Dasatinib and nonlinear configuration polyethylene glycol conjugate

• US 9,566,344 B2
• Filed: 12/16/2015
• Issued: 02/14/2017
• Est. Priority Date: 06/18/2013
• Status: Active Grant

• Current Assignee: Jenkem Technology Co., Ltd. (Tanjin)
• Original Assignee: Jenkem Technology Co., Ltd. (Tanjin)
• Inventors: Wang, Jinliang, Zhao, Xuan, Wang, Zhenguo
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US14/971,903
• Publication Number:
  US 20160095934A1
• Time in Patent Office: 426 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

A dasatinib and nonlinear configuration polyethylene glycol conjugate represented by formula I, wherein core is the core structure of a nonlinear configuration of polyethylene glycol, selected from a residue of pentaerythritol, methylglucoside, sucrose, diethylene glycol, propanediol, glycerol or polyglycerol removaed the hydrogen atom from the hydroxyl group; P is a polyethylene glycol residue with a number-average molecular weight of 300-60000 Da; X is selected from single bond, —CH₂CO—, —CH₂CH₂OCO— or CH₂CH₂NHCO—; and i is selected from 3, 4, 6 or 8.

Claims

1. A dasatinib and nonlinear configuration polyethylene glycol conjugate shown as formula I

2. The conjugate of claim 1, wherein the said conjugate is shown as formula II:

3. The conjugate of claim 2, wherein the said conjugate is shown as formula IV:

4. The conjugate of claim 2, wherein the said conjugate is shown as formula V:

5. The conjugate of claim 2, wherein the said conjugate is shown as formula VI:

6. The conjugate of claim 2, wherein the said conjugate is shown as formula VII:

7. The conjugate of claim 2, wherein the nonlinear configuration polyethylene glycol has a number-average molecular weight of 5000-40000 Da and four branches.

8. The conjugate of claim 2, wherein the nonlinear configuration polyethylene glycol described above has a number-average molecular weight of 20000 Da and four branches.

9. The conjugate of claim 2, wherein the said conjugate is selected from the group as shown in formula VIII to formula XI:

10. A pharmaceutical composition comprising the conjugate of claim 1 and pharmaceutically acceptable carriers or excipients.

11. The pharmaceutical composition of claim 10, wherein the said pharmaceutical composition are tablets, capsules, pills, granules, powders, suppositories, injections, solutions, suspensions, ointments, patches, lotions, drops, linimentums, sprays or other dosage forms.

12. The use of dasatinib and nonlinear configuration polyethylene glycol conjugate of claim 1 in the preparation of antitumor drugs.