SYNTHESIS AND PHARMACOKINETIC ACTIVITIES OF PULMODIL AND PULMODIL-1, TWO CHLOROPHENYLPIPERAZINE SALT DERIVATIVES

• US 20100280040A1
• Filed: 11/17/2009
• Published: 11/04/2010
• Est. Priority Date: 04/30/2009
• Status: Abandoned Application

• Current Assignee: Kaohsiung Medical University
• Original Assignee: Kaohsiung Medical University
• Inventors: Chen, Ing-Jun
• Application Number:
  US12/620,485
• Publication Number:
  US 20100280040A1
• Time in Patent Office: Days
• US Class Current: 514/252.16
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: C07D 473/08 with methyl radicals in positions 1 and 3, e.g. theophylline
• CPC Class Codes: G01N 33/9453 Cardioregulators, e.g. antihypotensives, antiarrhythmics

Abstract

A compound including a salt derivative of the chlorophenylpiperazine moiety is provided, wherein the chlorophenylpiperazine moiety is derived from the reaction of a xanthine and a piperazine. The salt derivative thereof is non-toxic to the tracheal smooth muscle cells (TSMCs) and can be intravenously-, orally- or sublingually-dosed into the mammals.

Claims

1. A chemical compound comprising a formula I:

2. The compound according to claim 1, wherein the acid is one of an organic acid and an inorganic acid.

3. The compound according to claim 2, wherein the organic acid is one selected from a group consisting of a citric acid, a maleinic, acid, a fumaric acid, a tartaric acid, an oleic acid, a stearic acid, a benzenesulphonic acid, an ethyl benzenesulphonic acid, a benzoic acid, a succinic acid, a mesylic acid, a dimesylic acid, an acetic acid, a propionic acid, a pentanoic acid and an aspartic acid.

4. The compound according to claim 3, wherein the compound is solved in an anhydrous ethanol-polyethylene glycol-water when the acid is the citric acid.

5. The compound according to claim 4, wherein the anhydrous ethanol-polyethylene glycol-water has a ratio of anhydrous ethanol:

polyethylene glycol;

water of 5;

30;

65, and the compound has a pH value ranged between 4.5 and 4.8.

6. The compound according to claim 2, wherein the inorganic acid is one selected from a group consisting of a hydrochloride, a sulfuric acid, a phosphoric acid, a boric acid and a dihydrochloride.

7. The compound according to claim 6, wherein the compound is solved in a glucose solution when the acid is the hydrochloride.

8. The compound according to claim 7, wherein the glucose solution has a weight/volume concentration of 5%, and the compound has a pH value ranged between 5.8 and 6.4.

9. The compound according to claim 1 further comprising a pharmaceutically acceptable carrier.

19. A method for evaluating a pharmacokinetic parameter of a compound as claimed in claim 1, comprising steps of:

(a) providing a pharmaceutically effective amount of the compound to a subject; and

(b) determining the pharmacokinetic parameter in a blood of the subject.

20. The method according to claim 19, wherein the subject is a mammal being one selected from a group consisting of a human, a rat and a mouse, and the step (a) is performed by one selected from a group consisting of an oral administration, an intravenous injection and a sublingual administration.

10. A method for preparing a pharmaceutical compound having a formula I:

11. The method according to claim 10, wherein the theophylline is a 2-chloroethyl theophylline and the piperazine is a 2-chlorophenyl piperazine.

12. The method according to claim 10, wherein the step (a) is reacted in an ethanol solution having a first volume, the acid has a second volume, and the second volume is larger than the first volume.

13. The method according to claim 12, wherein the ethanol solution is a hydrous ethanol solution.

14. The method according to claim 10, wherein the step (a) further comprises a step (a1) of reacting the mediator with a base to obtain an intermediate.

15. The method according to claim 14, wherein the step (a) further comprises a step (a2) of concentrating the intermediate as a powder.

16. The method according to claim 14, wherein the base is one of a sodium hydroxide and a sodium hydrogen carbonate.

17. The method according to claim 10, wherein the step (b) further comprises a step (b1) of reacting the first mixture with an ethanol solution to form a saturated solution.

18. The method according to claim 17, wherein the step (b) further comprises a step (b2) of filtering the saturated solution to form a crystallized powder.