O-(2,4-二甲氧基苄基)羟胺 | 216067-66-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: O-(2,4-二甲氧基苄基)羟胺
• 中文别名: 2,4-二甲氧基苄氧胺盐酸盐
• 英文名称: O-(2,4-dimethoxybenzyl)hydroxylamine
• 英文别名: O-[(2,4-dimethoxyphenyl)methyl]hydroxylamine
• CAS: 216067-66-2
• 化学式: C₉H₁₃NO₃
• mdl: MFCD11594390
• 分子量: 183.207
• InChiKey: HNACNYOQQGUSRD-UHFFFAOYSA-N

物化性质

• 沸点：
  321.6±32.0 °C(Predicted)
• 密度：
  1.118

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2922299090

反应信息

• 作为反应物：
  描述：

  O-(2,4-二甲氧基苄基)羟胺 在 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 2-amino-N-(2,4-dimethoxybenzyloxy)-3-hydroxypropionamide
  参考文献：
  名称：

  High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of Escherichia coli LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties

  摘要：

  LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wildtype Pseudomonas aeruginosa. Inhibition of the E coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.

  DOI：

  10.1021/ja0209114
• 作为产物：
  描述：

  2,4-二甲氧基苄醇 在 三苯基膦 、 甲基肼 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 22.0h， 生成 O-(2,4-二甲氧基苄基)羟胺
  参考文献：
  名称：

  O-Protected N-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates

  摘要：

  本文描述了新型O保护N-(2-硝基苯磺酰)羟胺（8a-e）的制备方法。它们作为多羟肟酸中间体的多功能性通过合成一种非酰胺的DFO类似物22得到了体现。

  DOI：

  10.1055/s-2001-14567

文献信息

• [EN] ACYLUREA CONNECTED AND SULFONYLUREA CONNECTED HYDROXAMATES<br/>[FR] HYDROXAMATES CONNECTES A L'ACYLUREE ET A LA SULFONYLUREE
  申请人：S BIO PTE LTD

  公开号：WO2005040101A1

  公开（公告）日：2005-05-06

  The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to acylurea/sulfonylurea containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with enzymes having histone deacetylase activities.

  本发明涉及羟肟酸酯化合物，这些化合物是组蛋白去乙酰化酶的抑制剂。更具体地，本发明涉及含有酰脲/磺酰脲的化合物及其制备方法。这些化合物可能作为治疗增殖性疾病以及涉及、与组蛋白去乙酰化酶活性有关的其他疾病的药物而有用。
• Thienopyrimidine compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06297379B1

  公开（公告）日：2001-10-02

  A compound of formula (I) wherein R1 and R2 each is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkoxy-carbonyl or C1-4 alkyl which may be substituted; R3 is hydrogen, halogen, hydroxy or C1-4 alkoxy which may be substituted; or adjacent two R3 may form C1-4 alkylenedioxy; R4 is hydrogen or C1-4 alkyl; R6 is C1-4 alkyl which may be substituted or a group of the formula (A) wherein R5 is hydrogen of R4 and R5 may form heterocycle; and n is 0-5, or a salt thereof, has an excellent GnRH-antagonizing activity, and is useful for preventing or treating sex hormone-dependent diseases.

  式（I）的化合物，其中R1和R2分别是氢、羟基、C1-4烷氧基、C1-4烷氧羰基或C1-4烷基，可以被取代；R3是氢、卤素、羟基或C1-4烷氧基，可以被取代；或相邻的两个R3可以形成C1-4烷二氧基；R4是氢或C1-4烷基；R6是可以被取代的C1-4烷基或具有式（A）的基团，其中R5是R4的氢或R4和R5可以形成杂环；n为0-5，或其盐，具有出色的GnRH拮抗活性，并且用于预防或治疗性激素依赖性疾病。
• New α-Substituted Succinate-Based Hydroxamic Acids as TNFα Convertase Inhibitors
  作者：Bernard Barlaam、T. Geoffrey Bird、Christine Lambert-van der Brempt、Douglas Campbell、Steve J. Foster、Rose Maciewicz

