6-(4-methylpiperazin-1-yl)-1,3-benzothiazol-2-amine | 950769-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-(4-methylpiperazin-1-yl)-1,3-benzothiazol-2-amine
• 英文别名: 6-(4-methyl-piperazin-1-yl)-benzothiazol-2-ylamine
• CAS: 950769-57-0
• 化学式: C₁₂H₁₆N₄S
• 分子量: 248.352
• InChiKey: CNGGWHKXVXVWMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(4-methylpiperazin-1-yl)-1,3-benzothiazol-2-amine 、 4-氯-6,7-二甲氧基喹唑啉 在 tris(dibenzylideneacetone)dipalladium (0) potassium phosphate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以56%的产率得到N-(6,7-dimethoxyquinazolin-4-yl)-6-(4-methylpiperazin-1-yl)benzo[d]thiazol-2-amine
  参考文献：
  名称：

  过渡金属催化的芳香胺化方案在药物化学中的适用性

  摘要：

  研究了钯和铜催化反应在药理学相关支架的芳族胺化反应中的应用。重点放在几种引入结构广泛的胺的方案的范围上，从而可以合成一种生物命中结构的多种衍生物，以便在生物测定系统中进行筛选。因此，获得最佳收率和TON并不是主要优先事项，最重要的是实践方面，即无需设想进一步纯化和干燥试剂和溶剂，理想情况下，仅需使用几种基于过渡金属的方案即可进行合成结构上足够多样（几毫克）的化合物，无需任何条件和催化系统的微调即可进行筛选。

  DOI：

  10.1002/adsc.200700133
• 作为产物：
  描述：

  4-(4-甲基哌嗪)苯胺 、 硫氰酸铵 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 以57%的产率得到6-(4-methylpiperazin-1-yl)-1,3-benzothiazol-2-amine
  参考文献：
  名称：

  Identification of 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 Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm9007533

文献信息

• Imidazolothiazole compounds for the treatment of disease
  申请人：Bhagwat Shripad

  公开号：US20070232604A1

  公开（公告）日：2007-10-04

  Compounds, compositions and methods are provided for modulating the activity of receptor kinases and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by receptor kinases.

  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。
• Novel Heterocyclic NF-kB Inhibitors
  申请人：LEBAN Johann

  公开号：US20100004258A1

  公开（公告）日：2010-01-07

  The present invention relates to compounds of the general formula (III): or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof.

  本发明涉及一般式（III）的化合物：或其与酸或碱的药学上可接受的盐，或药学上可接受的前药或其立体异构体。
• Novel heterocyclic NF-kB inhibitors
  申请人：Leban Johann

  公开号：US20060247253A1

  公开（公告）日：2006-11-02

  The present invention relates to compounds of the general formula (III) or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof, wherein R 3 is H, —C(O)NR a R b , halogen, alkyl, haloalkyl, aryl, heteroaryl, OH, SH, NR 4′ OR 5′ , NH 2 , amine, alkylamine, alkoxy, cycloalkyl, heterocycloalkyl, hydroxyalkyl, or haloalkyloxy; R 4 is H, halogen, alkyl, —C(NR 7 )NR 7 R 8 , —(CH 2 ) p aryl, —(CH 2 ) p NR 7 R 8 , —C(O)NR 7 R 8 , —N═CR 7 R 8 , —NR 7 C(O)R 8 , cycloalkyl, heterocycloalkyl, haloalkyl, hydroxyalkyl, hyodroxyalkylamino, alkylamino, heteroaryl, or aryl; R 5 is halogen, alkyl, —C(NR 7 )NR 7 R 8 , —(CH 2 ) p aryl, —(CH 2 ) p NR 7 R 8 , —C(O)NR 7 R 8 , —N═CR 7 R 8 , —NR 7 C(O)R 8 , cycloalkyl, heterocycloalkyl, haloalkyl, hydroxyalkyl, hydroxyalkylamino, alkylamino, heteroaryl, or aryl.

