CA2515939A1 - Novel compounds - Google Patents
Novel compounds Download PDFInfo
- Publication number
- CA2515939A1 CA2515939A1 CA002515939A CA2515939A CA2515939A1 CA 2515939 A1 CA2515939 A1 CA 2515939A1 CA 002515939 A CA002515939 A CA 002515939A CA 2515939 A CA2515939 A CA 2515939A CA 2515939 A1 CA2515939 A1 CA 2515939A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- cr10r20
- optionally substituted
- compound according
- nr4r14
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 283
- 238000000034 method Methods 0.000 claims abstract description 104
- 201000010099 disease Diseases 0.000 claims abstract description 63
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 63
- -1 1,5,7-trisubstituted quinoline-2(1H)-one compounds Chemical class 0.000 claims abstract description 46
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims abstract description 46
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims abstract description 39
- 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims abstract description 34
- 230000001404 mediated effect Effects 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 246
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 91
- 125000001072 heteroaryl group Chemical group 0.000 claims description 67
- 125000003118 aryl group Chemical group 0.000 claims description 56
- 150000002431 hydrogen Chemical group 0.000 claims description 53
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 47
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical group 0.000 claims description 41
- 241000124008 Mammalia Species 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000003107 substituted aryl group Chemical group 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 241000700605 Viruses Species 0.000 claims description 26
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 241000430519 Human rhinovirus sp. Species 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 206010040070 Septic Shock Diseases 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 241000709661 Enterovirus Species 0.000 claims description 14
- 206010062106 Respiratory tract infection viral Diseases 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 230000002685 pulmonary effect Effects 0.000 claims description 11
- 201000005569 Gout Diseases 0.000 claims description 10
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 10
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 206010003246 arthritis Diseases 0.000 claims description 10
- 210000004556 brain Anatomy 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- AHCYGXRBOJTSOA-UHFFFAOYSA-N 7-bromo-1,5-bis(2-chlorophenyl)-1,6-naphthyridin-2-one Chemical compound ClC1=CC=CC=C1C1=NC(Br)=CC2=C1C=CC(=O)N2C1=CC=CC=C1Cl AHCYGXRBOJTSOA-UHFFFAOYSA-N 0.000 claims description 8
- 206010035664 Pneumonia Diseases 0.000 claims description 8
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 206010022000 influenza Diseases 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 241000712461 unidentified influenza virus Species 0.000 claims description 8
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 206010028289 Muscle atrophy Diseases 0.000 claims description 7
- 206010033078 Otitis media Diseases 0.000 claims description 7
- 206010063837 Reperfusion injury Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 208000002780 macular degeneration Diseases 0.000 claims description 7
- 201000008482 osteoarthritis Diseases 0.000 claims description 7
- 201000009890 sinusitis Diseases 0.000 claims description 7
- 241000701161 unidentified adenovirus Species 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 241000711573 Coronaviridae Species 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 208000002606 Paramyxoviridae Infections Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 6
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 6
