CGRP ANTAGONISTS

• US 20110059954A1
• Filed: 10/16/2008
• Published: 03/10/2011
• Est. Priority Date: 10/18/2007
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Stenkamp, Dirk, Schaenzle, Gerhard, Doods, Henri, Dahmann, Georg, Rudolf, Klaus, Mueller, Stephan Georg, Heimann, Annekatrin, Gottschling, Dirk
• Application Number:
  US12/682,760
• Publication Number:
  US 20110059954A1
• Time in Patent Office: Days
• US Class Current: 514/221
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

The present invention relates to new CGRP-antagonists of general formula I

wherein U, V, X, Y, R¹, R² and R³ are defined as stated hereinafter, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

Claims

1. A compound of the formula I

2. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formula II

3. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formulae

4. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formulae

5. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formula

6. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formula

7. A compound of the formula I according to claim 1, wherein R² denotes a hydrogen atom,

or a tautomer or salt thereof.

8. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formula III

9. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formulae III

10. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formulae III

11. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formula

12. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formulae III

13. Compounds of general formula I according to claim 1, wherein U, V, X, Y, R¹ and R² are defined as in claim 1, 2, 3, 4, 5, 6 or 7 and

R³ denotes a group of general formulae III

14. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formula IIIa

115. A compound of the formula I according to claim 1, wherein

R³ denotes a group of the formula

16. A compound of the formula I according to claim 1, wherein

U-V-X denotes

—

N═

N—

(C—

R¹¹)═

, —

N═

(C—

R¹⁰)—

N═

, —

N═

(C—

R¹⁰)—

(C—

H)═

, —

(N-oxide)=(C—

R¹⁰)—

(C—

R¹¹)═

, —

(CR⁹)═

N—

N═

, —

(CR⁹)═

N—

(CR¹¹)═

, —

(C—

R⁹)═

N(oxide)-(C—

R¹¹)═

, —

(CR⁹)═

(C—

R¹⁰)—

N═

, —

(CR⁹)═

(C—

R⁰)—

(N-oxide)=, or —

(CR⁹)═

(C—

R¹⁰)—

(CR¹¹)═

,

R⁹ denotes

(a) H,

(b) a C_1-6-alkyl- or C_1-3-alkyl-O—

group which may each be substituted by a group R^9.1,

(c) R^9.2R^9.3N, R^9.2R^9.3N—

C_1-3-alkylene-,

(d) halogen, —

CN, —

OH, —

COOH, C_1-3-alkyl-O—

C_1-3-alkylene-, C_3-6-cycloalkyl, C_3-6-cycloalkyl-C_1-4-alkylene-, C_1-3-alkyl-C(O)—

O—

C_1-3-alkylene,

(e) a C_1-3-alkyl or C_1-3-alkyl-O—

group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,

R^9.1 denotes H, OH or —

O—

CH₃,

R^9.2 denotes H or C_1-3-alkyl,

R^9.3 denotes H or C_1-3-alkyl, or

R^9.2 and R^9.3 together with the nitrogen atom to which they are attached denote a 3- to 6-membered heterocyclic group,

R¹⁰ denotes

(a) H,

(b) a C_1-6-alkyl or C_1-3-alkyl-CO—

group which may each be substituted by a group R^10.1,

(c) —

NR^10.1R^10.2, NR^10.1R^10.2—

C_1-3-alkylene-,

(d) halogen, —

CN, —

OH, C_1-3-alkyl-O—

C_1-3-alkylene, C_3-6-cycloalkyl, C_3-6-cycloalkyl-C_1-4-alkylene, C_1-3-alkyl-C(O)—

O—

C_1-3-alkylene,

(e) aryl-C_0-3-alkylene-O—

,

(f) a C_1-3-alkyl or C_1-3-alkyl-O—

group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,

R^10.1 denotes H, OH or —

O—

CH₃,

R^10.2 denotes H or C_1-6-alkyl,

R^10.3 denotes H, C_1-6-alkyl or —

SO₂—

C_1-3-alkyl,

R¹¹ denotes

(a) H,

(b) a C_1-6-alkyl- or C_1-3-alkyl-O—

group which may each be substituted by a group R^11.1,

(c) R^11.2R^11.3N, R^11.2R^11.3N—

C_1-3-alkylene-,

(d) halogen, —

CN, —

OH, —

COOH, C_1-3-alkyl-O—

C_1-3-alkylene, C_3-6-cycloalkyl, C_3-6-cycloalkyl-C_1-4-alkylene, C_1-3-alkyl-C(O)—

O—

C_1-3-alkylene,

(e) a C_1-3-alkyl or C_1-3-alkyl-O—

group wherein each methylene group is substituted by up to two fluorine atoms and each methyl group is substituted by up to three fluorine atoms,

R^11.1 denotes H, OH or —

O—

CH₃,

R^11.2 denotes H or C_1-3-alkyl,

R^11.3 denotes H or C_1-3-alkyl, or

R^11.2 and R^11.3 together with the nitrogen atom to which they are attached denote a 3- to 6-membered heterocyclic group,

or a tautomer or salt thereof.

17. A compound of the formula I according to claim 1, wherein

the ring

18. A compound of the formula I according to claim 1, wherein

R¹ denotes a group of the formula

19. A compound according to claim 1 selected from the group consisting of:

20. A physiologically acceptable salt of a compound according to any one of claims 1 to 18.

21. A pharmaceutical composition comprising a compound according to any one of claims 1 to 18, or a physiologically acceptable salt thereof, and a carrier or diluent.

22. A method of treating headache, migraine headache and cluster headache which comprises administering to a host suffering from the same a therapeutically effective amount of a compound according to any one of claims 1 to 18, or a physiologically acceptable salt thereof.

23-24. -24. (canceled)