methyl (1R,3R)-1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate | 1262447-31-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: methyl (1R,3R)-1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
• 英文别名: (1R,3R)-methyl 1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate；Methyl (1R,3R)-1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1262447-31-3
• 化学式: C₁₉H₁₆Cl₂N₂O₂
• 分子量: 375.254
• InChiKey: CWEDPVSIJOZZDP-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (1R,3R)-1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 在 碳酸氢钠 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 16.0h， 生成 (6R,12aR)-6-(3,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
  参考文献：
  名称：

  Synthesis and Molecular Modeling of Novel Tetrahydro-β-carboline Derivatives with Phosphodiesterase 5 Inhibitory and Anticancer Properties

  摘要：

  New derivatives based upon the tetrahydro-beta-carboline-hydantoin and tetrahydro-beta-carboline-piperazinedione scaffolds were synthesized. All compounds were evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with IC50 values in the low nanomolar range were identified including compounds derived from L-tryptophan. Compounds with high potency versus PDE5 were then evaluated for inhibitory activity against other PDEs to assess isozyme selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2-ethyl-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)dione 14 showed a selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile, 6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong potency for inhibition of PDE11 with an IC50 value of 11 nM, representing the most potent PDE11 inhibitor thus far reported. Docking experiments differentiated between active and inactive analogues and revealing the conformational, steric, and lipophilic necessities for potent PDE5 inhibition. Many derivatives, including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB-231 breast tumor cell line with low micromolar potency.

  DOI：

  10.1021/jm100842v
• 作为产物：
  描述：

  D-色氨酸 在 乙酰氯 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 methyl (1R,3R)-1-(3,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
  参考文献：
  名称：

  Synthesis and Molecular Modeling of Novel Tetrahydro-β-carboline Derivatives with Phosphodiesterase 5 Inhibitory and Anticancer Properties

  摘要：

  New derivatives based upon the tetrahydro-beta-carboline-hydantoin and tetrahydro-beta-carboline-piperazinedione scaffolds were synthesized. All compounds were evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with IC50 values in the low nanomolar range were identified including compounds derived from L-tryptophan. Compounds with high potency versus PDE5 were then evaluated for inhibitory activity against other PDEs to assess isozyme selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2-ethyl-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)dione 14 showed a selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile, 6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong potency for inhibition of PDE11 with an IC50 value of 11 nM, representing the most potent PDE11 inhibitor thus far reported. Docking experiments differentiated between active and inactive analogues and revealing the conformational, steric, and lipophilic necessities for potent PDE5 inhibition. Many derivatives, including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB-231 breast tumor cell line with low micromolar potency.

  DOI：

  10.1021/jm100842v

文献信息

• Malaria Box-Inspired Discovery of <i>N</i>-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials
  作者：Jopaul Mathew、Sha Ding、Kevin A. Kunz、Emily E. Stacy、Joshua H. Butler、Reagan S. Haney、Emilio F. Merino、Grant J. Butschek、Zaira Rizopoulos、Maxim Totrov、Maria B. Cassera、Paul R. Carlier

  DOI：10.1021/acsmedchemlett.1c00663

  日期：2022.3.10

  but none potently inhibited growth of the malaria parasite Plasmodium falciparum. Interestingly, 7e, a minor byproduct of these syntheses, proved to be potent in vitro against P. falciparum and was orally efficacious (40 mg/kg) in an in vivo mouse model of malaria.

  使用源自抗疟药 MMV008138 的药效团对公开可用的抗疟药数据库进行虚拟配体筛选，发现 TCMDC-140230（一种四氢-β-咔啉酰胺）值得探索。该结构的所有四种立体异构体均已合成，但没有一种能有效抑制疟疾寄生虫恶性疟原虫的生长。有趣的是，这些合成的次要副产品7e被证明在体外有效对抗恶性疟原虫，并且在疟疾的体内小鼠模型中口服有效 (40 mg/kg) 。
• KUMAR, SHIV;SETH, M.;BHADURI, A. P., INDIAN J. CHEM., 1982, 20, N 12, 1078-1079
  作者：KUMAR, SHIV、SETH, M.、BHADURI, A. P.

  DOI：——

  日期：——
• Synthesis and Molecular Modeling of Novel Tetrahydro-β-carboline Derivatives with Phosphodiesterase 5 Inhibitory and Anticancer Properties
  作者：Heba A. Mohamed、Nancy M. R. Girgis、Rainer Wilcken、Matthias R. Bauer、Heather N. Tinsley、Bernard D. Gary、Gary A. Piazza、Frank M. Boeckler、Ashraf H. Abadi

  DOI：10.1021/jm100842v

  日期：2011.1.27

  New derivatives based upon the tetrahydro-beta-carboline-hydantoin and tetrahydro-beta-carboline-piperazinedione scaffolds were synthesized. All compounds were evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with IC50 values in the low nanomolar range were identified including compounds derived from L-tryptophan. Compounds with high potency versus PDE5 were then evaluated for inhibitory activity against other PDEs to assess isozyme selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2-ethyl-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)dione 14 showed a selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile, 6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong potency for inhibition of PDE11 with an IC50 value of 11 nM, representing the most potent PDE11 inhibitor thus far reported. Docking experiments differentiated between active and inactive analogues and revealing the conformational, steric, and lipophilic necessities for potent PDE5 inhibition. Many derivatives, including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB-231 breast tumor cell line with low micromolar potency.