2-chloro-4-(3-endo-hydroxy-8-azabicyclo[3.2.1]oct-8-yl)benzonitrile | 899821-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-chloro-4-(3-endo-hydroxy-8-azabicyclo[3.2.1]oct-8-yl)benzonitrile
• CAS: 899821-15-9
• 化学式: C₁₄H₁₅ClN₂O
• 分子量: 262.739
• InChiKey: BHWQQOLNTHEQMF-PJXYFTJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.26
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (1R,3S,5S)-tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate 在 potassium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 22.0~120.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 2-chloro-4-(3-endo-hydroxy-8-azabicyclo[3.2.1]oct-8-yl)benzonitrile
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators

  摘要：

  To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.

  DOI：

  10.1021/jm501995n

文献信息

• Aminophenyl derivatives as selective androgen receptor modulators
  申请人：Schlienger Nathalie

  公开号：US20060160845A1

  公开（公告）日：2006-07-20

  Disclosed herein is a novel class of aminophenyl compounds having the structure: wherein R 1 is cyano or nitro and ring A is a bi- or tricyclic bridged heterocycle and to their use as modulators of androgen receptor for the treatment or prevention of conditions relating thereto.

  本文揭示了一类新颖的氨基苯基化合物，其结构为：其中R1为氰基或硝基，环A为双环或三环桥联杂环，并且它们可用作雄激素受体调节剂，用于治疗或预防相关疾病。
• AMINOPHENYL DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
  申请人：SCHLIENGER NATHALIE

  公开号：US20090270449A1

  公开（公告）日：2009-10-29

  Disclosed herein is a novel class of aminophenyl compounds having the structure: wherein R 1 is cyano or nitro and ring A is a bi- or tricyclic bridged heterocycle and to their use as modulators of androgen receptor for the treatment or prevention of conditions relating thereto.

  本文揭示了一种新的氨基苯基化合物类，具有以下结构：其中R1是氰基或硝基，环A是一个双环或三环的桥接杂环，并且这些化合物可用作雄激素受体调节剂，用于治疗或预防与之相关的疾病。
• Synthesis, Structure−Activity Relationships, and Characterization of Novel Nonsteroidal and Selective Androgen Receptor Modulators
  作者：Nathalie Schlienger、Birgitte W. Lund、Jan Pawlas、Fabrizio Badalassi、Fabio Bertozzi、Rasmus Lewinsky、Alma Fejzic、Mikkel B. Thygesen、Ali Tabatabaei、Stefania Risso Bradley、Luis R. Gardell、Fabrice Piu、Roger Olsson

  DOI：10.1021/jm901149c

  日期：2009.11.26

  Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound 1, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, 13, had antagonist activity at the AR T877A mutant involved in prostate cancer.
• US7585877B2
  申请人：——

  公开号：US7585877B2

  公开（公告）日：2009-09-08
• Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators
  作者：Henrik Sundén、Mareike C. Holland、Pekka K. Poutiainen、Tiina Jääskeläinen、Juha T. Pulkkinen、Jorma J. Palvimo、Roger Olsson

  DOI：10.1021/jm501995n

  日期：2015.2.12

  To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.