2-(4-氨基苯基)咪唑并[2,1-b][1,3]苯并噻唑-7-醇 | 1132827-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(4-氨基苯基)咪唑并[2,1-b][1,3]苯并噻唑-7-醇
• 中文别名: 2-(4-氨基苯基)咪唑并[2,1-B]苯并噻唑-7-醇
• 英文名称: 4-(7-hydroxyimidazo[2,1-b]benzothiazol-2-yl)benzenamine
• 英文别名: 2-(4-aminophenyl)imidazo[2,1-b][1,3]benzothiazol-7-ol；2-(4-aminophenyl)imidazo[2,1-b][1,3]benzothiazol-6-ol
• CAS: 1132827-30-5
• 化学式: C₁₅H₁₁N₃OS
• 分子量: 281.338
• InChiKey: HTPOSANNBYPDRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-氨基苯基)咪唑并[2,1-b][1,3]苯并噻唑-7-醇 、 5-叔丁基-3-异氰酰基异噁唑 以 四氢呋喃 为溶剂， 以69%的产率得到N-(5-tert-butylisoxazol-3-yl)-N'-[4-(7-hydroxyimidazo[2,1-b][1,3]benzothiazol-2-yl)phenyl]urea
  参考文献：
  名称：

  Imidazolothiazole compounds for the treatment of disease

  摘要：

  提供了用于调节受体激酶活性以及用于治疗、预防或改善由受体激酶介导的一种或多种疾病或紊乱症状的化合物、组合物和方法。

  公开号：

  US20070232604A1
• 作为产物：
  描述：

  N-[4-(2-溴乙酰基)苯基)乙酰胺 在 水 、 三溴化硼 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-(4-氨基苯基)咪唑并[2,1-b][1,3]苯并噻唑-7-醇
  参考文献：
  名称：

  Synthesis and Evaluation of ¹¹C-Labeled Imidazo[2,1-b]benzothiazoles (IBTs) as PET Tracers for Imaging β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  We report a novel series of C-11-labeled imidazo[2,1-b]benzothiazoles (IBTs) as tracers for imaging of cerebral beta-amyloid (A beta) deposits in patients with Alzheimer's disease (AD) by means of positron emission tomography (PET). From a series of 11 compounds, candidates were identified to have a high binding affinity for A beta. Selected compounds were prepared as O- or N-[C-11]methyl derivatives and shown to have a high initial brain uptake in wild-type mice (range 1.9-9.2% I.D./g at 5 min). 2-(p-[C-11]Methylaminophenyl)-7-methoxyimidazo[2,1-b] benzothiazole ([C-11]5) was identified as a lead based on the combined favorable properties of high initial brain uptake, rapid clearance from normal brain, and high in vitro affinity for A beta(1-40) (K-i = 3.5 nM) and A beta(1-42) (5.8 nM), which were superior to the Pittsburgh compound B (1a). In an APP/PSI mouse model of AD (Tg), we demonstrate a specific uptake of [C-11]5 in A beta-containing telencephalic brain regions by means of small-animal PET that was confirmed by regional brain biodistribution, ex vivo autoradiography, and immunohistochemistry. Analysis of brain sections of Tg mice receiving a single bolus injection of [C-11]5 and [H-3]1a together revealed that the tracers bind to A beta plaques in the brain of Tg mice in a comparable pattern. Taken together, these data suggest that IBTs represent useful PET imaging agents for high-sensitivity detection of A beta plaques.

  DOI：

  10.1021/jm101129a

文献信息

• Compounds and methods for the targeted degradation of fetal liver kinase polypeptides
  申请人：Arvinas Operations, Inc.

  公开号：US10806737B2

  公开（公告）日：2020-10-20

  The present disclosure relates to bifunctional compounds, which find utility as modulators of FLT3 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein FLT3, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of the target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 FLT3（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与 E3 泛素连接酶结合的 Von Hppel-Lindau（脑龙）配体，另一端含有与靶蛋白 FLT3 结合的分子，从而将靶蛋白置于泛素连接酶附近，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白聚集或积聚而导致的疾病或失调。
• [EN] SOLID FORMS COMPRISING N-(5-TERT-BUTYL-ISOXAZOL-3-YL)-N'-{4-[7-(2-MORPHOLIN-4-YL-ETHOXY)IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL]PHENYL}UREA, COMPOSITIONS THEREOF, AND USES THEREWITH<br/>[FR] FORMES SOLIDES COMPRENANT DE LA N-(5-TERT-BUTYL-ISOXAZOL-3-YL)-N'-{4-[7-(2-MORPHOLIN-4-YL-ÉTHOXY)IMIDAZO[2,L-B][L,3]BENZOTHIAZOL-2-YL]PHÉNYL}URÉE, COMPOSITIONS EN CONTENANT ET LEURS UTILISATIONS
  申请人：AMBIT BIOSCIENCES CORP

  公开号：WO2009038757A3

  公开（公告）日：2009-05-28
• Identification of <i>N</i>-(5-<i>tert</i>-Butyl-isoxazol-3-yl)-<i>N</i>′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-<i>b</i>][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor
  作者：Qi Chao、Kelly G. Sprankle、Robert M. Grotzfeld、Andiliy G. Lai、Todd A. Carter、Anne Marie Velasco、Ruwanthi N. Gunawardane、Merryl D. Cramer、Michael F. Gardner、Joyce James、Patrick P. Zarrinkar、Hitesh K. Patel、Shripad S. Bhagwat

  DOI：10.1021/jm9007533

  日期：2009.12.10

  Treatment of AM L patients with small molecule inhibitors of FLT3 kinase has been explored as a viable therapy. However, these agents arc found to be less than optimal for the treatment of AM L because of lack of sufficient potency or suboptimal oral pharmacokinetics (PK) or lack of adequate tolerability at efficacious doses. We have developed a series of extremely potent and highly selective FLT3 inhibitors with good oral PK properties. The first series Of Compounds represented by 1 (A13530) was found to be a potent and selective FLT3 kinase inhibitor with good PK properties. The aqueous solubility and oral PK properties at higher doses in rodents were found to be less than optimal for clinical development. A novel series of compounds were designed lacking the carboxamide group of 1 with an added water solubilizing group. Compound 7 (AC220) was identified front this series to be the most potent and selective FLT3 inhibitor with good pharmaceutical properties, excellent PK profile, and superior efficacy and tolerability in tumor xenograft models. Compound 7 has demonstrated a desirable safety and PK profile in humans and is currently in phase II clinical trials.
• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF FETAL LIVER KINASE POLYPEPTIDES
  申请人：Arvinas Operations, Inc.

  公开号：EP3559006A1

  公开（公告）日：2019-10-30
• [EN] COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF FETAL LIVER KINASE POLYPEPTIDES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LA DÉGRADATION CIBLÉE DE POLYPEPTIDES DE KINASE DU FOIE FŒTAL
  申请人：ARVINAS INC

  公开号：WO2018118598A1

  公开（公告）日：2018-06-28

  The present disclosure relates to bifunctional compounds, which find utility as modulators of FLT3 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein FLT3, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of the target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.