Theophylline-based nitophenylpiperazine derivatives for enhancing aortic smooth muscle relaxation

• US 20080064705A1
• Filed: 09/12/2006
• Published: 03/13/2008
• Est. Priority Date: 09/12/2006
• Status: Abandoned Application

• Current Assignee: Kaohsiung Medical University
• Original Assignee: Kaohsiung Medical University
• Inventors: Chen, Ing-Jun
• Application Number:
  US11/520,174
• Publication Number:
  US 20080064705A1
• Time in Patent Office: Days
• US Class Current: 514/252.16
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: C07D 473/08 with methyl radicals in positions 1 and 3, e.g. theophylline

Abstract

A substance for enhancing an aortic smooth muscle relaxation is provided. The substance is one selected from the group consisting of a compound of formula (I), a pharmaceutical acceptable therefrom and a solvate therefrom,

wherein either of R1 and R2 is one of a hydrogen and a nitro group.

Claims

1. A substance for enhancing an aortic smooth muscle relaxation, being one selected from the group consisting of a compound of formula (I), a pharmaceutical acceptable therefrom and a solvate therefrom,

2. The substance as claimed in claim 1, wherein R1 is a nitro group.

3. The substance as claimed in claim 1, wherein R2 is a nitro group.

4. A pharmaceutical composition for enhancing an aortic smooth muscle relaxation, comprising a substance of claim 1 and one selected from the group consisting of a pharmaceutical excipient, a diluent and a carrier.

5. A method for synthesizing a compound for enhancing an aortic smooth muscle relaxation, comprising the following steps:

(1) dissolving theophylline into 1,2-dibromoethane to form a mixture;

(2) adding NaOH into the mixture to obtain an oil-like solution;

(3) purifying the oil-like solution to obtain an oil-like compound;

(4) adding piperazine to react with the oil-like compound to obtain a first coarse crystal;

(5) recrystallizing and purifying the first coarse crystal to obtain the first crystal compound;

(6) dissolving the first crystal compound in a solvent to form a first solution;

(7) dissolving 2-chloronitrobenzene and 4-chloronitrobenzene respectively in the first solution to form a second solution;

(8) obtaining the compound from the second solution.

6. The method as claimed in claim 5, wherein the reaction temperature of the step (2) is performed at approximately 90-120°

C.

7. The method as claimed in claim 5, wherein the reaction temperature of the step (2) is performed at 100°

C.

8. The method as claimed in claim 5, wherein a first methanol solution is used for the step (3) and a second methanol solution is used for the step (5).

9. The method as claimed in claim 5, wherein a solvent mixture of n-hexane and ethylacetate is used for the step (3).

10. The method as claimed in claim 5, wherein the steps (3) and (5) are performed by a column.

11. The method as claimed in claim 5, wherein the column has a packing gel being silica gel 60.

12. The method as claimed in claim 5, wherein the solvent in the step (6) is methanol.

13. The method as claimed in claim 5, wherein the step (8) is performed by a refluxing.

14. A method for enhancing an aortic smooth muscle relaxation of a mammal, comprising:

administrating to the mammal one of the group consisting of a compound of formula (I), a salt thereof and a solvate thereof, and a pharmaceutical carrier,