- 230000002917 arthritic effect Effects 0.000 claims description 6
- 230000000747 cardiac effect Effects 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 201000009240 nasopharyngitis Diseases 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 5
- 125000006374 C2-C10 alkenyl group Chemical class 0.000 claims description 5
- 206010063094 Cerebral malaria Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 206010010741 Conjunctivitis Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 5
- 206010014824 Endotoxic shock Diseases 0.000 claims description 5
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 5
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 5
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims description 5
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 5
- 201000009906 Meningitis Diseases 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 5
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 5
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 5
- 208000033464 Reiter syndrome Diseases 0.000 claims description 5
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
- 201000010001 Silicosis Diseases 0.000 claims description 5
- 206010042496 Sunburn Diseases 0.000 claims description 5
- 208000007536 Thrombosis Diseases 0.000 claims description 5
- 206010048873 Traumatic arthritis Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 5
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 5
- 230000002491 angiogenic effect Effects 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 208000019664 bone resorption disease Diseases 0.000 claims description 5
- 206010006451 bronchitis Diseases 0.000 claims description 5
- 208000007451 chronic bronchitis Diseases 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 5
- 230000000302 ischemic effect Effects 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 208000002574 reactive arthritis Diseases 0.000 claims description 5
- 201000005404 rubella Diseases 0.000 claims description 5
- 230000036303 septic shock Effects 0.000 claims description 5
- 201000004595 synovitis Diseases 0.000 claims description 5
- FGRCFQSRHJPOOF-UHFFFAOYSA-N 1,5-bis(4-fluorophenyl)quinolin-2-one Chemical compound C1=CC(F)=CC=C1C1=CC=CC2=C1C=CC(=O)N2C1=CC=C(F)C=C1 FGRCFQSRHJPOOF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- YGRYGQKVGGEPER-UHFFFAOYSA-N 5-(2,4-difluorophenyl)-1-(4-fluorophenyl)-1,8-naphthyridin-2-one Chemical compound C1=CC(F)=CC=C1N1C(=O)C=CC2=C(C=3C(=CC(F)=CC=3)F)C=CN=C21 YGRYGQKVGGEPER-UHFFFAOYSA-N 0.000 claims description 4
- LIYRXUGPUPJBLG-UHFFFAOYSA-N 5-(2,4-difluorophenyl)-1-(4-fluorophenyl)quinolin-2-one Chemical compound C1=CC(F)=CC=C1N1C(=O)C=CC2=C(C=3C(=CC(F)=CC=3)F)C=CC=C21 LIYRXUGPUPJBLG-UHFFFAOYSA-N 0.000 claims description 4
- APKKZTGSYROVPP-UHFFFAOYSA-N 5-phenyl-1h-1,6-naphthyridin-2-one Chemical compound N1=CC=C2NC(=O)C=CC2=C1C1=CC=CC=C1 APKKZTGSYROVPP-UHFFFAOYSA-N 0.000 claims description 4
- CNFITDNLXNAZHQ-UHFFFAOYSA-N 7-bromo-1,5-bis(2-chlorophenyl)-3,4-dihydro-1,6-naphthyridin-2-one Chemical compound ClC1=CC=CC=C1N1C(C=C(Br)N=C2C=3C(=CC=CC=3)Cl)=C2CCC1=O CNFITDNLXNAZHQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 208000018652 Closed Head injury Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- RBYQNKUAGUQDAA-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-(1h-imidazol-2-ylmethylamino)-1,6-naphthyridin-2-one Chemical compound ClC1=CC=CC=C1C1=NC(NCC=2NC=CN=2)=CC2=C1C=CC(=O)N2C1=CC=CC=C1Cl RBYQNKUAGUQDAA-UHFFFAOYSA-N 0.000 claims description 3
- UTEMMEATFDOJTF-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-[2-(propan-2-ylamino)ethylamino]-1,6-naphthyridin-2-one Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=NC(NCCNC(C)C)=CC=2N1C1=CC=CC=C1Cl UTEMMEATFDOJTF-UHFFFAOYSA-N 0.000 claims description 3
- GMZQTGQJWIBEEA-UHFFFAOYSA-N 1,5-bis(4-fluorophenyl)-1,8-naphthyridin-2-one Chemical compound C1=CC(F)=CC=C1C1=CC=NC2=C1C=CC(=O)N2C1=CC=C(F)C=C1 GMZQTGQJWIBEEA-UHFFFAOYSA-N 0.000 claims description 3
