SK284287B6 - Heterocyklické zlúčeniny ako inhibítory adhézie leukocytov a antagonisty VLA-4, spôsob ich prípravy a farmaceutický prostriedok, ktorý ich obsahuje - Google Patents

Info

Publication number

SK284287B6

SK284287B6 SK1527-97A SK152797A SK284287B6 SK 284287 B6 SK284287 B6 SK 284287B6 SK 152797 A SK152797 A SK 152797A SK 284287 B6 SK284287 B6 SK 284287B6

Authority

SK

Slovakia

Prior art keywords

carbon atoms

group

alkyl

moiety

aryl

Prior art date

1996-11-15

Links

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• 108010008212 Integrin alpha4beta1 Proteins 0.000 title claims abstract description 59
• 238000000034 method Methods 0.000 title claims abstract description 34
• 210000000265 leukocyte Anatomy 0.000 title claims abstract description 29
• 238000002360 preparation method Methods 0.000 title claims abstract description 26
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
• 150000002391 heterocyclic compounds Chemical class 0.000 title claims description 24
• 239000005557 antagonist Substances 0.000 title abstract description 10
• 239000003112 inhibitor Substances 0.000 title abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 166
• 238000011282 treatment Methods 0.000 claims abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 238000011321 prophylaxis Methods 0.000 claims abstract description 16
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 230000005012 migration Effects 0.000 claims abstract description 14
• 238000013508 migration Methods 0.000 claims abstract description 14
• 230000008569 process Effects 0.000 claims abstract description 13
• 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims abstract description 12
• 230000004054 inflammatory process Effects 0.000 claims abstract description 10
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 933
• 125000000217 alkyl group Chemical group 0.000 claims description 538
• 125000003118 aryl group Chemical group 0.000 claims description 337
• -1 phenylene, phenylene Chemical group 0.000 claims description 290
• 150000003254 radicals Chemical class 0.000 claims description 173
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 122
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 121
• 125000001072 heteroaryl group Chemical group 0.000 claims description 96
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 94
• 125000000623 heterocyclic group Chemical group 0.000 claims description 94
• 125000003545 alkoxy group Chemical group 0.000 claims description 90
• 229910052717 sulfur Inorganic materials 0.000 claims description 81
• 125000003107 substituted aryl group Chemical group 0.000 claims description 80
• 239000000203 mixture Substances 0.000 claims description 69
• 229910052760 oxygen Inorganic materials 0.000 claims description 65
• 229910052799 carbon Inorganic materials 0.000 claims description 62
• 150000003839 salts Chemical class 0.000 claims description 62
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 53
• 239000011593 sulfur Substances 0.000 claims description 53
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 52
• 239000001301 oxygen Substances 0.000 claims description 52
• 229910052757 nitrogen Inorganic materials 0.000 claims description 46
• 239000002253 acid Substances 0.000 claims description 44
• 125000002947 alkylene group Chemical group 0.000 claims description 43
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
• 125000005842 heteroatom Chemical group 0.000 claims description 39
• 125000004122 cyclic group Chemical group 0.000 claims description 36
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 36
• 125000004429 atom Chemical group 0.000 claims description 32
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 31
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 30
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 28
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• 125000001424 substituent group Chemical group 0.000 claims description 27
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
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• 125000002619 bicyclic group Chemical group 0.000 claims description 24
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 23
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
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• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 21
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 20
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 20
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 20
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 19
• 108010016626 Dipeptides Proteins 0.000 claims description 19
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• 125000000524 functional group Chemical group 0.000 claims description 18
• 150000002367 halogens Chemical class 0.000 claims description 18
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
• 125000006239 protecting group Chemical group 0.000 claims description 18
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 17
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 230000002829 reductive effect Effects 0.000 claims description 17
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
• 125000003367 polycyclic group Chemical group 0.000 claims description 16
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 15
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• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
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• 125000004434 sulfur atom Chemical group 0.000 claims description 14
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical class [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 13
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 12
• 229910052727 yttrium Inorganic materials 0.000 claims description 12
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 11
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
• 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 10
• 125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 10
• 150000001408 amides Chemical class 0.000 claims description 10
• 125000000539 amino acid group Chemical group 0.000 claims description 10
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 8
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 7
• 206010020751 Hypersensitivity Diseases 0.000 claims description 7
• 206010061218 Inflammation Diseases 0.000 claims description 7
• 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 7
• 125000004450 alkenylene group Chemical group 0.000 claims description 7
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 7
• 230000007815 allergy Effects 0.000 claims description 7
• 235000008206 alpha-amino acids Nutrition 0.000 claims description 7
• 125000005096 aminoalkylaminocarbonyl group Chemical group 0.000 claims description 7
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 7
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 7
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
• 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
• 125000001624 naphthyl group Chemical group 0.000 claims description 7
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 7
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 7
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• 238000009833 condensation Methods 0.000 claims description 6
• 230000005494 condensation Effects 0.000 claims description 6
• 230000001419 dependent effect Effects 0.000 claims description 6
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• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 6
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
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• HHAVGBXLGVYXFF-AWEZNQCLSA-N (2r)-n-[3-(heptylamino)-3-oxopropyl]-2,4-dihydroxy-3,3-dimethylbutanamide Chemical compound CCCCCCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO HHAVGBXLGVYXFF-AWEZNQCLSA-N 0.000 claims description 4
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
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• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
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• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 claims description 3
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
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