(4-bromo-methylbenzyl)phosphonic acid dimethyl ester | 140866-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-bromo-methylbenzyl)phosphonic acid dimethyl ester
• 英文别名: 1-(Bromomethyl)-4-(dimethoxyphosphorylmethyl)benzene
• CAS: 140866-78-0
• 化学式: C₁₀H₁₄BrO₃P
• 分子量: 293.097
• InChiKey: NJYUCTVVAZRLDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-bromo-methylbenzyl)phosphonic acid dimethyl ester 在 sodium azide 、 三苯基膦 作用下， 以 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (4-Aminomethyl-benzyl)-phosphonic acid dimethyl ester
  参考文献：
  名称：

  Solid phase synthesis of a biased mini tetrapeptoid-library for the discovery of monodentate itam mimics as ZAP-70 inhibitors

  摘要：

  The biased library was composed of a novel phosphotyrosine mimic fixed in the P1 position of a tetrapeptoid and combined with three lipophilic N-substituents at the remaining positions giving a total of 27 single compounds. Screening for ZAP-70 antagonism identified 8 as a novel selective monodentate ZAP-70 antagonist and lead in the search for new immunosuppressive drugs. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00043-2
• 作为产物：
  描述：

  二甲基(4-甲基苄基)膦酸酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 3.0h， 以55%的产率得到(4-bromo-methylbenzyl)phosphonic acid dimethyl ester
  参考文献：
  名称：

  D，L-fmoc保护的4-膦酰基甲基苯丙氨酸衍生物的新合成及其酶拆分

  摘要：

  描述了适用于固相肽合成的N - Fmoc 4-膦酰基甲基-D，L-苯丙氨酸在二叔丁基或二甲基膦酸酯形式（Fmoc-Pmp（OR）2）保护下的新合成方法。这些O的水解稳定类似物的拆分通过非对映异构体盐的部分重结晶或使用枯草杆菌蛋白酶嘉士伯酯酶尝试了β-磷酸酪氨酸。只有4-[（（二甲基膦酰基）甲基]乙基-D，L-苯丙氨酸乙酯的酶促拆分成功。通过与文献数据进行比较来讨论这些结果。氨基酸的L和d被用来分别制备，通过固相肽合成，接着在乙腈中由三甲基甲dimethylphosphonate基的脱保护（TMSI），GLU-ASP-Val-的L和d异构体PMP -Glu-ASN -Leu-His-Thr，一种肽，对应于磷酸酶PTP 1C的潜在磷酸化位点。

  DOI：

  10.1016/0040-4020(95)01003-3

文献信息

• Synthesis of constrained 4-(phosphonomethyl)phenylalanine derivatives as hydrolytically stable analogs of O-phosphotyrosine
  作者：Wang-Qing Liu、François Carreaux、Hervé Meudal、Bernard P. Roques、Christiane Garbay-Jaureguiberry

  DOI：10.1016/0040-4020(96)00085-3

  日期：1996.3

  hydrolytically stable analogue, the 4-(phosphonomethyl)phenylalanine (Pmp). Introduced in peptide sequences, this residue, which is resistant to phosphatase action, was shown also able to inhibit substrate recognition by protein targets. With the aim to design peptidomimetics endowed with improved affinity and selectivity, we report in this study the synthesis of five new sterically hindered amino acids derived

  为了阐明蛋白酪氨酸磷酸化在各种细胞内信号通路中的作用，含有O的肽已经开发了磷酸酪氨酸。然而，为了提高磷酸化氨基酸的稳定性，我们几年前设计了一种水解稳定的类似物4-（膦酰基甲基）苯丙氨酸（Pmp）。在肽序列中引入的该残基对磷酸酶的作用具有抗性，也显示出它能够抑制蛋白质靶标对底物的识别。为了设计具有改善的亲和力和选择性的拟肽药物，我们在本研究中报告了五种衍生自Pmp的新的空间位阻氨基酸的合成。这些修饰包括Pmp的α-甲基，β-甲基，β，β-二甲基取代，Pmp的α，β-环化和Pmp的磷甲基上的甲基取代。
• [EN] HETERO BIARYL DERIVATIVES AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] DERIVES HETERO BIARYLE INHIBITEURS DE LA METALLOPROTEASE MATRICIELLE
  申请人：WARNER LAMBERT CO

  公开号：WO2004014366A1

  公开（公告）日：2004-02-19

  This invention provides compounds defined by Formula I or a pharmaceutically acceptable salt thereof, wherein Rl, Q, S, T, U, V, and R2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a' pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a' compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency,,inflammatory bowel, disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically, acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active, component as described in the specification.