- IGZZQGLWJPZOIX-UHFFFAOYSA-N 7-amino-1,5-bis(2-chlorophenyl)-1,6-naphthyridin-2-one Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=NC(N)=CC=2N1C1=CC=CC=C1Cl IGZZQGLWJPZOIX-UHFFFAOYSA-N 0.000 claims description 3
- HYXWKBBZPPNFRK-UHFFFAOYSA-N 7-chloro-1,5-bis(2-chlorophenyl)-1,6-naphthyridin-2-one Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=NC(Cl)=CC=2N1C1=CC=CC=C1Cl HYXWKBBZPPNFRK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- PNBNHPIRIQEGTR-UHFFFAOYSA-N 1-benzyl-5-phenyl-1,6-naphthyridin-2-one Chemical compound O=C1C=CC2=C(C=3C=CC=CC=3)N=CC=C2N1CC1=CC=CC=C1 PNBNHPIRIQEGTR-UHFFFAOYSA-N 0.000 claims description 2
- PIOGKVWSMAZIFA-UHFFFAOYSA-N 1-methyl-5-phenyl-1,6-naphthyridin-2-one Chemical compound C=12C=CC(=O)N(C)C2=CC=NC=1C1=CC=CC=C1 PIOGKVWSMAZIFA-UHFFFAOYSA-N 0.000 claims description 2
- 230000035939 shock Effects 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims 3
- 208000020832 chronic kidney disease Diseases 0.000 claims 3
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 3
- 208000010247 contact dermatitis Diseases 0.000 claims 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 3
- 208000037803 restenosis Diseases 0.000 claims 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- PYQCKLNGCQVGFP-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-(1,3-dihydroxypropan-2-ylamino)-1,6-naphthyridin-2-one Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=NC(NC(CO)CO)=CC=2N1C1=CC=CC=C1Cl PYQCKLNGCQVGFP-UHFFFAOYSA-N 0.000 claims 2
- AHUOKSBJVXQBQH-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-(1,3-dihydroxypropan-2-ylamino)quinolin-2-one Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3)Cl)C2=CC(NC(CO)CO)=CC=1C1=CC=CC=C1Cl AHUOKSBJVXQBQH-UHFFFAOYSA-N 0.000 claims 2
- WLVWEQBXJOIHES-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-[2-(propan-2-ylamino)ethylamino]quinolin-2-one Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3)Cl)C2=CC(NCCNC(C)C)=CC=1C1=CC=CC=C1Cl WLVWEQBXJOIHES-UHFFFAOYSA-N 0.000 claims 2
- NCVGTRDMXZGULL-UHFFFAOYSA-N 1-(4-fluorophenyl)-5-(4-methylphenyl)quinolin-2-one Chemical compound C1=CC(C)=CC=C1C1=CC=CC2=C1C=CC(=O)N2C1=CC=C(F)C=C1 NCVGTRDMXZGULL-UHFFFAOYSA-N 0.000 claims 2
- OZRPUNDRYYIJFC-UHFFFAOYSA-N 6-bromo-1,5-bis(2-chlorophenyl)-7-methoxyquinolin-2-one Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=C(Br)C(OC)=CC=2N1C1=CC=CC=C1Cl OZRPUNDRYYIJFC-UHFFFAOYSA-N 0.000 claims 2
- IURAJLZDFDIJDK-UHFFFAOYSA-N n-[2-[[1,5-bis(2-chlorophenyl)-2-oxo-1,6-naphthyridin-7-yl]amino]ethyl]acetamide Chemical compound O=C1C=CC=2C(C=3C(=CC=CC=3)Cl)=NC(NCCNC(=O)C)=CC=2N1C1=CC=CC=C1Cl IURAJLZDFDIJDK-UHFFFAOYSA-N 0.000 claims 2
- GMGXDNHBKGSSGN-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-(1,3-dihydroxypropan-2-ylamino)-1,8-naphthyridin-2-one Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3)Cl)C2=NC(NC(CO)CO)=CC=1C1=CC=CC=C1Cl GMGXDNHBKGSSGN-UHFFFAOYSA-N 0.000 claims 1
- LNDRWHWANLOMIC-UHFFFAOYSA-N 1,5-bis(2-chlorophenyl)-7-[2-(propan-2-ylamino)ethylamino]-1,8-naphthyridin-2-one Chemical compound C=12C=CC(=O)N(C=3C(=CC=CC=3)Cl)C2=NC(NCCNC(C)C)=CC=1C1=CC=CC=C1Cl LNDRWHWANLOMIC-UHFFFAOYSA-N 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 13
- 238000002560 therapeutic procedure Methods 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 6
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- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 24
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- 150000001408 amides Chemical class 0.000 description 18
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
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- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
