3,5-二氨基-6-氯吡啶-2-甲酸,6-氯-3,5-二氨基吡啶-2-甲酸 | 465513-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3,5-二氨基-6-氯吡啶-2-甲酸,6-氯-3,5-二氨基吡啶-2-甲酸
• 英文名称: 3,5-diamino-6-chloropyridine-2-carboxylic acid
• 英文别名: 3,5-Diamino-6-chloropicolinic acid
• CAS: 465513-12-6
• 化学式: C₆H₆ClN₃O₂
• 分子量: 187.586
• InChiKey: SUSDUMOMNPRDOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3,5-二氨基-6-氯吡啶-2-甲酸,6-氯-3,5-二氨基吡啶-2-甲酸 在 potassium tert-butylate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 (3,5-diamino-6-chloropyridine-2-carbonyl)guanidine hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of aroylguanidines related to amiloride as inhibitors of the human platelet Na+/H+ exchanger

  摘要：

  Pyridine and benzene bioisosteres of amiloride were synthesized and evaluated for their inhibitory Potency against the sodium-hydrogen exchanger (NHE) involved in intracellular pH regulation. The inhibition of NHE was determined by using the platelet swelling assay (PSA) in which the swelling of human platelets was induced by their incubation in an acid buffer (pH 6.7). Additionally, the inhibitory potency of the most active compounds was assessed by measuring the inhibition of the EIPA-sensitive Na-22 (+) uptake (UIA) by human platelets after intracellular acidosis. The results indicated that several benzene derivatives and compounds bearing an carbonylguanidine moiety in the meta position of the pyridine nitrogen were much more potent than amiloride (PSA:IC50 = 43.5 muM, UIA:IC50 = 100.1 muM), but less than EIPA, a pyrazine NHE inhibitor (PSA:IC50=0.08 muM, UIA: IC50 - 0.5 muM). In both biological assays (2-amino-5-bromo-pyridine-3-carbonyl)guanidine (32) was the most active molecule (PSA: IC50 = 0.8 muM, UIA : IC50 = 0.8 muM). Our investigations demonstrated that the replacement of the pyrazine ring of amiloride e by a pyridine ora phenyl ring improved the NHE inhibitory potency (phenyl >pyridine >pyrazine). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00022-6
• 作为产物：
  描述：

  3,5-diamino-2-chloro-6-methylpyridine 在 sodium hydroxide 、 potassium permanganate 、 magnesium sulfate 作用下， 以 水 为溶剂， 反应 4.5h， 生成 3,5-二氨基-6-氯吡啶-2-甲酸,6-氯-3,5-二氨基吡啶-2-甲酸
  参考文献：
  名称：

  Synthesis and biological evaluation of aroylguanidines related to amiloride as inhibitors of the human platelet Na+/H+ exchanger

  摘要：

  Pyridine and benzene bioisosteres of amiloride were synthesized and evaluated for their inhibitory Potency against the sodium-hydrogen exchanger (NHE) involved in intracellular pH regulation. The inhibition of NHE was determined by using the platelet swelling assay (PSA) in which the swelling of human platelets was induced by their incubation in an acid buffer (pH 6.7). Additionally, the inhibitory potency of the most active compounds was assessed by measuring the inhibition of the EIPA-sensitive Na-22 (+) uptake (UIA) by human platelets after intracellular acidosis. The results indicated that several benzene derivatives and compounds bearing an carbonylguanidine moiety in the meta position of the pyridine nitrogen were much more potent than amiloride (PSA:IC50 = 43.5 muM, UIA:IC50 = 100.1 muM), but less than EIPA, a pyrazine NHE inhibitor (PSA:IC50=0.08 muM, UIA: IC50 - 0.5 muM). In both biological assays (2-amino-5-bromo-pyridine-3-carbonyl)guanidine (32) was the most active molecule (PSA: IC50 = 0.8 muM, UIA : IC50 = 0.8 muM). Our investigations demonstrated that the replacement of the pyrazine ring of amiloride e by a pyridine ora phenyl ring improved the NHE inhibitory potency (phenyl >pyridine >pyrazine). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00022-6

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20140121208A1

  公开（公告）日：2014-05-01

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运体调节剂化合物（公式A、公式B、公式C或公式D）的制药组合物。本发明还涉及其制药配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化病的方法。