Abstract:
Disclosed are compounds which inhibit the activity of NAMPT, compositions
containing the compounds and methods of treating diseases during which
NAMPT is expressed.
Claims:
1-10. (canceled)
11. A method of treating inflammatory and tissue repair disorders;
particularly rheumatoid arthritis, inflammatory bowel disease, asthma and
COPD (chronic obstructive pulmonary disease), osteoarthritis,
osteoporosis and fibrotic diseases; dermatosis, including psoriasis,
atopic dermatitis and ultra-violet induced skin damage; autoimmune
diseases including systemic lupus erythematosis, multiple sclerosis,
psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection,
Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes,
glomerulonephritis, cancer, particularly wherein the cancer is selected
from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder,
pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation
associated with infection and certain viral infections, including
Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress
syndrome, and ataxia telengiectasia in a patient, said method comprising
administering to the patient a therapeutically effective amount of a
compound or a therapeutically acceptable salt thereof, selected from the
group consisting of:
5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[
3.3.1.1.sup.3,7]dec-
-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethy-
l)thiophene-2-carboxamide;
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-1-[2-(piperazin-1-yl-
)ethyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl-
}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;
5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin--
4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophen-
e-2-carboxamide; and
S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen--
2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-
-oxoethyl}-L-cysteine.
12. A method of treating inflammatory and tissue repair disorders;
particularly rheumatoid arthritis, inflammatory bowel disease, asthma and
COPD (chronic obstructive pulmonary disease), osteoarthritis,
osteoporosis and fibrotic diseases; dermatosis, including psoriasis,
atopic dermatitis and ultra-violet induced skin damage; autoimmune
diseases including systemic lupus erythematosis, multiple sclerosis,
psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection,
Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes,
glomerulonephritis, cancer, particularly wherein the cancer is selected
from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder,
pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation
associated with infection and certain viral infections, including
Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress
syndrome, and ataxia telengiectasia or spleen cancer in a patient, said
method comprising administering to the patient therapeutically effective
amount of the compound or a therapeutically acceptable salt thereof,
selected from the group consisting of:
5-[1-({3,5-dimethyl-7-[2-(methylamino)ethoxy]tricyclo[
3.3.1.1.sup.3,7]dec-
-1-yl}methyl)-5-methyl-1H-pyrazol-4-yl]-N-(imidazo[1,2-a]pyridin-7-ylmethy-
l)thiophene-2-carboxamide;
N-(imidazo[1,2-a]pyridin-7-ylmethyl)-5-[1-({4-methyl-[2-(piperazin-1-yl)e-
thyl]piperidin-4-yl}methyl)-1H-pyrazol-4-yl]thiophene-2-carboxamide;
S-(2-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen-2-yl-
}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-2-oxoethyl)-L-cysteine;
5-(1-{[1-(15-amino-4,7,10,13-tetraoxapentadecan-1-oyl)-4-methylpiperidin--
4-yl]methyl}-1H-pyrazol-4-yl)-N-(imidazo[1,2-a]pyridin-7-ylmethyl)thiophen-
e-2-carboxamide; and
S-{2-[(3-{4-[(4-{5-[(imidazo[1,2-a]pyridin-7-ylmethyl)carbamoyl]thiophen--
2-yl}-1H-pyrazol-1-yl)methyl]-4-methylpiperidin-1-yl}-3-oxopropyl)amino]-2-
-oxoethyl}-1-cysteine; and a therapeutically effective amount of one
additional therapeutic agent or more than one additional therapeutic
agent.
Description:
