KR20030082989A - 메탈로프로테이나제 억제제 - Google Patents
메탈로프로테이나제 억제제 Download PDFInfo
- Publication number
- KR20030082989A KR20030082989A KR10-2003-7011987A KR20037011987A KR20030082989A KR 20030082989 A KR20030082989 A KR 20030082989A KR 20037011987 A KR20037011987 A KR 20037011987A KR 20030082989 A KR20030082989 A KR 20030082989A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- formula
- alkylamino
- heteroaryl
- compound
- Prior art date
Links
- 239000003475 metalloproteinase inhibitor Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 214
- -1 guanidino, N-cyano-guanidino Chemical group 0.000 claims description 109
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 125000006413 ring segment Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 30
- 238000001727 in vivo Methods 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 102000005741 Metalloproteases Human genes 0.000 claims description 23
- 108010006035 Metalloproteases Proteins 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 8
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 7
- 125000006168 tricyclic group Chemical group 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 6
- 150000001356 alkyl thiols Chemical class 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 150000003573 thiols Chemical class 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 150000007942 carboxylates Chemical class 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 2
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims description 2
- 125000005418 aryl aryl group Chemical group 0.000 claims description 2
- 150000001504 aryl thiols Chemical class 0.000 claims description 2
- BSGRLBPZSRZQOR-UHFFFAOYSA-N ethene-1,1-diamine Chemical compound NC(N)=C BSGRLBPZSRZQOR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- 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 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005362 aryl sulfone group Chemical group 0.000 claims 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 21
- 102100027998 Macrophage metalloelastase Human genes 0.000 abstract description 7
- 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 abstract description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 61
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 239000000243 solution Substances 0.000 description 47
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- 239000007787 solid Substances 0.000 description 38
- 239000002904 solvent Substances 0.000 description 36
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 34
- 239000000047 product Substances 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 230000015572 biosynthetic process Effects 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 238000003786 synthesis reaction Methods 0.000 description 29
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 26
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 21
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 20
- 229940093499 ethyl acetate Drugs 0.000 description 20
- 239000007858 starting material Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 19
- 108090000790 Enzymes Proteins 0.000 description 19
- 239000012043 crude product Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- 229940088598 enzyme Drugs 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 102100027995 Collagenase 3 Human genes 0.000 description 16
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical group O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 16
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 11
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 11
- 102100030416 Stromelysin-1 Human genes 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 238000002390 rotary evaporation Methods 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 10
- 102100030411 Neutrophil collagenase Human genes 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 206010003246 arthritis Diseases 0.000 description 10
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 125000005647 linker group Chemical group 0.000 description 8
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
- 201000008482 osteoarthritis Diseases 0.000 description 8
- 102000003390 tumor necrosis factor Human genes 0.000 description 8
- 239000011701 zinc Substances 0.000 description 8
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 7
- NXKTUUPSINAQEA-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(F)C=C1 NXKTUUPSINAQEA-UHFFFAOYSA-N 0.000 description 7
- 101710108790 Stromelysin-1 Proteins 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000001207 fluorophenyl group Chemical group 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 229910052725 zinc Inorganic materials 0.000 description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 6
- 206010014561 Emphysema Diseases 0.000 description 6
- 229940124761 MMP inhibitor Drugs 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- JTZDWXOSZJWUGF-UHFFFAOYSA-N 5-chloro-2-(1-methylsulfonylpiperidin-4-yl)oxypyridine Chemical compound C1CN(S(=O)(=O)C)CCC1OC1=CC=C(Cl)C=N1 JTZDWXOSZJWUGF-UHFFFAOYSA-N 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
- 101000990908 Homo sapiens Neutrophil collagenase Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 101710118230 Neutrophil collagenase Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 210000002744 extracellular matrix Anatomy 0.000 description 5
- 229940091173 hydantoin Drugs 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 description 5
- NZFOMJUWHPFHLQ-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)phenyl]piperazine Chemical compound C1=CC(F)=CC=C1C1=CC=C(N2CCNCC2)C=C1 NZFOMJUWHPFHLQ-UHFFFAOYSA-N 0.000 description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 description 4
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 4
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 4
- 101710170181 Metalloproteinase inhibitor Proteins 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 102000005353 Tissue Inhibitor of Metalloproteinase-1 Human genes 0.000 description 4
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 4
- 239000001099 ammonium carbonate Substances 0.000 description 4
- 235000012501 ammonium carbonate Nutrition 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 125000000107 disulfanyl group Chemical group [*]SS[H] 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- ONPUSVLNMWPSKQ-UHFFFAOYSA-N ethyl 4-pyrimidin-2-ylbutanoate Chemical compound CCOC(=O)CCCC1=NC=CC=N1 ONPUSVLNMWPSKQ-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 229940126170 metalloproteinase inhibitor Drugs 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- RPUSRLKKXPQSGP-UHFFFAOYSA-N methyl 3-phenylpropanoate Chemical compound COC(=O)CCC1=CC=CC=C1 RPUSRLKKXPQSGP-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 229940124530 sulfonamide Drugs 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- XSHKXSKUJOYOEP-UHFFFAOYSA-N tert-butyl 4-(5-methoxypyridin-2-yl)oxypiperidine-1-carboxylate Chemical compound N1=CC(OC)=CC=C1OC1CCN(C(=O)OC(C)(C)C)CC1 XSHKXSKUJOYOEP-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- XEOZUNWHXSYISM-MRXNPFEDSA-N (5s)-5-[[4-(4-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O XEOZUNWHXSYISM-MRXNPFEDSA-N 0.000 description 3
- ZSPRGFGETQEKQE-UHFFFAOYSA-N 1-(4-phenylphenyl)sulfanylpropan-2-one Chemical compound C1=CC(SCC(=O)C)=CC=C1C1=CC=CC=C1 ZSPRGFGETQEKQE-UHFFFAOYSA-N 0.000 description 3
- JZMLLUROVHETBN-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-5-pyrimidin-2-ylpentan-2-one Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC(=O)CCCC=2N=CC=CN=2)CC1 JZMLLUROVHETBN-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- LHBSFKIPSOYDAD-UHFFFAOYSA-N 2-chloro-5-methoxy-1-oxidopyridin-1-ium Chemical compound COC1=CC=C(Cl)[N+]([O-])=C1 LHBSFKIPSOYDAD-UHFFFAOYSA-N 0.000 description 3
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 3
- CSZPBZUNXGHIIE-UHFFFAOYSA-N 5-methoxy-2-piperidin-4-yloxypyridine Chemical compound N1=CC(OC)=CC=C1OC1CCNCC1 CSZPBZUNXGHIIE-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 3
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 241000219061 Rheum Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- GXBXYLVXNQXXNV-RXMQYKEDSA-N [(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride Chemical compound ClS(=O)(=O)C[C@@]1(C)NC(=O)NC1=O GXBXYLVXNQXXNV-RXMQYKEDSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 238000011894 semi-preparative HPLC Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 230000006433 tumor necrosis factor production Effects 0.000 description 3
- QDXMWEMIYNOVGF-GFCCVEGCSA-N (5s)-5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSC[C@@]1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-GFCCVEGCSA-N 0.000 description 2
- SFJFBTPHDHUUPU-OAHLLOKOSA-N (5s)-5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O SFJFBTPHDHUUPU-OAHLLOKOSA-N 0.000 description 2
- NDQXJNHOGLQSMB-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylpropan-2-one Chemical compound CC(=O)CS(=O)(=O)C1=CC=C(C)C=C1 NDQXJNHOGLQSMB-UHFFFAOYSA-N 0.000 description 2
- TUSXGJAMYNWNJW-UHFFFAOYSA-N 1-(4-phenylphenyl)sulfonylpropan-2-one Chemical compound C1=CC(S(=O)(=O)CC(=O)C)=CC=C1C1=CC=CC=C1 TUSXGJAMYNWNJW-UHFFFAOYSA-N 0.000 description 2
- ZTLOZFLZBKZABP-UHFFFAOYSA-N 1-(5-chloropyridin-2-yl)piperazine Chemical compound N1=CC(Cl)=CC=C1N1CCNCC1 ZTLOZFLZBKZABP-UHFFFAOYSA-N 0.000 description 2
- XXTADFHLFQJHGI-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-phenylbutan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCC=2C=CC=CC=2)CC1 XXTADFHLFQJHGI-UHFFFAOYSA-N 0.000 description 2
- VYBROEDDFBJUNL-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-5-imidazol-1-ylpentan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCCN2C=NC=C2)CC1 VYBROEDDFBJUNL-UHFFFAOYSA-N 0.000 description 2
- MUFDDMXRRXYWAD-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-5-pyrimidin-2-ylpentan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCCC=2N=CC=CN=2)CC1 MUFDDMXRRXYWAD-UHFFFAOYSA-N 0.000 description 2
- VJRFNEMQCUNDMR-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl-5-pyrimidin-2-ylpentan-2-one Chemical compound N1=CC(Cl)=CC=C1N1CCN(S(=O)(=O)CC(=O)CCCC=2N=CC=CN=2)CC1 VJRFNEMQCUNDMR-UHFFFAOYSA-N 0.000 description 2
- ZSZJGZFGYAJPET-UHFFFAOYSA-N 1-[5-(4-fluorophenyl)pyridin-2-yl]piperazine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=CC=C(N2CCNCC2)N=C1 ZSZJGZFGYAJPET-UHFFFAOYSA-N 0.000 description 2
- NNINFNNFNRPXAY-UHFFFAOYSA-N 1-methylsulfonyl-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C1=CC=C(C(F)(F)F)C=N1 NNINFNNFNRPXAY-UHFFFAOYSA-N 0.000 description 2
- GCTFDMFLLBCLPF-UHFFFAOYSA-N 2,5-dichloropyridine Chemical compound ClC1=CC=C(Cl)N=C1 GCTFDMFLLBCLPF-UHFFFAOYSA-N 0.000 description 2
- CGGFOZFJXDOHDD-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)ethanesulfonyl chloride Chemical compound ClS(=O)(=O)CCC1NC(=O)NC1=O CGGFOZFJXDOHDD-UHFFFAOYSA-N 0.000 description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 2
- KUDNJELAUXSOIL-UHFFFAOYSA-N 2-piperidin-4-yloxy-5-(trifluoromethyl)pyridine Chemical compound N1=CC(C(F)(F)F)=CC=C1OC1CCNCC1 KUDNJELAUXSOIL-UHFFFAOYSA-N 0.000 description 2
- ILPIXXSCUKTFGB-UHFFFAOYSA-N 4-(4-fluorophenyl)piperidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1CCNCC1 ILPIXXSCUKTFGB-UHFFFAOYSA-N 0.000 description 2
- VJFNAMZBXGYXTM-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)ethynyl]-1,2,3,6-tetrahydropyridine;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C#CC1=CCNCC1 VJFNAMZBXGYXTM-UHFFFAOYSA-N 0.000 description 2
- GRQTUYVDWZPIBW-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)pyridin-2-yl]piperazine-1-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=CC=C(N2CCN(CC2)C=O)N=C1 GRQTUYVDWZPIBW-UHFFFAOYSA-N 0.000 description 2
- JPXWGTSKFAUDRY-UHFFFAOYSA-N 5-(3-aminopropyl)-5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CCCN)NC(=O)NC1=O JPXWGTSKFAUDRY-UHFFFAOYSA-N 0.000 description 2
- QDXMWEMIYNOVGF-UHFFFAOYSA-N 5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSCC1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-UHFFFAOYSA-N 0.000 description 2
- AMZYBOJPLHNYJD-UHFFFAOYSA-N 5-chloro-2-piperidin-4-yloxypyridine Chemical compound N1=CC(Cl)=CC=C1OC1CCNCC1 AMZYBOJPLHNYJD-UHFFFAOYSA-N 0.000 description 2
- GZPYXZFJWCXXAL-UHFFFAOYSA-N 5-methyl-5-[[4-[4-(trifluoromethoxy)phenyl]phenyl]sulfanylmethyl]imidazolidine-2,4-dione Chemical compound C=1C=C(C=2C=CC(OC(F)(F)F)=CC=2)C=CC=1SCC1(C)NC(=O)NC1=O GZPYXZFJWCXXAL-UHFFFAOYSA-N 0.000 description 2
- 102000016284 Aggrecans Human genes 0.000 description 2
- 108010067219 Aggrecans Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000000503 Collagen Type II Human genes 0.000 description 2
- 108010041390 Collagen Type II Proteins 0.000 description 2
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 102000056189 Neutrophil collagenases Human genes 0.000 description 2
- 108030001564 Neutrophil collagenases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- QRPMKCBTJIZVKF-REOHCLBHSA-N [(4r)-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride Chemical compound ClS(=O)(=O)C[C@@H]1NC(=O)NC1=O QRPMKCBTJIZVKF-REOHCLBHSA-N 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical compound SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- RDNHWIOBCYOAMM-UHFFFAOYSA-N ethyl 4-imidazol-1-ylbutanoate Chemical compound CCOC(=O)CCCN1C=CN=C1 RDNHWIOBCYOAMM-UHFFFAOYSA-N 0.000 description 2
