4-hydroxy-5-isopropylisophthalaldehyde | 99865-46-0

• 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-hydroxy-5-isopropylisophthalaldehyde
• 英文别名: 5-isopropyl-4-hydroxyisophthalaldehyde；4-Hydroxy-5-propan-2-ylbenzene-1,3-dicarbaldehyde
• CAS: 99865-46-0
• 化学式: C₁₁H₁₂O₃
• mdl: MFCD09037247
• 分子量: 192.214
• InChiKey: CZEHCACKNVCTRN-UHFFFAOYSA-N

物化性质

• 熔点：
  80-81 °C
• 沸点：
  286.4±40.0 °C(Predicted)
• 密度：
  1.191±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-5-isopropylisophthalaldehyde 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 三聚氯氰 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.92h， 生成 (±)-2-amino-3'-(3,4-dimethoxyphenyl)-8'-isopropyl-7,7-dimethyl-2',5-dioxo-5,6,7,8-tetrahydro-2'H,4H-4,6'-bichromene-3-carbonitrile
  参考文献：
  名称：

  Discovery of 3-Arylcoumarin-tetracyclic Tacrine Hybrids as Multifunctional Agents against Parkinson’s Disease

  摘要：

  A series of multifunctional directed 3-arylcoumarin-tetracyclic tacrine derivatives was designed and synthesized for the treatment of Parkinson's disease (PD). A number of derivatives (18, 19, 20, 21, and 24) demonstrated significant reduction of aggregation of "human" alphasynuclein (a-synuclein) protein, expressing on transgenic Caenorhabditis elegans (C. elegans) model NL5901. Moreover, compounds 16, 18, and 24 also exhibited good antioxidant properties and significantly increased the dopamine (DA) content in N2 and NL5901 strains of C. elegans. Interestingly, the protective efficacy of these hybrids seems to be mediated via activation of longevity promoting transcription factor DAF-16. In addition, molecular modeling studies have evidenced the exquisite interaction of most active compounds 18 and 24 with asynuclein protein. Taken together, the data indicate that the derivatives may be useful leads against aging and age associated PD.

  DOI：

  10.1021/ml500222g
• 作为产物：
  描述：

  异丙苯酚 、 乌洛托品 在 三氟乙酸 、 硫酸 、 水 作用下， 反应 6.0h， 以65%的产率得到4-hydroxy-5-isopropylisophthalaldehyde
  参考文献：
  名称：

  Hybrids of coumarin–indole: design, synthesis and biological evaluation in Triton WR-1339 and high-fat diet induced hyperlipidemic rat models

  摘要：

  新型香豆素-吲哚杂合物的降脂活性已被证实。

  DOI：

  10.1039/c6md00283h

文献信息

• Synthesis and bio-evaluation of indole-chalcone based benzopyrans as promising antiligase and antiproliferative agents
  作者：Sampa Gupta、Pooja Maurya、Akanksha Upadhyay、Pragati Kushwaha、Shagun Krishna、Mohammad Imran Siddiqi、Koneni V. Sashidhara、Dibyendu Banerjee

  DOI：10.1016/j.ejmech.2017.11.015

  日期：2018.1

  indole-chalcone based benzopyran compounds on cancer cells. One molecule called compound 27 showed a notable preference for inhibition of hLigI as compared to other ligases and showed enhanced cytotoxicity against colon cancer (DLD-1) cells as compared to normal cells. Mechanistic studies showed that compound 27 directly interacts with hLigI in a competitive manner and did not interact with the DNA substrate

  DNA复制和修复是复杂的过程，通过酶和蛋白质网络的协同作用来完成。DNA连接酶通过催化DNA链之间的缺口连接，在这些过程中起着至关重要的作用。与正常细胞相比，据报道在某些癌症中人类DNA连接酶I（hLigI）的水平升高。我们研究了抑制hLigI介导的DNA切口封闭活性，然后研究了基于吲哚-查尔酮的新型苯并吡喃化合物对癌细胞的抗增殖活性。与其他连接酶相比，一种称为化合物27的分子表现出对hLigI抑制的显着偏好，与正常细胞相比，对结肠癌（DLD-1）细胞的细胞毒性增强。机理研究表明，化合物27在连接过程中直接与hLigI相互作用，而与DNA底物不相互作用。这种新型有效的hLigI抑制剂对模拟实体瘤的DLD-1细胞的单层培养和3D培养均显示出显着抑制作用。它还影响了DLD-1细胞的迁移，表明其潜在的抗转移活性。因此，这种新颖的hLigI抑制剂可以作为抗癌药物开发的有希望的先导。
• Design, synthesis and in vitro evaluation of coumarin–imidazo[1,2-a]pyridine derivatives against cancer induced osteoporosis
  作者：Koneni V. Sashidhara、L. Ravithej Singh、Dharmendra Choudhary、Ashutosh Arun、Sampa Gupta、Sulekha Adhikary、Gopala Reddy Palnati、Rituraj Konwar、Ritu Trivedi

  DOI：10.1039/c6ra15674f

  日期：——

  Out of three promising compounds, 6l and 6o significantly induced apoptosis in MDA-MB-231 cancer cells via mitochondrial depolarisation without affecting normal cells. In an in vitro co-culture model of bone metastasis, we investigated the ability of coumarin–imidazo[1,2-a]pyridine hybrids to reverse the negative impact of MDA-MB-231 cancer cells on osteoblast differentiation. The results illustrate