  DOI：10.1021/jm990377j

  日期：1999.11.1

  to be a metalloproteinase closely related to matrix metalloproteinases (MMPs). Current inhibitors of TACE such as succinate-based hydroxamic acids exemplified by Marimastat (TACE IC(50): 3.8 nM; blood IC(50): 7 microM) and BB1101 (TACE IC(50): 0.2 nM; blood IC(50): 2.3 microM) suffer from modest potency in blood and poor in vivo properties. The introduction of new bulky alpha-substituents into these

  肿瘤坏死因子α转化酶（TACE）是负责将前TNFα转化为TNFα的酶，据报道是与基质金属蛋白酶（MMP）密切相关的金属蛋白酶。目前的TACE抑制剂，例如基于MarimasTAt（TACE IC（50）：3.8 nM;血液IC（50）：7 microM）和BB1101（TACE IC（50）：0.2 nM;血液IC（50）的琥珀酸异羟肟酸） ：2.3 microM）在血液中具有中等效力且体内特性较差。研究了将新的大体积α-取代基引入这些基于琥珀酸酯的异羟肟酸中。与MarimasTAt相比，诸如硫醚，磺酰胺和醚等取代物对TACE的效力有所改善。尽管这种改善并未转化为硫醚或醚取代基的更好的血液效力，与MarimasTAt相比，磺酰胺系列药物对TACE和血液的功效均得到改善。该磺酰胺系列的优化最终确定了杂环双环磺酰胺，例如3t（TACE IC（50）：0.57 nM；血液IC（50）：0.28 microM）。
• New hydroxylamines for the synthesis of hydroxamic acids
  作者：Bernard Barlaam、Annie Hamon、Mickaël Maudet

  DOI：10.1016/s0040-4039(98)01760-2

  日期：1998.10

  O-2,4-Dimethoxybenzyl hydroxylamine and O-2,4-dimethoxybenzyl-N-2,4,6-trimethoxybenzyl hydroxylamine have been prepared and used for the preparation of hydroxamic acid based inhibitors of biological interest.

  已经制备了O-2，4-二甲氧基苄基羟胺和O-2，4-二甲氧基苄基-N-2,4,6-三甲氧基苄基羟胺，并将其用于制备基于生物学的基于异羟肟酸的抑制剂。
• Discovery of a Thieno[2,3-<i>d</i>]pyrimidine-2,4-dione Bearing a <i>p</i>-Methoxyureidophenyl Moiety at the 6-Position:  A Highly Potent and Orally Bioavailable Non-Peptide Antagonist for the Human Luteinizing Hormone-Releasing Hormone Receptor
  作者：Satoshi Sasaki、Nobuo Cho、Yoshi Nara、Masataka Harada、Satoshi Endo、Nobuhiro Suzuki、Shuichi Furuya、Masahiko Fujino

  DOI：10.1021/jm020180i

  日期：2003.1.1

  (LHRH) receptor, a thieno[2,3-b]pyridin-4-one derivative, T-98475 (1). Extensive research on developing non-peptide LHRH antagonists has been carried out by employing a strategy of replacing the thienopyridin-4-one nucleus with other heterocyclic surrogates. We describe herein the design and synthesis of a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives containing a biaryl moiety, which led to the

  我们先前已经公开了第一种有效且口服有效的非肽类抗人黄体生成激素释放激素（LHRH）受体，即噻吩并[2,3-b]吡啶-4-酮衍生物T-98475（1）。已经通过采用用其他杂环代用品替代噻吩并吡啶-4-酮核的策略对开发非肽LHRH拮抗剂进行了广泛的研究。我们在本文中描述了一系列含有联芳基部分的噻吩并[2,3-d]嘧啶-2,4-二酮衍生物的设计和合成，这些衍生物导致发现了一种高效且口服活性的非肽LHRH拮抗剂， 5-（N-苄基-N-甲基氨基甲基）-1-（2,6-二氟苄基）-6- [4-（3-甲氧基脲基）苯基] -3-苯基噻吩并[2,3-d]嘧啶-2， 4（1H，3H）-二酮（9k：TAK-013）。化合物9k对人受体显示出高结合亲和力和有效的体外拮抗活性，其最大抑制浓度（IC（50））值分别为0.1和0.06 nM。口服9k能够以30 mg / kg的剂量在cast割的雄性食蟹猕猴中几乎完全抑制