2-(2-(6-(3-(aminomethyl)phenyl)picolinamido)phenyl)acetic acid

• 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: 2-(2-(6-(3-(aminomethyl)phenyl)picolinamido)phenyl)acetic acid
• 英文别名: 2-(2-(6-(3-(Aminomethyl)phenyl)picolinamido)phenyl)acetic acid；2-[2-[[6-[3-(aminomethyl)phenyl]pyridine-2-carbonyl]amino]phenyl]acetic acid
• 化学式: C₂₁H₁₉N₃O₃
• 分子量: 361.4
• InChiKey: ZOATTXXRBUVVPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氯吡啶-2-羧酸 、 (2-氨基-苯基)-乙酸甲酯盐酸盐 在 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.5h， 生成 2-(2-(6-(3-(aminomethyl)phenyl)picolinamido)phenyl)acetic acid
  参考文献：
  名称：

  Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway

  摘要：

  Complement factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diverse disorders such as age-related macular degeneration, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II, and paroxysmal nocturnal hemoglobinuria. Previously, we have reported the screening efforts and identification of reversible benzylamine-based FD inhibitors (1 and 2) binding to the open active conformation of FD. In continuation of our drug discovery program, we designed compounds applying structure-based approaches to improve interactions with FD and gain selectivity against S1 serine proteases. We report herein the design, synthesis, and medicinal chemistry optimization of the benzylamine series culminating in the discovery of 12, an orally bioavailable and selective FD inhibitor. 12 demonstrated systemic suppression of AP activation in a lipopolysaccharide-induced AP activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD.

  DOI：

  10.1021/acs.jmedchem.9b00271

文献信息

• [EN] AMINOMETHYL-BIARYL DERIVATIVES AS COMPLEMENT FACTOR D INHIBITORS AND USES THEREOF<br/>[FR] DÉRIVÉS D'AMINOMÉTHYL-BIARYL EN TANT QU'INHIBITEURS DU FACTEUR D DU COMPLÉMENT ET LEURS UTILISATIONS
  申请人：NOVARTIS AG

  公开号：WO2015009977A1

  公开（公告）日：2015-01-22

  The present invention provides a compound of formula (I), a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种公式(I)的化合物，一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药物活性剂的组合物和一种药物组合物。
• Aminomethyl-Biaryl Derivatives Complement Factor D inhibitors and uses thereof
  申请人：BELANGER David B.

  公开号：US20160145247A1

  公开（公告）日：2016-05-26

  The present invention provides a compound of formula (I), a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种公式（I）的化合物，一种制造本发明化合物的方法及其治疗用途。本发明还提供了一种药理活性剂的组合物和制药组合物。
• AMINOMETHYL-BIARYL DERIVATIVES AS COMPLEMENT FACTOR D INHIBITORS AND USES THEREOF
  申请人：Novartis AG

  公开号：EP3022182A1

  公开（公告）日：2016-05-25
• Design, Synthesis, and Preclinical Characterization of Selective Factor D Inhibitors Targeting the Alternative Complement Pathway
  作者：Rajeshri G. Karki、James Powers、Nello Mainolfi、Karen Anderson、David B. Belanger、Donglei Liu、Nan Ji、Keith Jendza、Christine F. Gelin、Aengus Mac Sweeney、Catherine Solovay、Omar Delgado、Maura Crowley、Sha-Mei Liao、Upendra A. Argikar、Stefanie Flohr、Laura R. La Bonte、Edwige L. Lorthiois、Anna Vulpetti、Ann Brown、Debby Long、Melissa Prentiss、Nathalie Gradoux、Andrea de Erkenez、Frederic Cumin、Christopher Adams、Bruce Jaffee、Muneto Mogi

  DOI：10.1021/acs.jmedchem.9b00271

  日期：2019.5.9

  Complement factor D (FD), a highly specific S1 serine protease, plays a central role in the amplification of the alternative complement pathway (AP) of the innate immune system. Dysregulation of AP activity predisposes individuals to diverse disorders such as age-related macular degeneration, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis type II, and paroxysmal nocturnal hemoglobinuria. Previously, we have reported the screening efforts and identification of reversible benzylamine-based FD inhibitors (1 and 2) binding to the open active conformation of FD. In continuation of our drug discovery program, we designed compounds applying structure-based approaches to improve interactions with FD and gain selectivity against S1 serine proteases. We report herein the design, synthesis, and medicinal chemistry optimization of the benzylamine series culminating in the discovery of 12, an orally bioavailable and selective FD inhibitor. 12 demonstrated systemic suppression of AP activation in a lipopolysaccharide-induced AP activation model as well as local ocular suppression in intravitreal injection-induced AP activation model in mice expressing human FD.