JP2005528374A - 粘液分泌過多の治療方法 - Google Patents
粘液分泌過多の治療方法 Download PDFInfo
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- JP2005528374A JP2005528374A JP2003581743A JP2003581743A JP2005528374A JP 2005528374 A JP2005528374 A JP 2005528374A JP 2003581743 A JP2003581743 A JP 2003581743A JP 2003581743 A JP2003581743 A JP 2003581743A JP 2005528374 A JP2005528374 A JP 2005528374A
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- alkyl
- carbon atoms
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- 210000003097 mucus Anatomy 0.000 title claims abstract description 67
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims abstract description 122
- 229940043355 kinase inhibitor Drugs 0.000 claims abstract description 116
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims abstract description 116
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 64
- 238000011282 treatment Methods 0.000 claims abstract description 52
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 834
- -1 1,2,4-triazin-5-yl Chemical group 0.000 claims description 682
- 125000004432 carbon atom Chemical group C* 0.000 claims description 585
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 255
- 125000003545 alkoxy group Chemical group 0.000 claims description 247
- 125000000623 heterocyclic group Chemical group 0.000 claims description 189
- 229910052736 halogen Inorganic materials 0.000 claims description 183
- 150000002367 halogens Chemical class 0.000 claims description 179
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 142
- 150000002825 nitriles Chemical class 0.000 claims description 132
- 125000003118 aryl group Chemical group 0.000 claims description 128
- 125000004076 pyridyl group Chemical group 0.000 claims description 121
- 125000001624 naphthyl group Chemical group 0.000 claims description 106
- 229910052717 sulfur Chemical group 0.000 claims description 104
- 229910052760 oxygen Inorganic materials 0.000 claims description 93
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 90
- 125000002883 imidazolyl group Chemical group 0.000 claims description 85
- 125000001072 heteroaryl group Chemical group 0.000 claims description 83
- 150000001875 compounds Chemical class 0.000 claims description 81
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 76
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 73
- 239000001257 hydrogen Substances 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 70
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims description 64
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 64
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 62
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 61
- 125000004043 oxo group Chemical group O=* 0.000 claims description 61
- 125000002541 furyl group Chemical group 0.000 claims description 60
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 59
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 57
- 125000001544 thienyl group Chemical group 0.000 claims description 57
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 49
- 229910052799 carbon Inorganic materials 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 43
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 42
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 42
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 42
- 125000004193 piperazinyl group Chemical group 0.000 claims description 42
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 39
- 125000003435 aroyl group Chemical group 0.000 claims description 37
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 34
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 34
- 125000002252 acyl group Chemical group 0.000 claims description 32
- 125000003282 alkyl amino group Chemical group 0.000 claims description 32
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000003386 piperidinyl group Chemical group 0.000 claims description 30
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 28
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 27
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 26
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 26
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 26
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 24
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 239000001301 oxygen Substances 0.000 claims description 23
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims description 22
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 22
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 22
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- QYCGBAJADAGLLK-UHFFFAOYSA-N 1-(cyclohepten-1-yl)cycloheptene Chemical group C1CCCCC=C1C1=CCCCCC1 QYCGBAJADAGLLK-UHFFFAOYSA-N 0.000 claims description 20
- VSIYJQNFMOOGCU-UHFFFAOYSA-N 1-(cyclohexen-1-yl)cyclohexene Chemical group C1CCCC(C=2CCCCC=2)=C1 VSIYJQNFMOOGCU-UHFFFAOYSA-N 0.000 claims description 20
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 20
- 125000001041 indolyl group Chemical group 0.000 claims description 20
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 239000011593 sulfur Chemical group 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 229930192474 thiophene Natural products 0.000 claims description 17
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 16
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 16
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 150000001721 carbon Chemical class 0.000 claims description 15
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 15
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 14
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 14
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 14
- 125000002757 morpholinyl group Chemical group 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 13
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 12
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 12
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000005046 dihydronaphthyl group Chemical group 0.000 claims description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 12
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 12
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004001 thioalkyl group Chemical group 0.000 claims description 12
- ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 claims description 11
- WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical group C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 claims description 11
- MAWOHFOSAIXURX-UHFFFAOYSA-N cyclopentylcyclopentane Chemical group C1CCCC1C1CCCC1 MAWOHFOSAIXURX-UHFFFAOYSA-N 0.000 claims description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 229910004013 NO 2 Inorganic materials 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 8