- 230000003176 fibrotic effect Effects 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 238000011540 hip replacement Methods 0.000 description 2
- ZTVZLYBCZNMWCF-UHFFFAOYSA-N homocystine Chemical compound [O-]C(=O)C([NH3+])CCSSCCC([NH3+])C([O-])=O ZTVZLYBCZNMWCF-UHFFFAOYSA-N 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 125000005462 imide group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- VUHTTZFQPPZFPA-UHFFFAOYSA-N n-(3-piperidin-4-yloxyphenyl)acetamide Chemical compound CC(=O)NC1=CC=CC(OC2CCNCC2)=C1 VUHTTZFQPPZFPA-UHFFFAOYSA-N 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 230000003239 periodontal effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- ZOWJTZMYSLZILG-UHFFFAOYSA-N tert-butyl 4-(4-iodophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(I)C=C1 ZOWJTZMYSLZILG-UHFFFAOYSA-N 0.000 description 2
- CQGJRVIBZKHVLE-UHFFFAOYSA-N tert-butyl 4-(4-pyridin-3-ylphenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(C=2C=NC=CC=2)C=C1 CQGJRVIBZKHVLE-UHFFFAOYSA-N 0.000 description 2
- YWAFIGDSGYOAEX-UHFFFAOYSA-N tert-butyl n-[3-[4-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-2,5-dioxoimidazolidin-4-yl]propyl]carbamate Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CCCNC(=O)OC(C)(C)C)NC(=O)NC1=O YWAFIGDSGYOAEX-UHFFFAOYSA-N 0.000 description 2
- 230000007838 tissue remodeling Effects 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 2
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 2
- 230000004572 zinc-binding Effects 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- APZZXMHZXPNPHL-MBRGGSNBSA-N (5S)-5-[[4-(5-fluoropiperidin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C[C@]1(C(=O)NC(=O)N1)CS(=O)(=O)N2CCC(CC2)OC3CCC(CN3)F APZZXMHZXPNPHL-MBRGGSNBSA-N 0.000 description 1
- SUSWVILXXZAPBA-OAQYLSRUSA-N (5S)-5-methyl-5-[[4-(4-pyridin-3-ylphenyl)piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C[C@]1(C(=O)NC(=O)N1)CS(=O)(=O)N2CCC(CC2)C3=CC=C(C=C3)C4=CN=CC=C4 SUSWVILXXZAPBA-OAQYLSRUSA-N 0.000 description 1
- ZVZGHTNUVMKNND-OAHLLOKOSA-N (5S)-5-methyl-5-[[4-[4-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C[C@]1(C(=O)NC(=O)N1)CS(=O)(=O)N2CCC(CC2)OC3=NC=CC(=C3)C(F)(F)F ZVZGHTNUVMKNND-OAHLLOKOSA-N 0.000 description 1
- QDXMWEMIYNOVGF-LBPRGKRZSA-N (5r)-5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSC[C@]1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-LBPRGKRZSA-N 0.000 description 1
- WLTILYXLAGUMGI-LBPRGKRZSA-N (5r)-5-[(4-phenylpiperazin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione Chemical compound O=C1NC(=O)N[C@H]1CS(=O)(=O)N1CCN(C=2C=CC=CC=2)CC1 WLTILYXLAGUMGI-LBPRGKRZSA-N 0.000 description 1
- FHJJKZGBVFRCLY-NRFANRHFSA-N (5r)-5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(3-pyrimidin-2-ylpropyl)imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)C[C@@]2(CCCC=3N=CC=CN=3)C(NC(=O)N2)=O)CC1 FHJJKZGBVFRCLY-NRFANRHFSA-N 0.000 description 1
- SFJFBTPHDHUUPU-HNNXBMFYSA-N (5r)-5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@]1(C)NC(=O)NC1=O SFJFBTPHDHUUPU-HNNXBMFYSA-N 0.000 description 1
- YPWNSTZPZZYYOB-FQEVSTJZSA-N (5r)-5-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylmethyl]-5-(3-pyrimidin-2-ylpropyl)imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1N1CCN(S(=O)(=O)C[C@@]2(CCCC=3N=CC=CN=3)C(NC(=O)N2)=O)CC1 YPWNSTZPZZYYOB-FQEVSTJZSA-N 0.000 description 1
- WFTHGYMQZQFDAG-SNVBAGLBSA-N (5s)-5-(3,6-dihydro-2h-pyridin-1-ylsulfonylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C1CC=CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O WFTHGYMQZQFDAG-SNVBAGLBSA-N 0.000 description 1
- ZUYAVWHXPSTEIF-QGZVFWFLSA-N (5s)-5-[(4-benzylpiperidin-1-yl)sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(CC=2C=CC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O ZUYAVWHXPSTEIF-QGZVFWFLSA-N 0.000 description 1
- WLTILYXLAGUMGI-GFCCVEGCSA-N (5s)-5-[(4-phenylpiperazin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione Chemical compound O=C1NC(=O)N[C@@H]1CS(=O)(=O)N1CCN(C=2C=CC=CC=2)CC1 WLTILYXLAGUMGI-GFCCVEGCSA-N 0.000 description 1
- KDQIRBVBCLHCQA-AWEZNQCLSA-N (5s)-5-[4-(5-chloropyridin-2-yl)piperidin-1-yl]sulfonyl-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)[C@]1(C)NC(=O)NC1=O KDQIRBVBCLHCQA-AWEZNQCLSA-N 0.000 description 1
- AAWXIZCRZHQDHL-MRXNPFEDSA-N (5s)-5-[[4-(2,4-difluorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C(=CC(F)=CC=2)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O AAWXIZCRZHQDHL-MRXNPFEDSA-N 0.000 description 1
- LSZRUZIBVBSJFA-MRXNPFEDSA-N (5s)-5-[[4-(2-fluorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C(=CC=CC=2)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O LSZRUZIBVBSJFA-MRXNPFEDSA-N 0.000 description 1
- UYUBMMLQUKYGHC-MRXNPFEDSA-N (5s)-5-[[4-(2-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2C(=CC=CC=2)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O UYUBMMLQUKYGHC-MRXNPFEDSA-N 0.000 description 1
- LDPFUPBBNYLXTE-QGZVFWFLSA-N (5s)-5-[[4-(2-methoxyphenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound COC1=CC=CC=C1C1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 LDPFUPBBNYLXTE-QGZVFWFLSA-N 0.000 description 1
- NAAXHZYMBYWVKD-MRXNPFEDSA-N (5s)-5-[[4-(3,4-dichlorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=C(Cl)C(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O NAAXHZYMBYWVKD-MRXNPFEDSA-N 0.000 description 1
- OHDQNLMKMQUOOA-MRXNPFEDSA-N (5s)-5-[[4-(3-chlorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=C(Cl)C=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O OHDQNLMKMQUOOA-MRXNPFEDSA-N 0.000 description 1
- RNPOUVLSVWAXBE-MRXNPFEDSA-N (5s)-5-[[4-(3-fluorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=C(F)C=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O RNPOUVLSVWAXBE-MRXNPFEDSA-N 0.000 description 1
- USKFKEWFMKFOII-MRXNPFEDSA-N (5s)-5-[[4-(3-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2C=C(F)C=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O USKFKEWFMKFOII-MRXNPFEDSA-N 0.000 description 1
- KVHGYOYLFGUTFO-QGZVFWFLSA-N (5s)-5-[[4-(3-methoxyphenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound COC1=CC=CC(OC2CCN(CC2)S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)=C1 KVHGYOYLFGUTFO-QGZVFWFLSA-N 0.000 description 1
- RTAZHJSLQPXRHO-MRXNPFEDSA-N (5s)-5-[[4-(4-chlorobenzoyl)piperazin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CN(C(=O)C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O RTAZHJSLQPXRHO-MRXNPFEDSA-N 0.000 description 1
- ZUGWYJYJZWGIPG-MRXNPFEDSA-N (5s)-5-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O ZUGWYJYJZWGIPG-MRXNPFEDSA-N 0.000 description 1
- FVDALFZPBSTSBT-OAHLLOKOSA-N (5s)-5-[[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O FVDALFZPBSTSBT-OAHLLOKOSA-N 0.000 description 1
- SGDUBFZMRJYGOI-MRXNPFEDSA-N (5s)-5-[[4-(4-chlorophenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O SGDUBFZMRJYGOI-MRXNPFEDSA-N 0.000 description 1
- HCAUADOJPJPKHW-MRXNPFEDSA-N (5s)-5-[[4-(4-chlorophenyl)sulfanylpiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(SC=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O HCAUADOJPJPKHW-MRXNPFEDSA-N 0.000 description 1
- YIQZOHDSIXEDJE-MRXNPFEDSA-N (5s)-5-[[4-(4-chlorophenyl)sulfonylpiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(S(=O)(=O)C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O YIQZOHDSIXEDJE-MRXNPFEDSA-N 0.000 description 1
- GYTMIEWWLMJDBS-MRXNPFEDSA-N (5s)-5-[[4-(4-fluoroanilino)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(NC=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O GYTMIEWWLMJDBS-MRXNPFEDSA-N 0.000 description 1
- SDDQKZWEGNKEHG-QGZVFWFLSA-N (5s)-5-[[4-(4-fluorobenzoyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C(=O)C=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O SDDQKZWEGNKEHG-QGZVFWFLSA-N 0.000 description 1
- NCROEDXPKVIJMH-MRXNPFEDSA-N (5s)-5-[[4-(4-fluorophenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O NCROEDXPKVIJMH-MRXNPFEDSA-N 0.000 description 1
- KVSAHPCSEBYPKJ-QGZVFWFLSA-N (5s)-5-[[4-(4-methoxyphenoxy)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 KVSAHPCSEBYPKJ-QGZVFWFLSA-N 0.000 description 1
- LLINLEGOXJIJOM-QGZVFWFLSA-N (5s)-5-[[4-(4-methoxyphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C1=CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 LLINLEGOXJIJOM-QGZVFWFLSA-N 0.000 description 1
- UTDQXAFBPYRTCD-QGZVFWFLSA-N (5s)-5-[[4-(4-methoxyphenyl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 UTDQXAFBPYRTCD-QGZVFWFLSA-N 0.000 description 1
- XXZIEQDLQRMZSN-OAHLLOKOSA-N (5s)-5-[[4-(5-bromopyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Br)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O XXZIEQDLQRMZSN-OAHLLOKOSA-N 0.000 description 1
- YPWNSTZPZZYYOB-HXUWFJFHSA-N (5s)-5-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylmethyl]-5-(3-pyrimidin-2-ylpropyl)imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1N1CCN(S(=O)(=O)C[C@]2(CCCC=3N=CC=CN=3)C(NC(=O)N2)=O)CC1 YPWNSTZPZZYYOB-HXUWFJFHSA-N 0.000 description 1
- RBQBLQLCNRDOBG-MRXNPFEDSA-N (5s)-5-[[4-(5-ethylpyrimidin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound N1=CC(CC)=CN=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 RBQBLQLCNRDOBG-MRXNPFEDSA-N 0.000 description 1
- VLEKQQGKCVMUJU-OAHLLOKOSA-N (5s)-5-[[4-(5-hydroxypyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(O)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O VLEKQQGKCVMUJU-OAHLLOKOSA-N 0.000 description 1
- WIDSAJAKNNFQDB-MRXNPFEDSA-N (5s)-5-[[4-(5-methoxypyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound N1=CC(OC)=CC=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 WIDSAJAKNNFQDB-MRXNPFEDSA-N 0.000 description 1
- CANLWIZMKXIWKH-OAHLLOKOSA-N (5s)-5-[[4-(6-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=C(Cl)C=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O CANLWIZMKXIWKH-OAHLLOKOSA-N 0.000 description 1
- WWRMWBJAERAKIH-OAHLLOKOSA-N (5s)-5-[[4-(6-chloropyridin-3-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2C=NC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O WWRMWBJAERAKIH-OAHLLOKOSA-N 0.000 description 1
- JGGYDLNDMISRRK-MRXNPFEDSA-N (5s)-5-[[4-(6-methoxypyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound COC1=CC=CC(OC2CCN(CC2)S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)=N1 JGGYDLNDMISRRK-MRXNPFEDSA-N 0.000 description 1
- UAQJOOIDROWKRQ-MRXNPFEDSA-N (5s)-5-[[4-(benzotriazol-1-yl)piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(N2C3=CC=CC=C3N=N2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O UAQJOOIDROWKRQ-MRXNPFEDSA-N 0.000 description 1
- AELWLRMVZWFDGW-LJQANCHMSA-N (5s)-5-[[4-[(2,5-dimethylphenyl)methoxy]piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound CC1=CC=C(C)C(COC2CCN(CC2)S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)=C1 AELWLRMVZWFDGW-LJQANCHMSA-N 0.000 description 1
- DSEMHXDLGLGPJS-JOCHJYFZSA-N (5s)-5-[[4-[(2-tert-butyl-1h-indol-5-yl)amino]piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C=1C=C2NC(C(C)(C)C)=CC2=CC=1NC(CC1)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O DSEMHXDLGLGPJS-JOCHJYFZSA-N 0.000 description 1
- OFLWZCBSODNPSR-LJQANCHMSA-N (5s)-5-[[4-[(3,4-dimethylphenyl)methoxy]piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1=C(C)C(C)=CC=C1COC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 OFLWZCBSODNPSR-LJQANCHMSA-N 0.000 description 1
- VNCQBDRNBFLLAX-GOSISDBHSA-N (5s)-5-[[4-[2-(4-chlorophenyl)ethynyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C#CC=2C=CC(Cl)=CC=2)=CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O VNCQBDRNBFLLAX-GOSISDBHSA-N 0.000 description 1
- PTWFMNBNFDOHFX-MRXNPFEDSA-N (5s)-5-[[4-[3,5-bis(trifluoromethyl)phenyl]piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O PTWFMNBNFDOHFX-MRXNPFEDSA-N 0.000 description 1
- BXJYLZCCUAMRGD-QGZVFWFLSA-N (5s)-5-[[4-[3-(furan-2-yl)-1h-pyrazol-5-yl]piperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(C=2NN=C(C=2)C=2OC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O BXJYLZCCUAMRGD-QGZVFWFLSA-N 0.000 description 1
- XUCDVMCMOPQRRD-HXUWFJFHSA-N (5s)-5-[[4-[5-(4-chlorophenyl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O XUCDVMCMOPQRRD-HXUWFJFHSA-N 0.000 description 1
- JYIBMAYPRMCNSS-HXUWFJFHSA-N (5s)-5-[[4-[5-(4-fluorophenyl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O JYIBMAYPRMCNSS-HXUWFJFHSA-N 0.000 description 1
- SJQSBCRXSKRJBC-OAQYLSRUSA-N (5s)-5-[[4-[5-(4-methoxyphenyl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2CCN(CC2)S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)N=C1 SJQSBCRXSKRJBC-OAQYLSRUSA-N 0.000 description 1
- OWTSPGCLTFPURD-GOSISDBHSA-N (5s)-5-[[4-[5-(furan-2-yl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2OC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O OWTSPGCLTFPURD-GOSISDBHSA-N 0.000 description 1
- YPSQADYDIPTJKN-SNVBAGLBSA-N (5s)-5-methyl-5-(piperidin-1-ylsulfonylmethyl)imidazolidine-2,4-dione Chemical compound C1CCCCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O YPSQADYDIPTJKN-SNVBAGLBSA-N 0.000 description 1
- UOERVGNOVYNMRV-MRXNPFEDSA-N (5s)-5-methyl-5-[(4-phenoxypiperidin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2C=CC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O UOERVGNOVYNMRV-MRXNPFEDSA-N 0.000 description 1
- BXLKCBVKVSAIIQ-XFULWGLBSA-N (5s)-5-methyl-5-[(4-piperidin-1-ylpiperidin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(N2CCCCC2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O BXLKCBVKVSAIIQ-XFULWGLBSA-N 0.000 description 1
