methyl 1-(3-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate | 184168-05-6

• 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 1-(3-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
• 英文别名: Methyl 1,2,3,4-tetrahydro-1-(3-chlorophenyl)-9h-pyrido[3,4-b]indole-3-carboxylate；methyl 1-(3-chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 184168-05-6
• 化学式: C₁₉H₁₇ClN₂O₂
• 分子量: 340.809
• InChiKey: OBFZEESSNDQCJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 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 1-(3-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 在 碘苯二乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以90%的产率得到methyl 1-(3-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  受疟疾盒启发发现 N-氨基烷基-β-咔啉-3-甲酰胺，一种新型口服活性抗疟药

  摘要：

  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) 。

  DOI：

  10.1021/acsmedchemlett.1c00663
• 作为产物：
  描述：

  3-氯苯甲醛 、 甲基色氨酸 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到methyl 1-(3-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
  参考文献：
  名称：

  The Discovery of Tadalafil:  A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1H-imidazo[1‘,5‘:1,6]pyrido[3,4-b]indole-1,3(2H)-dione Analogues

  摘要：

  Starting from ethyl beta-carboline-3-carboxylate (beta-CCE), 1, a modest inhibitor of type 5 phosphodiesterase (PDE5), a series of functionalized tetrahydro-p-carboline derivatives has been identified as a novel chemical class of potent and selective PDE5 inhibitors. Optimization of the side chain on the hydantoin ring of initial lead compound 2 and of the aromatic ring on position 5 led to the identification of compound 6e, a highly potent and selective PDE5 inhibitor, with greater selectivity for PDE5 vs PDE1-4 than sildenafil. Compound 6e demonstrated a long-lasting and significant blood pressure lowering effect after iv administration in the spontaneously hypertensive rat model but showed only moderate oral in vivo efficacy.

  DOI：

  10.1021/jm030056e

文献信息

• Potent 1,3-Disubstituted-9<i>H</i>-pyrido[3,4-<i>b</i>]indoles as New Lead Compounds in Antifilarial Chemotherapy^,
  作者：Sanjay K. Srivastava、Alka Agarwal、Prem M. S. Chauhan、Shiv K. Agarwal、Amiya P. Bhaduri、Som N. Singh、Nigar Fatima、Ranjit K. Chatterjee

  DOI：10.1021/jm9800705

  日期：1999.5.1

  Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either > 90% micro- or macrofilaricidal activity or sterlization of female worms. These compounds have also been screened against Litomosoides carinii, and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure-activity relationship (SAR) associated with position 1 and 3 substituents in beta-carbolines has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b] indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days tip! and against B. malayi at 50 mg/kg x 5 days tip) or at 200 mg/kg x 5 days (po).
• US06001847
  申请人：——

  公开号：——

  公开（公告）日：——
• TETRAHYDROIMIDAZOPYRIDOINDOLEDIONES AS INHIBITORS OF cGMP SPECIFIC PDE
  申请人：ICOS CORPORATION

  公开号：EP0859778B1

  公开（公告）日：2001-12-19
• US6001847A
  申请人：——

  公开号：US6001847A

  公开（公告）日：1999-12-14
• US6143757A
  申请人：——

  公开号：US6143757A

  公开（公告）日：2000-11-07