Imidazopyridazine compounds

1. A compound of Formula I

wherein:

A is pyridyl, pyrrolidinyl, or pyrazolyl, substituted with one or more A′;

each A′ is independently pyrrolidinyl or piperidinyl, optionally substituted with lower alkyl;

n is 0, 1 or 2;

B is phenyl, pyridyl, pyrrolidinyl, or piperidinyl;

each R is independently halo, hydroxy, lower alkyl, lower alkoxy, lower haloalkyl, cyano, heterocycloalkyl lower alkyl, —NH(C═O)R 1 , —C(═O)R 1 , —C(═O)OR′, —O(CH 2 ) p R 1 , CH 2 R 1 , CH 2 NHR 1 , or —C(═O)NHR 1 ;

or two R together form a bicyclic heteroaryl or heterocycloalkyl ring system;

R 1 is H or R 1′ ;

R 1′ is lower alkyl, phenyl, indolyl, indazolyl, heteroaryl lower alkyl, or heterocycloalkyl, optionally substituted with one or more R 1″ ;

each R 1″ is hydroxy, lower alkyl, lower alkoxy, carboxy, amido, amino, dialkyl amino, or oxo; and

p is 0, 1, or 2;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein A is pyridyl, substituted with one or more A′.

3. The compound of claim 2 , wherein B is phenyl.

4. The compound of claim 3 , wherein A′ is pyrrolidinyl, optionally substituted with one or more lower alkyl.

5. The compound of claim 4 , wherein A′ is methyl pyrrolidinyl or dimethyl pyrrolidinyl.

6. The compound of claim 5 , wherein R is C(═O)NHR 1 .

7. The compound of claim 5 , wherein R is —C(═O)OH.

8. The compound of claim 5 , wherein R is —NH(C═O)R 1 .

9. The compound of claim 3 , wherein n is 0 or two R together form a bicyclic heteroaryl or heterocycloalkyl ring system.

10. The compound of claim 6 , wherein R1 is phenyl, indolyl, or indazolyl, optionally substituted with one or more R 1″ .

11. A compound selected from the group consisting of:

(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(6-trifluoromethyl-pyridin-2-yl)-amine;

(5-Ethyl-pyridin-2-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-6′-yl)-amine;

(6-Phenyl-imidazo[1,2-b]pyridazin-8-yl)-(6-pyrrolidin-1-yl-pyridin-2-yl)-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

(1-tert-Butyl-1H-pyrazol-3-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

8-(2,2-Dimethyl-pyrrolidin-1-yl)-6-phenyl-imidazo[1,2-b]pyridazine;

3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid methyl ester;

3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

4-(3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoylamino)-benzoic acid;

Sodium 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoate;

3-{ 8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

(2-Methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-6′-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

4-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid methyl ester;

4-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

4-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-N-(2-pyridin-4-yl-ethyl)-benzamide;

4-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

(6-Benzo[1,3]dioxol-5-yl-imidazo[1,2-b]pyridazin-8-yl)-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(1H-Indazol-6-yl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

3-{8-[6-(2-Hydroxymethyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

[6-((R)-2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

3-[8-(6-Pyrrolidin-1-yl-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoic acid;

3-{8-[6-(3-Aza-bicyclo[3.1.0]hex-3-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

2-Methyl-3-{8-[6-((S)-2-methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

[6-(3-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

4-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoic acid;

4-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-(2-pyridin-4-yl-ethyl)-benzamide;

4-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-[2-(2-oxo-1,2-dihydro-pyridin-4-yl)-ethyl]-benzamide;

[6-(2,5-Dimethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(2-Ethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

{1-[6-(6-Phenyl-imidazo[1,2-b]pyridazin-8-ylamino)-pyridin-2-yl]-pyrrolidin-2-yl}-methanol;

[6-(2,2-Dimethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-]pyridazin-8-yl)-amine,

4-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-[2-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl)-ethyl]-benzamide;

[6-(3,3-Dimethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(2-Methoxymethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

3-{8-[6-(2-Methoxymethyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

[6-(1H-Indazol-5-yl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]amine;

3-[8-(3,5-Dimethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-1-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoic acid;

[6-(3-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

N-(2-Hydroxy-ethyl)-3-{8-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

N-(2-Hydroxy-1-methyl-ethyl)-3-{8-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]imidazo[1,2-b]pyridazin-6-yl}-benzamide;

(3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-phenyl)-morpholin-4-yl-methanone;

