NOVEL TRICYCLIC DIHYDROPYRAZINES AS POTASSIUM CHANNEL OPENERS

• US 20070191382A1
• Filed: 02/01/2007
• Published: 08/16/2007
• Est. Priority Date: 02/10/2006
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Sui, Zhihua, Zhang, Xuqing
• Granted Patent: US 7,674,793 B2
• Time in Patent Office: Days
• US Class Current: 514/250
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 241/38 with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms

Abstract

The present invention is directed to novel tricyclic dihydropyrazine derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders related to potassium channel.

Claims

1. The invention is directed to a compound of formula I:

2. A compound as in claim 3, wherein

R¹ is selected from the group consisting of hydrogen, fluoro,bromo, chloro, cyano;

R² is selected from the group consisting of hydrogen, fluoro, chloro, bromo, cyano;

n is selected from 1 to 2.

R³ is hydrogen;

or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1.

4. A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier.

5. A method of treating a disorder related to ion channels, comprising administering, to a subject in need thereof, a therapeutically effective amount of the compound of claim 1.

6. The method of claim 5, wherein the ion channel is a potassium ion channel.

7. The method of claim 6, wherein the ion channel is an ATP-sensitive potassium ion channel.

8. The method of claim 5, wherein the disorder related to ion channels is selected from the group consisting of urinary incontinence, overactive bladder, hypertension, erectile dysfunction, female sexual disorders, dysmenorrhea, irritable bowl syndrome, airway hyperactivity, epilepsy, stroke, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, myocardial injury, coronary artery disease, hair loss and baldness.

9. The method of claim 8, wherein the disorder related to ion channels is selected from the group consisting of urinary incontinence and overactive bladder.

10. A method of treating a disorder selected from the group consisting of urinary incontinence, overactive bladder, hypertension, erectile dysfunction, female sexual disorders, dysmenorrhea, irritable bowl syndrome, airway hyperactivity, epilepsy, stroke, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, myocardial injury, coronary artery disease, hair loss and baldness, comprising administering, to a subject in need thereof, a therapeutically effective amount of the composition of claim 1.