3-(5-amino-6-chloropyrimidin-4-ylamino)propan-ol | 89893-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(5-amino-6-chloropyrimidin-4-ylamino)propan-ol
• 英文别名: 5-Amino-6-chlor-4-<3-hydroxy-propyl>-pyrimidin；3-(5-amino-6-chloro-pyrimidin-4-ylamino)-propan-1-ol；4-(3-hydroxypropyl)-amino-5-amino-6-chloropyrimidine；3-[(5-amino-6-chloropyrimidin-4-yl)amino]propan-1-ol
• CAS: 89893-31-2
• 化学式: C₇H₁₁ClN₄O
• mdl: MFCD05819951
• 分子量: 202.644
• InChiKey: AQYOZAZSTDPWMK-UHFFFAOYSA-N

物化性质

• 沸点：
  443.7±45.0 °C(Predicted)
• 密度：
  1.446±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  84.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(5-amino-6-chloropyrimidin-4-ylamino)propan-ol 在 吡啶 、 4-二甲氨基吡啶 、 氨 、 乙酸酐 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 acetic acid 3-(6-aminopurin-9-yl)-propyl ester
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h
• 作为产物：
  描述：

  4,6-二氯-5-氨基嘧啶 、 3-氨基-1-丙醇 以 乙醇 为溶剂， 反应 1.0h， 以80%的产率得到3-(5-amino-6-chloropyrimidin-4-ylamino)propan-ol
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h

文献信息

• 2-(Substituted heterocyclic amine)benzoic acids
  申请人：Science Union et Cie

  公开号：US04100286A1

  公开（公告）日：1978-07-11

  Heterocyclic compounds of the formula: ##STR1## WHEREIN ONE OF Y and Z is CH, the other being N, A is a straight or branched saturated hydrocarbon chain from C.sub.2 to C.sub.6 inclusive, X is chlorine, hydroxy, alkoxy or alkylthio each from C.sub.1 to C.sub.5 inclusive, R is hydrogen, alkyl, hydroxyalkyl or dihydroxyalkyl each from C.sub.1 to C.sub.3 inclusive, R' is halogen, alkyl or alkoxy each from C.sub.1 to C.sub.3 inclusive and n is 0, 1 or 2. These compounds, their optical isomers and their physiologically tolerable salts are used as medicines especially in the treatment of central nervous system disorders.

  杂环化合物的公式为：##STR1## 其中Y和Z中的一个为CH，另一个为N，A为直链或支链饱和碳链，范围从C.sub.2到C.sub.6，X为氯、羟基、烷氧基或烷硫基，每个范围从C.sub.1到C.sub.5，R为氢、烷基、羟基烷基或二羟基烷基，每个范围从C.sub.1到C.sub.3，R'为卤素、烷基或烷氧基，每个范围从C.sub.1到C.sub.3，n为0、1或2。这些化合物及其光学异构体和生理耐受盐被用作药物，特别用于治疗中枢神经系统疾病。
• Orally Active Purine-Based Inhibitors of Heat Shock Protein 90
  申请人：Kasibhatla R. Srinivas

  公开号：US20070129334A1

  公开（公告）日：2007-06-07

  Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention, and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90's) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.

  本发明描述了新型嘌呤化合物及其互变异构体和药学上可接受的盐，以及包含它们的制药组合物、包含它们的复合物（例如HSP90复合物）和使用它们的方法。使用本发明的新型嘌呤化合物、互变异构体和药学上可接受的盐的方法包括在抑制热休克蛋白90（HSP90）中使用它们，从而治疗或预防HSP90依赖性疾病，例如增生性疾病如乳腺癌。
• US4100286A
  申请人：——

  公开号：US4100286A

  公开（公告）日：1978-07-11
• [EN] ORALLY ACTIVE PURINE-BASED INHIBITORS OF HEAT SHOCK PROTEIN 90<br/>[FR] INHIBITEURS A BASE DE PURINE ORALEMENT ACTIFS DE LA PROTEINE DE CHOC THERMIQUE 90
  申请人：CONFORMA THERAPEUTICS CORP

  公开号：WO2007075572A2

  公开（公告）日：2007-07-05

  [EN] Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention,and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90*s) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.
  [FR] La présente invention concerne des composés de purine innovants, leurs tautomères et leurs sels pharmaceutiquement acceptables ainsi que les compositions pharmaceutiquement et les complexes qui les comprennent, par exemple les complexes de HSP90, et leurs procédés d'utilisation. Les procédés d'utilisation des composés de purine innovants de l'invention, de leurs tautomères et de leurs sels pharmaceutiquement acceptables incluent leur utilisation pour inhiber les protéines de choc thermique 90 (HSP90) afin de traiter ou de prévenir les maladies liées aux HSP90, par exemple les troubles prolifératifs tels que le cancer du sein.
• 7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors
  作者：Lin Zhang、Junhua Fan、Khang Vu、Kevin Hong、Jean-Yves Le Brazidec、Jiandong Shi、Marco Biamonte、David J. Busch、Rachel E. Lough、Roy Grecko、Yingqing Ran、John L. Sensintaffar、Adeela Kamal、Karen Lundgren、Francis J. Burrows、Robert Mansfield、Gregg A. Timony、Edgar H. Ulm、Srinivas R. Kasibhatla、Marcus F. Boehm

  DOI：10.1021/jm051146h

  日期：2006.8.1

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).