(双-叔丁氧基羰基甲基-氨基)-乙酸 | 171557-31-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 甘氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (双-叔丁氧基羰基甲基-氨基)-乙酸
• 中文别名: N,N-双[2-(叔丁氧基)-2-氧代乙基]甘氨酸
• 英文名称: bis(2-(tert-butoxy)-2-oxoethyl)glycine
• 英文别名: 2-[Bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]azaniumyl]acetate
• CAS: 171557-31-6
• 化学式: C₁₄H₂₅NO₆
• 分子量: 303.356
• InChiKey: DEUFNPOTWJNGNL-UHFFFAOYSA-N

物化性质

• 熔点：
  85-87°C
• 沸点：
  399.2±37.0 °C(Predicted)
• 密度：
  1.129
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• pKa：
  1.96±0.10 (Predicted,Most Acidic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2922509090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (双-叔丁氧基羰基甲基-氨基)-乙酸 在 柠檬酸 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 生成 bis(tert-butoxycarbonylmethyl)aminoacetic acid 2,5-dioxo-pyrrolidin-1-yl ester
  参考文献：
  名称：

  Peptides for Treatment of Obesity

  摘要：

  本发明涉及一种新型肽化合物，其有效调节一个或多个黑色素皮质素受体类型，以及该类化合物在治疗中的应用，包括通过将该类化合物用于需要的患者进行治疗的方法，以及该类化合物在制造药物中的应用。本发明的化合物在治疗肥胖以及与肥胖相关的各种疾病或症状方面具有特别的兴趣。

  公开号：

  US20130012432A1
• 作为产物：
  描述：

  碘乙酸叔丁酯 在 palladium on activated charcoal pH 7.0 phosphate buffer 、 氢气 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 80.0h， 生成 (双-叔丁氧基羰基甲基-氨基)-乙酸
  参考文献：
  名称：

  Stereocontrolled Synthesis of DTPA Analogs Branched in the Ethylene Unit

  摘要：

  Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substituted on the ethylene backbones with methyl groups, the chiral center a to the terminal nitrogen being derived from (S)- or (R)-alanine, has been achieved. The key intermediate (S)-propylenediaminetriacetic acid triester was synthesized via selective detosylation of the alkylation product derived from (S)-alanine and tert-butyl glycinate. Attaching the remaining modified alanine (or glycine) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substituted DTPA analogues. Ester differentiation has been accomplished through alkylation rather than acylation of the (S)-propylenediaminetriacetic acid triester. A byproduct from this alkylation is the oxazoloisoindole formed by internal alkylation of the oxygen of the phthaloyl protecting group. Phthaloyl deprotection followed by dialkylation afforded the ester-differentiated (S,S)-dipropylenetriaminepentaacetic esters. The enantiomeric purity of the chiral intermediates (S)-alaninol and (S)-propylenediamines were determined by HPLC using epimeric standards.

  DOI：

  10.1021/jo00126a059

文献信息

• Design of a binuclear Ni(II)–iminodiacetic acid (IDA) complex for selective recognition and covalent labeling of His-tag fused proteins
  作者：Ikuko Takahira、Hirokazu Fuchida、Shigekazu Tabata、Naoya Shindo、Shohei Uchinomiya、Itaru Hamachi、Akio Ojida

  DOI：10.1016/j.bmcl.2014.04.096

  日期：2014.7

  Selective protein labeling with a small molecular probe is a versatile method for elucidating protein functions under live-cell conditions. In this Letter, we report the design of the binuclear Ni(II)–iminodiacetic acid (IDA) complex for selective recognition and covalent labeling of His-tag-fused proteins. We found that the Ni(II)–IDA complex 1-2Ni(II) binds to the His6-tag (HHHHHH) with a strong

  用小分子探针进行选择性蛋白质标记是阐明活细胞条件下蛋白质功能的通用方法。在这封信中，我们报告了双核Ni（II）-亚氨基二乙酸（IDA）复合物的设计，该复合物用于选择性识别和共价标记His-tag融合蛋白。我们发现，Ni（II）–IDA配合物1 -2Ni（II）以很强的结合亲和力（K d  = 24 nM）与His6-tag（HHHHHH）结合，其值比H（-）高16倍。常规Ni（II）–NTA络合物（K d = 390 nM）。Ni（II）-IDA复合物的强结合亲和力已成功用于位于活细胞表面的His-tag融合GPCR（G蛋白偶联受体）的共价标记和荧光生物成像。
• 三羰基锝-99m或铼-188标记的环RGD衍生物、 其制备方法和包含所述衍生物作为活性成分用 于诊断或治疗血管发生相关疾病的药物组合物
  申请人：韩国生物医学影像株式会社

