Pyrazolo pyridine derivatives as NADPH oxidase inhibitors
The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).
1. A pyrazolo pyridine derivative according to Formula (I):
wherein G 1 is selected from —C(O)—R 1 and —(CH 2 ), —C(O)—R 4 ; R 1 is selected from H; optionally substituted amino; optionally substituted alkoxy; optionally substituted alkoxy C 1 -C 6 alkyl; —NR 2 R 3 ; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; optionally substituted C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl; R 2 and R 3 independently selected from H, optionally substituted C 1 -C 6 alkyl; C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl or —NR 2 R 3 can form together a ring selected from optionally substituted heteroaryl or optionally substituted heterocycloalkyl; R 4 is selected from H; optionally substituted alkoxy; optionally substituted alkoxy C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; optionally substituted C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted C 1 -C 6 alkyl; n is an integer selected from 1 to 5; G 2 is selected from H; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; heteroaryl; optionally substituted alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl; G 3 is selected from H; optionally substituted amino; optionally substituted aminoalkyl; optionally substituted aminocarbonyl; optionally substituted alkoxy; optionally substituted alkoxy C 1 -C 6 alkyl; optionally substituted carbonyl; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; optionally substituted C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl; G 4 is selected from H; optionally substituted acyl; optionally substituted acyl amino; optionally substituted acyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; optionally substituted C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl; G 5 is selected from H; optionally substituted C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkynyl; optionally substituted aryl; optionally substituted C 1 -C 6 alkyl aryl; optionally substituted aryl C 1 -C 6 alkyl; optionally substituted heteroaryl; optionally substituted C 1 -C 6 alkyl heteroaryl; optionally substituted heteroaryl C 1 -C 6 alkyl; optionally substituted C 2 -C 6 alkenyl aryl; optionally substituted aryl C 2 -C 6 alkenyl; optionally substituted C 2 -C 6 alkenyl heteroaryl; optionally substituted heteroaryl C 2 -C 6 alkenyl; optionally substituted C 3 -C 8 -cycloalkyl; optionally substituted heterocycloalkyl; optionally substituted C 1 -C 6 alkyl C 3 -C 8 -cycloalkyl; optionally substituted C 3 -C 8 -cycloalkyl C 1 -C 6 alkyl; optionally substituted C 1 -C 6 alkyl heterocycloalkyl and optionally substituted heterocycloalkyl C 1 -C 6 alkyl; and pharmaceutically acceptable salts thereof.
2. The derivative according to claim 1 wherein G 1 is —C(O)—R 1 ; R 1 is as defined in claim 1 .
3. The derivative according to claim 1 wherein G 1 is —(CH 2 ) n —C(O)—R 4 ; R 4 and n are as defined in claim 1 .
4. The derivative according to claim 1 wherein R 1 is optionally substituted C 1 -C 6 alkyl.
5. The derivative according to claim 1 wherein R 1 is optionally substituted alkoxy C 1 -C 6 alkyl.
6. The derivative according to claim 1 wherein R 1 is optionally substituted aryl C 1 -C 6 alkyl.
7. The derivative according to claim 1 wherein R 1 is optionally substituted heterocycloalkyl.
8. The derivative according to claim 1 wherein G 3 is optionally substituted C 1 -C 6 alkyl.
9. The derivative according to claim 1 wherein G 4 is optionally substituted C 1 -C 6 alkyl.
10. The derivative according to claim 1 wherein G 4 is optionally substituted amino.
11. The derivative according to claim 1 wherein G 5 is H.
12. The derivative according to claim 1 selected from the following compounds:
1-acetyl-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;
tert-butyl 4-{[4-methyl-3,6-dioxo-2-phenyl-5-(pyridin-3-ylmethyl)-2,3,5,6-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl]carbonyl}piperidine-1-carboxylate;
1-(methoxyacetyl)-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;
4-methyl-1-(4-phenoxybutanoyl)-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;
1-[(3-methoxyphenyeacetyl]-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione;
1-acetyl-4-methyl-2-(2-methylphenyl)-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione; or
1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione.
13. A pharmaceutical composition containing at least one derivative according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient thereof.