罗希吐碱 | 71294-60-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 罗希吐碱
• 英文名称: rohitukine
• 英文别名: 5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-2-methylchromen-4-one
• CAS: 71294-60-5
• 化学式: C₁₆H₁₉NO₅
• 分子量: 305.331
• InChiKey: MOCVYVBNJQIVOV-TVQRCGJNSA-N

物化性质

• 沸点：
  494.8±45.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  90.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  罗希吐碱 生成 5,7-dihydroxy-8-[(3S,4R)-3-hydroxypiperidin-4-yl]-2-methylchromen-4-one
  参考文献：
  名称：

  KATTIGE, SAMBA LAXMINARAYAN;NAIK, RAMCHANDRA GANAPATI;LAKDAWALLA, AFTAB D+

  摘要：

  DOI：
• 作为产物：
  描述：

  8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-5,7-dimethoxy-2-methylchromen-4-one 生成 罗希吐碱
  参考文献：
  名称：

  KATTIGE, SAMBA LAXMINARAYAN;NAIK, RAMCHANDRA GANAPATI;LAKDAWALLA, AFTAB D+

  摘要：

  DOI：

文献信息

• Synthesis, biological evaluation, and molecular docking study of some new rohitukine analogs as protein tyrosine phosphatase 1B inhibitors
  作者：V.M. Balaramnavar、R. Srivastava、S. Varshney、S. Kumar、A.K. Rawat、H. Chandasana、Y.S. Chhonker、R.S. Bhatta、A.K. Srivastava、A.N. Gaikwad、V. Lakshmi、A.K. Saxena

  DOI：10.1016/j.bioorg.2021.104829

  日期：2021.5

  MDI-induced adipogenesis in 3 T3-L1 preadipocytes, at 10 µM and 20 µM concentration. These results were compared with the parent compound RH which inhibited 35% and 45% lipid accumulation while the RH analog K5 inhibited the lipid accumulation by 41% and 51% at 10 and 20 µM concentration, respectively. These results well corroborated with in-silico studies.

  Rohitukine ( RH ) 是从Dysoxylum binectariferum Hook的茎皮中提取的。通过用相应的芳基磺酰氯处理，将其衍生为不同的芳基硫酰胺。在体外测试了这些衍生物对蛋白质酪氨酸磷酸酶 1B (PTP1B) 的抑制作用。在这些活性化合物中，K2、K3、K5和K8在 10 µg/ml 时分别显着抑制 PTP1B 51.3%、65.6%、71.9% 和 55.9%，该结果也得到了硅片对接实验的支持。分析了最有效的化合物K5 的体内抗糖尿病和抗血脂异常活性. 它显示 db/db 小鼠的血糖水平（随机和禁食）和血清胰岛素水平显着降低。通过口服葡萄糖耐量试验 (OGTT) 确定，它改善了葡萄糖耐受不良。这些 NCE（新化学实体）还降低了 db/db 小鼠的胆固醇和甘油三酯谱，同时改善了高密度脂蛋白胆固醇。所述K5进一步评价对MDI antiadipogenic活性（甲基异
• Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin-Dependent Kinase Inhibitor
  作者：Sandip B. Bharate、Vikas Kumar、Shreyans K. Jain、Mubashir J. Mintoo、Santosh K. Guru、Vijay K. Nuthakki、Mohit Sharma、Sonali S. Bharate、Sumit G. Gandhi、Dilip M. Mondhe、Shashi Bhushan、Ram A. Vishwakarma

  DOI：10.1021/acs.jmedchem.7b01765

  日期：2018.2.22

  growth (GI50 < 1.0 μM) and was found to be highly selective for cancer cells over normal fibroblast cells. It inhibited the cell growth of MIAPaCa-2 cells via caspase-dependent apoptosis. It achieved 71% oral bioavailability with in vivo efficacy in pancreatic, colon, and leukemia xenografts at 50 mg/kg, po. It did not have CYP/efflux-pump liability, was not mutagenic/genotoxic or cardiotoxic, and was metabolically

  Rohitukine（1）是从印度药用植物Dysoxylum binectariferum中分离出的一种色酮生物碱，激发了黄酮哌啶醇和riviciclib的发现，这两种药物仅可通过静脉途径生物利用。为了解决该支架的口服生物利用度问题，制备了四组罗基图宁衍生物，并筛选了其对Cdk的抑制作用和细胞的抗增殖活性。2,6-二氯苯乙烯基衍生物IIIM-290（11d）显示出对Cdk-9 / T1（IC 50 1.9 nM）激酶和Molt-4 / MIAPaCa-2细胞生长（GI 50）的强烈抑制作用小于1.0μM），并且发现它对癌细胞的选择性高于正常成纤维细胞。它通过caspase依赖性凋亡抑制MIAPaCa-2细胞的细胞生长。它在胰腺，结肠和白血病异种移植中的口服剂量达到50 mg / kg时，具有71％的口服生物利用度并具有体内功效。它没有CYP /外排泵责任，没有诱变/遗传毒性或心脏毒性，并且
• NOVEL CHROMONE ALKALOID DYSOLINE FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISORDERS
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH

  公开号：US20160046611A1

  公开（公告）日：2016-02-18

  The present invention relates to novel chromone alkaloid of formula 1 isolated from the plant Dysoxylum binectariferum. The compound 5,7-dihydroxy-6-(3-hydroxy-1-methylpiperidin-4-yl)-2-methyl-4H-chromen-4-one, is found to be a potential inhibitor of cell growth and proliferation and also inhibits production of pro-inflammatory cytokines. The formulations of this particular compound can be used for treatment of cancer and inflammation.

  本发明涉及从Dysoxylum binectariferum植物中分离得到的一种新型香豆素生物碱1的化合物。该化合物5,7-二羟基-6-(3-羟基-1-甲基哌啶-4-基)-2-甲基-4H-香豆素-4-酮，被发现是一种潜在的细胞生长和增殖抑制剂，同时还抑制前炎性细胞因子的产生。该特定化合物的配方可用于治疗癌症和炎症。
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.