7-(3,4-Dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid | 343240-67-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 7-(3,4-Dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid
• 英文别名: 7-(3,4-Dichlorophenyl)-5-methyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-carboxylic acid
• CAS: 343240-67-5
• 化学式: C₁₄H₁₁Cl₂N₃O₂
• 分子量: 324.166
• InChiKey: ZOGRENDZOKGTNP-UHFFFAOYSA-N

物化性质

• 沸点：
  525.8±50.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(3,4-Dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid 、 N~1~-甲基-4-(三氟甲基)苯-1,2-二胺 在 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 生成 7-(3,4-Dichlorophenyl)-5-methyl-6-[1-methyl-5-(trifluoromethyl)benzimidazol-2-yl]-4,7-dihydropyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Dihydropyrazolopyrimidines containing benzimidazoles as KV1.5 potassium channel antagonists

  摘要：

  Dihydropyrazolopyrimidines with a C6 heterocycle substituent were found to have high potency for block of K(V)1.5. Investigation of the substitution in the benzimidazole ring and the substituent in the 5-position of the dihydropyrazolopyrimidine ring produced 31 a with an IC50 for K(V)1.5 block of 0.030 mu M without significant block of other cardiac ion channels. This compound also showed good bioavailability in rats and robust pharmacodynamic effects in a rabbit model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.083
• 作为产物：
  描述：

  7-(3,4-Dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid 1,1-dimethylethyl ester 生成 7-(3,4-Dichlorophenyl)-4,7-dihydro-5-methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid
  参考文献：
  名称：

  Heterocyclic dihydropyrimidine compounds

  摘要：

  新型杂环二氢嘧啶化合物，可用作钾通道功能抑制剂（特别是Kv1亚家族电压门控K+通道的抑制剂，特别是Kv1.5抑制剂，该抑制剂已与超快速激活延迟整流K+电流IKur相关联），使用这种化合物预防和治疗心律失常和IKur相关疾病的方法，以及含有这种化合物的药物组合物。

  公开号：

  US06706720B2

文献信息

• [EN] HETEROCYCLIC DIHYDROPYRIMIDINES AS POTASSIUM CHANNEL INHIBITORS<br/>[FR] DIHYDROPYRIMIDINES HETEROCYCLIQUES UTILES EN TANT QU'INHIBITEURS DES CANAUX POTASSIUM
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2001040231A1

  公开（公告）日：2001-06-07

  Novel heterocyclic dihydropyrimidine compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors K¿v?1.5 which has been linked to the ultra-rapidly activating delayed rectifier K?+¿ current I¿Kur?), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

  新型杂环二氢嘧啶化合物可作为钾通道功能抑制剂使用（特别是Kv1亚家族电压门控K+通道的抑制剂，特别是与超快速激活延迟整流K+电流IKur相关的Kv1.5抑制剂），使用这种化合物预防和治疗心律失常和IKur相关疾病的方法，以及含有这种化合物的制药组合物。
• Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)
  作者：Wayne Vaccaro、Tram Huynh、John Lloyd、Karnail Atwal、Heather J. Finlay、Paul Levesque、Mary Lee Conder、Tonya Jenkins-West、Hong Shi、Lucy Sun

  DOI：10.1016/j.bmcl.2008.10.099

  日期：2008.12

  A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I-Kur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. (C) 2008 Elsevier Ltd. All rights reserved.
• Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers
  作者：John Lloyd、Heather J. Finlay、Wayne Vacarro、Tram Hyunh、Alexander Kover、Rao Bhandaru、Lin Yan、Karnail Atwal、Mary Lee Conder、Tonya Jenkins-West、Hong Shi、Christine Huang、Danshi Li、Huabin Sun、Paul Levesque

  DOI：10.1016/j.bmcl.2009.12.085

  日期：2010.2

  Design and synthesis of pyrazolodihydropyrimidines as K(V)1.5 blockers led to the discovery of 7d as a potent and selective antagonist. This compound showed atrial selective prolongation of effective refractory period in rabbits and was selected for clinical development. (C) 2010 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC DIHYDROPYRIMIDINES AS POTASSIUM CHANNEL INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1237891A1

  公开（公告）日：2002-09-11
• US6706720B2
  申请人：——

  公开号：US6706720B2

  公开（公告）日：2004-03-16