- BGXMALBWCKBHAJ-OAHLLOKOSA-N (5s)-5-methyl-5-[(4-pyridin-2-yloxypiperidin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O BGXMALBWCKBHAJ-OAHLLOKOSA-N 0.000 description 1
- OCPXBDIJWCRSLU-PFEQFJNWSA-N (5s)-5-methyl-5-[(4-pyrrolidin-1-ylpiperidin-1-yl)sulfonylmethyl]imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(N2CCCC2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O OCPXBDIJWCRSLU-PFEQFJNWSA-N 0.000 description 1
- VYNOEDGTNBDPBR-QGZVFWFLSA-N (5s)-5-methyl-5-[[4-(2-oxo-3h-benzimidazol-1-yl)piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(N2C(NC3=CC=CC=C32)=O)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O VYNOEDGTNBDPBR-QGZVFWFLSA-N 0.000 description 1
- AQCDGSMOWICYDJ-QGZVFWFLSA-N (5s)-5-methyl-5-[[4-(4-methylphenoxy)piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 AQCDGSMOWICYDJ-QGZVFWFLSA-N 0.000 description 1
- LCEPCJLGIGNQJS-QGZVFWFLSA-N (5s)-5-methyl-5-[[4-(4-methylphenyl)piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1C1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 LCEPCJLGIGNQJS-QGZVFWFLSA-N 0.000 description 1
- GDVPSYFHVQKBRG-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-(5-methylpyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound N1=CC(C)=CC=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 GDVPSYFHVQKBRG-MRXNPFEDSA-N 0.000 description 1
- FXBWCJIVIVPVSQ-JOCHJYFZSA-N (5s)-5-methyl-5-[[4-(5-phenylmethoxypyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(OCC=3C=CC=CC=3)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O FXBWCJIVIVPVSQ-JOCHJYFZSA-N 0.000 description 1
- QFAQNEBTKIPFRC-LJQANCHMSA-N (5s)-5-methyl-5-[[4-(5-pyridin-3-ylpyridin-2-yl)piperazin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2C=NC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O QFAQNEBTKIPFRC-LJQANCHMSA-N 0.000 description 1
- IEJLMIXRLCSYEC-LNUXAPHWSA-N (5s)-5-methyl-5-[[4-(oxolane-2-carbonyl)piperazin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CN(C(=O)C2OCCC2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O IEJLMIXRLCSYEC-LNUXAPHWSA-N 0.000 description 1
- IIEYBSNNKWMKAW-LJQANCHMSA-N (5s)-5-methyl-5-[[4-[2-(4-methylphenyl)ethynyl]-3,6-dihydro-2h-pyridin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1C#CC1=CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 IIEYBSNNKWMKAW-LJQANCHMSA-N 0.000 description 1
- JLHIOOQPYFJSCF-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[3-(trifluoromethoxy)phenoxy]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2C=C(OC(F)(F)F)C=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O JLHIOOQPYFJSCF-MRXNPFEDSA-N 0.000 description 1
- WOQYAJWLBQTPOT-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(C=2C=C(C=CC=2)C(F)(F)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O WOQYAJWLBQTPOT-MRXNPFEDSA-N 0.000 description 1
- DJXZXNHJKPAVOT-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2C=CC(OC(F)(F)F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O DJXZXNHJKPAVOT-MRXNPFEDSA-N 0.000 description 1
- MZVHTCKLQCVIBM-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[4-(trifluoromethoxy)phenyl]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(C=2C=CC(OC(F)(F)F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O MZVHTCKLQCVIBM-MRXNPFEDSA-N 0.000 description 1
- NZWCKNGEMCPIOP-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[4-(trifluoromethyl)phenoxy]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2C=CC(=CC=2)C(F)(F)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O NZWCKNGEMCPIOP-MRXNPFEDSA-N 0.000 description 1
- IBQHWWGWJOZBML-MRXNPFEDSA-N (5s)-5-methyl-5-[[4-[4-(trifluoromethyl)phenyl]piperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(C=2C=CC(=CC=2)C(F)(F)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O IBQHWWGWJOZBML-MRXNPFEDSA-N 0.000 description 1
- RRKSYBSOMOZHAJ-GOSISDBHSA-N (5s)-5-methyl-5-[[4-[5-(1h-pyrrol-2-yl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2NC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O RRKSYBSOMOZHAJ-GOSISDBHSA-N 0.000 description 1
- BUIQIPOWCYDCBN-OAHLLOKOSA-N (5s)-5-methyl-5-[[4-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(=CC=2)C(F)(F)F)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O BUIQIPOWCYDCBN-OAHLLOKOSA-N 0.000 description 1
- UKSMRIVYNZTVMD-HXUWFJFHSA-N (5s)-5-methyl-5-[[4-[5-[4-(trifluoromethoxy)phenyl]pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C1CN(C=2N=CC(=CC=2)C=2C=CC(OC(F)(F)F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O UKSMRIVYNZTVMD-HXUWFJFHSA-N 0.000 description 1
- MBTFRSBWSLYBAU-UHFFFAOYSA-N (diaminomethylideneamino)-nitrocarbamic acid Chemical group C(=NN(C(=O)O)[N+](=O)[O-])(N)N MBTFRSBWSLYBAU-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- SVYOXGBINYWSDQ-UHFFFAOYSA-N 1,4-dioxane;ethanol Chemical compound CCO.C1COCCO1 SVYOXGBINYWSDQ-UHFFFAOYSA-N 0.000 description 1
- HCLMSQXPPXNNKE-UHFFFAOYSA-N 1-(4-bromophenyl)sulfanylpropan-2-one Chemical compound CC(=O)CSC1=CC=C(Br)C=C1 HCLMSQXPPXNNKE-UHFFFAOYSA-N 0.000 description 1
- CZUGGAGWAUSXMD-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C1=CC=C(F)C=C1 CZUGGAGWAUSXMD-UHFFFAOYSA-N 0.000 description 1
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 1
- QZICDENDIVEPPE-UHFFFAOYSA-N 1-(4-pyridin-3-ylphenyl)piperazine Chemical compound C1CNCCN1C1=CC=C(C=2C=NC=CC=2)C=C1 QZICDENDIVEPPE-UHFFFAOYSA-N 0.000 description 1
- QWQDSHFVNFFBHB-UHFFFAOYSA-N 1-(4-pyrimidin-2-ylpiperazin-1-yl)sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCN1C1=NC=CC=N1 QWQDSHFVNFFBHB-UHFFFAOYSA-N 0.000 description 1
- QOULRSKFPDYZAJ-UHFFFAOYSA-N 1-(5-pyridin-3-ylpyridin-2-yl)piperazine;hydrochloride Chemical compound Cl.C1CNCCN1C1=CC=C(C=2C=NC=CC=2)C=N1 QOULRSKFPDYZAJ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- IWQSKHYHXALZML-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC=C(F)C=C1 IWQSKHYHXALZML-UHFFFAOYSA-N 0.000 description 1
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- AAMXIXZAPOPAEG-UHFFFAOYSA-N 1-[1-(4-fluorophenyl)cyclohexa-2,4-dien-1-yl]piperazine Chemical compound C1=CC(F)=CC=C1C1(N2CCNCC2)C=CC=CC1 AAMXIXZAPOPAEG-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- NKRXVDIGDQPQSE-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)piperidin-1-yl]sulfonyl-3-(oxan-4-yl)propan-2-one Chemical compound C1=CC(Cl)=CC=C1C1CCN(S(=O)(=O)CC(=O)CC2CCOCC2)CC1 NKRXVDIGDQPQSE-UHFFFAOYSA-N 0.000 description 1
- ONEXXGAUORNHOD-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)piperidin-1-yl]sulfonyl-5-morpholin-4-ylpentan-2-one Chemical compound C1=CC(Cl)=CC=C1C1CCN(S(=O)(=O)CC(=O)CCCN2CCOCC2)CC1 ONEXXGAUORNHOD-UHFFFAOYSA-N 0.000 description 1
- QJCNTFREKKHFGZ-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)piperazin-1-yl]sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCN1C1=CC=C(F)C=C1 QJCNTFREKKHFGZ-UHFFFAOYSA-N 0.000 description 1
- VWXCZCBIPLOYBO-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-3-(oxan-4-yl)propan-2-one Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC(=O)CC2CCOCC2)CC1 VWXCZCBIPLOYBO-UHFFFAOYSA-N 0.000 description 1
- WUQKDVJNZNPSRL-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-4-pyrimidin-2-ylbutan-2-one Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC(=O)CCC=2N=CC=CN=2)CC1 WUQKDVJNZNPSRL-UHFFFAOYSA-N 0.000 description 1
- CSGCGKZWMJIROI-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-3-(3-methylphenyl)propan-2-one Chemical compound CC1=CC=CC(CC(=O)CS(=O)(=O)N2CCC(CC2)OC=2N=CC(Cl)=CC=2)=C1 CSGCGKZWMJIROI-UHFFFAOYSA-N 0.000 description 1
- SYPQHDDEJAGJQH-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-3-(oxan-4-yl)propan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CC2CCOCC2)CC1 SYPQHDDEJAGJQH-UHFFFAOYSA-N 0.000 description 1
- CVWDSUXGESAMDO-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-(1,2,4-triazol-1-yl)butan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCN2N=CN=C2)CC1 CVWDSUXGESAMDO-UHFFFAOYSA-N 0.000 description 1
- IVBNMHCZKICVFX-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-methylpentan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)CC(C)C)CCC1OC1=CC=C(Cl)C=N1 IVBNMHCZKICVFX-UHFFFAOYSA-N 0.000 description 1
- UWRGKKILYFJQES-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-morpholin-4-ylbutan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCN2CCOCC2)CC1 UWRGKKILYFJQES-UHFFFAOYSA-N 0.000 description 1
- JHHXDQIWQVGFHG-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-pyrimidin-2-ylbutan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCC=2N=CC=CN=2)CC1 JHHXDQIWQVGFHG-UHFFFAOYSA-N 0.000 description 1
- JFXZNLIPQLFLFK-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-5-morpholin-4-ylpentan-2-one Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCCN2CCOCC2)CC1 JFXZNLIPQLFLFK-UHFFFAOYSA-N 0.000 description 1
- UDLRPOZQBLSLMU-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylbutan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)CC)CCC1OC1=CC=C(Cl)C=N1 UDLRPOZQBLSLMU-UHFFFAOYSA-N 0.000 description 1
- UEZBDQLBEGVFKG-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylpentan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)CCC)CCC1OC1=CC=C(Cl)C=N1 UEZBDQLBEGVFKG-UHFFFAOYSA-N 0.000 description 1
- ROIFLZSXJWPESS-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCC1OC1=CC=C(Cl)C=N1 ROIFLZSXJWPESS-UHFFFAOYSA-N 0.000 description 1
- BUKXSXBPSDSUPA-UHFFFAOYSA-N 1-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCN1CC1=CC=C(F)C=C1 BUKXSXBPSDSUPA-UHFFFAOYSA-N 0.000 description 1
- DDAHDIFQVFEWPR-UHFFFAOYSA-N 1-[4-[4-(trifluoromethoxy)phenyl]phenyl]sulfanylpropan-2-one Chemical compound C1=CC(SCC(=O)C)=CC=C1C1=CC=C(OC(F)(F)F)C=C1 DDAHDIFQVFEWPR-UHFFFAOYSA-N 0.000 description 1
- JKMLCIDLILWYRS-UHFFFAOYSA-N 1-[4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCN1C1=CC=C(C(F)(F)F)C=N1 JKMLCIDLILWYRS-UHFFFAOYSA-N 0.000 description 1
- GOCAUPHHJFGJIT-UHFFFAOYSA-N 1-[5-(1h-pyrrol-2-yl)pyridin-2-yl]piperazine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=CC=C(C=2NC=CC=2)C=N1 GOCAUPHHJFGJIT-UHFFFAOYSA-N 0.000 description 1
- CQHDWPSFYFXRQF-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)pyridin-2-yl]piperazine;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C1=CC=C(N2CCNCC2)N=C1 CQHDWPSFYFXRQF-UHFFFAOYSA-N 0.000 description 1
- NUGLGRJQFBIRQL-UHFFFAOYSA-N 1-[5-(4-methoxyphenyl)pyridin-2-yl]piperazine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=C(N2CCNCC2)N=C1 NUGLGRJQFBIRQL-UHFFFAOYSA-N 0.000 description 1
- WUFAWZSDFUMPGN-UHFFFAOYSA-N 1-[5-(furan-2-yl)pyridin-2-yl]piperazine;hydrochloride Chemical compound Cl.C1CNCCN1C1=CC=C(C=2OC=CC=2)C=N1 WUFAWZSDFUMPGN-UHFFFAOYSA-N 0.000 description 1
- BNMSJUIMZULLAS-UHFFFAOYSA-N 1-[5-(trifluoromethyl)pyridin-2-yl]piperazine Chemical compound N1=CC(C(F)(F)F)=CC=C1N1CCNCC1 BNMSJUIMZULLAS-UHFFFAOYSA-N 0.000 description 1
- ILSUPLSMEKEQEM-UHFFFAOYSA-N 1-[5-[4-(trifluoromethoxy)phenyl]pyridin-2-yl]piperazine;hydrochloride Chemical compound Cl.C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(N2CCNCC2)N=C1 ILSUPLSMEKEQEM-UHFFFAOYSA-N 0.000 description 1
- XFGPSHWWPIFPNL-UHFFFAOYSA-N 1-bromo-4-(4-fluorophenyl)benzene Chemical group C1=CC(F)=CC=C1C1=CC=C(Br)C=C1 XFGPSHWWPIFPNL-UHFFFAOYSA-N 0.000 description 1
- PTZNCCIULVXFIJ-UHFFFAOYSA-N 1-o-tert-butyl 4-o-methyl piperidine-1,4-dicarboxylate Chemical class COC(=O)C1CCN(C(=O)OC(C)(C)C)CC1 PTZNCCIULVXFIJ-UHFFFAOYSA-N 0.000 description 1
- ILMLIGLQFXAYPB-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;4-[4-(trifluoromethoxy)phenyl]piperidine Chemical compound OC(=O)C(F)(F)F.C1=CC(OC(F)(F)F)=CC=C1C1CCNCC1 ILMLIGLQFXAYPB-UHFFFAOYSA-N 0.000 description 1
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
- WJAQMHVKRHWMJF-UHFFFAOYSA-N 2-(4-methylsulfonylpiperazin-1-yl)pyrimidine Chemical compound C1CN(S(=O)(=O)C)CCN1C1=NC=CC=N1 WJAQMHVKRHWMJF-UHFFFAOYSA-N 0.000 description 1
- UZNRTXNWHDCSNN-UHFFFAOYSA-N 2-[2-(1,2,3,6-tetrahydropyridin-4-yl)ethynyl]pyridine Chemical compound C1NCCC(C#CC=2N=CC=CC=2)=C1 UZNRTXNWHDCSNN-UHFFFAOYSA-N 0.000 description 1
- DSMFICBSXLCYFB-UHFFFAOYSA-N 2-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-1-(1h-imidazol-5-yl)ethanone Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC(=O)C=2N=CNC=2)CC1 DSMFICBSXLCYFB-UHFFFAOYSA-N 0.000 description 1
- ZUZNHHREGDQHCO-UHFFFAOYSA-N 2-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-1-(1h-imidazol-5-yl)ethanone Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)C=2N=CNC=2)CC1 ZUZNHHREGDQHCO-UHFFFAOYSA-N 0.000 description 1
- LOXDNXFPZAGXPE-UHFFFAOYSA-N 2-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-1-(4-fluorophenyl)ethanone Chemical compound C1=CC(F)=CC=C1C(=O)CS(=O)(=O)N1CCC(OC=2N=CC(Cl)=CC=2)CC1 LOXDNXFPZAGXPE-UHFFFAOYSA-N 0.000 description 1
- QFDNAUZLROIZSG-UHFFFAOYSA-N 2-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-1-phenylethanone Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)C=2C=CC=CC=2)CC1 QFDNAUZLROIZSG-UHFFFAOYSA-N 0.000 description 1
- MJPPGVVIDGQOQT-UHFFFAOYSA-N 2-bromo-5-(2-bromo-2-nitroethenyl)furan Chemical class [O-][N+](=O)C(Br)=CC1=CC=C(Br)O1 MJPPGVVIDGQOQT-UHFFFAOYSA-N 0.000 description 1
- BZUUVQCSPHPUQA-UHFFFAOYSA-N 2-bromo-5-chloropyridine Chemical compound ClC1=CC=C(Br)N=C1 BZUUVQCSPHPUQA-UHFFFAOYSA-N 0.000 description 1
- GMEWYAFXVANUNL-UHFFFAOYSA-N 2-chloro-1-oxido-5-phenylmethoxypyridin-1-ium Chemical compound C1=C(Cl)[N+]([O-])=CC(OCC=2C=CC=CC=2)=C1 GMEWYAFXVANUNL-UHFFFAOYSA-N 0.000 description 1
