NBI 34041 | 268545-87-5

• 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 34041
• 英文别名: NBI-34041；1-(2,4-Dichlorophenyl)-5-(heptan-4-yl)-7-methyl-4,5-dihydro-3H-2,2a,5,8-tetraazaacenaphthylene；3-(2,4-dichlorophenyl)-9-heptan-4-yl-6-methyl-1,2,5,9-tetrazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene
• CAS: 268545-87-5
• 化学式: C₂₂H₂₆Cl₂N₄
• 分子量: 417.381
• InChiKey: AKLMUGFDGONMAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 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：

  2,2',4'-三氯苯乙酮 在 盐酸肼 、 氢溴酸 、 sodium hydride 、 对甲苯磺酸 、 一水合肼 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二苯醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 63.67h， 生成 NBI 34041
  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

文献信息

• CRF receptor antagonists and methods relating thereto
  申请人：Neurocrine Biosciences, Inc.

  公开号：US06514982B1

  公开（公告）日：2003-02-04

  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 a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure: including stereoisomers and pharmaceutically acceptable salts thereof, wherein n, m, A, B, C, R, R1, R2 and Ar 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，其在治疗多种疾病方面具有用途，包括治疗温血动物中CRF分泌过多表现的疾病，例如中风。本发明的CRF受体拮抗剂具有以下结构：包括立体异构体和其药学上可接受的盐，其中n、m、A、B、C、R、R1、R2和Ar的定义如本文所述。本发明还揭示了含有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。
• 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。
• 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
• 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.