CA2274063C - Substituted pyrimidine compounds and their use - Google Patents
Substituted pyrimidine compounds and their use Download PDFInfo
- Publication number
- CA2274063C CA2274063C CA002274063A CA2274063A CA2274063C CA 2274063 C CA2274063 C CA 2274063C CA 002274063 A CA002274063 A CA 002274063A CA 2274063 A CA2274063 A CA 2274063A CA 2274063 C CA2274063 C CA 2274063C
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- Prior art keywords
- amino
- radicals
- alkyl
- alkoxy
- radical
- Prior art date
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- 150000003230 pyrimidines Chemical class 0.000 title abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 108090001007 Interleukin-8 Proteins 0.000 claims abstract description 25
- 108090001005 Interleukin-6 Proteins 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 238000011321 prophylaxis Methods 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 206010061218 Inflammation Diseases 0.000 claims abstract description 10
- 230000004054 inflammatory process Effects 0.000 claims abstract description 10
- -1 heterocyclyl radicals Chemical class 0.000 claims description 1095
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 370
- 150000003254 radicals Chemical class 0.000 claims description 364
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 253
- 125000004414 alkyl thio group Chemical group 0.000 claims description 171
- 125000003118 aryl group Chemical group 0.000 claims description 154
- 125000003282 alkyl amino group Chemical group 0.000 claims description 143
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 128
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 120
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 117
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 105
- 125000000217 alkyl group Chemical group 0.000 claims description 95
- 125000003545 alkoxy group Chemical group 0.000 claims description 85
- 125000000623 heterocyclic group Chemical group 0.000 claims description 83
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 78
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 76
- 125000001072 heteroaryl group Chemical group 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 64
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000001188 haloalkyl group Chemical group 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 34
- 108010002352 Interleukin-1 Proteins 0.000 claims description 27
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 27
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 24
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 15
- 150000005840 aryl radicals Chemical group 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 14
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 13
- 125000001589 carboacyl group Chemical group 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 11
- 229960004666 glucagon Drugs 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 102000051325 Glucagon Human genes 0.000 claims description 9
- 108060003199 Glucagon Proteins 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 9
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 9
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 7
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 6
- 229910006069 SO3H Inorganic materials 0.000 claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 5
- 239000005557 antagonist Substances 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 4
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 4
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- HAOYRMOYPXUUBE-UHFFFAOYSA-N 2-[(2,6-dichlorophenyl)methyl]-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1CC1=C(Cl)C=CC=C1Cl HAOYRMOYPXUUBE-UHFFFAOYSA-N 0.000 claims description 3
- AQASPACMJACZAD-UHFFFAOYSA-N 2-[2-(2-chlorophenyl)ethylamino]-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(O)=NC=1NCCC1=CC=CC=C1Cl AQASPACMJACZAD-UHFFFAOYSA-N 0.000 claims description 3
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- DAMZFIYOEBDWLN-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(3-phenylpropylamino)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1NCCCC1=CC=CC=C1 DAMZFIYOEBDWLN-UHFFFAOYSA-N 0.000 claims description 2
