Novel Compounds
The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): And salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.
1 - 12 . (canceled)
13 . A compound of formula (I):
wherein
R 1 is 9- or 10-membered bicyclic heteroaryl wherein the 9- or 10-membered bicyclic heteroaryl contains from one to three heteroatoms independently selected from oxygen and nitrogen and is optionally substituted by C 1-6 alkyl, C 3-6 cycloalkyl, halo, —CN or —NHSO 2 R 5 , or
pyridinyl optionally substituted by one or two substituents independently selected from C 1-6 alkyl, —OR 6 , halo and —NHSO 2 R 7 ;
R 2 and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6- or 7-membered heterocyclyl wherein the 6- or 7-membered heterocyclyl optionally contains an oxygen atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from C 1-6 alkyl;
R 4 is hydrogen or methyl;
R 6 is hydrogen or C 1-4 alkyl; and
R 5 and R 7 are each independently C 1-6 alkyl, or phenyl optionally substituted by one or two substituents independently selected from halo;
or a salt thereof.
14 . A compound according to claim 13 , or a salt thereof, wherein R 1 is 9-membered bicyclic heteroaryl wherein the 9-membered bicyclic heteroaryl contains one or two nitrogen atoms, or pyridinyl optionally substituted by one or two substituents independently selected from —OR 6 and —NHSO 2 R 7 .
15 . A compound according to claim 13 , or a salt thereof, wherein R 1 is indolyl.
16 . A compound according to claim 13 , or a salt thereof, wherein R 1 is pyridinyl optionally substituted by one or two substituents independently selected from —OR 6 and —NHSO 2 R 7 .
17 . A compound according to claim 13 , or a salt thereof, wherein R 2 and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl wherein the 6-membered heterocyclyl optionally contains an oxygen atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from C 1-6 alkyl.
18 . A compound according to claim 13 , or a salt thereof, wherein R 2 and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl wherein the 6-membered heterocyclyl contains an oxygen atom and is optionally substituted by one or two substituents independently selected from C 1-4 alkyl.
19 . A compound according to claim 13 , or a salt thereof, wherein R 2 and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl wherein the 6-membered heterocyclyl contains a further nitrogen atom and is optionally substituted by C 1-4 alkyl.
20 . A compound according to claim 13 , or a salt thereof, wherein R 4 is hydrogen.
21 . A compound according to claim 13 in the form of a pharmaceutically acceptable salt thereof.
22 . A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.
23 . A method of treating a disorder mediated by inappropriate PI3-kinase activity comprising administering a safe and effective amount of a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.
24 . A method according to claim 23 wherein the disorder mediated by inappropriate PI3-kinase activity is a respiratory disease, a viral infection, a non-viral respiratory infection, an allergic disease, an autoimmune disease, an inflammatory disorder, a cardiovascular disease, a hematologic malignancy, a neurodegenerative disease, pancreatitis, multiorgan failure, kidney disease, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection, lung injury, or pain.
25 . A method according to claim 23 wherein the disorder mediated by inappropriate PI3-kinase activity is asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), viral respiratory tract infections, viral exacerbation of respiratory diseases, aspergillosis, leishmaniasis, allergic rhinitis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, thrombosis, atherosclerosis, hematologic malignancy, neurodegenerative disease, pancreatitis, multiorgan failure, kidney disease, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection, lung injury, pain associated with rheumatoid arthritis or osteoarthritis, back pain, general inflammatory pain, post hepatic neuralgia, diabetic neuropathy, inflammatory neuropathic pain (trauma), trigeminal neuralgia or Central pain.