Carbamate-substituted pyrazolopyridines

• US 20060052397A1
• Filed: 04/25/2003
• Published: 03/09/2006
• Est. Priority Date: 05/08/2002
• Status: Active Grant

• Current Assignee: Adverio Pharma GmbH (Bayer AG)
• Original Assignee: Bayer Healthcare AG (Bayer AG)
• Inventors: Stasch, Johannes-Peter, Feurer, Achim, Weigand, Stefan, Bischoff, Erwin, Alonso-Alija, Cristina, Munter, Klaus, Stahl, Elke
• Granted Patent: US 7,173,037 B2
• Time in Patent Office: Days
• US Class Current: 514/256
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• 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 471/04 Ortho-condensed systems

Abstract

The present invention relates to compounds which stimulate soluble guanylate cyclase, to the preparation thereof and to the use thereof as medicaments, in particular as medicaments for the treatment of cardiovascular disorders and/or sexual dysfunction.

Claims

1. A compound of the formula (I)

2. The compound of claim 1,

in which

R¹ is —

NR³C(═

O)OR⁴,

R² is hydrogen or NH₂,

R³ is (C₁-C₄)-alkyl,

R⁴ is (C₁-C₄)-alkyl,

or a salt, isomer or hydrate thereof.

3. The compound of claim 1,

in which

R¹ is —

NR³C(═

O)OR⁴,

R² is NH₂,

R³ is methyl or ethyl,

R⁴ is methyl, ethyl or isopropyl,

or a salt, isomer or hydrate thereof.

4. The compound of claim 1 having the following structure:

methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl(methyl)carbamate

or a salt isomer or hydrate thereof.

5. Process for the preparation of compounds of the formula (I) as defined in claim 1, characterized in that either

[A] compounds of the formula (Ia)

in which

R⁴ is as defined in claim 1,

are reacted with compounds of the formula (II)

R³—

X¹ 

 

(II),

in which

R³ is as defined in claim 1,

and

X¹ is a leaving group,

or

[B] the compound of the formula (III)

is reacted with compounds of the formula (IV)

in which

R⁴ is as defined in claim 1,

or

[C] the compound of the formula (V)

is reacted with compounds of the formula (VI)

in which

R³ and R⁴ are as defined in claim 1,

to give compounds of the formula (Ib)

in which

R³ and R⁴ are as defined in claim 1.

7. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1, and at least one further excipient.

8. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1 in combination with at least one organic nitrate or NO donor.

9. A pharmaceutical composition comprising at least one compound of the formula (I) as defined in claim 1 in combination with at least one compound which inhibits the breakdown of cyclic guanosine monophosphate (cGMP).

10. A method for the treatment of cardiovascular disorders, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.

11. A method for the treatment of hypertension, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.

12. A method for the treatment of thromboembolic disorders and ischaemias comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.

13. A method for the treatment of sexual dysfunction, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1.

14. The method of any of claims 10 to 13, where compounds of the formula (I) as defined in claim 1 are employed in combination with at least one organic nitrate or NO donor or in combination with at least one compound which inhibits the breakdown of cyclic guanosine monophosphate (cGMP).

15. The method of claim 13, wherein the sexual dysfunction is erectile dysfunction or female sexual dysfunction.

6. (canceled)