JPH11513017A - イミダゾール化合物 - Google Patents
イミダゾール化合物Info
- Publication number
- JPH11513017A JPH11513017A JP9502174A JP50217497A JPH11513017A JP H11513017 A JPH11513017 A JP H11513017A JP 9502174 A JP9502174 A JP 9502174A JP 50217497 A JP50217497 A JP 50217497A JP H11513017 A JPH11513017 A JP H11513017A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- formula
- aryl
- substituted
- optionally substituted
- 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.)
- Ceased
Links
- 150000002460 imidazoles Chemical class 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims description 252
- -1 1-imidazolyl Chemical group 0.000 claims description 199
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 182
- 125000003118 aryl group Chemical group 0.000 claims description 100
- 238000000034 method Methods 0.000 claims description 97
- 125000000623 heterocyclic group Chemical group 0.000 claims description 91
- 125000001072 heteroaryl group Chemical group 0.000 claims description 80
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 63
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 238000011282 treatment Methods 0.000 claims description 44
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 40
- 241000124008 Mammalia Species 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 238000004519 manufacturing process Methods 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 150000002466 imines Chemical class 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 239000001301 oxygen Substances 0.000 claims description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
- 230000001404 mediated effect Effects 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 239000011593 sulfur Substances 0.000 claims description 22
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 21
- 125000003107 substituted aryl group Chemical group 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- 230000006378 damage Effects 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 19
- 206010040070 Septic Shock Diseases 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 208000014674 injury Diseases 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 208000027418 Wounds and injury Diseases 0.000 claims description 14
- 229910017711 NHRa Inorganic materials 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 11
- 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims description 11
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 11
- 230000001684 chronic effect Effects 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 208000024891 symptom Diseases 0.000 claims description 10
- 206010040047 Sepsis Diseases 0.000 claims description 9
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 8
- 206010063837 Reperfusion injury Diseases 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 230000036407 pain Effects 0.000 claims description 8
- 150000003141 primary amines Chemical class 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 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 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 7
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 229950004696 flusalan Drugs 0.000 claims description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 7
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 7
- 230000002685 pulmonary effect Effects 0.000 claims description 7
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- FMEGHBNXOMKQPH-UHFFFAOYSA-N FC1=C(C=CC=C1)C=1N(C=CN1)C1CCN(CC1)C Chemical compound FC1=C(C=CC=C1)C=1N(C=CN1)C1CCN(CC1)C FMEGHBNXOMKQPH-UHFFFAOYSA-N 0.000 claims description 6
- 208000001132 Osteoporosis Diseases 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 230000002917 arthritic effect Effects 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 201000008482 osteoarthritis Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
- 206010063094 Cerebral malaria Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 206010010904 Convulsion Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 201000010001 Silicosis Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 208000024908 graft versus host disease Diseases 0.000 claims description 5