  公开号：CN102985413B

  公开（公告）日：2016-04-20

  本发明涉及三羰基锝-99m或铼-188标记的环RGD衍生物、其制备方法和包含所述衍生物作为活性成分用于诊断或治疗血管发生相关疾病的药物组合物。本发明的三羰基锝-99m或铼188标记的环RGD衍生物对在肿瘤诱导的血管发生作用中活化的α v β 3 整合素(也称作玻连蛋白受体)具有亚纳摩尔的高亲和力，反映为移植了癌细胞的动物在初始摄入三羰基锝-99m标记的环RGD衍生物后的高肿瘤图像，并且专一地作用于已经选择性活化了α v β 3 整合素的癌细胞，这是因为与现有已知的放射性同位素标记的环RGD衍生物相比肝和肠摄入大幅降低。这些结果表明：当通过尾静脉向肿瘤动物模型注射后，与仅注射盐水相比，铼-188标记的衍生物(与锝-99m标记的使用相同前体的治疗性核素)有效抑制肿瘤的生长，并且证明有治疗效果，因此可用作诊断或治疗血管发生相关疾病的药物。
• Synthesis and biological evaluation of RGD peptides with the^99mTc/¹⁸⁸Re chelated iminodiacetate core: highly enhanced uptake and excretion kinetics of theranostics against tumor angiogenesis
  作者：Byung Chul Lee、Byung Seok Moon、Ji Sun Kim、Jae Ho Jung、Hyun Soo Park、John A. Katzenellenbogen、Sang Eun Kim

  DOI：10.1039/c2ra22460g

  日期：——

  To develop a companion set of RGD-based agents for diagnostic and radiotherapeutic purposes, facile incorporation of 99mTc(CO)3 or 188Re(CO)3 into the same precursor produced, respectively, a structurally and functionally matched radiodiagnostic and radiotherapeutic—or theranostic—pair. This work presents the synthesis of two 99mTc-labeled RGD monomers (4 and 5) along with a 99mTc-labeled RGD dimer (6) and an investigation of the influence of the small-sized and negatively charged 99mTc-iminodiacetate (IDA) core on the in vitro and in vivo behavior of these three different RGD analogs for imaging integrin αvβ3 expression. Among the three 99mTc-IDA-RGD analogs, 6 exhibited the highest integrin binding affinity with an IC50 value of 0.5 nM and a tumor uptake with an ID/g value of 12.3 ± 5.15% at 60 min post-injection, whereas liver and intestinal levels remained relatively low with good metabolic stability (>97%), presumably because of the overall negative charge of the radiometal chelating system. Both 99mTc/188Re-labeled compounds (6 and 7), which were prepared from the precursor (18), provided a good tumor accumulation and a clearly visible image of the tumor with high contrast, as compared to the contralateral background in the U87-MG xenograft model. These data support the use of 99mTc- and 188Re-IDA-D-[c(RGDfK)]2 as a matched radio-theragnostic pair that can be used to individualize radiotherapy for angiogenesis-dependent cancer.

  为了开发用于诊断和放射治疗目的的 RGD 类配套制剂，将 99mTc(CO)3 或 188Re(CO)3 简单地掺入相同的前体，可分别产生结构和功能上匹配的放射诊断和放射治疗--或治疗--对。这项工作展示了两种 99mTc 标记的 RGD 单体（4 和 5）以及一种 99mTc 标记的 RGD 二聚体（6）的合成，并研究了小尺寸和带负电荷的 99mTc-iminodiacetate (IDA) 核心对这三种不同 RGD 类似物在体外和体内成像整合素 αvβ3 表达行为的影响。在三种 99mTc-IDA-RGD 类似物中，6 的整合素结合亲和力最高，IC50 值为 0.5 nM，注射后 60 分钟的肿瘤摄取 ID/g 值为 12.3 ± 5.15%，而肝脏和肠道中的含量相对较低，代谢稳定性良好（>97%），这可能是由于放射性金属螯合系统的整体负电荷。在 U87-MG 异种移植模型中，由前体（18）制备的两种 99mTc/188Re 标记化合物（6 和 7）都能提供良好的肿瘤蓄积和清晰可见的高对比度肿瘤图像。这些数据支持使用 99mTc- 和 188Re-IDA-D-[c(RGDfK)]2 作为匹配的放射-他诊断配对，可用于血管生成依赖性癌症的个体化放疗。
• [EN] METHOD FOR THE SYNTHESIS OF N-PHOSPHONOMETHYLIMINODIACETIC ACID<br/>[FR] PROCÉDÉ DE SYNTHÈSE D'ACIDE N-PHOSPHONOMÉTHYLIMINODIACÉTIQUE
  申请人：STRAITMARK HOLDING AG