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 1
- ZXGHKJHRHVDMSW-UHFFFAOYSA-N 2-chloro-5-methoxypyridine Chemical compound COC1=CC=C(Cl)N=C1 ZXGHKJHRHVDMSW-UHFFFAOYSA-N 0.000 description 1
- QLUMNDLJGBUHPB-UHFFFAOYSA-N 2-chloro-5-phenylmethoxypyridine Chemical compound C1=NC(Cl)=CC=C1OCC1=CC=CC=C1 QLUMNDLJGBUHPB-UHFFFAOYSA-N 0.000 description 1
- KUKRKVHPRGTMKR-UHFFFAOYSA-N 2-chloro-6-piperidin-4-yloxypyridine Chemical compound ClC1=CC=CC(OC2CCNCC2)=N1 KUKRKVHPRGTMKR-UHFFFAOYSA-N 0.000 description 1
- CCHNWURRBFGQCD-UHFFFAOYSA-N 2-chlorocyclohexan-1-one Chemical compound ClC1CCCCC1=O CCHNWURRBFGQCD-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- KOWNYZRYOXSALD-UHFFFAOYSA-N 2-methoxy-6-piperidin-4-yloxypyridine Chemical compound COC1=CC=CC(OC2CCNCC2)=N1 KOWNYZRYOXSALD-UHFFFAOYSA-N 0.000 description 1
- ZNZGJSLHXOMREP-UHFFFAOYSA-N 2-piperazin-1-ylpyrimidine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=NC=CC=N1 ZNZGJSLHXOMREP-UHFFFAOYSA-N 0.000 description 1
- NODURIKXPCDYHQ-UHFFFAOYSA-N 2-piperidin-4-yloxy-4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC(OC2CCNCC2)=N1 NODURIKXPCDYHQ-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- AHRQYEADQLLARU-UHFFFAOYSA-N 3-(3-benzylsulfanyl-2-oxopropyl)-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound O=C1C(C)(C)N(C)C(=O)N1CC(=O)CSCC1=CC=CC=C1 AHRQYEADQLLARU-UHFFFAOYSA-N 0.000 description 1
- SKCQKTIUCVINNH-UHFFFAOYSA-N 3-(3-bromo-2-oxopropyl)-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound CN1C(=O)N(CC(=O)CBr)C(=O)C1(C)C SKCQKTIUCVINNH-UHFFFAOYSA-N 0.000 description 1
- WFDQQPLDCKVMRK-JOPIAHFSSA-N 3-[1-[1-[(4S)-2,5-dioxoimidazolidin-4-yl]ethylsulfonyl]piperidin-4-yl]oxybenzonitrile Chemical compound CC([C@@H]1C(=O)NC(=O)N1)S(=O)(=O)N2CCC(CC2)OC3=CC=CC(=C3)C#N WFDQQPLDCKVMRK-JOPIAHFSSA-N 0.000 description 1
- NFOGURJSXAYFDU-UHFFFAOYSA-N 3-[[2,5-dioxo-4-[[4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]sulfonylmethyl]imidazolidin-4-yl]methyl]-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound O=C1C(C)(C)N(C)C(=O)N1CC1(CS(=O)(=O)N2CCN(CC2)C=2N=CC(=CC=2)C(F)(F)F)C(=O)NC(=O)N1 NFOGURJSXAYFDU-UHFFFAOYSA-N 0.000 description 1
- CUUUXOJQESAZLK-UHFFFAOYSA-N 3-[[4-(benzylsulfanylmethyl)-2,5-dioxoimidazolidin-4-yl]methyl]-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound O=C1C(C)(C)N(C)C(=O)N1CC1(CSCC=2C=CC=CC=2)C(=O)NC(=O)N1 CUUUXOJQESAZLK-UHFFFAOYSA-N 0.000 description 1
- CYXQXGDCBPUNIQ-UHFFFAOYSA-N 3-[[4-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-2,5-dioxoimidazolidin-4-yl]methyl]-1,5,5-trimethylimidazolidine-2,4-dione Chemical compound O=C1C(C)(C)N(C)C(=O)N1CC1(CS(=O)(=O)N2CCC(CC2)OC=2N=CC(Cl)=CC=2)C(=O)NC(=O)N1 CYXQXGDCBPUNIQ-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ZVXXHZKEDUZNMJ-UHFFFAOYSA-N 3-piperidin-4-yloxybenzonitrile Chemical compound N#CC1=CC=CC(OC2CCNCC2)=C1 ZVXXHZKEDUZNMJ-UHFFFAOYSA-N 0.000 description 1
- LJTKODIQFDAGSL-UHFFFAOYSA-N 4-(2,4-difluorophenoxy)piperidine Chemical compound FC1=CC(F)=CC=C1OC1CCNCC1 LJTKODIQFDAGSL-UHFFFAOYSA-N 0.000 description 1
- DQNSSLUVUXZLEO-UHFFFAOYSA-N 4-(3,4-dichlorophenoxy)piperidine Chemical compound C1=C(Cl)C(Cl)=CC=C1OC1CCNCC1 DQNSSLUVUXZLEO-UHFFFAOYSA-N 0.000 description 1
- BVLDWBQUULKRIL-UHFFFAOYSA-N 4-(3,4-difluorophenoxy)piperidine Chemical compound C1=C(F)C(F)=CC=C1OC1CCNCC1 BVLDWBQUULKRIL-UHFFFAOYSA-N 0.000 description 1
- DNZZLFXWMVOBBV-UHFFFAOYSA-N 4-(3-methoxyphenoxy)piperidine Chemical compound COC1=CC=CC(OC2CCNCC2)=C1 DNZZLFXWMVOBBV-UHFFFAOYSA-N 0.000 description 1
- VOQMPZXAFLPTMM-UHFFFAOYSA-N 4-(4-chlorophenoxy)piperidine Chemical compound C1=CC(Cl)=CC=C1OC1CCNCC1 VOQMPZXAFLPTMM-UHFFFAOYSA-N 0.000 description 1
- ZLGOGZBQLKYJRI-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-methylsulfonylpiperidine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(Cl)C=C1 ZLGOGZBQLKYJRI-UHFFFAOYSA-N 0.000 description 1
- KJZPSLZQMISKHY-UHFFFAOYSA-N 4-(4-chlorophenyl)piperidine;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C1CCNCC1 KJZPSLZQMISKHY-UHFFFAOYSA-N 0.000 description 1
- HRMYEAQYLDCUGG-UHFFFAOYSA-N 4-(4-methoxyphenoxy)piperidine Chemical compound C1=CC(OC)=CC=C1OC1CCNCC1 HRMYEAQYLDCUGG-UHFFFAOYSA-N 0.000 description 1
- AUBZXVDXUWPUBZ-UHFFFAOYSA-N 4-(5-bromopyridin-2-yl)piperazine-1-carbaldehyde Chemical compound N1=CC(Br)=CC=C1N1CCN(C=O)CC1 AUBZXVDXUWPUBZ-UHFFFAOYSA-N 0.000 description 1
- IECHLSVJFDLVFX-UHFFFAOYSA-N 4-(6-piperazin-1-ylpyridin-3-yl)benzonitrile;hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1C1=CC=C(N2CCNCC2)N=C1 IECHLSVJFDLVFX-UHFFFAOYSA-N 0.000 description 1
- BAPVTPBPDJTFPW-UHFFFAOYSA-N 4-[(2,5-dimethylphenyl)methoxy]piperidine;hydrochloride Chemical compound Cl.CC1=CC=C(C)C(COC2CCNCC2)=C1 BAPVTPBPDJTFPW-UHFFFAOYSA-N 0.000 description 1
- GDXPNWGZUSFWTE-UHFFFAOYSA-N 4-[(3,4-dimethylphenyl)methoxy]piperidine;hydrochloride Chemical compound Cl.C1=C(C)C(C)=CC=C1COC1CCNCC1 GDXPNWGZUSFWTE-UHFFFAOYSA-N 0.000 description 1
- YBUXZPWNDAQUKF-UHFFFAOYSA-N 4-[2-(4-methylphenyl)ethynyl]-1,2,3,6-tetrahydropyridine Chemical compound C1=CC(C)=CC=C1C#CC1=CCNCC1 YBUXZPWNDAQUKF-UHFFFAOYSA-N 0.000 description 1
- RSJYIBUWJRIPIJ-UHFFFAOYSA-N 4-[3-(trifluoromethoxy)phenoxy]piperidine Chemical compound FC(F)(F)OC1=CC=CC(OC2CCNCC2)=C1 RSJYIBUWJRIPIJ-UHFFFAOYSA-N 0.000 description 1
- AYDFGLQMQWCNOL-UHFFFAOYSA-N 4-[4-(2-oxopropylsulfanyl)phenyl]benzonitrile Chemical compound C1=CC(SCC(=O)C)=CC=C1C1=CC=C(C#N)C=C1 AYDFGLQMQWCNOL-UHFFFAOYSA-N 0.000 description 1
- NWAAUJPBGAOTMK-UHFFFAOYSA-N 4-[4-(2-oxopropylsulfonyl)phenyl]benzonitrile Chemical compound C1=CC(S(=O)(=O)CC(=O)C)=CC=C1C1=CC=C(C#N)C=C1 NWAAUJPBGAOTMK-UHFFFAOYSA-N 0.000 description 1
- PTVLUMZUHHJKIQ-UHFFFAOYSA-N 4-[4-[(4-methyl-2,5-dioxoimidazolidin-4-yl)methylsulfonyl]phenyl]benzonitrile Chemical compound C=1C=C(C=2C=CC(=CC=2)C#N)C=CC=1S(=O)(=O)CC1(C)NC(=O)NC1=O PTVLUMZUHHJKIQ-UHFFFAOYSA-N 0.000 description 1
- SSSYVFRSWAYOBK-OAQYLSRUSA-N 4-[6-[4-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperazin-1-yl]pyridin-3-yl]benzonitrile Chemical compound C1CN(C=2N=CC(=CC=2)C=2C=CC(=CC=2)C#N)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O SSSYVFRSWAYOBK-OAQYLSRUSA-N 0.000 description 1
- MFIGAVPTWOCNEH-QGZVFWFLSA-N 4-fluoro-n-[1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidin-4-yl]benzamide Chemical compound C1CC(NC(=O)C=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O MFIGAVPTWOCNEH-QGZVFWFLSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- KECCFSZFXLAGJS-UHFFFAOYSA-N 4-methylsulfonylphenol Chemical compound CS(=O)(=O)C1=CC=C(O)C=C1 KECCFSZFXLAGJS-UHFFFAOYSA-N 0.000 description 1
- IXBZJPOQTSAQHW-UHFFFAOYSA-N 4-phenylbutane-2-thione Chemical compound CC(=S)CCC1=CC=CC=C1 IXBZJPOQTSAQHW-UHFFFAOYSA-N 0.000 description 1
- DRIREFRFHFBPIN-UHFFFAOYSA-N 4-piperidin-4-yloxybenzonitrile Chemical compound C1=CC(C#N)=CC=C1OC1CCNCC1 DRIREFRFHFBPIN-UHFFFAOYSA-N 0.000 description 1
- ZSFWQLYGMPDZIZ-UHFFFAOYSA-N 5-[2-[2-(2,5-dioxoimidazolidin-4-yl)ethyldisulfanyl]ethyl]imidazolidine-2,4-dione Chemical compound O=C1NC(=O)NC1CCSSCCC1C(=O)NC(=O)N1 ZSFWQLYGMPDZIZ-UHFFFAOYSA-N 0.000 description 1
- XZUVRROBTPPUKD-UHFFFAOYSA-N 5-[2-[4-[4-(4-fluorophenyl)phenyl]piperazin-1-yl]sulfonylethyl]imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1=CC=C(N2CCN(CC2)S(=O)(=O)CCC2C(NC(=O)N2)=O)C=C1 XZUVRROBTPPUKD-UHFFFAOYSA-N 0.000 description 1
- QCCPMMLTAXPLTN-UHFFFAOYSA-N 5-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-oxopentanenitrile Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC(=O)CCC#N)CC1 QCCPMMLTAXPLTN-UHFFFAOYSA-N 0.000 description 1
- VWAOBTVUFKTLKJ-UHFFFAOYSA-N 5-[[4-(4-chlorophenyl)piperidin-1-yl]sulfonylmethyl]-5-(3-morpholin-4-ylpropyl)imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(Cl)=CC=C1C1CCN(S(=O)(=O)CC2(CCCN3CCOCC3)C(NC(=O)N2)=O)CC1 VWAOBTVUFKTLKJ-UHFFFAOYSA-N 0.000 description 1
- PWZSPUWYFJDIJU-UHFFFAOYSA-N 5-[[4-(4-chlorophenyl)piperidin-1-yl]sulfonylmethyl]-5-(oxan-4-ylmethyl)imidazolidine-2,4-dione Chemical compound C1=CC(Cl)=CC=C1C1CCN(S(=O)(=O)CC2(CC3CCOCC3)C(NC(=O)N2)=O)CC1 PWZSPUWYFJDIJU-UHFFFAOYSA-N 0.000 description 1
- KAAZGRCFKIVZQI-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperazin-1-yl]sulfonylmethyl]-5-[2-(5-fluoropyrimidin-2-yl)ethyl]imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1N1CCN(S(=O)(=O)CC2(CCC=3N=CC(F)=CN=3)C(NC(=O)N2)=O)CC1 KAAZGRCFKIVZQI-UHFFFAOYSA-N 0.000 description 1
- LDYFXQXSQMGKGU-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-(1h-imidazol-5-yl)imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC2(C(NC(=O)N2)=O)C=2N=CNC=2)CC1 LDYFXQXSQMGKGU-UHFFFAOYSA-N 0.000 description 1
- WQPPCTQWRSBWCX-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-(2-pyrimidin-2-ylethyl)imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC2(CCC=3N=CC=CN=3)C(NC(=O)N2)=O)CC1 WQPPCTQWRSBWCX-UHFFFAOYSA-N 0.000 description 1
- NSHAPGRAJPYKPM-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperidin-1-yl]sulfonylmethyl]-5-(oxan-4-ylmethyl)imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1CCN(S(=O)(=O)CC2(CC3CCOCC3)C(NC(=O)N2)=O)CC1 NSHAPGRAJPYKPM-UHFFFAOYSA-N 0.000 description 1
- ILFGLUVWGISQIB-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(1h-imidazol-5-yl)imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(C(NC(=O)N2)=O)C=2N=CNC=2)CC1 ILFGLUVWGISQIB-UHFFFAOYSA-N 0.000 description 1
- BXIPQFNVVKLXNL-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(2-methylpropyl)imidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CC(C)C)NC(=O)NC1=O BXIPQFNVVKLXNL-UHFFFAOYSA-N 0.000 description 1
- VAOBUXRORFLMPY-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(2-phenylmethoxyethyl)imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(CCOCC=3C=CC=CC=3)C(NC(=O)N2)=O)CC1 VAOBUXRORFLMPY-UHFFFAOYSA-N 0.000 description 1
- NFEKFUGTEUXBLX-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(4-fluorophenyl)imidazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C1(CS(=O)(=O)N2CCC(CC2)OC=2N=CC(Cl)=CC=2)C(=O)NC(=O)N1 NFEKFUGTEUXBLX-UHFFFAOYSA-N 0.000 description 1
- YUVSZTZTNMJJGC-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-(piperidin-4-ylmethyl)imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(CC3CCNCC3)C(NC(=O)N2)=O)CC1 YUVSZTZTNMJJGC-UHFFFAOYSA-N 0.000 description 1
- BESUBPYCNVTICF-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-[(3-methylphenyl)methyl]imidazolidine-2,4-dione Chemical compound CC1=CC=CC(CC2(CS(=O)(=O)N3CCC(CC3)OC=3N=CC(Cl)=CC=3)C(NC(=O)N2)=O)=C1 BESUBPYCNVTICF-UHFFFAOYSA-N 0.000 description 1
- GMYNWBWVIZZUAQ-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-[2-(1,2,4-triazol-1-yl)ethyl]imidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(CCN3N=CN=C3)C(NC(=O)N2)=O)CC1 GMYNWBWVIZZUAQ-UHFFFAOYSA-N 0.000 description 1
- APIPYYVDFXQUQK-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-ethylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CC)NC(=O)NC1=O APIPYYVDFXQUQK-UHFFFAOYSA-N 0.000 description 1
- PPRKUNBDOVTOPH-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-phenylimidazolidine-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(C(NC(=O)N2)=O)C=2C=CC=CC=2)CC1 PPRKUNBDOVTOPH-UHFFFAOYSA-N 0.000 description 1
- SBSGXWPPKVYHPM-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-piperidin-4-ylimidazolidine-2,4-dione;hydrochloride Chemical compound Cl.N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(C(NC(=O)N2)=O)C2CCNCC2)CC1 SBSGXWPPKVYHPM-UHFFFAOYSA-N 0.000 description 1
- RSESZCHJJYZCBI-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-propylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CCC)NC(=O)NC1=O RSESZCHJJYZCBI-UHFFFAOYSA-N 0.000 description 1
- GRNFBUHNBAFCOK-UHFFFAOYSA-N 5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-pyridin-4-ylimidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)CC2(C(NC(=O)N2)=O)C=2C=CN=CC=2)CC1 GRNFBUHNBAFCOK-UHFFFAOYSA-N 0.000 description 1
- CZPNBQDWNKXFHN-UHFFFAOYSA-N 5-bromo-2-piperidin-4-yloxypyridine;hydrochloride Chemical compound Cl.N1=CC(Br)=CC=C1OC1CCNCC1 CZPNBQDWNKXFHN-UHFFFAOYSA-N 0.000 description 1
- OVBVUIWELGPQID-UHFFFAOYSA-N 5-chloro-2-(4-methylsulfonylphenoxy)pyridine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1OC1=CC=C(Cl)C=N1 OVBVUIWELGPQID-UHFFFAOYSA-N 0.000 description 1
- GUBCBZCDYQSOBC-UHFFFAOYSA-N 5-chloro-2-piperidin-4-ylpyridine;hydrochloride Chemical compound Cl.N1=CC(Cl)=CC=C1C1CCNCC1 GUBCBZCDYQSOBC-UHFFFAOYSA-N 0.000 description 1
- LMBMTBHVEKCQPM-UHFFFAOYSA-N 5-ethyl-2-piperidin-4-yloxypyrimidine Chemical compound N1=CC(CC)=CN=C1OC1CCNCC1 LMBMTBHVEKCQPM-UHFFFAOYSA-N 0.000 description 1
- NTSLMRPNSUCFKM-UHFFFAOYSA-N 5-fluoro-2-piperidin-4-yloxypyrimidine Chemical compound N1=CC(F)=CN=C1OC1CCNCC1 NTSLMRPNSUCFKM-UHFFFAOYSA-N 0.000 description 1
- BJENRWCLFUGEIF-UHFFFAOYSA-N 5-methyl-2-piperidin-4-yloxypyridine Chemical compound N1=CC(C)=CC=C1OC1CCNCC1 BJENRWCLFUGEIF-UHFFFAOYSA-N 0.000 description 1
- OXODQHKWTFTCGC-UHFFFAOYSA-N 5-methyl-5-[(4-phenylphenyl)sulfonylmethyl]imidazolidine-2,4-dione Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1S(=O)(=O)CC1(C)NC(=O)NC1=O OXODQHKWTFTCGC-UHFFFAOYSA-N 0.000 description 1
- PHJQPALJNNEZBY-UHFFFAOYSA-N 5-methyl-5-[1-(4-methylphenyl)sulfonylcyclopentyl]imidazolidine-2,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C1(C2(C)C(NC(=O)N2)=O)CCCC1 PHJQPALJNNEZBY-UHFFFAOYSA-N 0.000 description 1
