NBI 35965 | 268546-19-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: NBI 35965
• 英文别名: NBI-35965；NBI35965；6-(cyclopropylmethyl)-2-(2,4-dichlorophenyl)-7-(S)-ethyl-7,8-dihydro-4-methyl-6H-1,3,6,8a-tetraazaacenaphthylene；Unii-sfq6J6N9F3；(10S)-9-(cyclopropylmethyl)-3-(2,4-dichlorophenyl)-10-ethyl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
• CAS: 268546-19-6
• 化学式: C₂₁H₂₂Cl₂N₄
• 分子量: 401.338
• InChiKey: SUCZRVASFXLXDM-HNNXBMFYSA-N

物化性质

• 沸点：
  563.1±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 氢溴酸 、 sodium hydride 、 对甲苯磺酸 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 40.17h， 生成 NBI 35965
  参考文献：
  名称：

  Design and Synthesis of Tricyclic Corticotropin-Releasing Factor-1 Antagonists

  摘要：

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF, antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship between structure and CRF, binding affinity, NBI 35965 (12a) was identified as a high-affinity antagonist with a pK(i) value of 8.5. Compound 12a proved to be a functional CRF, antagonist with pIC(50) values of 7.1 and 6.9 in the in vitro CRF-stimulated cAMP accumulation and ACTH production assays, respectively, and 12a also reduced CRF or stress induced ACTH production in vivo.

  DOI：

  10.1021/jm049085v
• 作为试剂：
  描述：

  在 NBI 35965 作用下， 以 二氯甲烷 为溶剂， 以58 %的产率得到3-(1,3-diphenyl-1H-pyrazol-5-yl)-2-phenyloxazolidin-4-one
  参考文献：
  名称：

  从二氮到含氮有机化合物：使用 Li2CN2 作为合成子

  摘要：

  介绍了一种将惰性 N 2转化为各种含氮有机化合物的策略。活性含氮物质Li 2 CN 2成功地从N 2气体、C和LiH中以高产率制备。Li 2 CN 2可以转化为一系列含氮有机化合物，包括氰胺、碳二亚胺、N-芳基氰胺和1,2,4-三唑衍生物。还从15 N 2气体制备了 15 N-标记的产物，包括恶唑烷衍生物。

  DOI：

  10.1002/anie.202219298

文献信息

• 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。
• CRF RECEPTOR ANTAGONISTS, THEIR PREPARATIONS, THEIR PHARMACEUTICAL COMPOSITION AND THEIR USES
  申请人：SB Pharmco Puerto Rico Inc.

  公开号：EP1722826A2

  公开（公告）日：2006-11-22
• GENETIC PREDICTORS OF A RESPONSE TO TREATMENT WITH CRHR1 ANTAGONISTS
  申请人：HMNC Value GmbH

  公开号：EP3277835B1

  公开（公告）日：2019-01-09
• Crf receptor antagonists, their preparations, their pharmaceutical composition, and their uses
  申请人：Grigoriadis Dimitri

  公开号：US20070129382A1

  公开（公告）日：2007-06-07

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in warm-blooded animals. CRF receptor antagonists which are labeled with a positron emitting isotope for use in PET are also disclosed.
• CRHR1 ANTAGONISTS FOR USE IN THE TREATMENT OF PATIENTS HAVING CRH OVERACTIVITY
  申请人：HOLSBOERMASCHMEYER NEUROCHEMIE GMBH

  公开号：US20150094310A1

  公开（公告）日：2015-04-02

  The present invention relates to a corticotropin releasing hormone receptor type 1 (CRHR1) antagonist for use in the treatment of depressive symptoms and/or anxiety symptoms in a novel group of patients, i.e. patients having corticotropin releasing hormone (CRH) overactivity.