(3S,4S)-N-(3-cyano-4-fluorophenyl)-1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide | 1424799-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (3S,4S)-N-(3-cyano-4-fluorophenyl)-1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
• 英文别名: SJ557733；SJ733；Sj-733；(3S,4S)-N-(3-cyano-4-fluorophenyl)-1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxamide
• CAS: 1424799-20-1
• 化学式: C₂₄H₁₆F₄N₄O₂
• 分子量: 468.41
• InChiKey: VKCPFWKTFZAOTO-LEWJYISDSA-N

物化性质

• 沸点：
  633.1±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：50 mg/ml（106.75 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (pyridine-3-ylmethylene)(2,2,2-trifluoroethyl)amine 在 硫酸 、 溶剂黄146 、 lithium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 19.0h， 生成 (3S,4S)-N-(3-cyano-4-fluorophenyl)-1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
  参考文献：
  名称：

  Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides

  摘要：

  Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(35,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.

  DOI：

  10.1021/acs.jmedchem.6b00752

文献信息

• NEW ANTI-MALARIAL AGENTS
  申请人：University Of Kentucky Research Foundation

  公开号：EP3892332A1

  公开（公告）日：2021-10-13

  The present invention is related to new derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to dihydroisoquinoline derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.

  本发明涉及制造预防或治疗疟疾药物的新衍生物。具体而言，本发明涉及二氢异喹啉衍生物，用于制备药物配方，以抑制疟原虫的增殖。
• SUBSTITUTED 2-ALKYL-1-OXO-N-PHENYL-3-HETEROARYL-1,2,3,4-TETRAHYDROISOQUINOLINE-4-CARBOXAMIDES FOR ANTIMALARIAL THERAPIES
  申请人：Guy Rodney Kiplin

  公开号：US20140235593A1

  公开（公告）日：2014-08-21

  In one aspect, the invention relates to novel substituted 2-alkyl-1-oxo-N-phenyl-3-heteroaryl-1,2,3,4-tetrahydroisoquinoline-4-carboxamides; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating and/or preventing malaria. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及新型取代的2-烷基-1-氧代-N-苯基-3-杂环芳基-1,2,3,4-四氢异喹啉-4-羧酰胺；合成制备该化合物的方法；包含该化合物的药物组合物；以及治疗和/或预防疟疾的方法。本摘要旨在作为特定领域搜索的扫描工具，并不限制本发明。
• [EN] SUBSTITUTED 2-ALKYL-1-OXO-N-PHENYL-3-HETEROARYL-1,2,3,4- TETRAHYDROISOQUINOLINE-4-CARBOXAMIDES FOR ANTIMALARIAL THERAPIES<br/>[FR] 2-ALKYL-1-OXO-N-PHÉNYL-3-HÉTÉROARYL-1,2,3,4- TÉTRAHYDROISOQUINOLÉINE-4-CARBOXAMIDES SUBSTITUÉS POUR THÉRAPIES ANTIPALUDÉENNES
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2013027196A9

  公开（公告）日：2013-04-18
• US9416124B2
  申请人：——

  公开号：US9416124B2

  公开（公告）日：2016-08-16
• Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides
  作者：David M. Floyd、Philip Stein、Zheng Wang、Jian Liu、Steve Castro、Julie A. Clark、Michele Connelly、Fangyi Zhu、Gloria Holbrook、Amy Matheny、Martina S. Sigal、Jaeki Min、Rajkumar Dhinakaran、Senthil Krishnan、Sridevi Bashyum、Spencer Knapp、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.6b00752

  日期：2016.9.8

  Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(35,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.