1-imino-4,7-bis(1-methylethoxy)-1H-isoindolin-3-amine | 201140-20-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1-imino-4,7-bis(1-methylethoxy)-1H-isoindolin-3-amine
• 英文别名: 4,7-diisopropyloxy-1,3-diiminoisoindoline；1-imino-4,7-bis(1-methylethoxy)-1H-isoindole-3-amine；4,7-(isopropyloxy)-1,3-iminoisoindoline；4,7-bis(isopropyloxy)-1,3-diiminoisoindoline；4,7-Diisopropoxy-1,3-diiminoisoindoline；3-imino-4,7-di(propan-2-yloxy)isoindol-1-amine
• CAS: 201140-20-7
• 化学式: C₁₄H₁₉N₃O₂
• 分子量: 261.324
• InChiKey: GNKWFXGEUNAQPK-UHFFFAOYSA-N

物化性质

• 熔点：
  144-148 °C
• 沸点：
  426.8±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  80.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-imino-4,7-bis(1-methylethoxy)-1H-isoindolin-3-amine 在 magnesium 、 三氟乙酸 、 正丁醇 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 22-N,22-N,23-N,23-N-tetramethyl-5,8,14,17,28,31-hexa(propan-2-yloxy)-2,11,20,25,33,34,35,36-octazaoctacyclo[24.6.1.13,10.112,19.121,24.04,9.013,18.027,32]hexatriaconta-1,3(36),4,6,8,10,12(35),13,15,17,19,21,23,26(33),27,29,31-heptadecaene-22,23-diamine
  参考文献：
  名称：

  Synthesis and structural characterization of 2,3,7,8,12,13,17,18-octakis(propyl), N, N, N′, N′-tetramethylaminoporphyrazines and 2,3,9,10,16,17,23,24-octa substituted phthalocyanine and the kinetic studies of their Co(II) and Cu(II) metalated complexes

  摘要：

  Three tetrapyrrole macrocyclic compounds 2,3,7,8,12,13,17,18-octakis(propyl)porphyrazine, N, N, N', N'-tetramethylamino porphyrazine hybrid and 2,3,9,10,16,17,23,24-octa substituted phthalocyanine were synthesized and characterized using elemental analysis, FTIR, H-1, C-13 NMR and UV-vis spectroscopic techniques. Kinetics of their metalation with Cu(II) and Co(II) and redox reaction of the complexes was studied and are reported here for the first time. It is suggested that deformation of the ring, which is a function of their peripheral functionalities, is essential for effective coordination of the ligands. The kinetic studies indicated metal based oxidation and ring based reduction for the reductants and oxidant respectively. The redox activity of the metal ions is dependent on the availability of their low energy level d-orbitals for charge transfer. It was therefore inferred that the nature of the metal ion and the peripheral substituents of these ligands and their complexes had significant effect on their reactivity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.dyepig.2014.05.013
• 作为产物：
  描述：

  3,6-二羟基邻苯二甲腈 在 氨 、 sodium 、 potassium carbonate 作用下， 以 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 1-imino-4,7-bis(1-methylethoxy)-1H-isoindolin-3-amine
  参考文献：
  名称：

  A Facile and Regioselective Synthesis of Trans-Heterofunctionalized Porphyrazine Derivatives

  摘要：

  New methodology was developed for the selective synthesis of regiochemically defined porphyrazines of the form M[pz(A(2);B-2)] (shown in Chart 1) where A and B represent peripheral functionalization attached to the P-positions of the pyrroles. Specifically, phthalonitriles or derivatives thereof with sterically bulky groups in positions 3 and 6, in particular 4,7-bis(isopropyloxy)-1,3-diiminoisoindoline (3) act as a "trans director" when macrocyclized with heteroatom-appended maleonitriles under Linstead conditions, the result being preferential formation of the trans-h[pz(A(2);B-2)] pigment where A = SR, NMe2, OR, as well as R (shown in Chart 2). Linstead crossover macrocyclization of 3 with 4, 11, 15, and 18 gave pigments 10, 14, 17, and 19, respectively. These pigments were characterized by H-1 NMR, C-13 NMR, UV-visible spectroscopy, mass spectrometry, microanalysis, and 17 was characterized by single-crystal X-ray analysis.

