Dihydropyrimidinone derivatives

Patent metadata

Field	Value
Publication number	US-9856232-B1
Application number	US-201715628476-A
Country	US
Kind code	B1
Filing date	Jun 20, 2017
Priority date	Jun 20, 2017
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

A dihydropyrimidinone derivative includes a compound having a chemical structure according to Formula 1:

wherein
Z is selected from CH 2 O, O, and N; X is selected from O and S; and R represents aryl, substituted aryl, heteroaryl, or substituted heteroaryl, wherein the substituted aryl or substituted heteroaryl have one or more substituents selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, hydroxyl, alkylthio, alkylamino, heteroaryl, aryloxy, haloaryloxy, arylthio, arylamino, and pharmaceutically acceptable salts thereof. The present subject matter also relates to a method of making a dihydropyrimidinone derivative, a method of treating a gastrointestinal disease, a method of treating an ulcer, a pharmaceutical composition, and a method of making a pharmaceutical composition.

First claim

We claim:

1. A dihydropyrimidinone derivative comprising a compound of Formula 1:

wherein
Z is selected from CH 2 , O, and N;
X is selected from O and S; and
R represents aryl, substituted aryl, heteroaryl, or substituted heteroaryl,

wherein the substituted aryl or substituted heteroaryl have one or more substituents selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, hydroxyl, alkylthio, alkylamino, heteroaryl, aryloxy, haloaryloxy, arylthio, arylamino, and to pharmaceutically acceptable salts thereof.

2. The dihydropyrimidinone derivative of claim 1 , wherein R is selected from the group consisting of 2-nitro phenyl, 3-nitro phenyl, 4-nitro phenyl, 4-chloro phenyl, 2,4-dichloro phenyl, 3,4-dimethoxy phenyl, 2-methoxy phenyl, 4-hydroxy phenyl, 3-hydroxy phenyl, dimethylamino phenyl, 3-methoxy phenyl, 4-ethoxy phenyl, 2,4,5-trimethoxy phenyl, 2,3,4-trimethoxy phenyl, 3,4,5-trimethoxy phenyl, 2,4,6-trimethoxy phenyl, and 2,4-dimethoxy phenyl.

3. The dihydropyrimidinone derivative of claim 1 , wherein the compound is selected from the group consisting of:

4. The dihydropyrimidinone derivative of claim 1 , wherein the compound is an anti-ulcer agent.

5. A method of treating a gastrointestinal disease, comprising:
administering to a patient in need thereof at least one compound of claim 1 .

6. The method of claim 5 , wherein the gastrointestinal disease is one of gastric ulcer, gastroesophagal reflux, and Zollinger-Elisson syndrome.

7. A pharmaceutical composition comprising:
the dihydropyrimidinone derivative of claim 1 ; and
a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition is in a unit dosage form.

9. The pharmaceutical composition of claim 8 , wherein the unit dosage form is a tablet, pill, capsule, granule, powder, ointment, sterile parenteral solution or suspension, metered aerosol or liquid spray, drops, ampule, injection, teaspoonful, or suppository.

10. A method of making a pharmaceutical composition according to claim 7 comprising:
mixing the dihydropyrimidinone derivative under sterile conditions with the pharmaceutically acceptable carrier to form a mixture; and
providing the mixture in a unit dosage form.

11. A method of treating an ulcer, comprising:
administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 7 .

12. The method of claim 11 , wherein the composition is administered orally, nasally, rectally, parenterally, intracisternally, intra-vaginally, intraperitoneally, topically, transdermally, or by surgical implantation.

13. The method of claim 11 , wherein the composition is administered in a form selected from the group consisting of liquid oral preparations, solid oral preparations, parenteral preparations, injectable suspensions, and liposomes.

14. A method of making a dihydropyrimidinone derivative, comprising:
refluxing 1-[4-(piperidin-1-yl) phenyl] ethan-1-one with dimethylforamide dimethylacetal (DMF-DMA) to obtain enaminone; and
refluxing a solution of enaminone, substituted benzaldehyde, urea, and Glacial acetic acid to yield a dihydropyrimidinone derivative having a structure of:

wherein
Z is selected from CH 2 , O, and N;
X is selected from O and S; and
R represents an aryl, substituted aryl, heteroaryl, or substituted heteroaryl,

wherein the substituted aryl or substituted heteroaryl have one or more substituents selected from the group consisting of halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, hydroxyl, alkylthio, alkylamino, heteroaryl, aryloxy, haloaryloxy, arylthio, arylamino, and pharmaceutically acceptable salts thereof.

15. The method of claim 14 , wherein R is selected from the group consisting of 2-nitro phenyl, 3-nitro phenyl, 4-nitro phenyl, 4-chloro phenyl, 2,4-dichloro phenyl, 3,4-dimethoxy phenyl, 2-methoxy phenyl, 4-hydroxy phenyl, 3-hydroxy phenyl, dimethylamino phenyl, 3-methoxy phenyl, 4-ethoxy phenyl, 2,4,5-trimethoxy phenyl, 2,3,4-trimethoxy phenyl, 3,4,5-trimethoxy phenyl, 2,4,6-trimethoxy phenyl, and 2,4-dimethoxy phenyl.

16. The method of claim 14 , wherein 1-[4-(piperidin-1-yl) phenyl] ethan-1-one is refluxed with dimethylforamide dimethylacetal (DMF-DMA) under a solvent free condition for about 10 hours.

17. The method of claim 14 , wherein the solution of enaminone, substituted benzaldehyde, urea, and Glacial acetic acid is refluxed for about 3 hours.

18. The method of claim 14 , further comprising:
recrystallizing the dihydropyrimidinone derivative from an ethanol and Glacial acetic acid mixture.

Assignees

• Univ King Saud

Inventors

• Bhat Mashooq Ahmad
• Al-Omar Mohamed Abdulrahman

Classifications

• C07D401/02 Primary

  containing two hetero rings · CPC title

• C07D221/00

  Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 · CPC title

• C07D239/10

  Oxygen or sulfur atoms · CPC title

• C07D227/02

  with only hydrogen or carbon atoms directly attached to the ring nitrogen atom · CPC title

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title