  利用银（I）催化的Groebke-Blackburn-Bienayme多组分反应合成了一系列具有重要生物学意义的6-（咪唑并[1,2 - a ]吡啶-2-基）-2 H -chromen-2-one衍生物。通过碱性磷酸酶测定法和茜素红-S染色测定法在原发性颅盖骨成骨细胞中测试了合成的化合物的可能的骨保护特性。此外，通过qPCR测量活性化合物6h，6l和6o对成骨基因BMP2，RUNX2，COL1和OCN表达的影响。在三种有前途的化合物中，每升6升6a和6o通过线粒体去极化显着诱导了MDA-MB-231癌细胞的凋亡，而不影响正常细胞。在体外骨转移共培养模型中，我们研究了香豆素-咪唑并[1,2- a ]吡啶杂化物逆转MDA-MB-231癌细胞对成骨细胞分化的负面影响的能力。结果说明了设计的杂交体重建骨骼稳态的潜力。这些发现证明了新合成的杂种作为先导分子的重要性，既具有抗骨质疏松性又具有抗癌性，可
• One-Pot Regioselective Synthesis of Imidazole and 2,3-Dihydroquinazolinone Derivatives - An Easy Access to ‘Nature-Like Molecules'; Part XIII in the Series: ‘Studies on Novel Synthetic Methodologies'
  作者：Koneni Sashidhara、Gopala Palnati、Ranga Dodda、Srinivasa Avula、Priyanka Swami

  DOI：10.1055/s-0033-1339466

  日期：——

  A mild and highly practical regioselective synthesis of imidazole and 2,3-dihydroquinazolinone derivatives from 5-alkyl-4-hydroxyisophthalaldehydes with suitable substrates in acetic acid is reported. Further exploration of the molecular diversity of 2,3-dihydroquinazolinone is demonstrated by the synthesis of diverse pharmacologically relevant natural-product-like scaffolds.

  报道了一种温和且高度实用的区域选择性合成咪唑和 2,3-二氢喹唑啉酮衍生物，由 5-烷基-4-羟基间苯二醛与合适的底物在乙酸中合成。2,3-二氢喹唑啉酮的分子多样性的进一步探索通过多种药理学相关的天然产物样支架的合成得到证明。
• Benzofuran-pyran hybrids: A new class of potential bone anabolic agents
  作者：Sampa Gupta、Sulekha Adhikary、Ram K. Modukuri、Dharmendra Choudhary、Ritu Trivedi、Koneni V. Sashidhara

  DOI：10.1016/j.bmcl.2018.04.041

  日期：2018.6

  analysis of these compounds on osteoblast cells revealed that compound 22 up-regulated the expression of osteogenic genes RUNX2, BMP-2, COL-1, thus substantiating that compound 22 having two geminal methyl groups in its R3 position is a potent osteogenic agent. Additionally, compound 22 enhanced the ability of bone marrow stromal cells to differentiate towards osteoblast lineage and therefore can be

  苯并呋喃部分是一种重要的药效团，对骨骼健康具有积极作用。在本研究中，合成了十六种苯并呋喃-吡喃杂化物，并评估了它们对从颅盖分离的原代成骨细胞的成骨作用。如通过碱性磷酸酶活性所评估的，发现化合物22和24在刺激成骨细胞分化方面是有效的。与MTT测定中的对照细胞相比，还发现这些化合物对成骨细胞无毒。此外，用于可视化钙结节的茜素红-S染色证实了化合物22和34在增强成骨细胞中的矿化作用方面发挥了积极作用。此外，这些化合物在成骨细胞上的转录分析表明，化合物22上调了成骨基因RUNX2，BMP-2，COL-1的表达，因此证实了在其R 3位具有两个双甲基的化合物22是有效的。成骨剂。另外，化合物22增强了骨髓基质细胞向成骨细胞谱系分化的能力，因此可以在体内在骨丢失模型中进行进一步研究。
• Synthesis and study of benzofuran-pyran analogs as BMP-2 targeted osteogenic agents
  作者：Pragati Kushwaha、Ashish Kumar Tripathi、Sampa Gupta、Priyanka Kothari、Akanksha Upadhyay、Naseer Ahmad、Tanuj Sharma、M.I. Siddiqi、Ritu Trivedi、Koneni V. Sashidhara

  DOI：10.1016/j.ejmech.2018.06.062

  日期：2018.8

  rat calvarial osteoblasts in vitro. Among all the compounds screened for the alkaline phosphatase activity, three compounds 4e, 4j and 4k showed potent activity at picomolar concentrations in osteoblast differentiating stimulation. Additionally, these compounds were found effective in mineralization, assessed by alizarin red-S staining assay. Compounds were again validated through a series of other in vitro

  二十四新颖苯并呋喃吡喃衍生物的合成和评价大鼠颅骨成骨细胞的初级培养物及其抗骨质疏松活性体外。在所有筛选出的碱性磷酸酶活性的化合物中，三种化合物4e，4j和4k在皮摩尔浓度下在成骨细胞分化刺激中均显示出有效的活性。另外，通过茜素红-S染色测定法评估发现这些化合物对矿化有效。化合物再次通过一系列其他体外验证实验。此外，分子动力学模拟表明，苯并呋喃和吡喃部分都必须适合BMP-2受体的活性位点，而BMP-2受体是成骨剂的关键靶标。所获得的结果有力地证明了化合物4e是合成系列中潜在的骨合成代谢剂，其可以作为治疗骨质疏松症的药物先导而进一步探索。