CA2739488A1 - Fused heteroaryl diamide compounds useful as mmp-13 inhibitors - Google Patents
Fused heteroaryl diamide compounds useful as mmp-13 inhibitors Download PDFInfo
- Publication number
- CA2739488A1 CA2739488A1 CA2739488A CA2739488A CA2739488A1 CA 2739488 A1 CA2739488 A1 CA 2739488A1 CA 2739488 A CA2739488 A CA 2739488A CA 2739488 A CA2739488 A CA 2739488A CA 2739488 A1 CA2739488 A1 CA 2739488A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- methyl
- cyclohexyl
- alkoxy
- furan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 heteroaryl diamide compounds Chemical class 0.000 title claims description 33
- 239000003112 inhibitor Substances 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 238000000034 method Methods 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 201000008482 osteoarthritis Diseases 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 206010027476 Metastases Diseases 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 23
- 102100027995 Collagenase 3 Human genes 0.000 abstract description 15
- 108050005238 Collagenase 3 Proteins 0.000 abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 18
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 102000000503 Collagen Type II Human genes 0.000 description 6
- 108010041390 Collagen Type II Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 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 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 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 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 3
- DMZHFCHDPVNSIO-LBPRGKRZSA-N 5-bromo-n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C1=CC=C(Br)O1 DMZHFCHDPVNSIO-LBPRGKRZSA-N 0.000 description 3
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000008355 cartilage degradation Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- RMZMHEQYBRSXPY-FQEVSTJZSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-(1h-indol-6-yl)furan-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC=CC3=CC=2)C(=O)NC)CCCCC1 RMZMHEQYBRSXPY-FQEVSTJZSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000001850 reproductive effect Effects 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- DWOZNANUEDYIOF-UHFFFAOYSA-L 4-ditert-butylphosphanyl-n,n-dimethylaniline;dichloropalladium Chemical compound Cl[Pd]Cl.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1.CN(C)C1=CC=C(P(C(C)(C)C)C(C)(C)C)C=C1 DWOZNANUEDYIOF-UHFFFAOYSA-L 0.000 description 2
- CMWDGPBTNRJHFL-SFHVURJKSA-N 5-(2-amino-3h-benzimidazol-5-yl)-n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]furan-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC(N)=NC3=CC=2)C(=O)NC)CCCCC1 CMWDGPBTNRJHFL-SFHVURJKSA-N 0.000 description 2
- DCOPMEVVTLQPKC-IBGZPJMESA-N 5-(3h-benzimidazol-5-yl)-n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]furan-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC=NC3=CC=2)C(=O)NC)CCCCC1 DCOPMEVVTLQPKC-IBGZPJMESA-N 0.000 description 2
- OKHLJJBWQJKRFE-NCOUDYQVSA-N 5-[2-(2,6-dimethylmorpholine-4-carbonyl)-1h-indol-6-yl]-n-[(2s)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]furan-2-carboxamide Chemical compound O1C(C(=O)N[C@H](C(=O)NC)C(C)C)=CC=C1C1=CC=C(C=C(N2)C(=O)N3CC(C)OC(C)C3)C2=C1 OKHLJJBWQJKRFE-NCOUDYQVSA-N 0.000 description 2
- 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 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 102100030411 Neutrophil collagenase Human genes 0.000 description 2
- 101710118230 Neutrophil collagenase Proteins 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- ZFJDWEISBLDKBC-VWLOTQADSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-(pyridin-4-ylmethyl)-3h-benzimidazol-5-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1N=C2CC1=CC=NC=C1 ZFJDWEISBLDKBC-VWLOTQADSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- PKPVJDGTMVAKEC-QRPNPIFTSA-N (2s)-2-amino-2-cyclohexyl-n-methylacetamide;hydrochloride Chemical compound Cl.CNC(=O)[C@@H](N)C1CCCCC1 PKPVJDGTMVAKEC-QRPNPIFTSA-N 0.000 description 1