- WSBVQXKMVHBYQU-UHFFFAOYSA-N 5-methyl-5-[[4-[4-(trifluoromethoxy)phenyl]phenyl]sulfinylmethyl]imidazolidine-2,4-dione Chemical compound C=1C=C(C=2C=CC(OC(F)(F)F)=CC=2)C=CC=1S(=O)CC1(C)NC(=O)NC1=O WSBVQXKMVHBYQU-UHFFFAOYSA-N 0.000 description 1
- IQUDNXJPYSTKRC-UHFFFAOYSA-N 5-phenylmethoxy-2-piperidin-4-yloxypyridine Chemical compound C=1C=CC=CC=1COC(C=N1)=CC=C1OC1CCNCC1 IQUDNXJPYSTKRC-UHFFFAOYSA-N 0.000 description 1
- OYGFAAMTZVWOEU-UHFFFAOYSA-N 6-(4-methylsulfonylpiperazin-1-yl)pyridine-3-carbonitrile Chemical compound C1CN(S(=O)(=O)C)CCN1C1=CC=C(C#N)C=N1 OYGFAAMTZVWOEU-UHFFFAOYSA-N 0.000 description 1
- HAFWBSVWHIRETN-MRXNPFEDSA-N 6-[1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidin-4-yl]oxypyridine-3-carbonitrile Chemical compound C1CC(OC=2N=CC(=CC=2)C#N)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O HAFWBSVWHIRETN-MRXNPFEDSA-N 0.000 description 1
- FMFPFNZRUCLSOT-UHFFFAOYSA-N 6-[4-(2-oxopropylsulfonyl)piperazin-1-yl]pyridine-3-carbonitrile Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCN1C1=CC=C(C#N)C=N1 FMFPFNZRUCLSOT-UHFFFAOYSA-N 0.000 description 1
- UKEVBZBGFLPGCS-UHFFFAOYSA-N 6-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound N1=CC(Cl)=CC=C1OC1CCN(S(=O)(=O)C2C3(C(NC(=O)N3)=O)CCCC2)CC1 UKEVBZBGFLPGCS-UHFFFAOYSA-N 0.000 description 1
- NABBFMHDCRCSSA-UHFFFAOYSA-N 6-benzylsulfanyl-1,3-diazaspiro[4.5]decane-2,4-dione Chemical compound N1C(=O)NC(=O)C11C(SCC=2C=CC=CC=2)CCCC1 NABBFMHDCRCSSA-UHFFFAOYSA-N 0.000 description 1
- KVCOOWROABTXDJ-UHFFFAOYSA-N 6-chloropyridin-3-ol Chemical compound OC1=CC=C(Cl)N=C1 KVCOOWROABTXDJ-UHFFFAOYSA-N 0.000 description 1
- CRTDCVQCQSHQQV-UHFFFAOYSA-N 6-piperidin-4-yloxypyridin-3-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CC(O)=CC=C1OC1CCNCC1 CRTDCVQCQSHQQV-UHFFFAOYSA-N 0.000 description 1
- DMACRLJFNVJPNR-UHFFFAOYSA-N 6-piperidin-4-yloxypyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1OC1CCNCC1 DMACRLJFNVJPNR-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 108091007504 ADAM10 Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- DQYXLMWHTHEPRP-UHFFFAOYSA-N C(=C[N+](=O)[O-])NC(=N[N+](=O)[O-])N Chemical compound C(=C[N+](=O)[O-])NC(=N[N+](=O)[O-])N DQYXLMWHTHEPRP-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- 102100039673 Disintegrin and metalloproteinase domain-containing protein 10 Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 1
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 description 1
- 101001011884 Homo sapiens Matrix metalloproteinase-15 Proteins 0.000 description 1
- 101001011886 Homo sapiens Matrix metalloproteinase-16 Proteins 0.000 description 1
- 101001011887 Homo sapiens Matrix metalloproteinase-17 Proteins 0.000 description 1
- 101000577874 Homo sapiens Stromelysin-2 Proteins 0.000 description 1
- 101000577877 Homo sapiens Stromelysin-3 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 206010062049 Lymphocytic infiltration Diseases 0.000 description 1
- 108030001712 Macrophage elastases Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010076501 Matrix Metalloproteinase 12 Proteins 0.000 description 1
- 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 1
- 102100030201 Matrix metalloproteinase-15 Human genes 0.000 description 1
- 102100030200 Matrix metalloproteinase-16 Human genes 0.000 description 1
- 102100030219 Matrix metalloproteinase-17 Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 102100028847 Stromelysin-3 Human genes 0.000 description 1
- 208000026062 Tissue disease Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- GXBXYLVXNQXXNV-YFKPBYRVSA-N [(4r)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride Chemical compound ClS(=O)(=O)C[C@]1(C)NC(=O)NC1=O GXBXYLVXNQXXNV-YFKPBYRVSA-N 0.000 description 1
- FXOMUPRUQAVPSB-UHFFFAOYSA-N [2,5-dioxo-4-(2-phenylmethoxyethyl)imidazolidin-4-yl]methanesulfonyl chloride Chemical compound C=1C=CC=CC=1COCCC1(CS(=O)(=O)Cl)NC(=O)NC1=O FXOMUPRUQAVPSB-UHFFFAOYSA-N 0.000 description 1
- UFVXHCDOOWOVJO-UHFFFAOYSA-N [2,5-dioxo-4-[(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)methyl]imidazolidin-4-yl]methanesulfonyl chloride Chemical compound O=C1C(C)(C)N(C)C(=O)N1CC1(CS(Cl)(=O)=O)C(=O)NC(=O)N1 UFVXHCDOOWOVJO-UHFFFAOYSA-N 0.000 description 1
- HUOFUOCSQCYFPW-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(OC(F)(F)F)C=C1 HUOFUOCSQCYFPW-UHFFFAOYSA-N 0.000 description 1
- KOOADCGQJDGAGA-UHFFFAOYSA-N [amino(dimethyl)silyl]methane Chemical compound C[Si](C)(C)N KOOADCGQJDGAGA-UHFFFAOYSA-N 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- XLUXHEZIGIDTCC-UHFFFAOYSA-N acetonitrile;ethyl acetate Chemical compound CC#N.CCOC(C)=O XLUXHEZIGIDTCC-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BZWUXSAUEMDLRU-UHFFFAOYSA-N benzene;propan-2-one;hydrate Chemical compound O.CC(C)=O.C1=CC=CC=C1 BZWUXSAUEMDLRU-UHFFFAOYSA-N 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 201000003149 breast fibroadenoma Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 208000034391 chronic adult periodontitis Diseases 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000037369 collagen remodeling Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000004734 cutaneous carcinogenesis Effects 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- MKYNHKOAYQRSBD-UHFFFAOYSA-N dioxouranium;nitric acid Chemical compound O=[U]=O.O[N+]([O-])=O.O[N+]([O-])=O MKYNHKOAYQRSBD-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000032692 embryo implantation Effects 0.000 description 1
- 238000009585 enzyme analysis Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- XZMZHLGLBXLEPY-UHFFFAOYSA-N ethyl 3-pyrimidin-2-ylpropanoate Chemical compound CCOC(=O)CCC1=NC=CC=N1 XZMZHLGLBXLEPY-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 210000004195 gingiva Anatomy 0.000 description 1
- 208000024693 gingival disease Diseases 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 102000047338 human MMP12 Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 1
- PXKMTGMNZZCQQB-UHFFFAOYSA-N imidazolidine-2,4-dione;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1CNC(=O)N1 PXKMTGMNZZCQQB-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000030776 invasive breast carcinoma Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- QLNWXBAGRTUKKI-UHFFFAOYSA-N metacetamol Chemical compound CC(=O)NC1=CC=CC(O)=C1 QLNWXBAGRTUKKI-UHFFFAOYSA-N 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
- GRBLFZTVZMMYOK-QGZVFWFLSA-N n-(4-fluorophenyl)-1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)NC=2C=CC(F)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O GRBLFZTVZMMYOK-QGZVFWFLSA-N 0.000 description 1
- CRESQTOXLGCJJR-UHFFFAOYSA-N n-(4-piperidin-4-yloxyphenyl)acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1CCNCC1 CRESQTOXLGCJJR-UHFFFAOYSA-N 0.000 description 1
- QFZGCABKVDHNDY-QGZVFWFLSA-N n-[1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidin-4-yl]benzamide Chemical compound C1CC(NC(=O)C=2C=CC=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O QFZGCABKVDHNDY-QGZVFWFLSA-N 0.000 description 1
- OQLUZWTZGADULM-GOSISDBHSA-N n-[3-[1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidin-4-yl]oxyphenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(OC2CCN(CC2)S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)=C1 OQLUZWTZGADULM-GOSISDBHSA-N 0.000 description 1
- OMLMUNKGQCXCOM-UHFFFAOYSA-N n-[3-[4-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-2,5-dioxoimidazolidin-4-yl]propyl]methanesulfonamide Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)CC1(CCCNS(=O)(=O)C)NC(=O)NC1=O OMLMUNKGQCXCOM-UHFFFAOYSA-N 0.000 description 1
- WPFVKCUEKOLQKC-GOSISDBHSA-N n-[4-[1-[[(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methylsulfonyl]piperidin-4-yl]oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1CCN(S(=O)(=O)C[C@]2(C)C(NC(=O)N2)=O)CC1 WPFVKCUEKOLQKC-GOSISDBHSA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 210000003681 parotid gland Anatomy 0.000 description 1
- 201000001219 parotid gland cancer Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- WBGHAVFTFDQINN-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate;dihydrate Chemical compound O.O.[Na+].CC1=CC=C(S([O-])=O)C=C1 WBGHAVFTFDQINN-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- LXEZGWLTOXJOGV-UHFFFAOYSA-N tert-butyl 2-[6-(4-formylpiperazin-1-yl)pyridin-3-yl]pyrrole-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C=CC=C1C1=CC=C(N2CCN(CC2)C=O)N=C1 LXEZGWLTOXJOGV-UHFFFAOYSA-N 0.000 description 1
- ZBCXTNPVDVWHNC-UHFFFAOYSA-N tert-butyl 2-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1O ZBCXTNPVDVWHNC-UHFFFAOYSA-N 0.000 description 1
- ADFSCQGCEAKLOE-UHFFFAOYSA-N tert-butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate Chemical compound COC(=O)CC1CCN(C(=O)OC(C)(C)C)CC1 ADFSCQGCEAKLOE-UHFFFAOYSA-N 0.000 description 1
- OHLLSFRHFHSUES-UHFFFAOYSA-N tert-butyl 4-(2-methoxy-2-oxoethylidene)piperidine-1-carboxylate Chemical compound COC(=O)C=C1CCN(C(=O)OC(C)(C)C)CC1 OHLLSFRHFHSUES-UHFFFAOYSA-N 0.000 description 1
- ZDWUDTMOOQHRFB-UHFFFAOYSA-N tert-butyl 4-(5-bromopyridin-2-yl)oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C(Br)C=N1 ZDWUDTMOOQHRFB-UHFFFAOYSA-N 0.000 description 1
- FPQVJHTWOWQFNT-UHFFFAOYSA-N tert-butyl 4-(5-chloropyridin-2-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(Cl)C=N1 FPQVJHTWOWQFNT-UHFFFAOYSA-N 0.000 description 1
- HAMXBDINJQJHJO-UHFFFAOYSA-N tert-butyl 4-(5-phenylmethoxypyridin-2-yl)oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC(N=C1)=CC=C1OCC1=CC=CC=C1 HAMXBDINJQJHJO-UHFFFAOYSA-N 0.000 description 1
- WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 1
- OVAPSFGYWUDJNA-UHFFFAOYSA-N tert-butyl 4-[2-(4-chlorophenyl)ethynyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C#CC=2C=CC(Cl)=CC=2)=C1 OVAPSFGYWUDJNA-UHFFFAOYSA-N 0.000 description 1
- ZJDOLYQMJLKQFO-UHFFFAOYSA-N tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C=CC(OC(F)(F)F)=CC=2)=C1 ZJDOLYQMJLKQFO-UHFFFAOYSA-N 0.000 description 1
- RDBYGNSYOIZOJG-UHFFFAOYSA-N tert-butyl 4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(OC(F)(F)F)C=C1 RDBYGNSYOIZOJG-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- YFWQFKUQVJNPKP-UHFFFAOYSA-N tert-butyl 4-iodopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(I)CC1 YFWQFKUQVJNPKP-UHFFFAOYSA-N 0.000 description 1
- NCZIHTFUQIAOLW-UHFFFAOYSA-N tert-butyl n-[5-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-4-oxopentyl]carbamate Chemical compound C1CN(S(=O)(=O)CC(=O)CCCNC(=O)OC(C)(C)C)CCC1OC1=CC=C(Cl)C=N1 NCZIHTFUQIAOLW-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 108010072415 tumor necrosis factor precursor Proteins 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 238000013389 whole blood assay Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- XPARCVGSTPKNNR-UHFFFAOYSA-M zinc;ethyl butanoate;bromide Chemical compound [Zn+2].[Br-].CCOC(=O)CC[CH2-] XPARCVGSTPKNNR-UHFFFAOYSA-M 0.000 description 1
- APPDFGHVJHZDKS-UHFFFAOYSA-M zinc;ethyl propanoate;bromide Chemical compound Br[Zn+].CCOC(=O)C[CH2-] APPDFGHVJHZDKS-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- C07D405/02—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Gastroenterology & Hepatology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Obesity (AREA)
- Otolaryngology (AREA)
- Reproductive Health (AREA)
Abstract
Description
5-[4-(4-클로로-페닐)-피페라진-1-술포닐메틸]-5-(3-피리미딘-2-일-프로필]-이미다졸리딘-2,4-디온 | |
5-[4-(4-플루오로-페닐)-피페라진-1-술포닐메틸]-5-[2-(5-플루오로-피리미딘-2-일)-에틸]-이미다졸리딘-2,4-디온 | |
5-[4-(5-클로로-피리딘-2-일)-피페라진-1-술포닐메틸]-5-[2-(5-플루오로-피리미딘-2-일)-에틸]-이미다졸리딘-2,4-디온 | |
5-[4-(3,4-디클로로-페닐)-피페라진-1-술포닐메틸]-5-(3-피리미딘-2-일-프로필]-이미다졸리딘-2,4-디온 |
Claims (16)
- 하기 화학식 I의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.<화학식 I>상기 식에서,X는 NR1, O 및 S로부터 선택되고;Y1및 Y2는 O 및 S로부터 독립적으로 선택되며;Z는 SO 및 SO2로부터 선택되고;m은 1 또는 2이며;A는 직접 결합, (C1-6)알킬, (C1-6)할로알킬, 및 N, O, S, SO, S02로부터 선택된 헤테로기를 함유하거나 또는 N, O, S, SO, S02로부터 선택되고 2개 이상의 탄소 원자에 의해 분리된 2개의 헤테로기를 함유하는 (C1-6)헤테로알킬로부터 선택되고;R1은 H, (C1-3)알킬 및 할로알킬로부터 선택되며;R2 및 R3은 각각 H, 할로겐, 알킬, 헤테로알킬, 시클로알킬, 헤테로시클로알킬, 아릴, 헤테로아릴, 알킬아릴, 알킬-헤테로아릴, 헤테로알킬-아릴, 헤테로알킬-헤테로아릴, 아릴-알킬, 아릴-헤테로알킬, 헤테로아릴-알킬, 헤테로아릴-헤테로알킬, 아릴-아릴, 아릴-헤테로아릴, 헤테로아릴-아릴, 헤테로아릴-헤테로아릴, 시클로알킬-알킬, 헤테로시클로알킬-알킬, 알킬-시클로알킬 및 알킬-헤테로시클로알킬로부터 독립적으로 선택되고;R4는 각각 H, 할로겐, (C1-3)알킬 및 할로알킬로부터 독립적으로 선택되며;R2 및 R3 라디칼은 각각 독립적으로 알킬, 헤테로알킬, 아릴, 헤테로아릴, 할로, 할로알킬, 히드록시, 알콕시, 할로알콕시, 티올, 알킬티올, 아릴 티올, 알킬술폰, 할로알킬술폰, 아릴술폰, 아미노술폰, N-알킬아미노술폰, N,N-디알킬아미노술폰, 아릴아미노술폰, 아미노, N-알킬아미노, N,N-디알킬아미노, 아미도, N-알킬아미도, N,N-디알킬아미도, 시아노, 술폰아미노, 알킬술폰아미노, 아릴술폰아미노, 아미디노, N-아미노술폰-아미디노, 구아니디노, N-시아노-구아니디노, 티오구아니디노, 2-니트로-에텐-1,1-디아민, 카르복시, 알킬-카르복시, 니트로 및 카르바메이트로부터 선택된 1개 이상의 기로 임의로 치환될 수 있고;임의로 R2와 R3이 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, R2와 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, 또는 R3과 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있으며;R5는 시클로알킬, 아릴, 헤테로시클로알킬 및 헤테로아릴로부터 독립적으로선택된 각각 7개 이하의 고리 원자를 포함하는 1개 내지 3개의 고리 구조를 포함하는 모노시클릭, 비시클릭 또는 트리시클릭기이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 알킬, 알콕시, 할로알콕시, 아미노, N-알킬아미노, N,N-디알킬아미노, 알킬술폰아미노, 알킬카르복시아미노, 시아노, 니트로, 티올, 알킬티올, 알킬술포닐, 할로알킬술포닐, 알킬아미노술포닐, 카르복실레이트, 알킬카르복실레이트, 아미노카르복시, N-알킬아미노-카르복시 및 N,N-디알킬아미노-카르복시로부터 독립적으로 선택된 1개 이상의 치환기로 독립적으로 치환되고, 임의의 치환기 중의 임의의 알킬 라디칼은 그 자체가 할로겐, 히드록시, 알콕시, 할로알콕시, 아미노, N-알킬아미노, N,N-디알킬아미노, N-알킬술폰아미노, N-알킬카르복시아미노, 시아노, 니트로, 티올, 알킬티올, 알킬술포닐, N-알킬아미노술포닐, 카르복실레이트, 알킬카르복시, 아미노카르복시, N-알킬아미노카르복시, N,N-디알킬아미노카르복시 및 카르바메이트로부터 선택된 1개 이상의 기로 임의로 치환될 수 있고;R5가 비시클릭 또는 트리시클릭기인 경우, 고리 구조 각각은 직접 결합, -O-, (C1-6)알킬, (C1-6)할로알킬, (C1-6)헤테로알킬, (C1-6)알케닐, (C1-6)알키닐, 술폰, CO, NCO, CON, NH, S 또는 C(OH)에 의해 이웃한 고리 구조와 결합되거나 또는 이웃한 고리 구조에 접합된다.