- XSGRYEKOYIWSTG-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(3-phenylpropylsulfanyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1SCCCC1=CC=CC=C1 XSGRYEKOYIWSTG-UHFFFAOYSA-N 0.000 claims description 2
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 87
- 241000124008 Mammalia Species 0.000 claims 16
- 230000036470 plasma concentration Effects 0.000 claims 8
- 150000001356 alkyl thiols Chemical class 0.000 claims 5
- 208000027520 Somatoform disease Diseases 0.000 claims 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims 4
- 208000027753 pain disease Diseases 0.000 claims 4
- 150000003180 prostaglandins Chemical class 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 1
- HJHGQAVUFBUUKT-UHFFFAOYSA-N 2-(2-anilinoethylsulfanyl)-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1SCCNC1=CC=CC=C1 HJHGQAVUFBUUKT-UHFFFAOYSA-N 0.000 claims 1
- CTZFGEUKZGVDSP-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(2-phenoxyethylsulfanyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1SCCOC1=CC=CC=C1 CTZFGEUKZGVDSP-UHFFFAOYSA-N 0.000 claims 1
- PUFINCKHIDBOBP-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(2-phenylethylsulfanyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1SCCC1=CC=CC=C1 PUFINCKHIDBOBP-UHFFFAOYSA-N 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 87
- 201000010099 disease Diseases 0.000 abstract description 24
- 102000004890 Interleukin-8 Human genes 0.000 abstract description 21
- 239000000543 intermediate Substances 0.000 abstract description 10
- 230000001404 mediated effect Effects 0.000 abstract description 10
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- 239000000651 prodrug Substances 0.000 abstract description 9
- 208000002193 Pain Diseases 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 238000005160 1H NMR spectroscopy Methods 0.000 description 100
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 94
- 125000005843 halogen group Chemical group 0.000 description 93
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 44
- 238000002360 preparation method Methods 0.000 description 40
- 102100040247 Tumor necrosis factor Human genes 0.000 description 39
- 101150041968 CDC13 gene Proteins 0.000 description 38
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000012458 free base Substances 0.000 description 36
- 125000004076 pyridyl group Chemical group 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 34
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- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 34
- 125000000714 pyrimidinyl group Chemical group 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 31
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- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 25
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- 239000007787 solid Substances 0.000 description 23
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 description 22
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- 125000004432 carbon atom Chemical group C* 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
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- 229940093499 ethyl acetate Drugs 0.000 description 12
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
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- 238000012360 testing method Methods 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 11
- 238000013459 approach Methods 0.000 description 11
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- LHLSGSPSOSTKCH-UHFFFAOYSA-N 2-chloro-5-(4-fluorophenyl)-4-pyridin-4-ylpyrimidine Chemical compound C1=CC(F)=CC=C1C1=CN=C(Cl)N=C1C1=CC=NC=C1 LHLSGSPSOSTKCH-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
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- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical class 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical class 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical class O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 150000008648 triflates Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- COHOGNZHAUOXPA-UHFFFAOYSA-N trimethyl(phenyl)stannane Chemical compound C[Sn](C)(C)C1=CC=CC=C1 COHOGNZHAUOXPA-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3212896P | 1996-12-05 | 1996-12-05 | |
US60/032,128 | 1996-12-05 | ||
US5095097P | 1997-06-13 | 1997-06-13 | |
US60/050,950 | 1997-06-13 | ||
US97605497A | 1997-11-21 | 1997-11-21 | |