  本发明涉及通式（III）的化合物或其药学上可接受的酸盐或碱盐，或其药学上可接受的前药或其立体异构体，其中R3为H，—C（O）NRaRb，卤素，烷基，卤代烷基，芳基，杂环芳基，OH，SH，NR4'OR5'，NH2，胺，烷基胺，烷氧基，环烷基，杂环环烷基，羟基烷基或卤代烷氧基；R4为H，卤素，烷基，—C（NR7）NR7R8，—（CH2）p 芳基，—（CH2）p NR7R8，—C（O）NR7R8，—N═CR7R8，—NR7C（O）R8，环烷基，杂环环烷基，卤代烷基，羟基烷基，羟基烷基氨基，烷基氨基，杂环芳基或芳基；R5为卤素，烷基，—C（NR7）NR7R8，—（CH2）p 芳基，—（CH2）p NR7R8，—C（O）NR7R8，—N═CR7R8，—NR7C（O）R8，环烷基，杂环环烷基，卤代烷基，羟基烷基，羟基烷基氨基，烷基氨基，杂环芳基或芳基。
• Novel Heterocyclic Nf-Kb Inhibitors
  申请人：Leban Johann

  公开号：US20080261971A1

  公开（公告）日：2008-10-23

  The present invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, (I) wherein R 1 is independently hydrogen, alkyl, cycloalkyl, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl or substituted arylalkyl; R 2 is independently —NR 3 R 4 , (II) or (III) R 3 is independently alkyl, cycloalkyl, alkoxy, alkylamine, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl, R 4 is independently alkyl, cycloalkyl, alkoxy, alkylamine, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R 5 is independently H, COR 6 , CO 2 R 6 , SOR 6 , SO 2 R 6 , SO 3 R 6 , alkyl, cycloalkyl, alkoxy, —NH 2 , alkylamine, —NR 7 COR 6 , halogen, —OH, —SH, alkylthio, hydroxyalkyl, haloalkyl, haloalkyloxy, aryl or heteroaryl; R 6 is independently H, alkyl, cycloalkyl, —NH 2 , alkylamine, aryl or heteroaryl; R 7 is independently H, alkyl, cycloalkyl, alkoxy, —OH, —SH, alkylthio, hydroxyalkyl, aryl, or heteroaryl; p is 0, or 1; q is 0, or 1; X is CO, or SO 2 .

  本发明涉及一般式(I)的化合物及其盐和生理功能衍生物，其中R1独立地为氢、烷基、环烷基、羟基烷基、卤代烷基、卤代烷氧基、芳基、取代芳基、杂环芳基、取代杂环芳基、芳基烷基或取代芳基烷基；R2独立地为—NR3R4、(II)或(III)，其中R3独立地为烷基、环烷基、烷氧基、烷基胺、—OH、—SH、烷硫基、羟基烷基、卤代烷基、卤代烷氧基、芳基或杂环芳基，R4独立地为烷基、环烷基、烷氧基、烷基胺、烷硫基、羟基烷基、卤代烷基、卤代烷氧基、芳基或杂环芳基；R5独立地为H、COR6、CO2R6、SOR6、SO2R6、SO3R6、烷基、环烷基、烷氧基、—NH2、烷基胺、—NR7COR6、卤素、—OH、—SH、烷硫基、羟基烷基、卤代烷基、卤代烷氧基、芳基或杂环芳基；R6独立地为H、烷基、环烷基、—NH2、烷基胺、芳基或杂环芳基；R7独立地为H、烷基、环烷基、烷氧基、—OH、—SH、烷硫基、羟基烷基、芳基或杂环芳基；p为0或1；q为0或1；X为CO或SO2。
• NOVEL HETEROCYCLIC NF-kB INHIBITORS
  申请人：Leban Johann

  公开号：US20100048574A1

  公开（公告）日：2010-02-25

  The present invention relates to compounds of the general formula (II): or pharmaceutically acceptable salts thereof with an acid or a base, or pharmaceutically acceptable prodrugs or a stereoisomer thereof.

  本发明涉及通式(II)的化合物或其与酸或碱的药物可接受盐，或药物可接受的前药，或其立体异构体。