  DOI：

  10.1021/jo971683c

文献信息

• Spectroscopy, Binding to Liposomes and Production of Singlet Oxygen by Porphyrazines with Modularly Variable Water Solubility
  作者：Alan Sholto、Sangwan Lee、Brian M. Hoffman、Anthony G. M. Barrett、Benjamin Ehrenberg

  DOI：10.1111/j.1751-1097.2007.00268.x

  日期：2008.5

  capability to tune the solubility, these molecules could make for better sensitizers because of optimized uptake by lipidic membranes and better optical properties. We tested several derivatives of the A4, A3B and A2B2 structures for their singlet oxygen quantum yields in methanol and in liposomes, using 9,10‐dimethyl anthracene (DMA) as a singlet oxygen target. Singlet oxygen quantum yields in liposomes

  合成了三类新型四氮杂卟啉类结构以形成模块化结构，其中可以调节亲脂性和水溶性。溶解度的细微改变是选择用于生物光敏化的化合物的重要标准。一般结构采用 H2[pz(AnB4−n)] 的形式，其中核心是四氮杂卟啉 (pz) 基团，A 是具有两个硫键（SR 部分）的吡咯环，B 是与 4 稠合的吡咯， 7-双（异丙氧基）苯并基团，n = 4、3 和 2。这些分子的最长波长吸收带在 700 到 810 nm 之间，因此在光动力疗法中可以使用更高组织穿透深度的激光束照射它们（太平洋夏令时）。拥有远红外和近红外（近红外）吸收带，以及调节溶解度的能力，由于脂质膜的优化吸收和更好的光学特性，这些分子可以成为更好的敏化剂。我们使用 9,10-二甲基蒽 (DMA) 作为单线态氧靶标，测试了 A4、A3B 和 A2B2 结构的几种衍生物在甲醇和脂质体中的单线态氧量子产率。脂质体中的单线态氧量子产率范围为 0.01 到
• Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation
  作者：Evan R. Trivedi、Allison S. Harney、Mary B. Olive、Izabela Podgorski、Kamiar Moin、Bonnie F. Sloane、Anthony G.M. Barrett、Thomas J. Meade、Brian M. Hoffman

  DOI：10.1073/pnas.0912811107

  日期：2010.1.26

  A chiral porphyrazine (pz), H ₂ [pz( trans - A ₂ B ₂ )] (247), has been prepared that exhibits preferential in vivo accumulation in the cells of tumors. Pz 247 exhibits near-infrared (NIR) emission with λ  > 700 nm in the required wavelength range for maximum tissue penetration. When MDA-MB-231 breast tumor cells are treated with 247, the agent shows strong intracellular fluorescence with an emission maximum, 704 nm, which indicates that it localizes within a hydrophobic microenvironment. Pz 247 is shown to associate with the lipophilic core of LDL and undergo cellular entry primarily through receptor-mediated endocytosis accumulating in lysosomes. Preliminary in vivo studies show that 247 exhibits preferential accumulation and retention in the cells of MDA-MB-231 tumors subcutaneously implanted in mice, thereby enabling NIR optical imaging with excellent contrast between tumor and surrounding tissue. The intensity of fluorescence from 247 within the tumor increases over time up to 48 h after injection presumably due to the sequestration of circulating 247/LDL complex by the tumor tissue. As the need for cholesterol, and thus LDL, is elevated in highly proliferative tumor cells over nontumorigenic cells, 247 has potential application for all such tumors.

  已制备出手性卟啉（pz）H2[pz（trans-A2B2）]（247），在体内表现出对肿瘤细胞的优先积累。Pz 247表现出近红外（NIR）发射，波长范围在要求的700 nm以上，以达到最大组织穿透深度。当MDA-MB-231乳腺肿瘤细胞接受247处理时，该剂量显示出强烈的胞内荧光，发射峰值为704 nm，表明它定位于一个疏水微环境内。研究表明，Pz 247与LDL的疏水性核心相结合，并主要通过受体介导的内吞作用进入细胞，积累在溶酶体内。初步的体内研究表明，247在小鼠皮下植入的MDA-MB-231肿瘤细胞中表现出优先积累和保留，从而实现了NIR光学成像，肿瘤和周围组织之间的对比度极佳。肿瘤内247的荧光强度随时间增加，48小时后注射，可能是由于肿瘤组织通过固定循环的247 / LDL复合物而产生。由于高度增殖性的肿瘤细胞需要胆固醇和LDL，因此247具有潜在的应用价值。
• Porphyrazine-chemotherapeutic agents conjugates
  申请人：Hoffman/Barrett, L.L.C.

