical compositions including the compounds of the invention, and methods of utilizing those compositions for modulating the activity of liver X receptors in the treatment of cancer.

  这项发明涉及调节肝X受体活性的化合物，包括该发明的化合物的药物组合物，以及利用这些组合物调节肝X受体活性治疗癌症的方法。
• Substituted propane-phosphinic acid compounds
  申请人：Ciba-Geigy Corporation

  公开号：US05064819A1

  公开（公告）日：1991-11-12

  Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.0 and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.0 is converted into --NH.sub.2.

  公式I的化合物##STR1##其中R表示具有2个或更多碳原子的脂肪族、环脂族、环脂族-脂肪族或芳基脂肪基，其中R.sup.1、R.sup.2和R.sup.3中的一个代表氢或脂肪族、环脂族、芳基脂肪基或芳香族基，R.sup.1、R.sup.2和R.sup.3中的另一个是氢或在R.sup.1和R.sup.2的情况下是羟基，而R.sup.1、R.sup.2和R.sup.3中的剩余一个是氢，或者R表示甲基，R.sub.1表示氢或羟基，R.sub.2表示芳基，R.sub.3表示氢，它们的盐具有GABA.sub.B-拮抗性质，可用作GABA.sub.B-拮抗剂。当在公式II的化合物中获得它们##STR2##其中R、R.sup.1、R.sup.2和R.sup.3具有其先前的含义，Z表示--NH.sub.2，R.sup.4表示羟基保护基R.sup.5或者当R.sup.1和R.sup.3表示氢且R.sup.2表示氢或烷基时，表示碱金属或铵离子R.sup.6，或者Z表示受保护或潜在的氨基Z.sup.0且R.sup.4表示氢或羟基保护基R.sup.5，任何一个R.sup.5或R.sup.6基团被氢取代，和/或任何一个Z.sup.0基团被转化为--NH.sub.2。
• Process for the preparation of phosphino compounds
  申请人：Hoechst Aktiengesellschaft

  公开号：US05166385A1

  公开（公告）日：1992-11-24

  Process for the preparation of phosphino compounds Phosphorus-containing compounds of the formula (I) (R.sup.1)(R.sup.2)P(O)--CR.sup.3 R.sup.4 --CHR.sup.5 R.sup.6 (I) in which R.sup.1 and R.sup.2 are alkyl, alkoxy or optionally substituted phenyl, R.sup.3 and R.sup.5 are H, R, optionally substituted phenyl, ROCO--, RO--CO--RO--, halogen, CN, RO--, RO--RO--R-CO--, H.sub.2 NCO--, RNHCO-- or RRNCO--, in which R is alkyl, R.sup.4 and R.sup.6 have the same meaning as defined for R.sup.1 and R.sup.2 or are a divalent radical --CO--R.sup.7 --CO in which R.sup.7 is oxygen, NR* or sulfur, and R* is H, optionally substituted phenyl or alkyl, are precursors for plant protection agents and fire retardants. According to the invention they can be prepared in high yields and high purity by reacting a compound (R.sup.1)(R.sup.2)P--OR.sup.8, in which R.sup.8 is alkyl or optionally substituted phenyl, with an alkene of the formula R.sup.3 R.sup.4 C.dbd.CR.sup.5 R.sup.6 and at least an equimolar amount of aprotic organic substance such as alcohols, amines, phenols, thiophenols or anilines.

  制备膦化合物的过程 磷含化合物的化学式（I）（R.sup.1）（R.sup.2）P（O)--CR.sup.3 R.sup.4 --CHR.sup.5 R.sup.6（I）其中R.sup.1和R.sup.2是烷基，烷氧基或可选择性取代的苯基，R.sup.3和R.sup.5是H，R，可选择性取代的苯基，ROCO--，RO--CO--RO--，卤素，CN，RO--，RO--RO--R-CO--，H.sub.2 NCO--，RNHCO--或RRNCO--，其中R是烷基，R.sup.4和R.sup.6具有与R.sup.1和R.sup.2定义的相同含义或是二价基团--CO--R.sup.7 --CO，其中R.sup.7是氧，NR*或硫，而R*是H，可选择性取代的苯基或烷基，是植物保护剂和阻燃剂的前体。根据本发明，它们可以通过将化合物（R.sup.1）（R.sup.2）P--OR.sup.8与具有化学式R.sup.3 R.sup.4 C.dbd.CR.sup.5 R.sup.6的烯烃和至少等摩尔量的无极性有机物质如醇，胺，酚，硫酚或苯胺反应，以高产率和高纯度制备。
• SUBSTITUTED POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE PRODRUG
  申请人：Takahashi Chika

  公开号：US20130197219A1

  公开（公告）日：2013-08-01

  The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.

  本发明提供了一种具有抗病毒效果的化合物，特别是对流感病毒具有生长抑制活性，该化合物的首选例子是一种具有依赖帽端核酸酶抑制活性的取代3-羟基-4-吡啶酮衍生物前药。
• Substituted aminoalkylphosphinic acids
  申请人：Ciba-Geigy Corporation

  公开号：US05461040A1

  公开（公告）日：1995-10-24

  P-substituted aminoalkylphosphinic acids of the formula ##STR1## wherein R denotes an optionally fluorinated methyl group, R.sub.1 denotes hydrogen, lower alkyl, lower alkoxy, hydroxy, halogen or a fluorinated methyl group and R.sub.2 and R.sub.3 denote hydrogen or R.sub.2 denotes hydroxy, lower alkoxy or halogen and R.sub.3 is hydrogen or R.sub.2 and R.sub.3 together represent an oxo group, and their pharmaceutically acceptable salts are active as GABA.sub.b -agonists and can be used in the treatment of spinal spasticity, multiple sclerosis and cerebral palsy, trigeminus neuralgia, drug withdrawal syndromes and/or conditions of pain. They can be manufactured by methods known per se and suitable such methods are described.

  公式为##STR1##的P-取代氨基烷基膦酸，其中R代表可选的氟代甲基基团，R.sub.1代表氢、低碳基、低碳氧基、羟基、卤素或氟代甲基基团，R.sub.2和R.sub.3代表氢或R.sub.2代表羟基、低碳氧基或卤素，而R.sub.3代表氢或R.sub.2和R.sub.3一起代表氧代基，它们的药学上可接受的盐作为GABA.sub.b-激动剂活性，并可用于治疗脊髓痉挛、多发性硬化症和脑瘫、三叉神经痛、戒断综合征和/或疼痛症状。它们可以通过已知的方法制造，适当的方法已经被描述。