US08/976,054 | 1997-11-21 | ||
PCT/US1997/022390 WO1998024782A2 (en) | 1996-12-05 | 1997-12-04 | Substituted pyrimidine compounds and their use |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2274063A1 CA2274063A1 (en) | 1998-06-11 |
CA2274063C true CA2274063C (en) | 2007-09-04 |
Family
ID=27364030
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002274063A Expired - Fee Related CA2274063C (en) | 1996-12-05 | 1997-12-04 | Substituted pyrimidine compounds and their use |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0948497A2 (cs) |
CN (1) | CN1246858A (cs) |
AR (1) | AR048564A1 (cs) |
AU (1) | AU733877C (cs) |
BG (1) | BG65128B1 (cs) |
BR (1) | BR9713850A (cs) |
CA (1) | CA2274063C (cs) |
CZ (1) | CZ296911B6 (cs) |
HU (1) | HUP0001698A3 (cs) |
IL (1) | IL130180A0 (cs) |
NZ (1) | NZ335997A (cs) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100860827B1 (ko) * | 2000-09-06 | 2008-09-30 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 글리코겐 합성효소 키나아제 3의 억제제 |
DE60231414D1 (de) | 2001-09-21 | 2009-04-16 | Braband Friedrich Wilhelm | 3-substituierte 4-pyrimidonderivate |
DK1427709T3 (da) | 2001-09-21 | 2006-04-03 | Mitsubishi Pharma Corp | 3-substituerede 4-pyrimidonderivater |
TWI330183B (cs) * | 2001-10-22 | 2010-09-11 | Eisai R&D Man Co Ltd | |
EP1340759A1 (en) * | 2002-02-28 | 2003-09-03 | Sanofi-Synthelabo | 1-[alkyl], 1-[(heteroaryl)alkyl] and 1-[(aryl)alkyl]-7-(pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-5(1H)-one derivatives |
CA2510170C (en) | 2002-12-16 | 2011-05-24 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
TWI357408B (en) | 2003-03-26 | 2012-02-01 | Mitsubishi Tanabe Pharma Corp | 3-substituted-4-pyrimidone derivatives |
MX337179B (es) * | 2010-10-18 | 2016-02-15 | Cerenis Therapeutics Holding Sa | Compuestos, composiciones y metodos utiles para la movilizacion de colesterol. |
TWI651310B (zh) * | 2014-02-20 | 2019-02-21 | 日商日本煙草產業股份有限公司 | 三化合物及其醫藥用途 |
KR102649802B1 (ko) * | 2015-10-29 | 2024-03-20 | 아스카 세이야쿠 가부시키가이샤 | 피리미딘 유도체 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE759176A (fr) * | 1969-11-20 | 1971-05-19 | Sandoz Sa | Derives de la pyrimidine, leur preparation et medicaments contenant cesderives |
US4438117A (en) * | 1980-09-03 | 1984-03-20 | E. I. Du Pont De Nemours And Company | 2-Substituted thio-4,5-diarylpyrimidines |
DE3319843A1 (de) * | 1983-06-01 | 1984-12-06 | Ali-Akbar Dipl.-Chem. Dr. 4300 Mülheim Pourzal | Verfahren zur herstellung von pyrimidinen aus nitrilen und alkinen |
US4500533A (en) * | 1983-06-22 | 1985-02-19 | Eli Lilly And Company | 2,4,5-Triaryl pyrimidines and a method of treating pain, fever, thrombosis, inflammation and arthritis |
US5077142A (en) * | 1989-04-20 | 1991-12-31 | Ricoh Company, Ltd. | Electroluminescent devices |
US5620999A (en) * | 1994-07-28 | 1997-04-15 | Weier; Richard M. | Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation |
-
1997
- 1997-12-04 CZ CZ0201599A patent/CZ296911B6/cs not_active IP Right Cessation
- 1997-12-04 CA CA002274063A patent/CA2274063C/en not_active Expired - Fee Related
- 1997-12-04 CN CN97181563A patent/CN1246858A/zh active Pending
- 1997-12-04 AU AU60120/98A patent/AU733877C/en not_active Ceased
- 1997-12-04 AR ARP970105689A patent/AR048564A1/es not_active Application Discontinuation
- 1997-12-04 HU HU0001698A patent/HUP0001698A3/hu unknown
- 1997-12-04 NZ NZ335997A patent/NZ335997A/xx unknown
- 1997-12-04 IL IL13018097A patent/IL130180A0/xx unknown
- 1997-12-04 BR BR9713850-9A patent/BR9713850A/pt not_active Application Discontinuation
- 1997-12-04 EP EP97954778A patent/EP0948497A2/en not_active Withdrawn
-
1999
- 1999-06-22 BG BG103512A patent/BG65128B1/bg unknown
Also Published As
Publication number | Publication date |
---|---|
EP0948497A2 (en) | 1999-10-13 |
BR9713850A (pt) | 2000-02-29 |
CA2274063A1 (en) | 1998-06-11 |
AU733877C (en) | 2003-05-08 |
CZ296911B6 (cs) | 2006-07-12 |
NZ335997A (en) | 2001-08-31 |
BG65128B1 (bg) | 2007-03-30 |
AU6012098A (en) | 1998-06-29 |
AU733877B2 (en) | 2001-05-31 |
BG103512A (en) | 2000-07-31 |
HUP0001698A2 (hu) | 2001-04-28 |
HUP0001698A3 (en) | 2002-07-29 |
AR048564A1 (es) | 2006-05-10 |
IL130180A0 (en) | 2000-06-01 |
CZ9902015A3 (cs) | 1999-11-17 |
CN1246858A (zh) | 2000-03-08 |
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EEER | Examination request | ||
MKLA | Lapsed |