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- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical class [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- FNXKBSAUKFCXIK-UHFFFAOYSA-M sodium;hydrogen carbonate;8-hydroxy-7-iodoquinoline-5-sulfonic acid Chemical class [Na+].OC([O-])=O.C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 FNXKBSAUKFCXIK-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
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- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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- 210000002268 wool Anatomy 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Rheumatology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
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- Oncology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
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- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US44741003P | 2003-02-14 | 2003-02-14 | |
| US60/447,410 | 2003-02-14 | ||
| US53809504P | 2004-01-21 | 2004-01-21 | |
| US60/538,095 | 2004-01-21 | ||
| PCT/US2004/004406 WO2004073628A2 (en) | 2003-02-14 | 2004-02-13 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2515939A1 true CA2515939A1 (en) | 2004-09-02 |
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| JP (1) | JP2006517976A (enExample) |
| AU (1) | AU2004212957A1 (enExample) |
| CA (1) | CA2515939A1 (enExample) |
| MX (1) | MXPA05008612A (enExample) |
| PL (1) | PL378111A1 (enExample) |
| WO (1) | WO2004073628A2 (enExample) |
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| PE20100741A1 (es) | 2005-03-25 | 2010-11-25 | Glaxo Group Ltd | COMPUESTOS DERIVADOS DE 3,4-DIHIDROPIRIMIDO[4,5-d]PIRIMIDIN-2(1H)-ONA COMO INHIBIDORES DE QUINASA p38 |
| TWI389690B (zh) | 2005-03-25 | 2013-03-21 | Glaxo Group Ltd | 新穎化合物（一） |
| BRPI0608907A2 (pt) * | 2005-05-10 | 2010-02-17 | Itermune Inc | método de modulação de sistema de proteìna cinase ativada por estresse |
| JPWO2008001929A1 (ja) | 2006-06-28 | 2009-12-03 | あすか製薬株式会社 | 炎症性腸疾患の処置剤 |
| AU2008215659B2 (en) | 2007-02-16 | 2012-11-01 | Aska Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising microparticle oily suspension |
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| AU2009267161B2 (en) * | 2008-07-03 | 2014-11-06 | Merck Patent Gmbh | Naphthyridininones as Aurora kinase inhibitors |
| CN103034654B (zh) * | 2011-10-10 | 2016-06-15 | 中国电信股份有限公司 | 社会化动态消息呈现控制方法及系统 |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| RU2692485C2 (ru) | 2014-04-02 | 2019-06-25 | Интермьюн, Инк. | Противофиброзные пиридиноны |
| JP6529085B2 (ja) * | 2014-04-18 | 2019-06-12 | 武田薬品工業株式会社 | 複素環化合物 |
| CA2986611C (en) | 2015-06-15 | 2023-10-03 | Nmd Pharma Aps | Compounds for use in treating neuromuscular disorders |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
| CA3127373A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce dux4 and downstream gene expression for the treatment of fshd |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| US11591284B2 (en) | 2017-12-14 | 2023-02-28 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US11730714B2 (en) | 2017-12-14 | 2023-08-22 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US11147788B2 (en) | 2017-12-14 | 2021-10-19 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US12440477B2 (en) | 2017-12-14 | 2025-10-14 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| CN116669726A (zh) * | 2020-12-29 | 2023-08-29 | 谛希诺生物科技有限公司 | 对外核苷酸焦磷酸酶-磷酸二酯酶具有抑制活性的新颖的萘啶酮衍生物及其用途 |
| WO2022146022A1 (ko) * | 2020-12-29 | 2022-07-07 | 주식회사 티씨노바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 나프티리딘온 유도체 및 이들의 용도 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA966134A (en) * | 1972-05-05 | 1975-04-15 | Haydn W.R. Williams | 1,8-naphthyridine compounds |
| US3962262A (en) * | 1973-04-11 | 1976-06-08 | Merck & Co., Inc. | 1,8-naphthyridine compounds |
| US4031103A (en) * | 1974-06-07 | 1977-06-21 | Merck Sharp & Dohme (I.A.) Corporation | 1,8-Naphthyridine compounds |
