CZ392597A3 - Imidazolové sloučeniny, způsob jejich přípravy, farmaceutické prostředky s jejich obsahem a způsob ošetřování - Google Patents

Info

Publication number

CZ392597A3

CZ392597A3 CZ973925A CZ392597A CZ392597A3 CZ 392597 A3 CZ392597 A3 CZ 392597A3 CZ 973925 A CZ973925 A CZ 973925A CZ 392597 A CZ392597 A CZ 392597A CZ 392597 A3 CZ392597 A3 CZ 392597A3

Authority

CZ

Czechia

Prior art keywords

alkyl

group

formula

aryl

heterocyclyl

Prior art date

1995-06-07

Links

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• 150000002460 imidazoles Chemical class 0.000 title claims abstract description 14
• 238000000034 method Methods 0.000 title claims description 104
• 238000002360 preparation method Methods 0.000 title claims description 17
• 230000008569 process Effects 0.000 title claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
• 238000011282 treatment Methods 0.000 title description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 278
• 150000001875 compounds Chemical class 0.000 claims description 250
• -1 1-imidazolyl Chemical group 0.000 claims description 187
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 165
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 130
• 125000003118 aryl group Chemical group 0.000 claims description 120
• 125000001072 heteroaryl group Chemical group 0.000 claims description 93
• 125000000623 heterocyclic group Chemical group 0.000 claims description 92
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 74
• 229910052736 halogen Inorganic materials 0.000 claims description 66
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 59
• 125000005843 halogen group Chemical group 0.000 claims description 51
• 201000010099 disease Diseases 0.000 claims description 48
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
• 239000001257 hydrogen Substances 0.000 claims description 48
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 46
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 46
• 238000006243 chemical reaction Methods 0.000 claims description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 44
• 239000002904 solvent Substances 0.000 claims description 41
• 125000001424 substituent group Chemical group 0.000 claims description 41
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
• 241000124008 Mammalia Species 0.000 claims description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
• 150000003839 salts Chemical class 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 25
• 150000002431 hydrogen Chemical class 0.000 claims description 25
• 150000002466 imines Chemical class 0.000 claims description 25
• 229910052717 sulfur Inorganic materials 0.000 claims description 25
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 239000001301 oxygen Substances 0.000 claims description 23
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 22
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 22
• 230000001404 mediated effect Effects 0.000 claims description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 239000011593 sulfur Chemical group 0.000 claims description 20
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
• 206010040070 Septic Shock Diseases 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
• 125000003107 substituted aryl group Chemical group 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
• 230000006378 damage Effects 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 14
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 14
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 108010084680 Heterogeneous-Nuclear Ribonucleoprotein K Proteins 0.000 claims description 11
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 claims description 11
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 11
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 9
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 9
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 9
• 150000003141 primary amines Chemical class 0.000 claims description 9
• 206010040047 Sepsis Diseases 0.000 claims description 8
• 150000001412 amines Chemical class 0.000 claims description 8
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 8
• 239000002243 precursor Substances 0.000 claims description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
• 238000006467 substitution reaction Methods 0.000 claims description 8
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
• 206010061218 Inflammation Diseases 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 150000001768 cations Chemical class 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 230000004054 inflammatory process Effects 0.000 claims description 7
• 125000003386 piperidinyl group Chemical class 0.000 claims description 7
• 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 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
• 206010014824 Endotoxic shock Diseases 0.000 claims description 6
• 201000005569 Gout Diseases 0.000 claims description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
• 208000006011 Stroke Diseases 0.000 claims description 6
• 206010044248 Toxic shock syndrome Diseases 0.000 claims description 6
• 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 210000003169 central nervous system Anatomy 0.000 claims description 6
• 239000003153 chemical reaction reagent Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 201000008482 osteoarthritis Diseases 0.000 claims description 6
• 125000004434 sulfur atom Chemical group 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
• 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
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 206010063837 Reperfusion injury Diseases 0.000 claims description 5
• 125000003435 aroyl group Chemical group 0.000 claims description 5
• 230000018044 dehydration Effects 0.000 claims description 5
• 238000006297 dehydration reaction Methods 0.000 claims description 5
• 201000006549 dyspepsia Diseases 0.000 claims description 5
• 208000024798 heartburn Diseases 0.000 claims description 5
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 5
• 238000011065 in-situ storage Methods 0.000 claims description 5
• 229910052744 lithium Inorganic materials 0.000 claims description 5
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 5
• 125000006239 protecting group Chemical group 0.000 claims description 5
• 230000002685 pulmonary effect Effects 0.000 claims description 5
• 208000024981 pyrosis Diseases 0.000 claims description 5
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
• 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
• OJBGEOXGUGYQKZ-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)-4-[1-(1-methylpiperidin-4-yl)imidazol-2-yl]-1h-pyrimidin-5-yl]amino]ethanol Chemical compound C1CN(C)CCC1N1C(C2(C(=CN=CN2)NCCO)C=2C=CC(F)=CC=2)=NC=C1 OJBGEOXGUGYQKZ-UHFFFAOYSA-N 0.000 claims description 4
• 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 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
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• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
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• 125000001589 carboacyl group Chemical group 0.000 claims description 4
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• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
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• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 4
• 230000004044 response Effects 0.000 claims description 4
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• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 3
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• 210000000988 bone and bone Anatomy 0.000 claims description 3
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• XFXPMWWXUTWYJX-UHFFFAOYSA-N isonitrile group Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 3
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