IP Library › Granted Patent US 8,227,502

Granted Patent B2

US 8,227,502 · App. 12/514,634 · Granted Jul 24, 2012

Amides acting on the adenosine receptors

Assignee: Anamar AB

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Quick Facts

Patent No.: US 8,227,502
App. No.: 12/514,634
Granted: Jul 24, 2012
Kind: B2

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Abstract

There are described Compounds of formula (I) in which R 3 to R 8 are independently selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide; R 1 is an optionally substituted phenyl, benzyl or cyclohexyl group; R 2 is selected from amino, substituted amino or guanidino groups, Z is a saturated or unsaturated C 1-5 hydrocarbon chain, and salts thereof. A process for their preparation and compositions containing them are also described. The Compounds are either agonists or antagonists of a specific adenosine receptor or a number of adenosine receptors and have usefulness for the treatment of inflammation, arthritic conditions, rheumatoid arthritis, osteoarthritis, mental disorders, or for inducing central nerve regeneration.

Claims (278)

1. A compound of general formula (I)

and tautomers, diastereomers, enantiomers, and mixtures thereof, wherein R 1 is selected from

in which @ denotes the position where R 1 is attached to the nitrogen atom;

Z is a saturated or unsaturated, straight or branched chain acyclic hydrocarbon group having 1, 2, 3, 4 or 5 carbon atoms;

R 2 is selected from an amino, alkylamino, dialkylamino, or a guanidine group;

R 3 , R 4 and R 5 are the same or different and are independently selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide;

R 6 , R 7 and R 8 , which may be the same or different, are selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide; and

R 9 , R 10 and R 11 , which may be the same or different, are selected from hydrogen, halogen, trihaloalkyl, alkyl having 1, 2, 3, 4 or 5 carbon atoms, electron donor groups selected from alkoxy having 1, 2, 3, 4 or 5 carbon atoms, trihaloalkoxy, hydroxy or amino, electron acceptor groups selected from cyano, sulphonic, nitro, or amide;

and salts thereof.

2. The compound of claim 1 , wherein Z has 1 or 2 carbon atoms.

3. The compound of claim 1 , wherein Z has 2 carbon atoms.

4. The compound of claim 1 , wherein at least one of R 3 , R 4 and R 5 is halogen or methyl.

5. The compound of claim 4 , wherein at least one of R 3 , R 4 and R 5 is fluoro, chloro, bromo or methyl.

6. The compound of claim 1 , wherein the groups R 3 , R 4 and R 5 are in the 2-, or 2,4-, or 2,4,6-positions relative to the point of attachment of the phenyl ring to which they are attached to the background chain.

7. The compound of claim 1 , wherein trihaloalkyl is selected from trifluoromethyl.

8. The compound of claim 1 in which R 2 is a methylamino, dimethylamino, ethylamino or diethylamino group.

9. The racemic or optically active compound of claim 1 , selected from the group consisting of:

No.

Compound name

salt

1:1

3-Amino-N-[(3-bromo-phenyl)-

HCl

cyclohexylcarbamoyl-methyl]-N-[2-(1H-indol-3-yl)-

ethyl]-propionamide

1:2

3-Amino-N-[(2-bromo-phenyl)-

HCl

cyclohexylcarbamoyl-methyl]-N-[2-(1H-indol-3-yl)-

ethyl]-propionamide

1:3

3-Amino-N-[(4-bromo-phenyl)-

HCl

cyclohexylcarbamoyl-methyl]-N-[2-(1H-indol-3-yl)-

ethyl]-propionamide

1:4

3-Amino-N-[cyclohexylcarbamoyl-(2,4-dibromo-

HCl

phenyl)-methyl]-N-[2-(1H-indol-3-yl)-ethyl]-

propionamide

1:5

3-Amino-N-[cyclohexylcarbamoyl-(2,5-dibromo-

HCl

phenyl)-methyl]-N-[2-(1H-indol-3-yl)-ethyl]-

propionamide

1:6

3-Amino-N-[benzylcarbamoyl-(2-bromo-phenyl)-

HCl

methyl]-N-[2-(1H-indol-3-yl)-ethyl]-propionamide

hydrochloride

1:7

N-[Benzylcarbamoyl-(2-bromo-phenyl)-methyl]-3-

dimethylamino-N-[2-(1H-indol-3-yl)-ethyl]-

propionamide acetamide

1:8

N-[Benzylcarbamoyl-(2-bromo-phenyl)-methyl]-N-

[2-(5-bromo-1H-indol-3-yl)-ethyl]-3-

dimethylamino-propionamide

1:9

3-Amino-N-[benzylcarbamoyl-(2,4-dibromo-

HCl

phenyl)-methyl]-N-[2-(1H-indol-3-yl)-ethyl]-

propionamide