  公开号：WO2014012986A1

  公开（公告）日：2014-01-23

  The present invention is related to a method for the synthesis of N- phosphonoalkyliminodiacetic acid or derivatives thereof comprising the steps of: a) forming a reaction mixture comprising an acid catalyst, a compound having the general formula R1 -CH2-NX-CH2-R2 and a compound having one or more P-O-P anhydride moieties, to form a compound having the general formula R1 - CH2-N-CH2(P03H2)-CH2-R2, its dehydrated forms or their derivatives, wherein - the compound of the formula R1 -CH2-NX-CH2-R2 is characterized in that: - X is -CH2-OH or -CH2-COOH; - R1 and R2 are independently selected from the group consisting of nitrile, C1 -C4 alkyl carboxylate, or are both carbonyl groups linked by means of a hydrogen substituted nitrogen atom or a C1 -C4- akyl substituted nitrogen atom; - the P-O-P anhydride comprising compound is characterized in that said anhydride moieties comprise one P atom at the oxidation state (+I II ) and one P atom at the oxidation state (+I II ) or (+V); and b) hydrolysing the reaction mixture to form N- phosphonomethyliminodiacetic acid or one of its derivatives.

  本发明涉及一种合成N-磷酸基烷基亚乙酸或其衍生物的方法，包括以下步骤：a）形成反应混合物，包括酸催化剂、具有一般式R1-CH2-NX-CH2-R2的化合物和具有一个或多个P-O-P酐基团的化合物，以形成一般式R1-CH2-N-CH2(P03H2)-CH2-R2的化合物、其脱水形式或其衍生物，其中-具有一般式R1-CH2-NX-CH2-R2的化合物的特点是：-X为-CH2-OH或-CH2-COOH；-R1和R2独立地选自由氰基、C1-C4烷基羧酸酯组成的群，或通过氢代氮原子或C1-C4烷基取代的氮原子连接的两个羰基基团；-包含P-O-P酐基团的化合物的特点是，所述酐基团包括一个氧化态为(+I II)的P原子和一个氧化态为(+I II)或(+V)的P原子；b）水解反应混合物以形成N-磷酸基甲基亚乙酸或其衍生物之一。
• METHOD FOR THE SYNTHESIS OF N-PHOSPHONOMETHYLIMINODIACETIC ACID
  申请人：STRAITMARK HOLDING AG

  公开号：US20150166584A1

  公开（公告）日：2015-06-18

  A method for synthesis of N-phosphonoalkyliminodiacetic acid or derivatives thereof by: 1) forming a reaction mixture having an acid catalyst, a compound having the general formula R 1 —CH 2 —NX—CH 2 —R 2 and a compound having one or more P—O—P anhydride moieties, to form a compound having the general formula R 1 —CH 2 —N—CH 2 (PO 3 H 2 )—CH 2 —R 2 , its dehydrated forms or their derivatives, wherein the compound of the formula R 1 —CH 2 —NX—CH 2 —R 2 is characterized in that: X is —CH 2 —OH or —CH 2 —COOH; and R 1 and R 2 are independently selected from the group consisting of nitrile, C 1 -C 4 alkyl carboxylate, or are both carbonyl groups linked by a hydrogen substituted nitrogen atom or a C 1 -C 4 -akyl substituted nitrogen atom; the P—O—P anhydride compound is characterized in that the anhydride moieties have one P atom at the oxidation state (+III) and one P atom at the oxidation state (+III) or (+V); and 2) hydrolysing the reaction mixture to form N-phosphonomethyliminodiacetic acid or one of its derivatives.

  一种合成N-磷酸脂肪基亚乙酸或其衍生物的方法，包括以下步骤：1）形成反应混合物，其中包括酸性催化剂、具有一般式R1-CH2-NX-CH2-R2的化合物和具有一个或多个P-O-P酸酐基团的化合物，以形成具有一般式R1-CH2-N-CH2(PO3H2)-CH2-R2的化合物、其脱水形式或其衍生物，其中一般式R1-CH2-NX-CH2-R2的化合物的特点在于：X为-CH2-OH或-CH2-COOH；R1和R2分别选自氰基、C1-C4烷基羧酸酯的群或由氢代替的氮原子或C1-C4烷基取代的氮原子连接的两个羰基基团；P-O-P酸酐化合物的特点在于酸酐基团具有一个P原子在氧化态(+III)，一个P原子在氧化态(+III)或(+V)；2）水解反应混合物，以形成N-磷酸甲基亚乙酸或其衍生物之一。