- 제1항에 있어서, X가 NR1이고, Z가 SO2또는 SO이며, Y1및 Y2중의 적어도 하나가 O이고, m이 1이며, R1이 H, (C1-3)알킬 또는 (C1-3)할로알킬인, 화학식 I의화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제1항 또는 2항에 있어서, R2가 H, 알킬, 히드록시알킬, 알콕시알킬, 아릴옥시 알킬, 아미노알킬, 시클로알킬-알킬, 알킬-시클로알킬, 아릴알킬, 알킬아릴, 알킬-헤테로아릴, 헤테로알킬, 헤테로시클로알킬-알킬, 알킬-헤테로시클로알킬, 헤테로아릴-알킬 또는 헤테로알킬-아릴인, 화학식 I의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제1항 내지 3항 중 어느 한 항에 있어서, R3 및 R4가 각각 H 또는 메틸로부터 독립적으로 선택된 것인, 화학식 I의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제1항 내지 제4항 중 어느 한 항에 있어서, R5가 1개 내지 3개 임의로 치환된 5 또는 6원 고리의 아릴 또는 헤테로아릴을 포함하는 것인, 화학식 I의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제1항 내지 제5항 중 어느 한 항에 있어서, R5가 2개 또는 3개 임의로 치환된 고리 구조를 포함하는 비시클릭 또는 트리시클릭기인, 화학식 I의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 하기 화학식 II의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.<화학식 II>상기 식에서,G1, G2 및 G4는 각각 시클로알킬, 아릴, 헤테로시클로알킬 및 헤테로아릴로부터 독립적으로 선택된 각각 7개 이하의 고리 원자를 포함하는 모노시클릭 고리 구조이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 할로알콕시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알킬, 알콕시, 알킬 술폰, 할로알킬 술폰, 알킬카르바메이트 및 알킬아미드로부터 독립적으로 선택된 1개 또는 2개의 치환기로 독립적으로 치환되며, 임의의 치환기 중의 임의의 알킬 라디칼은 그 자체가 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알콕시, 할로알콕시, 아릴옥시, 헤테로아릴옥시 및 카르바메이트로부터 선택된 1개 이상의 기로 임의로 치환될 수 있고;Z는 SO2이며;B 및 F는 각각 직접 결합, 0, (C1-6)알킬, (C1-6)헤테로알킬, 알키닐, CO, NCO, CON, NH 및 S로부터 독립적으로 선택되고;R2는 H, 알킬, 히드록시알킬, 알콕시알킬, 아릴옥시 알킬, 아미노알킬, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 아미도알킬, 티오알킬 시클로알킬-알킬, 알킬-시클로알킬, 아릴알킬, 알킬아릴, 알킬-헤테로아릴, 헤테로알킬, 헤테로시클로알킬-알킬, 알킬-헤테로시클로알킬, 헤테로아릴-알킬 및 헤테로알킬-아릴로부터 선택되며;R3 및 R4는 H 및 (C1-3)알킬로부터 독립적으로 선택되고;임의로 R2와 R3이 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, R2와 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, 또는 R3과 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있다.
- 제7항에 있어서, R2가 알킬, 아미노알킬, 알킬-헤테로아릴, 알킬-헤테로시클로알킬 또는 헤테로아릴-알킬인, 화학식 II의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 하기 화학식 IIa의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.<화학식 IIa>상기 식에서,G1 및 G2는 각각 시클로알킬, 아릴, 헤테로시클로알킬 및 헤테로아릴로부터 독립적으로 선택된 각각 7개 이하의 고리 원자를 포함하는 모노시클릭 고리 구조이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 할로알콕시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알킬, 알콕시, 알킬 술폰, 할로알킬 술폰, 알킬카르바메이트 및 알킬아미드로부터 독립적으로 선택된 1개 또는 2개의 치환기로 독립적으로 치환되고, 임의의 치환기 중의 임의의 알킬 라디칼은 그 자체가 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알콕시, 할로알콕시, 아릴옥시, 헤테로아릴옥시 및 카르바메이트로부터 선택된 1개 이상의 기로 임의로 치환될 수 있고;Z는 SO2이며;B는 직접 결합, O, (C1-6)알킬, (C1-6)헤테로알킬, CO, NCO, CON, NH, S 및 알키닐로부터 선택되고;R2는 H, (C1-6)알킬, 할로알킬, 히드록시알킬, 알콕시알킬, 아미노알킬, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 아미도알킬 및 티오알킬로부터 선택되거나, 또는 R2는 하기 화학식 III의 기이고,<화학식 III>C 및 D는 직접 결합, H, (C1-C6)알킬, (C1-C6)할로알킬, 및 N, O 또는 S로부터 선택된 1개 또는 2개의 헤테로 원자 (2개의 헤테로원자가 존재하는 경우 이들은 2개 이상의 탄소 원자에 의해 분리됨)를 함유하는 (C1-C6)헤테로알킬로부터 독립적으로 선택되고;G3은 시클로알킬, 아릴, 헤테로시클로알킬 및 헤테로아릴로부터 독립적으로 선택된 7개 이하의 고리 원자를 포함하는 모노시클릭 고리 구조이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알킬, 알콕시, 알킬 술폰, 할로알킬 술폰, 및 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알콕시 또는 할로알콕시로부터 선택된 1개 이상의 기로 치환된 알킬로부터 독립적으로 선택된 1개 또는 2개의 치환기로 치환되며;임의로 R2는 할로, 할로알킬, 히드록시, 알콕시, 할로알콕시, 아미노, 아미노알킬, N-알킬아미노, N,N-디알킬아미노, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 알킬술폰, 아미노술폰, N-알킬아미노-술폰, N,N-디알킬아미노술폰, 아미도, N-알킬아미도, N,N-디알킬아미도, 시아노, 술폰아미노, 알킬-술폰아미노, 아미디노, N-아미노술폰-아미디노, 구아니디노, N-시아노-구아니디노, 티오구아니디노, 2-니트로구아니디노, 카르복시, 알킬카르복시 또는 카르바메이트로 치환되고;R3 및 R4는 H 및 (C1-3)알킬로부터 독립적으로 선택되며;임의로 R2와 R3이 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, R2와 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, 또는 R3과 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있다.
- 제9항에 있어서, B가 직접 결합, O, CO, S 및 알키닐로부터 선택된 것인, 화학식 IIa의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제9항 또는 10항에 있어서, R2가 H, 할로, 할로알킬, 히드록시, 알콕시, 할로알콕시, 아미노, 아미노알킬, N-알킬아미노, N,N-디알킬아미노, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 알킬술폰, 아미노술폰, N-알킬아미노-술폰, N,N-디알킬아미노-술폰, 아미도, N-알킬아미도, N,N-디알킬아미도, 카르바메이트, 시아노, 술폰아미노, 알킬술폰아미노, 아미디노, N-아미노술폰-아미디노, 구아니디노, N-시아노-구아니디노, 티오구아니디노, 2-니트로구아니디노, 2-니트로-에텐-1,1-디아미노, 카르복시, 알킬카르복시 또는 카르바메이트로 임의로 치환된, (C1-6)알킬, 아릴-(C1-6)알킬 및 헤테로아릴-(C1-6)알킬로부터 선택된 것인, 화학식 IIa의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 제9항 내지 11항 중 어느 한 항에 있어서, R3 및 R4가 각각 H인 화학식 IIa의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.
- 하기 화학식 IIb의 화합물 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르.<화학식 IIb>상기 식에서,G1은 각각 시클로알킬, 아릴, 헤테로시클로알킬 및 헤테로아릴로부터 독립적으로 선택된 각각 7개 이하의 고리 원자를 포함하는 모노시클릭 고리 구조이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 할로알콕시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알킬, 알콕시, 알킬 술폰, 할로알킬 술폰, 알킬카르바메이트 및 알킬아미드로부터 독립적으로 선택된 1개 또는 2개의 치환기로 독립적으로 치환되며, 임의의 치환기 중의 임의의 알킬 라디칼은 그 자체가 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알콕시, 할로알콕시, 아릴옥시, 헤테로아릴옥시 또는 카르바메이트로부터 선택된 1개 이상의 기로 임의로 치환될 수 있고;G2는 임의로 치환된 피페리딘 또는 피페라진이며;B는 직접 결합, O, (C1-6)알킬, (C1-6)헤테로알킬, CO, NCO, CON, NH, S 및 알키닐로부터 선택되고;R2는 H, (C1-6)알킬, 할로알킬, 히드록시알킬, 알콕시알킬, 아미노알킬, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 아미도알킬 및 티오알킬로부터 선택되거나, 또는 R2는 하기 화학식 III의 기이며,<화학식 III>C 및 D는 직접 결합, H, (C1-C6)알킬, (C1-C6)할로알킬, 및 N, O 또는 S로부터 선택된 1개 또는 2개의 헤테로 원자 (2개의 헤테로원자가 존재하는 경우 이들은 2개 이상의 탄소 원자에 의해 분리됨)를 함유하는 (C1-C6)헤테로알킬로부터 독립적으로 선택되고;G3은 시클로알킬, 아릴, 헤테로시클로알킬 또는 헤테로아릴로부터 독립적으로 선택된 7개 이하의 고리 원자를 포함하는 모노시클릭 고리 구조이며, 각 고리 구조는 임의로는 할로겐, 히드록시, 아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알킬, 알콕시, 알킬 술폰, 할로알킬 술폰, 또는 할로겐, 히드록시,아미노, N-알킬아미노, N,N-디알킬아미노, 시아노, 니트로, 알콕시 및 할로알콕시로부터 선택된 1개 이상의 기로 치환된 알킬로부터 독립적으로 선택된 1개 또는 2개의 치환기로 치환되며;임의로 R2는 할로, 할로알킬, 히드록시, 알콕시, 할로알콕시, 아미노, 아미노알킬, N-알킬아미노, N,N-디알킬아미노, (N-알킬아미노)알킬, (N,N-디알킬아미노)알킬, 알킬술폰, 아미노술폰, N-알킬아미노-술폰, N,N-디알킬아미노술폰, 아미도, N-알킬아미도, N,N-디알킬아미도, 시아노, 술폰아미노, 알킬-술폰아미노, 아미디노, N-아미노술폰-아미디노, 구아니디노, N-시아노-구아니디노, 티오구아니디노, 2-니트로구아니디노, 카르복시, 알킬카르복시 또는 카르바메이트로 치환되고;R3 및 R4는 H 및 (C1-3)알킬로부터 독립적으로 선택되며;임의로 R2와 R3이 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, R2와 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있거나, 또는 R3과 R4가 결합하여 7개 이하의 고리 원자를 포함하는 고리를 형성할 수 있다.
- 제1항의 화학식 I의 화합물, 제7항의 화학식 II의 화합물, 제9항의 화학식 IIa의 화합물, 제13항의 화학식 IIb의 화합물, 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르 및 제약학상 허용되는 담체를 포함하는 제약 조성물.
- 치료 유효량의 화학식 I, II, IIa 또는 IIb의 화합물, 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 에스테르를 온혈 동물에게 투여하는 것을 포함하는, 메탈로프로테이나제 매개된 질환 또는 상태의 치료 방법.