- IGJREDVLGVEPFI-UHFFFAOYSA-N 1,3-dimethylpyrazole-4-carbaldehyde Chemical compound CC1=NN(C)C=C1C=O IGJREDVLGVEPFI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- ZVMHOIWRCCZGPZ-UHFFFAOYSA-N 1h-indol-6-ylboronic acid Chemical compound OB(O)C1=CC=C2C=CNC2=C1 ZVMHOIWRCCZGPZ-UHFFFAOYSA-N 0.000 description 1
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 1
- QOYJKGGBFKVKDP-UHFFFAOYSA-N 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C([N+]([O-])=O)=C1 QOYJKGGBFKVKDP-UHFFFAOYSA-N 0.000 description 1
- PAEXAIBDCHBNDC-UHFFFAOYSA-N 2-pyridin-4-ylacetic acid Chemical compound OC(=O)CC1=CC=NC=C1 PAEXAIBDCHBNDC-UHFFFAOYSA-N 0.000 description 1
- WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 description 1
- IATYNYSCQZIMSN-SFHVURJKSA-N 5-(4-amino-3-nitrophenyl)-n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C1=CC=C(N)C([N+]([O-])=O)=C1 IATYNYSCQZIMSN-SFHVURJKSA-N 0.000 description 1
- DYQKAJUWEAWWSO-VIFPVBQESA-N 5-bromo-n-[(2s)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]furan-2-carboxamide Chemical compound CNC(=O)[C@H](C(C)C)NC(=O)C1=CC=C(Br)O1 DYQKAJUWEAWWSO-VIFPVBQESA-N 0.000 description 1
- QWWFFXGCWIVTGT-FQEVSTJZSA-N 6-[5-[[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]carbamoyl]furan-2-yl]-1h-indole-2-carboxylic acid Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC(=CC3=CC=2)C(O)=O)C(=O)NC)CCCCC1 QWWFFXGCWIVTGT-FQEVSTJZSA-N 0.000 description 1
- ZICCNXKKMZQZEK-QFIPXVFZSA-N 6-[5-[[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]carbamoyl]furan-2-yl]-n,n-dimethyl-1h-indole-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC(=CC3=CC=2)C(=O)N(C)C)C(=O)NC)CCCCC1 ZICCNXKKMZQZEK-QFIPXVFZSA-N 0.000 description 1
- YQZFABJMULTRRZ-NRFANRHFSA-N 6-[5-[[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]carbamoyl]furan-2-yl]-n-methyl-1h-indole-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2C=C3NC(=CC3=CC=2)C(=O)NC)C(=O)NC)CCCCC1 YQZFABJMULTRRZ-NRFANRHFSA-N 0.000 description 1
- GEDVWGDBMPJNEV-UHFFFAOYSA-N 6-bromo-1h-benzimidazole Chemical class BrC1=CC=C2N=CNC2=C1 GEDVWGDBMPJNEV-UHFFFAOYSA-N 0.000 description 1
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical class BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 1
- UXEKOPDUKHGZTL-UHFFFAOYSA-N 6-bromo-2-(pyridin-4-ylmethyl)-1h-benzimidazole Chemical compound N=1C2=CC(Br)=CC=C2NC=1CC1=CC=NC=C1 UXEKOPDUKHGZTL-UHFFFAOYSA-N 0.000 description 1
- 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- SKGQBKRHNVCZSF-YDALLXLXSA-N BrC1=CC=C(O1)C(=O)O.C1(CCCCC1)[C@@H](C(NC)=O)NC(=O)C=1OC(=CC1)Br Chemical compound BrC1=CC=C(O1)C(=O)O.C1(CCCCC1)[C@@H](C(NC)=O)NC(=O)C=1OC(=CC1)Br SKGQBKRHNVCZSF-YDALLXLXSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 241001492222 Epicoccum Species 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010017708 Ganglioneuroblastoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000627854 Homo sapiens Matrix metalloproteinase-26 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 1
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010073099 Lobular breast carcinoma in situ Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025312 Lymphoma AIDS related Diseases 0.000 description 1
- 101150014058 MMP1 gene Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100030417 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 1
- 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 description 1
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 1
- 102100024128 Matrix metalloproteinase-26 Human genes 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 206010027761 Mixed hepatocellular cholangiocarcinoma Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- QPVNGKBMEQJWTA-QHCPKHFHSA-N N-[(1S)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-(2,5-dimethylpyrazol-3-yl)-3H-benzimidazol-5-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1N=C2C1=CC(C)=NN1C QPVNGKBMEQJWTA-QHCPKHFHSA-N 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