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 8
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 8
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 7
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 7
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 7
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 7
- 125000005647 linker group Chemical group 0.000 claims description 7
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 7
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 claims description 7
- 150000003335 secondary amines Chemical class 0.000 claims description 7
- 150000003512 tertiary amines Chemical class 0.000 claims description 7
- 150000003536 tetrazoles Chemical class 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000002243 cyclohexanonyl group Chemical group *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 claims description 6
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 6
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 6
- 230000036961 partial effect Effects 0.000 claims description 6
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 6
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 5
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 5
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 claims description 5
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 5
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical compound OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 125000003113 cycloheptyloxy group Chemical group C1(CCCCCC1)O* 0.000 claims description 4
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 4
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 4
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 4
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 4
- NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 4
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02007699 | 2002-04-05 | ||
PCT/EP2003/003434 WO2003084503A2 (en) | 2002-04-05 | 2003-04-02 | P38 kinase inhibitors for treating mucus hypersecretion_ |
Publications (2)
Publication Number | Publication Date |
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JP2005528374A true JP2005528374A (ja) | 2005-09-22 |
JP2005528374A5 JP2005528374A5 (xx) | 2006-06-01 |
Family
ID=28685842
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2003581743A Pending JP2005528374A (ja) | 2002-04-05 | 2003-04-02 | 粘液分泌過多の治療方法 |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP1494645A2 (xx) |
JP (1) | JP2005528374A (xx) |
KR (1) | KR20040101398A (xx) |
CN (1) | CN1658834A (xx) |
AU (1) | AU2003224025A1 (xx) |
BR (1) | BR0309009A (xx) |
CA (1) | CA2479520A1 (xx) |
IL (1) | IL163737A0 (xx) |
MX (1) | MXPA04009605A (xx) |
NZ (1) | NZ536278A (xx) |
PL (1) | PL372963A1 (xx) |
RU (1) | RU2004132847A (xx) |
WO (1) | WO2003084503A2 (xx) |
ZA (1) | ZA200406910B (xx) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009545725A (ja) * | 2006-07-17 | 2009-12-24 | ルノー・エス・アー・エス | デバイスの故障検出のための確認プロセス |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004101529A1 (ja) * | 2003-05-19 | 2004-11-25 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環化合物およびその医薬用途 |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
WO2006137421A1 (ja) * | 2005-06-21 | 2006-12-28 | Kyowa Hakko Kogyo Co., Ltd. | 局所投与剤 |
GB0818033D0 (en) | 2008-10-02 | 2008-11-05 | Respivert Ltd | Novel compound |
WO2010038086A2 (en) | 2008-10-02 | 2010-04-08 | Respivert Limited | Novel compounds |
WO2010067131A1 (en) | 2008-12-11 | 2010-06-17 | Respivert Limited | P38 map kinase inhibitors |
GB0905955D0 (en) | 2009-04-06 | 2009-05-20 | Respivert Ltd | Novel compounds |
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 |
WO2019071147A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | INHIBITORS OF KINASE P38 REDUCING EXPRESSION OF DUX4 GENE AND DOWNSTREAM GENES FOR THE TREATMENT OF FSHD |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
NZ514711A (en) * | 1999-03-12 | 2004-02-27 | Boehringer Ingelheim Pharma | Compounds useful as anti-inflammatory agents |
ATE376547T1 (de) * | 1999-05-21 | 2007-11-15 | Scios Inc | Derivate des indol-typs als p38 kinase inhibitoren |
CN1304375C (zh) * | 1999-08-19 | 2007-03-14 | 信号药品公司 | 用作jnk抑制剂的吡唑并蒽酮及其衍生物和它们的组合物 |
BR0014041A (pt) * | 1999-09-17 | 2003-07-15 | Smithkline Beecham Corp | Utilização de csaids em infecção por rinovìrus |
CN100355750C (zh) * | 2000-09-15 | 2007-12-19 | 沃泰克斯药物股份有限公司 | 可用作蛋白激酶抑制剂的吡唑化合物 |
JP2004511542A (ja) * | 2000-10-19 | 2004-04-15 | スミスクライン・ビーチャム・コーポレイション | 煙の吸入の治療のためのp38阻害剤の使用 |
EP1381594A1 (en) * | 2001-04-13 | 2004-01-21 | Boehringer Ingelheim Pharmaceuticals Inc. | Urea compounds useful as anti-inflammatory agents |
TR200401028T2 (tr) * | 2001-11-09 | 2004-11-22 | Scios Inc. | Kistik fibrozun tedavisine yönelik metot |
-
2003
- 2003-04-02 PL PL03372963A patent/PL372963A1/xx not_active Application Discontinuation
- 2003-04-02 BR BR0309009-4A patent/BR0309009A/pt not_active Expired - Fee Related
- 2003-04-02 IL IL16373703A patent/IL163737A0/xx unknown
- 2003-04-02 JP JP2003581743A patent/JP2005528374A/ja active Pending
- 2003-04-02 CN CN038129884A patent/CN1658834A/zh active Pending
- 2003-04-02 NZ NZ536278A patent/NZ536278A/en unknown
- 2003-04-02 CA CA002479520A patent/CA2479520A1/en not_active Abandoned
- 2003-04-02 WO PCT/EP2003/003434 patent/WO2003084503A2/en not_active Application Discontinuation
- 2003-04-02 RU RU2004132847/15A patent/RU2004132847A/ru not_active Application Discontinuation
- 2003-04-02 KR KR10-2004-7015891A patent/KR20040101398A/ko not_active Application Discontinuation
- 2003-04-02 AU AU2003224025A patent/AU2003224025A1/en not_active Abandoned
- 2003-04-02 EP EP03720407A patent/EP1494645A2/en not_active Ceased
- 2003-04-02 MX MXPA04009605A patent/MXPA04009605A/es unknown
-
2004
- 2004-08-31 ZA ZA200406910A patent/ZA200406910B/xx unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009545725A (ja) * | 2006-07-17 | 2009-12-24 | ルノー・エス・アー・エス | デバイスの故障検出のための確認プロセス |
Also Published As
Publication number | Publication date |
---|---|
NZ536278A (en) | 2007-05-31 |
BR0309009A (pt) | 2005-03-22 |
CA2479520A1 (en) | 2003-10-16 |
RU2004132847A (ru) | 2006-08-20 |
CN1658834A (zh) | 2005-08-24 |
EP1494645A2 (en) | 2005-01-12 |
ZA200406910B (en) | 2006-06-28 |
AU2003224025A1 (en) | 2003-10-20 |
PL372963A1 (en) | 2005-08-08 |
MXPA04009605A (es) | 2005-01-11 |
WO2003084503A2 (en) | 2003-10-16 |
WO2003084503A3 (en) | 2004-04-08 |
KR20040101398A (ko) | 2004-12-02 |
IL163737A0 (en) | 2005-12-18 |
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