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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Applications Claiming Priority (5)
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| 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
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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 |
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| MY (1) | MY114014A (enExample) |
| NO (1) | NO975716L (enExample) |
| NZ (1) | NZ311403A (enExample) |
| PE (1) | PE7798A1 (enExample) |
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| TW (1) | TW442481B (enExample) |
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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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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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