- 1종 이상의 메탈로프로테이나제 효소에 의해 매개된 질환 또는 상태의 치료에 사용하기 위한 의약 제조에서의 화학식 I, II, IIa 또는 IIb의 화합물, 또는 그의 제약학상 허용되는 염 또는 생체내 가수분해성 전구체의 용도.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0100902A SE0100902D0 (sv) | 2001-03-15 | 2001-03-15 | Compounds |
SE0100902-6 | 2001-03-15 | ||
PCT/SE2002/000472 WO2002074767A1 (en) | 2001-03-15 | 2002-03-13 | Metalloproteinase inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20030082989A true KR20030082989A (ko) | 2003-10-23 |
KR100886315B1 KR100886315B1 (ko) | 2009-03-04 |
Family
ID=20283374
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020087017665A KR100879905B1 (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
KR1020037011987A KR100886315B1 (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
KR10-2003-7011982A KR20030082987A (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
KR10-2003-7011981A KR20030082986A (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020087017665A KR100879905B1 (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR10-2003-7011982A KR20030082987A (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
KR10-2003-7011981A KR20030082986A (ko) | 2001-03-15 | 2002-03-13 | 메탈로프로테이나제 억제제 |
Country Status (33)
Country | Link |
---|---|
US (8) | US20040106659A1 (ko) |
EP (4) | EP1370556B1 (ko) |
JP (4) | JP2004527515A (ko) |
KR (4) | KR100879905B1 (ko) |
CN (5) | CN101602731A (ko) |
AR (2) | AR035695A1 (ko) |
AT (3) | ATE333454T1 (ko) |
AU (2) | AU2002237626B2 (ko) |
BR (3) | BR0207984A (ko) |
CA (3) | CA2440630C (ko) |
CY (1) | CY1107525T1 (ko) |
CZ (3) | CZ20032500A3 (ko) |
DE (3) | DE60213216T2 (ko) |
DK (1) | DK1370556T3 (ko) |
EE (3) | EE200300449A (ko) |
ES (3) | ES2357138T3 (ko) |
HK (3) | HK1091492A1 (ko) |
HU (3) | HUP0400202A3 (ko) |
IL (5) | IL157656A0 (ko) |
IS (3) | IS6942A (ko) |
MX (3) | MXPA03008177A (ko) |
MY (2) | MY136141A (ko) |
NO (3) | NO327114B1 (ko) |
NZ (3) | NZ528107A (ko) |
PL (3) | PL205315B1 (ko) |
PT (1) | PT1370556E (ko) |
RU (3) | RU2293729C2 (ko) |
SE (1) | SE0100902D0 (ko) |
SI (1) | SI1370556T1 (ko) |
SK (3) | SK287766B6 (ko) |
UA (3) | UA78502C2 (ko) |
WO (3) | WO2002074748A1 (ko) |
ZA (4) | ZA200306732B (ko) |
Families Citing this family (67)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE0100903D0 (sv) * | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
SE0100902D0 (sv) * | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
CA2447475A1 (en) | 2001-05-25 | 2002-12-05 | Chu-Biao Xue | Hydantion derivatives as inhibitors of matrix metalloproteinases |
SE0103710D0 (sv) | 2001-11-07 | 2001-11-07 | Astrazeneca Ab | Compounds |
DE10221018A1 (de) * | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
SE0202539D0 (sv) * | 2002-08-27 | 2002-08-27 | Astrazeneca Ab | Compounds |
SE0202693D0 (sv) * | 2002-09-11 | 2002-09-11 | Astrazeneca Ab | Compounds |
GB0221246D0 (en) * | 2002-09-13 | 2002-10-23 | Astrazeneca Ab | Compounds |
WO2004033632A2 (en) * | 2002-10-04 | 2004-04-22 | Bristol-Myers Squibb Company | Hydantoin derivatives as inhibitors of matrix metalloproteinases and/or tnf-alpha converting enzyme (tace) |
US7632950B2 (en) | 2003-08-18 | 2009-12-15 | Fujifilm Finechemicals Co., Ltd | Pyridyltetrahydropyridines and pyridylpiperidines and method of manufacturing them |
WO2005090316A1 (en) * | 2004-03-12 | 2005-09-29 | Wyeth | HYDANTOINS HAVING RNase MODULATORY ACTIVITY |
SE0401762D0 (sv) * | 2004-07-05 | 2004-07-05 | Astrazeneca Ab | Novel compounds |
SE0401763D0 (sv) * | 2004-07-05 | 2004-07-05 | Astrazeneca Ab | Compounds |
US7648992B2 (en) * | 2004-07-05 | 2010-01-19 | Astrazeneca Ab | Hydantoin derivatives for the treatment of obstructive airway diseases |
WO2006029173A2 (en) * | 2004-09-08 | 2006-03-16 | Boys Town National Research Hospital | Treatment of glomerular basement membrane disease involving matrix metalloproteinase-12 |
CN101083994A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 杂环衍生物及其用作硬脂酰CoA去饱和酶抑制剂的用途 |
CN101083992A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 抑制人硬脂酰CoA去饱和酶的哒嗪衍生物 |
AR051093A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa desaturasa |
CA2580762A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
BRPI0515483A (pt) * | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos para o tratamento de doenças mediadas por enzimas estearoil-coa desaturase |
JP2008513515A (ja) | 2004-09-20 | 2008-05-01 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環誘導体および治療薬としてのそれらの使用 |
AR051091A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
GB0427403D0 (en) * | 2004-12-15 | 2005-01-19 | Astrazeneca Ab | Novel compounds I |
SE0403085D0 (sv) * | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Novel componds |
SE0403086D0 (sv) * | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Compounds |
WO2006099598A2 (en) * | 2005-03-16 | 2006-09-21 | Sensus Metering Systems Inc. | Determining a physical location of a sensor |
MX2007015216A (es) | 2005-06-03 | 2008-02-22 | Xenon Pharmaceuticals Inc | Derivados de aminotiazol y sus usos como agentes terapeuticos. |
WO2007078335A2 (en) * | 2005-12-21 | 2007-07-12 | Decode Genetics, Ehf. | Biaryl nitrogen heterocycle inhibitors of lta4h for treating inflammation |
AR059037A1 (es) | 2006-01-17 | 2008-03-12 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
TW200740769A (en) * | 2006-03-16 | 2007-11-01 | Astrazeneca Ab | Novel process |
TW200800954A (en) * | 2006-03-16 | 2008-01-01 | Astrazeneca Ab | Novel crystal modifications |
MX2008013624A (es) * | 2006-05-12 | 2008-10-30 | Sca Hygiene Prod Ab | Laminado elastico y un metodo para producir un laminado elastico. |
CN101460128B (zh) * | 2006-05-12 | 2012-07-18 | Sca卫生产品股份公司 | 裤型吸湿制件以及裤型吸湿制件的生产方法 |
WO2008053199A1 (en) * | 2006-10-30 | 2008-05-08 | Astrazeneca Ab | Combination therapy for the treatment of respiratory diseases |
TW200831488A (en) * | 2006-11-29 | 2008-08-01 | Astrazeneca Ab | Novel compounds |
GB0702456D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination |
WO2009007747A2 (en) * | 2007-07-11 | 2009-01-15 | Astrazeneca Ab | Hydantoin derivatives used as mmp12 inhibitors |
WO2009064224A1 (en) | 2007-11-14 | 2009-05-22 | Sca Hygiene Products Ab | Method of producing an absorbent garment, and an absorbent garment produced according to the method |
BRPI0722259A2 (pt) | 2007-11-14 | 2014-04-08 | Sca Hygiene Prod Ab | Método para produção de um vestuário absorvente, e vestuário absorvente produzido de acordo com o método |
FR2927330B1 (fr) * | 2008-02-07 | 2010-02-19 | Sanofi Aventis | Derives de 5,6-bisaryl-2-pyridine-carboxamide, leur preparation et leur application en therapeutique comme antagonistes des recepteurs a l'urotensine ii |
JP5539965B2 (ja) | 2008-04-28 | 2014-07-02 | レバレジオ コーポレイション | 多発性硬化症を治療するための組成物および方法 |
FR2944524B1 (fr) * | 2009-04-17 | 2012-11-30 | Ipsen Pharma Sas | Derives d'imidazolidine-2,4-dione et leur utilisation comme medicament |
ES2525353T3 (es) | 2009-04-28 | 2014-12-22 | Chugai Seiyaku Kabushiki Kaisha | Derivado de espiroimidazolona |
GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
CN102711991B (zh) * | 2009-11-06 | 2015-01-21 | 巴斯夫欧洲公司 | 含铁和锰的非均相催化剂和通过一氧化碳与氢气反应而制备烯烃的方法 |
WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
US20110202284A1 (en) * | 2010-02-10 | 2011-08-18 | Mcreynolds Cristopher | Novel groups of biomarkers for diagnosing alzheimer's disease |
CN103096893B (zh) | 2010-06-04 | 2016-05-04 | 阿尔巴尼分子研究公司 | 甘氨酸转运体-1抑制剂、其制备方法及其用途 |
GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
CN103958480B (zh) * | 2012-09-04 | 2016-04-06 | 上海恒瑞医药有限公司 | 咪唑啉类衍生物、其制备方法及其在医药上的应用 |
MA38250B1 (fr) | 2012-12-10 | 2017-10-31 | Chugai Pharmaceutical Co Ltd | Nouveau dérivés d'hydantoïne pour leurs utilisations dans le traitement de maladies, comme l'osteoporose et la thrombocytopenie |
FI3068413T4 (fi) * | 2013-11-13 | 2023-08-31 | Rehun täydennysaine, joka käsittää hartsihappoa | |
WO2015100613A1 (en) * | 2013-12-31 | 2015-07-09 | Beaufour Ipsen Tianjin Pharmaceutical Co., Ltd | Novel imidazolidine-2, 4-dione derivatives |
EP2907512A1 (en) | 2014-02-14 | 2015-08-19 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Inhibitors of MMP-12 as antiviral Agents |
US9993462B2 (en) * | 2014-06-09 | 2018-06-12 | Chugai Seiyaku Kabushiki Kaisha | Hydantoin derivative-containing pharmaceutical composition |
KR102134171B1 (ko) | 2014-10-24 | 2020-07-15 | 란도스 바이오파마, 인크. | 란티오닌 합성효소 c-유사 2-계 치료제 |
JO3501B1 (ar) | 2014-12-22 | 2020-07-05 | Servier Lab | مشتقات 5-{(بيبرازين - 1-يل)-3-أوكسو - بروبيل}- إيميدازوليدين-2، 4 - دايون كمثبطات ل adamts لمعالجة هشاشة العظام) |
CN109803961B (zh) * | 2016-09-23 | 2021-03-23 | 科研制药株式会社 | (r)-5-(3,4-二氟苯基)-5-[(3-甲基-2-氧代吡啶-1(2h)-基)甲基]咪唑烷-2,4-二酮的制造方法及用于该制造的中间体 |
WO2021011723A1 (en) * | 2019-07-18 | 2021-01-21 | Avidence Therapeutics, Inc. | Anti-osteoarthritis hydantoin compounds and related compositions and methods |
CN115667227B (zh) * | 2019-11-14 | 2024-11-01 | 逸达生物科技股份有限公司 | 基质金属蛋白酶(mmp)抑制剂及其使用方法 |
EP3927427B1 (en) | 2019-12-20 | 2024-02-07 | Nimmune Biopharma, Inc. | Lanthionine c-like protein 2 ligands, cells prepared therewith, and therapies using same |
US12234578B2 (en) | 2020-01-29 | 2025-02-25 | Wisconsin Alumni Research Foundation | Tannin composite fibers |
EP4171553A1 (en) | 2020-06-26 | 2023-05-03 | The University Of Birmingham | Mmp-9 and mmp-12 inhibition for treating spinal cord injury or related injury to neurological tissue |
CN115720578A (zh) * | 2020-07-09 | 2023-02-28 | 深圳信立泰药业股份有限公司 | 并三环类衍生物、其制备方法及其在医药上的应用 |
CN112574193B (zh) * | 2020-12-31 | 2022-05-17 | 南京医科大学 | 一类口服gsnor抑制剂及其药物用途 |
Family Cites Families (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2327890A (en) * | 1940-04-17 | 1943-08-24 | Parke Davis & Co | Substituted phenoxyalkyl ethers |
US2745875A (en) | 1953-06-30 | 1956-05-15 | Hoechst Ag | Preparation of nu-acylamino-phenylpropane diols |
US3452040A (en) | 1966-01-05 | 1969-06-24 | American Home Prod | 5,5-disubstituted hydantoins |
US3529019A (en) * | 1968-04-23 | 1970-09-15 | Colgate Palmolive Co | Alkylaryloxy alanines |
CS152617B1 (ko) | 1970-12-29 | 1974-02-22 | ||
CS151744B1 (ko) | 1971-01-19 | 1973-11-19 | ||
US3849574A (en) * | 1971-05-24 | 1974-11-19 | Colgate Palmolive Co | Alpha-substituted-beta-arylthioalkyl amino-acids,for increasing heart rate |
US4315031A (en) | 1977-09-01 | 1982-02-09 | Science Union Et Cie | Thiosubstituted amino acids |
GB1601310A (en) * | 1978-05-23 | 1981-10-28 | Lilly Industries Ltd | Aryl hydantoins |
JPS6172762A (ja) | 1984-09-17 | 1986-04-14 | Kanegafuchi Chem Ind Co Ltd | 光学活性ヒダントイン類の製造法 |
JPS61212292A (ja) | 1985-03-19 | 1986-09-20 | Mitsui Toatsu Chem Inc | D−α−アミノ酸の製造方法 |
CA1325222C (en) | 1985-08-23 | 1993-12-14 | Lederle (Japan), Ltd. | Process for producing 4-biphenylylacetic acid |
GB8618559D0 (en) | 1986-07-30 | 1986-09-10 | Genetics Int Inc | Rhodococcus bacterium |
JPH0279879A (ja) | 1988-09-17 | 1990-03-20 | Canon Inc | 画像形成装置 |
US4983771A (en) * | 1989-09-18 | 1991-01-08 | Hexcel Corporation | Method for resolution of D,L-alpha-phenethylamine with D(-)mandelic acid |
NL9000386A (nl) | 1990-02-16 | 1991-09-16 | Stamicarbon | Werkwijze voor de bereiding van optisch aktief aminozuuramide. |
DK161690D0 (da) | 1990-07-05 | 1990-07-05 | Novo Nordisk As | Fremgangsmaade til fremstilling af enantiomere forbindelser |
IL99957A0 (en) | 1990-11-13 | 1992-08-18 | Merck & Co Inc | Piperidinylcamphorsulfonyl oxytocin antagonists and pharmaceutical compositions containing them |
PH31245A (en) | 1991-10-30 | 1998-06-18 | Janssen Pharmaceutica Nv | 1,3-Dihydro-2H-imidazoÄ4,5-BÜ-quinolin-2-one derivatives. |
US5308853A (en) | 1991-12-20 | 1994-05-03 | Warner-Lambert Company | Substituted-5-methylidene hydantoins with AT1 receptor antagonist properties |
US5246943A (en) | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
NL9201230A (nl) | 1992-07-09 | 1994-02-01 | Dsm Nv | Werkwijze voor de bereiding van optisch aktief methionineamide. |
EP0640594A1 (en) | 1993-08-23 | 1995-03-01 | Fujirebio Inc. | Hydantoin derivative as metalloprotease inhibitor |
JPH07105549A (ja) | 1993-09-30 | 1995-04-21 | Canon Inc | 光学的情報記録再生方法及び光学的情報記録再生装置 |
JPH09505310A (ja) | 1993-11-16 | 1997-05-27 | メルク エンド カンパニー インコーポレーテッド | ピペリジンショウノウスルホニルオキシトシン拮抗剤 |
BR9408506A (pt) | 1994-01-31 | 1997-08-05 | Pfizer | Compostos neuroprotetores |
DE69534213T2 (de) | 1994-10-25 | 2006-01-12 | Astrazeneca Ab | Therapeutisch wirksame Heterocyclen |
ZA96211B (en) | 1995-01-12 | 1996-07-26 | Teva Pharma | Compositions containing and methods of using 1- aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
US6166041A (en) | 1995-10-11 | 2000-12-26 | Euro-Celtique, S.A. | 2-heteroaryl and 2-heterocyclic benzoxazoles as PDE IV inhibitors for the treatment of asthma |
CZ291337B6 (cs) | 1995-11-22 | 2003-02-12 | Darwin Discovery Limited | Merkaptoalkylpeptidylová sloučenina, její použití pro výrobu přípravku pro léčení nebo prevenci stavu souvisejícího s metalloproteinázou nebo TNFalfa a farmaceutický přípravek ji obsahující |
GB9616643D0 (en) * | 1996-08-08 | 1996-09-25 | Chiroscience Ltd | Compounds |
US5919790A (en) * | 1996-10-11 | 1999-07-06 | Warner-Lambert Company | Hydroxamate inhibitors of interleukin-1β converting enzyme |
ATE212619T1 (de) | 1996-10-22 | 2002-02-15 | Upjohn Co | Alpha-amino sulfonyl hydroxamsäure als matrix metalloproteinase inhibitoren |
EP0983239A1 (en) | 1997-05-06 | 2000-03-08 | Novo Nordisk A/S | Novel heterocyclic compounds |
ES2165640T3 (es) | 1997-05-09 | 2002-03-16 | Hoechst Ag | Acidos diaminocarboxilicos sustituidos. |
ES2247707T3 (es) | 1997-06-21 | 2006-03-01 | Roche Diagnostics Gmbh | Derivados del acido barbiturico con actividad antimetastasica y antitumoral. |
DE19726427A1 (de) | 1997-06-23 | 1998-12-24 | Boehringer Mannheim Gmbh | Pyrimidin-2,4,6-trion-Derivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
TR199903287T2 (xx) * | 1997-07-31 | 2000-09-21 | Abbott Laboratories | Matriks metaloproteinazlar�n�n ters hidroksamat inhibit�rleri. |
TW514634B (en) | 1997-10-14 | 2002-12-21 | Lilly Co Eli | Process to make chiral compounds |
KR100609926B1 (ko) | 1997-11-12 | 2006-08-04 | 다윈 디스커버리 리미티드 | 엠엠피와 티엔에프 억제 활성을 갖는 히드록삼산 및카르복실산 유도체 |
SK11692000A3 (sk) | 1998-02-04 | 2001-02-12 | Novartis Ag | Sulfonylaminoderiváty, ktoré inhibujú metaloproteinázy degradujúce matricu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje |
US6329418B1 (en) | 1998-04-14 | 2001-12-11 | The Procter & Gamble Company | Substituted pyrrolidine hydroxamate metalloprotease inhibitors |
EP1077974A1 (en) | 1998-05-14 | 2001-02-28 | Du Pont Pharmaceuticals Company | Substituted aryl hydroxamic acids as metalloproteinase inhibitors |
SK18302000A3 (sk) | 1998-06-03 | 2001-06-11 | Gpi Nil Holdings, Inc. | N-viazané sulfónamidy n-heterocyklických karboxylových kyselín a izosterov karboxylových kyselín, farmaceutický prostriedok s ich obsahom a ich použitie |
