4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine | 202580-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine
• 英文别名: 4-chloro-8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazine；4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]-pyrazolotriazin
• CAS: 202580-70-9
• 化学式: C₁₃H₉Cl₃N₄
• 分子量: 327.6
• InChiKey: SUIBMWPIPMENNY-UHFFFAOYSA-N

物化性质

• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-乙基正丁胺 、 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine 以 四氢呋喃 为溶剂， 生成 Butyl-[8-(2,4-dichloro-phenyl)-2,7-dimethyl-pyrazolo[1,5-a][1,3,5]triazin-4-yl]-ethyl-amine
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351
• 作为产物：
  描述：

  2,4-二氯苯乙腈 在 sodium ethanolate 、 sodium 、 一水合肼 、 溶剂黄146 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 51.0h， 生成 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine
  参考文献：
  名称：

  4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist

  摘要：

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.

  DOI：

  10.1021/jm9904351

文献信息

• Synthesis of [O-methyl-11C]-4-(1,3-dimethoxy-2-propylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine ([11C]DMP696): a potential PET ligand for CRF1 receptors
  作者：J. S. Dileep Kumar、Vattoly J. Majo、Norman R. Simpson、Jaya Prabhakaran、Ronald L. Van Heertum、J. John Mann

  DOI：10.1002/jlcr.885

  日期：2004.11

  Synthesis of [O-methyl-11C]-4-(1,3-dimethoxy-2-propylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]pyrazolo-1,3,5-triazine ([11C]DMP696), a highly selective CRF1 antagonist has been achieved. The total time required for the synthesis of [11C]DMP696 is 30 min from EOB using [11C]methyl triflate in THF, with a 16% yield (EOS) and >99% chemical and radiochemical purities along with a specific activity of >2000 Ci/mmol (EOS). Copyright © 2004 John Wiley & Sons, Ltd.

  高选择性 CRF1 拮抗剂[O-甲基-11C]-4-(1,3-二甲氧基-2-丙基氨基)-2,7-二甲基-8-(2,4-二氯苯基)[1,5-a]吡唑并-1,3,5-三嗪（[11C]DMP696）的合成已经完成。在 THF 中使用 [11C]methyl triflate 从 EOB 合成 [11C]DMP696 总共需要 30 分钟，收率为 16%（EOS），化学纯度和放射化学纯度大于 99%，比活度大于 2000 Ci/mmol（EOS）。Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.
• Azolo triazines and pyrimidines
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US06358950B1

  公开（公告）日：2002-03-19

  Corticotropin releasing factor (CRF) antagonists of formula I or II: and their use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

  公告释放因子（CRF）拮抗剂I或II的公式：及其在治疗焦虑，抑郁和其他精神，神经系统疾病以及免疫，心血管或心脏相关疾病的治疗中的使用，以及与心理病理障碍和压力相关的结肠过敏性治疗。
• 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-<i>a</i>]-1,3,5-triazine:  A Potent, Orally Bioavailable CRF₁ Receptor Antagonist
  作者：Liqi He、Paul J. Gilligan、Robert Zaczek、Lawrence W. Fitzgerald、John McElroy、H-S. L. Shen、Jo Anne Saye、Ned H. Kalin、Steven Shelton、David Christ、George Trainor、Paul Hartig

  DOI：10.1021/jm9904351

  日期：2000.2.1

  Structure-activity studies; in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF(1) receptor antagonist (K-i = 1.7 nM vs 7.5 nM for alpha-hel-CRF(9-41), hCRF(1) adenylate cyclase IC50 = 82 nM vs 286 nM for alpha-hel-CRF(9-41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.