[6-((S)-2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

(5,6-Dimethoxy-pyridin-2-yl)-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(2-Chloro-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]amine;

N-(2-Dimethylamino-ethyl)-3-{8-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-o-tolyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-[6-(2-trifluoromethyl-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-amine;

3-{8-[6-((S)-2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

4-{8-[6-((S)-2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

3-{8-[6((S)-2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

(6-Benzothiazol-6-yl-imidazo[1,2-b]pyridazin-8-yl)-[6-((S)-2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(2,5-Dimethyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-phenyl-imidazo[1,2-b]pyridazin-8-yl)-amine;

4-{3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoylamino}-benzoic acid;

3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-(1H-indazol-5-yl)-benzamide;

3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-(1-oxo-2,3-dihydro-H-isoindol-5-yl)-benzamide;

4-{3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoylamino}-2-methoxy-benzoic acid;

3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-N-(2-oxo-2,3-dihydro-1H-indol-5-yl)-benzamide;

3-{8-[6-(3,3-Dimethyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

3-{8-[6-(2,5-Dimethyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

3-[8-(4,4-Dimethyl-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-6-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoic acid;

[6-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-[6-(1,2,3,4-tetrahydro-quinolin-7-yl)-imidazo[1,2-b]pyridazin-8-yl]-amine;

1-(7-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-3,4-dihydro-1H-isoquinolin-2-yl)-ethanone;

3-{8-[6-(3-tert-Butyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid methyl ester;

3-{8-[6-(3-tert-Butyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzoic acid;

3-{8-[6-(3-tert-Butyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzamide;

(3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-phenyl)-methanol;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-[6-(3-piperidin-1-ylmethyl-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-[6-(3-pyrrolidin-1-ylmethyl-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-amine;

[6-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-((S)-2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

N-{1-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-piperidin-3-yl}-terephthalamic acid;

1-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-piperidine-3-carboxylic acid (1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl)-amide;

4-({1-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-piperidine-3-carbonyl}-amino)-benzoic acid;

4-({1-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidine-3-carbonyl}-amino)-benzoic acid;

N-{1-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidin-3-yl}-terephthalamic acid;

4-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-phenol;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-pyridin-3-yl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-benzonitrile;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-(6-pyridin-4-yl-imidazo[1,2-b]pyridazin-8-yl)-amine;

[6-(5-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

[6-(3-Aminomethyl-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(4-tert-Butyl-phenyl)-imidazo[1,2-b]pyridazin-8-yl]-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

3-{8-[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-ylamino]-imidazo[1,2-b]pyridazin-6-yl}-phenol;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[3-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[3-(2-morpholin-4-yl-ethoxy)-phenyl]imidazo[1,2-b]pyridazin-8-yl}-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

{6-[3-(2-Diethylamino-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

{6-[4-(2-Diethylamino-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-[6-(2-methyl-pyrrolidin-1-yl)-pyridin-2-yl]-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[3-(piperidin-4-ylaminomethyl)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

[6-(2-Methyl-pyrrolidin-1-yl)-pyridin-2-yl]-{6-[3-(2-piperazin-1-yl-ethoxy)-phenyl]-imidazo[1,2-b]pyridazin-8-yl}-amine;

3-[8-(5,6-Dimethoxy-pyridin-2-ylamino)-imidazo[1,2-b]pyridazin-6-yl]-benzoic acid; and

3-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(4-(methylcarbamoyl)phenyl)benzamide,

or a pharmaceutically acceptable salt thereof.

12. A method for treating an inflammatory or autoimmune condition comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

13. The method of claim 12 , further comprising administering an additional therapeutic agent selected from a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating diabetes, or an agent for treating immunodeficiency disorders.

14. A method for treating an inflammatory condition comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

15. A method for treating rheumatoid arthritis comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

16. A method for treating asthma comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

17. A method for treating an immune disorder including lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes, complications from organ transplants, xeno transplantation, diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, and Leukemia, comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

18. A method for treating an inflammatory condition comprising co-administering to a patient in need thereof a therapeutically effective amount of an anti-inflammatory compound in combination with a therapeutically effective amount of the compound of claim 1 .

19. A method for treating an immune disorder comprising co-administering to a patient in need thereof a therapeutically effective amount of an immunosuppressant compound in combination with a therapeutically effective amount of the compound of claim 1 .

20. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, admixed with at least one pharmaceutically acceptable carrier, excipient or diluent.

21. The pharmaceutical composition of claim 20 , further comprising an additional therapeutic agent selected from a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating diabetes, and an agent for treating immunodeficiency disorders.