- 238000011065 in-situ storage Methods 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- FTVFPPFZRRKJIH-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidin-4-amine Chemical compound CC1(C)CC(N)CC(C)(C)N1 FTVFPPFZRRKJIH-UHFFFAOYSA-N 0.000 claims description 4
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 4
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
- UHVAZVWTFCJNPH-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-n-phenylpyridin-2-amine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=C(NC=3C=CC=CC=3)N=CC=2)N(C2CCNCC2)C=N1 UHVAZVWTFCJNPH-UHFFFAOYSA-N 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 229960005235 piperonyl butoxide Drugs 0.000 claims description 3
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical class 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 150000004678 hydrides Chemical class 0.000 claims description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N isonitrile group Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- ANSMHXIZDOWIBA-UHFFFAOYSA-M n-[4-(4-hydroxyphenyl)-2-methylpentan-2-yl]carbamate Chemical compound [O-]C(=O)NC(C)(C)CC(C)C1=CC=C(O)C=C1 ANSMHXIZDOWIBA-UHFFFAOYSA-M 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 claims 4
- 206010038687 Respiratory distress Diseases 0.000 claims 2
- 150000003973 alkyl amines Chemical class 0.000 claims 2
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical compound C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 claims 1
- LAXPDWNGVMRQAT-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-(1-methylpiperidin-4-yl)imidazol-4-yl]-n-(3-morpholin-4-ylpropyl)pyrimidin-2-amine Chemical compound C1CN(C)CCC1N1C(C=2N=C(NCCCN3CCOCC3)N=CC=2)=C(C=2C=CC(F)=CC=2)N=C1 LAXPDWNGVMRQAT-UHFFFAOYSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- CCOXWRVWKFVFDG-UHFFFAOYSA-N pyrimidine-2-carbaldehyde Chemical compound O=CC1=NC=CC=N1 CCOXWRVWKFVFDG-UHFFFAOYSA-N 0.000 claims 1
- 108090000695 Cytokines Chemical class 0.000 abstract description 44
- 102000004127 Cytokines Human genes 0.000 abstract description 44
- 239000000203 mixture Substances 0.000 abstract description 33
- 239000003112 inhibitor Substances 0.000 abstract description 8
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 59
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 59
- 239000007787 solid Substances 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 210000004027 cell Anatomy 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- 102000004890 Interleukin-8 Human genes 0.000 description 32
- 108090001007 Interleukin-8 Proteins 0.000 description 32
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 30
- 229940096397 interleukin-8 Drugs 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 27
- 239000002585 base Substances 0.000 description 26
- 239000000460 chlorine Substances 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- 230000002401 inhibitory effect Effects 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 108090001005 Interleukin-6 Proteins 0.000 description 19
- 102000004889 Interleukin-6 Human genes 0.000 description 19
- 229940100601 interleukin-6 Drugs 0.000 description 19
- 239000003054 catalyst Substances 0.000 description 18
- 125000001207 fluorophenyl group Chemical group 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- 241000725303 Human immunodeficiency virus Species 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 14
- 210000001616 monocyte Anatomy 0.000 description 14
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 13
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 13
- 210000001744 T-lymphocyte Anatomy 0.000 description 13
- 230000002757 inflammatory effect Effects 0.000 description 13
- GACUCTNCAUTQPH-UHFFFAOYSA-N 2-methylpyrimidine-4-carbothialdehyde Chemical compound CC1=NC=CC(C=S)=N1 GACUCTNCAUTQPH-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 241000700605 Viruses Species 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
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- 238000003786 synthesis reaction Methods 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 210000004556 brain Anatomy 0.000 description 11