- 108030001564 Neutrophil collagenases Proteins 0.000 description 1
- 102000056189 Neutrophil collagenases Human genes 0.000 description 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000002774 Paraproteinemias Diseases 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046458 Urethral neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 102000036861 Zinc-dependent endopeptidases Human genes 0.000 description 1
- 108091006982 Zinc-dependent endopeptidases Proteins 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
- 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000005389 breast carcinoma in situ Diseases 0.000 description 1
- FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 208000030239 cerebral astrocytoma Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 108700004333 collagenase 1 Proteins 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000011588 combined hepatocellular carcinoma and cholangiocarcinoma Diseases 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 1
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 108060002894 fibrillar collagen Proteins 0.000 description 1
- 102000013373 fibrillar collagen Human genes 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 description 1
- 201000008893 intraocular retinoblastoma Diseases 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000011059 lobular neoplasia Diseases 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 208000030883 malignant astrocytoma Diseases 0.000 description 1
- 208000020984 malignant renal pelvis neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000000716 merkel cell Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000037890 multiple organ injury Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- KKXJXKNYHQBELN-IBGZPJMESA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-(1h-pyrrolo[3,2-c]pyridin-6-yl)furan-2-carboxamide Chemical compound C1([C@H](NC(=O)C=2OC(=CC=2)C=2N=CC=3C=CNC=3C=2)C(=O)NC)CCCCC1 KKXJXKNYHQBELN-IBGZPJMESA-N 0.000 description 1
- BXLLVYNERLZPLT-SFHVURJKSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-(3,4-diaminophenyl)furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C1=CC=C(N)C(N)=C1 BXLLVYNERLZPLT-SFHVURJKSA-N 0.000 description 1
- INHYPJNUAWJADB-DEOSSOPVSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-(morpholin-4-ylmethyl)-3h-benzimidazol-5-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1N=C2CN1CCOCC1 INHYPJNUAWJADB-DEOSSOPVSA-N 0.000 description 1
- OLNLCNLPKNAMRC-DEOSSOPVSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-(morpholine-4-carbonyl)-1h-indol-6-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1C=C2C(=O)N1CCOCC1 OLNLCNLPKNAMRC-DEOSSOPVSA-N 0.000 description 1
- JIHHGPRGNMSYJM-VWLOTQADSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-(pyridin-3-ylmethyl)-3h-benzimidazol-5-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1N=C2CC1=CC=CN=C1 JIHHGPRGNMSYJM-VWLOTQADSA-N 0.000 description 1
- KCXIGAYVRLTFJQ-DEOSSOPVSA-N n-[(1s)-1-cyclohexyl-2-(methylamino)-2-oxoethyl]-5-[2-[(2-oxopyrrolidin-1-yl)methyl]-3h-benzimidazol-5-yl]furan-2-carboxamide Chemical compound N([C@H](C(=O)NC)C1CCCCC1)C(=O)C(O1)=CC=C1C(C=C1N2)=CC=C1N=C2CN1CCCC1=O KCXIGAYVRLTFJQ-DEOSSOPVSA-N 0.000 description 1
- SBKXJBVRARTGLG-QFIPXVFZSA-N n-[(2s)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-5-[2-(4-methylpiperazine-1-carbonyl)-1h-indol-6-yl]furan-2-carboxamide Chemical compound O1C(C(=O)N[C@H](C(=O)NC)C(C)C)=CC=C1C1=CC=C(C=C(N2)C(=O)N3CCN(C)CC3)C2=C1 SBKXJBVRARTGLG-QFIPXVFZSA-N 0.000 description 1
- YNHLZCJZPQYFHX-NRFANRHFSA-N n-[(2s)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]-5-[2-(morpholine-4-carbonyl)-1h-indol-6-yl]furan-2-carboxamide Chemical compound O1C(C(=O)N[C@H](C(=O)NC)C(C)C)=CC=C1C1=CC=C(C=C(N2)C(=O)N3CCOCC3)C2=C1 YNHLZCJZPQYFHX-NRFANRHFSA-N 0.000 description 1