  公开号：EP2599497A2

  公开（公告）日：2013-06-05

  Conjugates of Porphyrazines capable of localizing in a tumor of a mammal are disclosed. The porphyrazines are used in methods of imaging a tumor and in methods of treating tumors, in combination with a chemotherapeutic agent and/or radiation.

  本发明公开了能够在哺乳动物肿瘤中定位的卟吩嗪类共轭物。卟嗪类化合物与化疗药物和/或放射线结合使用，可用于肿瘤成像方法和肿瘤治疗方法。
• Surface-Bound Porphyrazines:  Controlling Reduction Potentials of Self-Assembled Monolayers through Molecular Proximity/Orientation to a Metal Surface
  作者：Benjamin J. Vesper、Khalid Salaita、Hong Zong、Chad A. Mirkin、Anthony G. M. Barrett、Brian M. Hoffman

  DOI：10.1021/ja045270m

  日期：2004.12.1

  We report the preparation of two novel H-2[pz(A(n);B4-n)] porphyrazines (pzs) which were designed to position themselves quite differently when attached to a surface: one to form a standard self-assembled monolayer (SAM) roughly perpendicular to a surface, the other to lie horizontally along a surface. As the former, we synthesized a pz, 1, where one pyrrole group is functionalized with two thioethers terminated in mercaptides (SR, R = (CH2)(3)CONH(CH2)(2)S-), each protected as a disulfide, and -S-Me is attached to the other pyrrole sites; the latter is a pz, 2, with dialkoxybenzo groups fused to two trans-pyrroles of the pz ring, and SR groups are attached to the other pair of pyrroles. Nanostructures of 1 and 2 were successfully patterned on gold surfaces via dip-pen nanolithography, and the predicted molecular orientation of the resulting structures was confirmed by topographic AFM images. The two pzs exhibit similar reduction potentials in solution. Both show large shifts in potential upon surface binding, with the magnitude of the shift depending on the proximity/orientation of the pz to the surface. The first reduction potential of the "vertically" aligned 1 shifts by ca. +430 mV when incorporated in a binary pz/hexanethiol SAM, while that for 2, which lies flat, shifts by ca. +800 mV; the potential thus shifts by ca. +370 mV upon taking a given pz that stands atop a two-legged insulating "standoff" in a traditional SAM and "laying it down". We suggest these observed effects can be explained by image-charge energetics, and this is supported by a simple model.
• Synthesis of Near-IR Absorbing/Emitting Porphyrazine Derivatives with Tunable Solubility
  作者：Sangwan Lee、Andrew J. P. White、David J. Williams、Anthony G. M. Barrett、Brian M. Hoffman

  DOI：10.1021/jo001220y

  日期：2001.1.1

  We report the synthesis of porphyrazines (pzs), or tetraazaporphyrins, of the form H(2)[pz(A(n;)B(4-n))], where A is [S(CH(2))(3)COOR](2) (R = n-Pr, H) and B is a fused beta,beta'-diisopropyloxybenzo group, including the compounds with n = 4 (6), n = 3 (7) and the trans compound with n = 2 (8) (Scheme 1). The synthesis employs Linstead crossover macrocyclization of dimethyl 6,7-dicyano-5,8-dithia-6(Z)dodecenedioate, MNT(C(4)O(2)Me)2 (2), with 1-imino-4,7-bis(1-methylethoxy)-1H-isoindole-3-amine (4). These pigments were characterized by (1)H NMR, 13C NMR, absorbance/fluorescence spectroscopy, mass spectrometry, and microanalysis. An X-ray crystal structure of 8 is presented. Of particular note, 6-8 display intense near-IR absorbance and dual UV-visible/near-IR emission which are very important in potential biomedical applications, both for cancer therapy (photodyanamic therapy, PDT) and cancer diagnosis (optical tumor imaging). For example, the trans-porphyrazine 8 has an intense long-wavelength absorption at ca. 800 nm (log epsilon = 4.18) and S1 fluorescence at similar to 820 nm, where mammalian tissue is effectively penetrated by light. Transformation of the ester group permits a wide range of functionality and solubility to be generated without change in optical properties. As an example, hydrolysis of these compounds by LiOH in THF/H(2)O gives the corresponding carboxylato-functionalized pigments 9-11, which are described. The last of these dissolves without aggregation in fetal calf serum.