  该发明提供了由式I定义或其药用盐组成的化合物，其中R1、Q、S、T、U、V和R2如规范中所定义。该发明还提供了包括式I的化合物或其药用盐以及药用载体、稀释剂或赋形剂的药物组合物，如规范中所定义。该发明还提供了在动物体内抑制MMP-13酶的方法，包括向动物体内给予式I的化合物或其药用盐。该发明还提供了治疗患有MMP-13酶介导疾病的患者的方法，包括向患者体内给予式I的化合物或其药用盐，单独或与药物组合使用。该发明还提供了治疗心脏病、多发性硬化症、骨关节炎和类风湿性关节炎、非骨关节炎或类风湿性关节炎的关节炎、心力衰竭、炎性肠病、心力衰竭、年龄相关性黄斑变性、慢性阻塞性肺病、哮喘、牙周疾病、牛皮癣、动脉粥样硬化和骨质疏松症的方法，包括向患者体内给予式I的化合物或其药用盐，单独或与药物组合使用。该发明还提供了组合物，包括式I的化合物或其药用盐，以及规范中描述的另一种药用活性成分。
• Hetero biaryl derivatives as matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20040048863A1

  公开（公告）日：2004-03-11

  This invention provides compounds defined by Formula I 1 or a pharmaceutically acceptable salt thereof, wherein R 1 , Q, S, T, U, V, and R 2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification.

  本发明提供了由公式I1定义的化合物或其药学上可接受的盐，其中R1、Q、S、T、U、V和R2如规范中所定义。本发明还提供了包括公式I的化合物或其药学上可接受的盐的制药组合物，以及药学上可接受的载体、稀释剂或赋形剂。本发明还提供了抑制动物中MMP-13酶的方法，包括向动物中给予公式I的化合物或其药学上可接受的盐。本发明还提供了治疗由MMP-13酶介导的疾病的方法，包括向患者中给予公式I的化合物或其药学上可接受的盐，单独或与制药组合物一起。本发明还提供了治疗心脏病、多发性硬化症、骨关节炎和类风湿性关节炎、除骨关节炎和类风湿性关节炎外的其他关节炎、心力衰竭、炎症性肠病、心力衰竭、年龄相关性黄斑变性、慢性阻塞性肺疾病、哮喘、牙周病、银屑病、动脉粥样硬化和骨质疏松症的方法，包括向患者中给予公式I的化合物或其药学上可接受的盐，单独或与制药组合物一起。本发明还提供了包括公式I的化合物或其药学上可接受的盐和规范中描述的另一个药学活性成分的组合物。
• HETERO BIARYL DERIVATIVES AS MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Bunker Amy Mae

  公开号：US20090029995A1

  公开（公告）日：2009-01-29

  This invention provides compounds defined by Formula I or a pharmaceutically acceptable salt thereof, wherein R 1 , Q, S, T, U, V, and R 2 are as defined in the specification. The invention also provides pharmaceutical compositions and methods of treating diseases.

  该发明提供了由式I或其药学上可接受的盐定义的化合物，其中R1、Q、S、T、U、V和R2如规范中所定义。该发明还提供了药物组合物和治疗疾病的方法。
• Synthesis and Structure–Activity Relationship Studies of Pyrido [1,2-e]Purine-2,4(1H,3H)-Dione Derivatives Targeting Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis
  作者：Nicolas G. Biteau、Vincent Roy、Cyril Nicolas、Hubert F. Becker、Jean-Christophe Lambry、Hannu Myllykallio、Luigi A. Agrofoglio

  DOI：10.3390/molecules27196216

  日期：——

  In 2002, a new class of thymidylate synthase (TS) involved in the de novo synthesis of dTMP named Flavin-Dependent Thymidylate Synthase (FDTS) encoded by the thyX gene was discovered; FDTS is present only in 30% of prokaryote pathogens and not in human pathogens, which makes it an attractive target for the development of new antibacterial agents, especially against multi-resistant pathogens. We report herein the synthesis and structure-activity relationship of a novel series of hitherto unknown pyrido[1,2-e]purine-2,4(1H,3H)-dione analogues. Several synthetics efforts were done to optimize regioselective N1-alkylation through organopalladium cross-coupling. Modelling of potential hits were performed to generate a model of interaction into the active pocket of FDTS to understand and guide further synthetic modification. All those compounds were evaluated on an in-house in vitro NADPH oxidase assays screening as well as against Mycobacterium tuberculosis ThyX. The highest inhibition was obtained for compound 23a with 84.3% at 200 µM without significant cytotoxicity (CC50 > 100 μM) on PBM cells.

  在2002年，发现了一种新型胸腺嘧啶酸合酶（TS），参与dTMP的新生合成，名为黄酮依赖性胸腺嘧啶酸合酶（FDTS），由thyX基因编码；FDTS仅存在于30％的原核病原体中，而不在人类病原体中，这使其成为开发新的抗多重耐药病原体的抗菌剂的有吸引力的靶点。我们在此报告了一系列迄今为止未知的新型吡啶[1,2-e]嘌呤-2,4（1H,3H）-二酮类似物的合成和构效关系。进行了多次合成尝试以优化通过有机钯交叉偶联的区域选择性N1-烷基化。对潜在药效团进行建模，以生成与FDTS活性口袋的相互作用模型，以理解和指导进一步的合成修饰。所有这些化合物都在内部进行了体外NADPH氧化酶活性筛选，以及对结核分枝杆菌ThyX的抑制活性评估。化合物23a在200 µM时获得了84.3％的最高抑制率，对PBM细胞没有显着的细胞毒性（CC50> 100μM）。