Verucerfont; 3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-a]嘧啶-7-胺 | 885220-61-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: Verucerfont; 3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-a]嘧啶-7-胺
• 中文别名: Verucerfont;3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-a]嘧啶-7-胺；3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-A]嘧啶-7-胺
• 英文名称: Verucerfont
• 英文别名: 2,5-dimethyl-3-[2-methyl-4-(methyloxy)phenyl]-N-[(1S)-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pyrazolo[1,5-a]pyrimidin-7-amine；NBI-77860；3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-N-[(1S)-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]pyrazolo[1,5-a]pyrimidin-7-amine
• CAS: 885220-61-1
• 化学式: C₂₂H₂₆N₆O₂
• 分子量: 406.487
• InChiKey: VKHVAUKFLBBZFJ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Verucerfont; 3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-a]嘧啶-7-胺 、 甲烷磺酸 以 乙酸丁酯 为溶剂， 反应 3.0h， 生成 [3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]-[(S)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)propyl]amine mesylate
  参考文献：
  名称：

  WO2006/44958

  摘要：

  公开号：
• 作为产物：
  描述：

  [(Z)-1-aminoethylideneamino] (2S)-2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]butanoate 生成 Verucerfont; 3-(4-甲氧基-2-甲基苯基)-2,5-二甲基-N-[(1S)-1-(3-甲基-1,2,4-恶二唑-5-基)丙基]吡唑并[1,5-a]嘧啶-7-胺
  参考文献：
  名称：

  Pyrazolo[1,5-alpha]pyrimidinyl derivatives useful as corticotropin-releasing factor (CRF) receptor antagonists

  摘要：

  本发明公开了CRF受体拮抗剂，可用于治疗多种疾病，包括治疗哺乳动物CRF分泌过多所表现出的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药学上可接受的盐、酯、溶剂合物、立体异构体和前药，其中R1、R2a、R2b、Y、Het、n、o、R6、Ar和R7如本文所定义。本发明还公开了含有CRF受体拮抗剂和药学上可接受的载体组合的组合物，以及使用它们的方法。

  公开号：

  US07879862B2

文献信息

• Pyrazolo[1,5-Alpha]Pyrimidinyl Derivatives Useful as Corticotropin-Releasing Factor (Crf) Receptor Antagonists
  申请人：Lanier Marion

  公开号：US20080194589A1

  公开（公告）日：2008-08-14

  CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R 1 , R 2a , R 2b , Y, Het, n, o, R 6 , Ar and R 7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，可能在治疗多种疾病方面有用，包括治疗哺乳动物CRF过度分泌引起的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药物学上可接受的盐，酯，溶剂合物，立体异构体和前药，其中R1，R2a，R2b，Y，Het，n，o，R6，Ar和R7如本文所定义。还揭示了含有CRF受体拮抗剂与药学可接受载体组合的组合物，以及使用它们的方法。
• Method for predicting a treatment response to a CRHR1 antagonist and/or a V1B antagonist in a patient with depressive and/or anxiety symptoms
  申请人：MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V.

  公开号：US10190168B2

  公开（公告）日：2019-01-29

  The present invention relates to a method for predicting a treatment response to a corticotropin releasing hormone receptor type 1 (CRHR1) antagonist and/or a vasopressin receptor 1B (V1B) antagonist in a patient with depressive and/or anxiety symptoms. The present invention furthermore relates to a V1B receptor antagonist and/or CRHR1 antagonist for use in the treatment of depressive symptoms and/or anxiety symptoms in a patient. Also, kits, diagnostic compositions, devices and microarrays allowing the determination of the presence or absence of at least one polymorphic variant in the AVPR1B gene in combination with the presence or absence of at least one polymorphic variant in the patient's genome excluding the AVPR1B gene in the nucleic acid sample are described.

  本发明涉及一种预测抑郁和/或焦虑症状患者对促肾上腺皮质激素释放激素受体1型（CRHR1）拮抗剂和/或血管加压素受体1B（V1B）拮抗剂的治疗反应的方法。本发明还涉及用于治疗患者抑郁症状和/或焦虑症状的V1B受体拮抗剂和/或CRHR1拮抗剂。此外，本发明还描述了试剂盒、诊断组合物、装置和微阵列，这些试剂盒、诊断组合物、装置和微阵列可结合核酸样本中患者基因组中排除 AVPR1B 基因的至少一种多态变体的存在与否来确定 AVPR1B 基因中至少一种多态变体的存在与否。
• Treatment of congenital adrenal hyperplasia
  申请人：Neurocrine Biosciences, Inc.

  公开号：US10905690B2

  公开（公告）日：2021-02-02

  CRF1 receptor antagonists have the potential to directly inhibit ACTH release in patients with CAH and thereby allow normalization of androgen production while using lower, more physiologic doses of hydrocortisone, and thus reducing treatment-associated side effects.

  CRF1 受体拮抗剂有可能直接抑制 CAH 患者的促肾上腺皮质激素释放，从而使雄激素分泌正常化，同时使用更低、更符合生理剂量的氢化可的松，从而减少与治疗相关的副作用。
• Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1) receptor antagonist with improved pharmacokinetic properties
  作者：John E. Tellew、Marion Lanier、Manisha Moorjani、Emily Lin、Zhiyong Luo、Deborah H. Slee、Xiaohu Zhang、Sam R.J. Hoare、Dimitri E. Grigoriadis、Yves St. Denis、Romano Di Fabio、Enza Di Modugno、John Saunders、John P. Williams

  DOI：10.1016/j.bmcl.2010.10.095

  日期：2010.12

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF1 antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a functional CRF1 antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH production assay. (C) 2010 Elsevier Ltd. All rights reserved.
• Bioorg. Med. Chem. Lett. 2010, 20, 7259-7264
  作者：

  DOI：——

  日期：——