- 125000001309 chloro group Chemical group Cl* 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 150000002527 isonitriles Chemical class 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 10
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 10
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000002158 endotoxin Substances 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 125000001153 fluoro group Chemical group F* 0.000 description 10
- 229920006008 lipopolysaccharide Polymers 0.000 description 10
- 210000000440 neutrophil Anatomy 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- 230000006433 tumor necrosis factor production Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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- C07D405/14—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 three or more hetero rings
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47339695A | 1995-06-07 | 1995-06-07 | |
| US08/473,396 | 1995-06-07 | ||
| US63677996A | 1996-04-19 | 1996-04-19 | |
| US08/636,779 | 1996-04-19 | ||
| PCT/US1996/010039 WO1996040143A1 (en) | 1995-06-07 | 1996-06-07 | Imidazole compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11513017A true JPH11513017A (ja) | 1999-11-09 |
Family
ID=27044121
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9502174A Ceased JPH11513017A (ja) | 1995-06-07 | 1996-06-07 | イミダゾール化合物 |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US5658903A (OSRAM) |
| EP (2) | EP1314728A1 (OSRAM) |
| JP (1) | JPH11513017A (OSRAM) |
| KR (1) | KR19990022574A (OSRAM) |
| CN (1) | CN1130358C (OSRAM) |
| AT (1) | ATE233561T1 (OSRAM) |
| BR (1) | BR9608591A (OSRAM) |
| CA (1) | CA2223533A1 (OSRAM) |
| CZ (1) | CZ392597A3 (OSRAM) |
| DE (1) | DE69626513T2 (OSRAM) |
| DZ (1) | DZ2043A1 (OSRAM) |
| ES (1) | ES2194106T3 (OSRAM) |
| HU (1) | HUP9802259A3 (OSRAM) |
| IL (1) | IL118544A (OSRAM) |
| IN (1) | IN186434B (OSRAM) |
| MA (1) | MA24242A1 (OSRAM) |
| MY (1) | MY114014A (OSRAM) |
| NO (1) | NO975716L (OSRAM) |
| NZ (1) | NZ311403A (OSRAM) |
| PE (1) | PE7798A1 (OSRAM) |
| PL (1) | PL185515B1 (OSRAM) |
| TR (1) | TR199701574T2 (OSRAM) |
| TW (1) | TW442481B (OSRAM) |
| WO (1) | WO1996040143A1 (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006522768A (ja) * | 2003-04-11 | 2006-10-05 | ノバルティス アクチエンゲゼルシャフト | アミノピリミジン誘導体およびそれらの医学的使用 |
| JP2020518621A (ja) * | 2017-05-03 | 2020-06-25 | ザ ユニヴァーシティー オブ メルボルン | 呼吸器疾患の治療のための化合物 |
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- 1996-06-04 IN IN1210DE1996 patent/IN186434B/en unknown
- 1996-06-05 MY MYPI96002184A patent/MY114014A/en unknown
- 1996-06-05 DZ DZ960087A patent/DZ2043A1/fr active
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006522768A (ja) * | 2003-04-11 | 2006-10-05 | ノバルティス アクチエンゲゼルシャフト | アミノピリミジン誘導体およびそれらの医学的使用 |
| JP2020518621A (ja) * | 2017-05-03 | 2020-06-25 | ザ ユニヴァーシティー オブ メルボルン | 呼吸器疾患の治療のための化合物 |
Also Published As
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|---|---|
| EP0831830A4 (en) | 1998-12-02 |
| PE7798A1 (es) | 1998-03-20 |
| ES2194106T3 (es) | 2003-11-16 |
| HUP9802259A3 (en) | 2002-02-28 |
| DZ2043A1 (fr) | 2002-10-23 |
| CA2223533A1 (en) | 1996-12-19 |
| ATE233561T1 (de) | 2003-03-15 |
| NO975716L (no) | 1998-02-04 |
| DE69626513D1 (en) | 2003-04-10 |
| CZ392597A3 (cs) | 1998-09-16 |
| NZ311403A (en) | 1999-11-29 |
| BR9608591A (pt) | 1999-01-05 |
| WO1996040143A1 (en) | 1996-12-19 |
| TR199701574T2 (xx) | 1999-09-21 |
| NO975716D0 (no) | 1997-12-05 |
| US5658903A (en) | 1997-08-19 |
| CN1130358C (zh) | 2003-12-10 |
| DE69626513T2 (de) | 2003-12-24 |
| AU6272696A (en) | 1996-12-30 |
| EP1314728A1 (en) | 2003-05-28 |
| MY114014A (en) | 2002-07-31 |
| IL118544A (en) | 2001-08-08 |
| PL323916A1 (en) | 1998-04-27 |
| PL185515B1 (pl) | 2003-05-30 |
| MA24242A1 (fr) | 1998-07-01 |
| AU699646B2 (en) | 1998-12-10 |
| US6218537B1 (en) | 2001-04-17 |
| KR19990022574A (ko) | 1999-03-25 |
| EP0831830A1 (en) | 1998-04-01 |
| HUP9802259A2 (hu) | 1999-09-28 |
| IL118544A0 (en) | 1997-03-18 |
| TW442481B (en) | 2001-06-23 |
| IN186434B (OSRAM) | 2001-09-01 |
| CN1192147A (zh) | 1998-09-02 |
| EP0831830B1 (en) | 2003-03-05 |
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