EP1087937A1 (en) | 1998-06-17 | 2001-04-04 | Du Pont Pharmaceuticals Company | Cyclic hydroxamic acids as metalloproteinase inhibitors |
FR2782082B3 (fr) * | 1998-08-05 | 2000-09-22 | Sanofi Sa | Formes cristallines de (r)-(+)-n-[[3-[1-benzoyl-3-(3,4- dichlorophenyl)piperidin-3-yl]prop-1-yl]-4-phenylpiperidin-4 -yl]-n-methylacetamide (osanetant) et procede pour la preparation dudit compose |
US6339101B1 (en) | 1998-08-14 | 2002-01-15 | Gpi Nil Holdings, Inc. | N-linked sulfonamides of N-heterocyclic carboxylic acids or isosteres for vision and memory disorders |
JP2000127349A (ja) * | 1998-08-21 | 2000-05-09 | Komori Corp | 凹版印刷機 |
US6479502B1 (en) | 1998-08-29 | 2002-11-12 | British Biotech Pharmaceuticals | Hydroxamic acid derivatives as proteinase inhibitors |
GB9919776D0 (en) | 1998-08-31 | 1999-10-27 | Zeneca Ltd | Compoujnds |
DE69907238T2 (de) | 1998-10-07 | 2003-11-06 | Yazaki Corp., Tokio/Tokyo | Sol-gel verfahren unter verwendung poröser formen |
DE69915004T2 (de) * | 1998-11-05 | 2004-09-09 | Pfizer Products Inc., Groton | 5-Oxo-pyrrolidine-2-Carbonsäure-Hydroxamidderivate |
JP2002532479A (ja) | 1998-12-18 | 2002-10-02 | アクシス・ファーマシューティカルズ・インコーポレイテッド | プロテアーゼインヒビター |
CA2356689A1 (en) * | 1998-12-31 | 2000-07-13 | Michael J. Janusz | 1-carboxymethyl-2-oxo-azepan derivatives useful as selective inhibitors of mmp-12 |
US6340691B1 (en) * | 1999-01-27 | 2002-01-22 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors |
CN1343219A (zh) | 1999-01-28 | 2002-04-03 | 中外制药株式会社 | 取代的苯乙基胺衍生物 |
US6294694B1 (en) | 1999-06-04 | 2001-09-25 | Wisconsin Alumni Research Foundation | Matrix metalloproteinase inhibitors and method of using same |
GB9916562D0 (en) | 1999-07-14 | 1999-09-15 | Pharmacia & Upjohn Spa | 3-Arylsulfonyl-2-(substituted-methyl) propanoic acid derivatives as matrix metalloproteinase inhibitora |
US20020006920A1 (en) | 1999-07-22 | 2002-01-17 | Robinson Ralph Pelton | Arylsulfonylamino hydroxamic acid derivatives |
US6266453B1 (en) | 1999-07-26 | 2001-07-24 | Computerized Medical Systems, Inc. | Automated image fusion/alignment system and method |
DE60026404T2 (de) | 1999-08-02 | 2006-10-19 | F. Hoffmann-La Roche Ag | Verfahren zur Herstellung von Benzothiophen-Derivaten |
BR0013143A (pt) | 1999-08-12 | 2002-06-11 | Pharmacia Italia Spa | Derivados de 3 (5) amino pirazol, processo para sua preparação e uso dos mesmos como agentes antitumorais |
JP3710964B2 (ja) | 1999-08-26 | 2005-10-26 | 富士通株式会社 | ディスプレイデバイスのレイアウト設計方法 |
SE9904044D0 (sv) | 1999-11-09 | 1999-11-09 | Astra Ab | Compounds |
US6525202B2 (en) | 2000-07-17 | 2003-02-25 | Wyeth | Cyclic amine phenyl beta-3 adrenergic receptor agonists |
CA2419008A1 (en) | 2000-08-11 | 2003-02-11 | Kaken Pharmaceutical Co., Ltd. | 2,3-diphenylpropionic acid derivatives or their salts, medicines or cell adhesion inhibitors containing the same, and their usage |
US20020065219A1 (en) | 2000-08-15 | 2002-05-30 | Naidu B. Narasimhulu | Water soluble thiazolyl peptide derivatives |
US20020091107A1 (en) | 2000-09-08 | 2002-07-11 | Madar David J. | Oxazolidinone antibacterial agents |
WO2002020515A1 (en) | 2000-09-08 | 2002-03-14 | Abbott Laboratories | Oxazolidinone antibacterial agents |
EP1191024A1 (en) | 2000-09-22 | 2002-03-27 | Harald Tschesche | Thiadiazines and their use as inhibitors of metalloproteinases |
SE0100902D0 (sv) | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
EE200300439A (et) | 2001-03-15 | 2003-12-15 | Astrazeneca Ab | Metalloproteinaasi inhibiitorid |
SE0100903D0 (sv) | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
CA2447475A1 (en) | 2001-05-25 | 2002-12-05 | Chu-Biao Xue | Hydantion derivatives as inhibitors of matrix metalloproteinases |
GB0114004D0 (en) * | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
SE0103710D0 (sv) | 2001-11-07 | 2001-11-07 | Astrazeneca Ab | Compounds |
JP4485941B2 (ja) | 2002-06-05 | 2010-06-23 | 株式会社カネカ | 光学活性α−メチルシステイン誘導体の製造方法 |
SE0202539D0 (sv) | 2002-08-27 | 2002-08-27 | Astrazeneca Ab | Compounds |
SE0202693D0 (sv) | 2002-09-11 | 2002-09-11 | Astrazeneca Ab | Compounds |
SE0202692D0 (sv) | 2002-09-11 | 2002-09-11 | Astrazeneca Ab | Compounds |
GB0221250D0 (en) | 2002-09-13 | 2002-10-23 | Astrazeneca Ab | Compounds |
GB0221246D0 (en) * | 2002-09-13 | 2002-10-23 | Astrazeneca Ab | Compounds |
US6890913B2 (en) * | 2003-02-26 | 2005-05-10 | Food Industry Research And Development Institute | Chitosans |
US20040266832A1 (en) * | 2003-06-26 | 2004-12-30 | Li Zheng J. | Crystal forms of 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl pyridine |
TWI220073B (en) | 2003-07-24 | 2004-08-01 | Au Optronics Corp | Method for manufacturing polysilicon film |
SE0401763D0 (sv) | 2004-07-05 | 2004-07-05 | Astrazeneca Ab | Compounds |
SE0401762D0 (sv) | 2004-07-05 | 2004-07-05 | Astrazeneca Ab | Novel compounds |
US7648992B2 (en) | 2004-07-05 | 2010-01-19 | Astrazeneca Ab | Hydantoin derivatives for the treatment of obstructive airway diseases |
SE0403085D0 (sv) | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Novel componds |
SE0403086D0 (sv) | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Compounds |
TW200740769A (en) * | 2006-03-16 | 2007-11-01 | Astrazeneca Ab | Novel process |
TW200800954A (en) | 2006-03-16 | 2008-01-01 | Astrazeneca Ab | Novel crystal modifications |
TW200831488A (en) | 2006-11-29 | 2008-08-01 | Astrazeneca Ab | Novel compounds |
-
2001
- 2001-03-15 SE SE0100902A patent/SE0100902D0/xx unknown
-
2002
- 2002-03-13 ES ES06008158T patent/ES2357138T3/es not_active Expired - Lifetime
- 2002-03-13 NZ NZ528107A patent/NZ528107A/en unknown
- 2002-03-13 HU HU0400202A patent/HUP0400202A3/hu unknown
- 2002-03-13 SK SK1096-2003A patent/SK287766B6/sk not_active IP Right Cessation
- 2002-03-13 US US10/471,500 patent/US20040106659A1/en not_active Abandoned
- 2002-03-13 AT AT02704031T patent/ATE333454T1/de active
- 2002-03-13 CZ CZ20032500A patent/CZ20032500A3/cs unknown
- 2002-03-13 UA UA2003098171A patent/UA78502C2/uk unknown
- 2002-03-13 DK DK02704031T patent/DK1370556T3/da active
- 2002-03-13 CN CNA200910147512XA patent/CN101602731A/zh active Pending
- 2002-03-13 UA UA2003098168A patent/UA77408C2/uk unknown
- 2002-03-13 KR KR1020087017665A patent/KR100879905B1/ko not_active IP Right Cessation
- 2002-03-13 US US10/471,900 patent/US7427631B2/en not_active Expired - Fee Related
- 2002-03-13 BR BR0207984-4A patent/BR0207984A/pt not_active IP Right Cessation
- 2002-03-13 HU HU0400327A patent/HUP0400327A3/hu unknown
- 2002-03-13 CZ CZ20032497A patent/CZ20032497A3/cs unknown
- 2002-03-13 ES ES02704031T patent/ES2267986T3/es not_active Expired - Lifetime
- 2002-03-13 KR KR1020037011987A patent/KR100886315B1/ko not_active IP Right Cessation
- 2002-03-13 EE EEP200300449A patent/EE200300449A/xx unknown
- 2002-03-13 MY MYPI20020904A patent/MY136141A/en unknown
- 2002-03-13 JP JP2002573776A patent/JP2004527515A/ja not_active Withdrawn
- 2002-03-13 DE DE60213216T patent/DE60213216T2/de not_active Expired - Lifetime
- 2002-03-13 HU HU0400194A patent/HUP0400194A3/hu unknown
- 2002-03-13 NZ NZ528140A patent/NZ528140A/en not_active IP Right Cessation
- 2002-03-13 EP EP02704031A patent/EP1370556B1/en not_active Expired - Lifetime
- 2002-03-13 US US10/471,810 patent/US7368465B2/en not_active Expired - Fee Related
- 2002-03-13 IL IL15765602A patent/IL157656A0/xx unknown
- 2002-03-13 PL PL364706A patent/PL205315B1/pl not_active IP Right Cessation
- 2002-03-13 KR KR10-2003-7011982A patent/KR20030082987A/ko not_active Application Discontinuation
- 2002-03-13 UA UA2003098170A patent/UA77667C2/uk unknown
- 2002-03-13 EP EP06008158A patent/EP1676846B1/en not_active Expired - Lifetime
- 2002-03-13 AU AU2002237626A patent/AU2002237626B2/en not_active Ceased
- 2002-03-13 AT AT02704037T patent/ATE484496T1/de not_active IP Right Cessation
- 2002-03-13 MY MYPI20020910A patent/MY136789A/en unknown
- 2002-03-13 IL IL15765702A patent/IL157657A0/xx unknown
- 2002-03-13 SI SI200230386T patent/SI1370556T1/sl unknown
- 2002-03-13 BR BR0208104-0A patent/BR0208104A/pt not_active IP Right Cessation
- 2002-03-13 CN CNB02810093XA patent/CN1269804C/zh not_active Expired - Fee Related
- 2002-03-13 CA CA2440630A patent/CA2440630C/en not_active Expired - Fee Related
- 2002-03-13 AT AT06008158T patent/ATE493406T1/de not_active IP Right Cessation
- 2002-03-13 KR KR10-2003-7011981A patent/KR20030082986A/ko not_active IP Right Cessation
- 2002-03-13 PL PL02364707A patent/PL364707A1/xx not_active Application Discontinuation
- 2002-03-13 MX MXPA03008177A patent/MXPA03008177A/es active IP Right Grant
- 2002-03-13 DE DE60237965T patent/DE60237965D1/de not_active Expired - Lifetime
- 2002-03-13 WO PCT/SE2002/000473 patent/WO2002074748A1/en active IP Right Grant
- 2002-03-13 MX MXPA03008191A patent/MXPA03008191A/es active IP Right Grant
- 2002-03-13 SK SK1092-2003A patent/SK287834B6/sk not_active IP Right Cessation
- 2002-03-13 WO PCT/SE2002/000478 patent/WO2002074751A1/en active Application Filing
- 2002-03-13 CN CNB02809915XA patent/CN100526307C/zh not_active Expired - Fee Related
- 2002-03-13 CN CN2006101061525A patent/CN1962641B/zh not_active Expired - Fee Related
- 2002-03-13 EP EP02704037A patent/EP1370537B1/en not_active Expired - Lifetime
- 2002-03-13 CA CA002440631A patent/CA2440631A1/en not_active Abandoned
- 2002-03-13 MX MXPA03008181A patent/MXPA03008181A/es unknown
- 2002-03-13 RU RU2003127735/04A patent/RU2293729C2/ru not_active IP Right Cessation
- 2002-03-13 IL IL15765202A patent/IL157652A0/xx unknown
- 2002-03-13 CZ CZ20032499A patent/CZ20032499A3/cs unknown
- 2002-03-13 CA CA2440473A patent/CA2440473C/en not_active Expired - Fee Related
- 2002-03-13 DE DE60238794T patent/DE60238794D1/de not_active Expired - Lifetime
- 2002-03-13 CN CNB028097882A patent/CN1304377C/zh not_active Expired - Fee Related
- 2002-03-13 JP JP2002573757A patent/JP2004523581A/ja active Pending
- 2002-03-13 BR BR0207983-6A patent/BR0207983A/pt not_active IP Right Cessation
- 2002-03-13 PL PL02365099A patent/PL365099A1/xx unknown
- 2002-03-13 PT PT02704031T patent/PT1370556E/pt unknown
- 2002-03-13 RU RU2003127734/04A patent/RU2288228C2/ru not_active IP Right Cessation
- 2002-03-13 ES ES02704037T patent/ES2352246T3/es not_active Expired - Lifetime
- 2002-03-13 AU AU2002237632A patent/AU2002237632B2/en not_active Ceased
- 2002-03-13 EE EEP200300445A patent/EE05431B1/xx not_active IP Right Cessation
- 2002-03-13 EE EEP200300451A patent/EE05364B1/xx not_active IP Right Cessation
- 2002-03-13 RU RU2003127733/04A patent/RU2285695C2/ru not_active IP Right Cessation
- 2002-03-13 NZ NZ528106A patent/NZ528106A/en not_active IP Right Cessation
- 2002-03-13 JP JP2002573760A patent/JP4390457B2/ja not_active Expired - Fee Related
- 2002-03-13 EP EP02704032A patent/EP1370534A1/en not_active Withdrawn
- 2002-03-13 WO PCT/SE2002/000472 patent/WO2002074767A1/en active IP Right Grant
- 2002-03-13 SK SK1095-2003A patent/SK10952003A3/sk not_active Application Discontinuation
- 2002-03-15 AR ARP020100943A patent/AR035695A1/es unknown
- 2002-03-15 AR ARP020100944A patent/AR035443A1/es active IP Right Grant
-
2003
- 2003-08-28 IL IL157652A patent/IL157652A/en not_active IP Right Cessation
- 2003-08-28 ZA ZA200306732A patent/ZA200306732B/en unknown
- 2003-08-28 ZA ZA200306734A patent/ZA200306734B/en unknown
- 2003-08-28 ZA ZA200306731A patent/ZA200306731B/en unknown
- 2003-08-28 ZA ZA200306737A patent/ZA200306737B/en unknown
- 2003-08-28 IL IL157656A patent/IL157656A/en not_active IP Right Cessation
- 2003-09-09 IS IS6942A patent/IS6942A/is unknown
- 2003-09-09 IS IS6943A patent/IS6943A/is unknown
- 2003-09-10 IS IS6946A patent/IS6946A/is unknown
- 2003-09-12 NO NO20034045A patent/NO327114B1/no not_active IP Right Cessation
- 2003-09-12 NO NO20034042A patent/NO326087B1/no not_active IP Right Cessation
- 2003-09-12 NO NO20034044A patent/NO20034044L/no unknown
-
2004
- 2004-04-21 HK HK06112181.8A patent/HK1091492A1/xx not_active IP Right Cessation
- 2004-04-21 HK HK04102796A patent/HK1059932A1/xx not_active IP Right Cessation
- 2004-04-23 HK HK04102888.7A patent/HK1060121A1/xx not_active IP Right Cessation
-
2006
- 2006-10-13 CY CY20061101477T patent/CY1107525T1/el unknown
-
2007
- 2007-10-30 US US11/928,040 patent/US7625934B2/en not_active Expired - Fee Related
-
2008
- 2008-05-05 US US12/114,901 patent/US7666892B2/en not_active Expired - Fee Related
- 2008-05-06 US US12/115,785 patent/US7754750B2/en not_active Expired - Fee Related
-
2009
- 2009-11-09 JP JP2009256358A patent/JP5140058B2/ja not_active Expired - Fee Related
-
2010
- 2010-01-26 US US12/693,852 patent/US8153673B2/en not_active Expired - Fee Related
- 2010-07-06 US US12/830,763 patent/US20110003853A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100886315B1 (ko) | 메탈로프로테이나제 억제제 | |
KR20030082990A (ko) | 메탈로프로테이나제 억제제 | |
AU2002237626A1 (en) | Metalloproteinase inhibitors | |
AU2002237632A1 (en) | Metalloproteinase inhibitors | |
NO326088B1 (no) | Metalloproteinaseinhibitorer, farmasoytiske sammensetninger inneholdende slike samt anvendelser derav | |
AU2002237629A1 (en) | Metalloproteinase inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PA0105 | International application |
Patent event date: 20030915 Patent event code: PA01051R01D Comment text: International Patent Application |
|
PG1501 | Laying open of application | ||
A201 | Request for examination | ||
PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20070313 Comment text: Request for Examination of Application |
|
E902 | Notification of reason for refusal | ||
PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20080314 Patent event code: PE09021S01D |
|
E902 | Notification of reason for refusal | ||
PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20080901 Patent event code: PE09021S01D |
|
E701 | Decision to grant or registration of patent right | ||
PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20090209 |
|
GRNT | Written decision to grant | ||
PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20090223 Patent event code: PR07011E01D |
|
PR1002 | Payment of registration fee |
Payment date: 20090223 End annual number: 3 Start annual number: 1 |
|
PG1601 | Publication of registration | ||
PR1001 | Payment of annual fee |
Payment date: 20120131 Start annual number: 4 End annual number: 4 |
|
FPAY | Annual fee payment |
Payment date: 20130201 Year of fee payment: 5 |
|
PR1001 | Payment of annual fee |
Payment date: 20130201 Start annual number: 5 End annual number: 5 |
|
FPAY | Annual fee payment |
Payment date: 20140205 Year of fee payment: 6 |
|
PR1001 | Payment of annual fee |
Payment date: 20140205 Start annual number: 6 End annual number: 6 |
|
FPAY | Annual fee payment |
Payment date: 20150120 Year of fee payment: 7 |
|
PR1001 | Payment of annual fee |
Payment date: 20150120 Start annual number: 7 End annual number: 7 |
|
LAPS | Lapse due to unpaid annual fee | ||
PC1903 | Unpaid annual fee |
Termination category: Default of registration fee Termination date: 20170109 |