| ZA803539B (en) | 1979-06-14 | 1982-01-27 | Wellcome Found | Alkoxybenzylrimidines method for their preparation formulation thereof and their use in medicine |
| PT79699B (en) * | 1983-12-22 | 1986-12-10 | Pfizer | Process for preparing quinolone inotropic agents |
| US4560691A (en) * | 1984-07-13 | 1985-12-24 | Sterling Drug Inc. | 5-(Phenyl)-1,6-naphthyridin-2(1H)-ones, their cardiotonic use and preparation |
| US4650806A (en) * | 1985-01-14 | 1987-03-17 | Sterling Drug Inc. | Cardiotonic 5-(heterylcarbonyl)-pyridones |
| US4567186A (en) * | 1985-01-14 | 1986-01-28 | Sterling Drug Inc. | 5-Heteryl-1,6-naphthyridin-2(1H)-ones, cardiotonic use thereof and intermediates therefor |
| NZ214837A (en) * | 1985-01-28 | 1988-10-28 | Sterling Drug Inc | 5-substituted 1,6 naphthyridin-2(1h)-ones |
| EP0278686A1 (en) | 1987-02-07 | 1988-08-17 | The Wellcome Foundation Limited | Pyridopyrimidines methods for their preparation and pharmaceutical formulations thereof |
| JPH01261306A (ja) | 1988-04-13 | 1989-10-18 | Nippon Kayaku Co Ltd | ２−アルキルチオ−４−アミノピリミジン誘導体を有効成分とする開花促進剤 |
| DE3911064A1 (de) * | 1989-04-06 | 1990-10-11 | Bayer Ag | Substituierte 1,8-naphthyridine |
| WO1992020642A1 (en) | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| DE4131029A1 (de) | 1991-09-18 | 1993-07-29 | Basf Ag | Substituierte pyrido (2,3-d) pyrimidine als antidots |
| US5426110A (en) | 1993-10-06 | 1995-06-20 | Eli Lilly And Company | Pyrimidinyl-glutamic acid derivatives |
| US5547954A (en) | 1994-05-26 | 1996-08-20 | Fmc Corporation | 2,4-Diamino-5,6-disubstituted-and 5,6,7-trisubstituted-5-deazapteridines as insecticides |
| US5817670A (en) | 1994-08-29 | 1998-10-06 | Yamanouchi Pharmaceutical Co., Ltd. | Naphthyridine derivatives and pharmaceutical compositions thereof |
| US5620981A (en) | 1995-05-03 | 1997-04-15 | Warner-Lambert Company | Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| US6875769B2 (en) | 1996-05-23 | 2005-04-05 | Pfizer Inc. | Substituted6,6-hetero-bicyclicderivatives |
| US5989588A (en) | 1996-10-04 | 1999-11-23 | Merck & Co., Inc. | Methods and compositions for preventing and treating heartburn |
| US6498163B1 (en) | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
| US5945422A (en) | 1997-02-05 | 1999-08-31 | Warner-Lambert Company | N-oxides of amino containing pyrido 2,3-D! pyrimidines |
| KR20010041015A (ko) | 1998-02-17 | 2001-05-15 | 윌리엄 제이. 리플린 | 항바이러스성 피리미딘 유도체 |
| HRP20020851A2 (en) * | 2000-04-28 | 2005-02-28 | Pfizer Products Inc. | Sodium-hydrogen exchanger type 1 inhibitor (nhe-1) |
| EP1345603A4 (en) * | 2000-12-20 | 2004-09-08 | Merck & Co Inc | (HALO-BENZO-CARBONYL) HETEROCYCLO-CONDENSED PHENYL-P38-KINASE INHIBITING AGENTS |
| JP4178783B2 (ja) | 2001-10-19 | 2008-11-12 | 三菱化学株式会社 | 光学記録媒体 |
-
2004
- 2004-02-13 JP JP2006503591A patent/JP2006517976A/ja active Pending
- 2004-02-13 WO PCT/US2004/004406 patent/WO2004073628A2/en not_active Ceased
- 2004-02-13 MX MXPA05008612A patent/MXPA05008612A/es unknown
- 2004-02-13 US US10/545,565 patent/US7550480B2/en not_active Expired - Fee Related
- 2004-02-13 EP EP04711237A patent/EP1596860A4/en not_active Withdrawn
- 2004-02-13 CA CA002515939A patent/CA2515939A1/en not_active Abandoned
- 2004-02-13 AU AU2004212957A patent/AU2004212957A1/en not_active Abandoned
- 2004-02-13 PL PL378111A patent/PL378111A1/pl not_active Application Discontinuation
-
2009
- 2009-05-15 US US12/466,401 patent/US20090239897A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20060211727A1 (en) | 2006-09-21 |
| US7550480B2 (en) | 2009-06-23 |
| US20090239897A1 (en) | 2009-09-24 |
| WO2004073628A3 (en) | 2005-05-12 |
| JP2006517976A (ja) | 2006-08-03 |
| EP1596860A2 (en) | 2005-11-23 |
| MXPA05008612A (es) | 2005-12-05 |
| EP1596860A4 (en) | 2009-05-27 |
| WO2004073628A2 (en) | 2004-09-02 |
| AU2004212957A1 (en) | 2004-09-02 |
| PL378111A1 (pl) | 2006-03-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |