替吉环素盐酸盐 | 197654-04-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 中文名称: 替吉环素盐酸盐
• 英文名称: Tigecycline hydrochloride
• 英文别名: (4S,4aS,5aR,12aR)-9-[[2-(tert-butylamino)acetyl]amino]-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide;hydrochloride
• CAS: 197654-04-9
• 化学式: C29H40ClN5O8
• 分子量: 622.1
• InChiKey: FHFADVHACRVXAT-KXLOKULZSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  0.78
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  206
• 氢给体数：
  8
• 氢受体数：
  11

制备方法与用途

生物活性

Tigecycline hydrochloride (GAR-936 hydrochloride) 是一种广谱的甘氨酰环素抗生素。Tigecycline 对 E. coli (MG1655 菌株) 的平均抑制浓度 (MIC) 约为 125 ng/ mL。对 Acinetobacter baumannii (A. baumannii) 的 MIC50 和 MIC90 分别为 1 和 2 mg/L。

靶点

Mean MIC: 125 ng/mL ( E. coli )
MIC50: 1 mg/mL ( A. baumannii )
MIC90: 2 mg/mL ( A. baumannii )

体外研究

Tigecycline (0.63-30 µM, preincubated for 4 days, treated for 72 h) inhibits AML2 cells and HL-60 cells with IC ₅₀ s of 4.72±0.54 and 3.06±0.85 μM (freshly prepared). Tigecycline inhibits AML2 cells and HL-60 cells with IC ₅₀ s of 5.64±0.55 and 4.27±0.45 μM (1 day preincubation). Tigecycline inhibits AML2 cells and HL-60 cells with IC ₅₀ s of 5.02±0.60 and 4.39±0.44 μM (2 day preincubation). Tigecycline inhibits AML2 cells and HL-60 cells with IC ₅₀ s of 4.09±0.41 and 3.95±0.39 μM (3 day preincubation). After a 4 day preincubation of Tigecycline in saline, Tigecycline lost its ability to kill TEX human leukemia cells (from IC ₅₀ ~5 µM when freshly prepared to IC ₅₀ >50 µM after 4 days preincubation) as measured by CellTiter Flour assay.

Cell Viability Assay

Cell Line:	Human leukemic OCI-AML2, HL-60 (ATCC) and TEX cell lines
Concentration:	0.63-30 µM
Incubation Time:	Preincubated for 4 days, treated for 72 hours
Result:	Inhibited AML2 cells and HL-60 cells with IC 50 s of 4.72±0.54 and 3.06±0.85 μM (freshly prepared).

体内研究

Tigecycline (50 mg/kg; intraperitoneal injection; twice a day; for 11 days) reduces tumor volume and weight in NOD/SCID mice.
The peak plasma concentration (C _max ), the terminal half-life (t _1/2 ), area under the plasma concentration-time curve (AUC), clearance (CL) and volume of distribution (Vz) are 22.8μg/mL, 108.9 min, 1912.2min*μg/mL, 26.1 mL/min/kg, 4109.4 mL/kg for Tigecycline in saline, respectively. The peak plasma concentration (C _max ), the terminal half-life (t _1/2 ), area under the plasma concentration-time curve (AUC), clearance (CL) and volume of distribution (Vz) are15.7μg/mL, 110.3 min, 2036.5 min*μg/mL, 24.6 mL/min/kg, 3906.2 mL/kg for Tigecycline in formulation (60 mg/mL pyruvate, 3 mg/mL ascorbic acid, pH 7 in saline) , respectively.

Animal Model:	NOD/SCID mice with OCI-AML2 acute myeloid leukemia (AML) xenograft model
Dosage:	50 mg/kg
Administration:	Intraperitoneal injection; twice a day; for 11 days
Result:	Reduced tumor volume and weight.

Animal Model:	NOD/SCID mice
Dosage:	50 mg/kg
Administration:	Intraperitoneal injection; 360 minutes
Result:	The peak plasma concentration (C max ), the terminal half-life (t 1/2 ), area under the plasma concentration-time curve (AUC), clearance (CL) and volume of distribution (Vz) are 22.8 μg/mL, 108.9 min, 1912.2 min*μg/mL, 26.1 mL/min/kg, 4109.4 mL/kg, respectively.

反应信息

• 作为反应物：
  描述：

  替加环素 、 disodium;carbonate 、 、 盐酸 、 替吉环素盐酸盐 、 氨 在 Dichloride methane 、 水 作用下， 以 水 、 isopropanol-diethyl ether 、 甲醇 、 乙腈 、 N,N-二甲基丙烯基脲 为溶剂， 反应 10.5h， 以to give a tigecycline hydrate (9.6 g)的产率得到Tigecycline
  参考文献：
  名称：

  TIGECYCLINE CRYSTALLINE HYDRATE AND PREPARATION METHOD THEREFOR AND USE THEREOF

  摘要：

  提供了一种替吉奥霉素水合晶体，以及其制备方法和用途。该水合晶体具有高稳定性，可用于制造治疗或预防人或动物呼吸系统、肝胆系统、面部特征、泌尿生殖系统、骨骼和关节、皮肤和软组织以及由革兰氏阳性或阴性细菌、厌氧菌、沙眼衣原体和支原体引起的心内膜炎、败血症、脑膜炎等感染的药物。

  公开号：

  US20140107357A1
• 作为产物：
  描述：

  替加环素 、 盐酸 以 乙腈 为溶剂， 反应 21.0h， 生成 替吉环素盐酸盐
  参考文献：
  名称：

  CRYSTALLINE FORMS OF TIGECYCLINE HYDROCHLORIDE

  摘要：

  本发明涉及替吉环素盐酸盐晶型A和B的制备方法。此外，本发明涉及将替吉环素盐酸盐晶型A和B用作制备抗感染药物的中间体。此外，本发明涉及含有替吉环素盐酸盐晶型A的药物组合物，并将替吉环素盐酸盐晶型A用作抗感染药物。

  公开号：

  US20110105772A1

文献信息

• CRYSTALLINE FORM C OF TIGECYCLINE DIHYDROCHLORIDE AND METHODS FOR ITS PREPARATION
  申请人：Hotter Andreas

  公开号：US20120022025A1

  公开（公告）日：2012-01-26

  The present invention relates to crystalline form C of Tigecycline dihydrochloride and to methods for the preparation of the same. Furthermore the present invention relates to the use of crystalline form C of Tigecycline dihydrochloride as an intermediate for the preparation of an anti-infective medicament. Moreover the present invention relates to pharmaceutical compositions comprising crystalline form C of Tigecycline dihydrochloride in an effective amount and to the use of crystalline form C of Tigecycline dihydrochloride as an anti-infective medicament.

  本发明涉及替吉环素双盐酸盐的晶型C以及其制备方法。此外，本发明还涉及将替吉环素双盐酸盐的晶型C用作抗感染药物制剂的中间体。此外，本发明还涉及含有替吉环素双盐酸盐晶型C的有效量的制药组合物，以及将替吉环素双盐酸盐晶型C用作抗感染药物的用途。
• Crystalline forms of tigecycline hydrochloride
  申请人：Sandoz AG

  公开号：US08252946B2

  公开（公告）日：2012-08-28

  The present invention relates to crystalline forms A and B of Tigecycline hydrochloride and to methods for the preparation of the same. Furthermore the present invention relates to the use of crystalline forms A and B of Tigecycline hydrochloride as intermediates for the formulation of an anti-infective medicament. Moreover the present invention relates to pharmaceutical compositions comprising crystalline form A of Tigecycline hydrochloride in an effective amount and to the use of crystalline form A of Tigecycline hydrochloride as anti-infective medicament.

  本发明涉及替吉环素盐酸盐的晶体形式A和B以及制备它们的方法。此外，本发明还涉及使用替吉环素盐酸盐的晶体形式A和B作为制备抗感染药物的中间体。此外，本发明还涉及包含替吉环素盐酸盐晶体形式A的有效量的制药组合物，并涉及使用替吉环素盐酸盐晶体形式A作为抗感染药物。
• Crystalline form C of tigecycline dihydrochloride and methods for its preparation
  申请人：Hotter Andreas

  公开号：US08513224B2

  公开（公告）日：2013-08-20

  The present invention relates to crystalline form C of Tigecycline dihydrochloride and to methods for the preparation of the same. Furthermore the present invention relates to the use of crystalline form C of Tigecycline dihydrochloride as an intermediate for the preparation of an anti-infective medicament. Moreover the present invention relates to pharmaceutical compositions comprising crystalline form C of Tigecycline dihydrochloride in an effective amount and to the use of crystalline form C of Tigecycline dihydrochloride as an anti-infective medicament.

  本发明涉及替吉环素二盐酸盐的晶型C及其制备方法。此外，本发明还涉及使用替吉环素二盐酸盐晶型C作为抗感染药物制备的中间体。此外，本发明还涉及含有替吉环素二盐酸盐晶型C的药物组合物，并且涉及使用替吉环素二盐酸盐晶型C作为抗感染药物。