- OEBPVAYBIWRIQV-VIFPVBQESA-N n-[(2s)-3-methyl-1-(methylamino)-1-oxobutan-2-yl]furan-2-carboxamide Chemical compound CNC(=O)[C@H](C(C)C)NC(=O)C1=CC=CO1 OEBPVAYBIWRIQV-VIFPVBQESA-N 0.000 description 1
- GRIOMWQLXUWOJG-UHFFFAOYSA-N n-methyl-1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)NC)=CC2=C1 GRIOMWQLXUWOJG-UHFFFAOYSA-N 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000002956 necrotizing effect Effects 0.000 description 1
- 208000023833 nerve sheath neoplasm Diseases 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 208000010916 pituitary tumor Diseases 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- ZSOWARDRPIJGTQ-UHFFFAOYSA-N tert-butyl 5-bromo-2-(pyridin-4-ylmethyl)benzimidazole-1-carboxylate Chemical compound N=1C2=CC(Br)=CC=C2N(C(=O)OC(C)(C)C)C=1CC1=CC=NC=C1 ZSOWARDRPIJGTQ-UHFFFAOYSA-N 0.000 description 1
- XYLPFMPZJBJCTI-UHFFFAOYSA-N tert-butyl 6-(5-formylfuran-2-yl)pyrrolo[3,2-c]pyridine-1-carboxylate Chemical compound C1=C2N(C(=O)OC(C)(C)C)C=CC2=CN=C1C1=CC=C(C=O)O1 XYLPFMPZJBJCTI-UHFFFAOYSA-N 0.000 description 1
- UFVUYSVJZHVOLD-UHFFFAOYSA-N tert-butyl 6-bromopyrrolo[3,2-c]pyridine-1-carboxylate Chemical compound N1=C(Br)C=C2N(C(=O)OC(C)(C)C)C=CC2=C1 UFVUYSVJZHVOLD-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
Classifications
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
- A61P19/08—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
- 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
- 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
- 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
- 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
- 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
- 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)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10545508P | 2008-10-15 | 2008-10-15 | |
| US61/105,455 | 2008-10-15 | ||
| PCT/US2009/060439 WO2010045190A1 (en) | 2008-10-15 | 2009-10-13 | Fused heteroaryl diamide compounds useful as mmp-13 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2739488A1 true CA2739488A1 (en) | 2010-04-22 |
Family
ID=41382316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2739488A Abandoned CA2739488A1 (en) | 2008-10-15 | 2009-10-13 | Fused heteroaryl diamide compounds useful as mmp-13 inhibitors |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US8338367B2 (https=) |
| EP (1) | EP2344480A1 (https=) |
| JP (1) | JP2012505892A (https=) |
| CA (1) | CA2739488A1 (https=) |
| WO (1) | WO2010045190A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8338367B2 (en) | 2008-10-15 | 2012-12-25 | Boehringer Ingelheim International Gmbh | Fused heteroaryl diamide compounds useful as MMP-13 inhibitors |
| US8785489B2 (en) | 2008-10-17 | 2014-07-22 | Boehringer Ingelheim International Gmbh | Heteroaryl substituted indole compounds useful as MMP-13 inhibitors |
| EP2346831B1 (en) | 2008-11-17 | 2015-01-07 | Boehringer Ingelheim International GmbH | Heteroaryl diamide compounds useful as mmp-13 inhibitors |
| MX2013003019A (es) | 2010-09-15 | 2013-05-28 | Hoffmann La Roche | Compuestos de azabenzotiazol, composiciones y metodos de uso. |
| AR086113A1 (es) | 2011-04-30 | 2013-11-20 | Abbott Lab | Isoxazolinas como agentes terapeuticos |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2164300A (en) | 1998-12-04 | 2000-06-26 | N.V. Organon | Substituted thiazoles for treatment of human diseases involving modulators of p-, l- and e- selectin |
| US20020165222A1 (en) * | 1999-02-19 | 2002-11-07 | Smithkline Beecham Corporation | Protease inhibitors |
| CN1362947A (zh) | 1999-03-15 | 2002-08-07 | Axys药物公司 | 用作蛋白酶抑制剂的n－氰基甲基酰胺 |
| MXPA03000923A (es) | 2000-07-31 | 2003-06-09 | Smithkline Beecham Plc | Compuestos de carboxamida y su uso como antagonistas de un receptor 11cby humano. |
| GB0018758D0 (en) | 2000-07-31 | 2000-09-20 | Smithkline Beecham Plc | Novel use and compunds |
| WO2002016348A1 (en) | 2000-08-09 | 2002-02-28 | Astrazeneca Ab | Antiangiogenic bicyclic derivatives |
| DE10229070A1 (de) | 2002-06-28 | 2004-01-15 | Merck Patent Gmbh | Phenylderivate 5 |
| US20050004111A1 (en) * | 2003-01-03 | 2005-01-06 | Aventis Pharma Deutschland Gmbh | Selective MMP-13 inhibitors |
| US7470807B2 (en) | 2003-08-14 | 2008-12-30 | Asahi Kasei Pharma Corporation | Substituted arylalkanoic acid derivatives and use thereof |
| US20080275028A1 (en) | 2004-07-20 | 2008-11-06 | Giovanni Gaviraghi | Modulators or Alpha7 Nicotinic Acetylcholine Receptors and Therapeutic Uses Thereof |
| EP1838690A2 (en) | 2004-12-21 | 2007-10-03 | Devgen N.V. | Compounds with kv4 ion channel activity |
| GT200600042A (es) | 2005-02-10 | 2006-09-27 | Aventis Pharma Inc | Compuestos de bis arilo y heteroarilo sustituido como antagonistas selectivos de 5ht2a |
| KR20080038416A (ko) | 2005-08-19 | 2008-05-06 | 아벤티스 파마슈티칼스 인크. | 수면제와 치환된 비스 아릴 및 헤테로아릴 화합물의 배합물및 이의 치료요법적 용도 |
| US8338367B2 (en) | 2008-10-15 | 2012-12-25 | Boehringer Ingelheim International Gmbh | Fused heteroaryl diamide compounds useful as MMP-13 inhibitors |
| US8785489B2 (en) | 2008-10-17 | 2014-07-22 | Boehringer Ingelheim International Gmbh | Heteroaryl substituted indole compounds useful as MMP-13 inhibitors |
| EP2346831B1 (en) | 2008-11-17 | 2015-01-07 | Boehringer Ingelheim International GmbH | Heteroaryl diamide compounds useful as mmp-13 inhibitors |
-
2009
- 2009-10-13 US US13/123,002 patent/US8338367B2/en active Active
- 2009-10-13 CA CA2739488A patent/CA2739488A1/en not_active Abandoned
- 2009-10-13 WO PCT/US2009/060439 patent/WO2010045190A1/en not_active Ceased
- 2009-10-13 JP JP2011532177A patent/JP2012505892A/ja not_active Withdrawn
- 2009-10-13 EP EP09740587A patent/EP2344480A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP2344480A1 (en) | 2011-07-20 |
| US8338367B2 (en) | 2012-12-25 |
| JP2012505892A (ja) | 2012-03-08 |
| WO2010045190A1 (en) | 2010-04-22 |
| US20110269668A1 (en) | 2011-11-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2340243B1 (en) | Heteroaryl substituted indole compounds useful as mmp-13 inhibitors | |
| CN113811300A (zh) | Tead转录因子的新型小分子抑制剂 | |
| SK16972002A3 (sk) | Beta-karbolínové deriváty použiteľné ako inhibítory fosfodiesterázy | |
| CN105008354A (zh) | 蛋白激酶抑制剂 | |
| JP2008523071A (ja) | Ｍａｐキナーゼの尿素インヒビター | |
| CA3050770C (en) | Compounds and pharmaceutical compositions for modulating sgk activity, and methods thereof | |
| CN108530310A (zh) | 2-(取代苯杂基)芳香甲酸类fto抑制剂，其制备方法及其应用 | |
| EP1532124B1 (en) | Use of nitrile derivatives as medicament. | |
| CN107879975B (zh) | 组蛋白去乙酰化酶抑制剂及其应用 | |
| CN113166105B (zh) | 作为cdk-hdac双通路抑制剂的杂环化合物 | |
| CN100482665C (zh) | 吡唑并[1,5-a]嘧啶衍生物 | |
| US8338367B2 (en) | Fused heteroaryl diamide compounds useful as MMP-13 inhibitors | |
| WO2009140101A2 (en) | Imidazopyridine compounds useful as mmp-13 inhibitors | |
| JP5584696B2 (ja) | Ｍｍｐ−１３阻害剤として有用なヘテロアリールジアミド化合物 | |
| CN110234640B (zh) | 作为抗癌剂的苯并咪唑衍生物 | |
| EP2391624A1 (en) | Azaquinazolinediones useful as chymase inhibitors | |
| CA2504153C (en) | Pyrimidine-4,6-dicarboxylic acid diamides for selectively inhibiting collagenases | |
| WO2008098096A1 (en) | Anti-cytokine heterocyclic compounds | |
| CN115353508B (zh) | 5-吡啶-1h-吲唑类化合物、药物组合物和应用 | |
| CN115197221B (zh) | 二氢吡唑并嘧啶酮类大环衍生物及其用途 | |
| RS59787B1 (sr) | Novo heterociklično jedinjenje, metoda za pripremu istog, i farmaceutska kompozicija koja sadrži isto | |
| EP4313294B1 (en) | 3-substituted 1h-pyrrolo[2,3-b]pyridine as grk5 modulators | |
| KR102670554B1 (ko) | 캐스파제 저해제로서의 신규한 이소인돌리논 유도체 화합물 | |
| Hu et al. | An efficient synthesis of Erismodegib | |
| JP2003513959A (ja) | カルボキサミド置換ベンゾイミダゾール誘導体、それらの調製方法及び医薬組成物としてのそれらの使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20141015 |