SK48499A3 - Heteroaryl succinamides and their use as metalloproteinase inhibitors - Google Patents
Heteroaryl succinamides and their use as metalloproteinase inhibitors Download PDFInfo
- Publication number
- SK48499A3 SK48499A3 SK484-99A SK48499A SK48499A3 SK 48499 A3 SK48499 A3 SK 48499A3 SK 48499 A SK48499 A SK 48499A SK 48499 A3 SK48499 A3 SK 48499A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- formula
- pharmaceutically acceptable
- pyrrol
- acid
- Prior art date
Links
- -1 Heteroaryl succinamides Chemical class 0.000 title claims description 404
- 239000003475 metalloproteinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 230000000694 effects Effects 0.000 claims abstract description 14
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 7
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 278
- 229910052799 carbon Inorganic materials 0.000 claims description 261
- 238000000034 method Methods 0.000 claims description 145
- 229910052757 nitrogen Inorganic materials 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims description 92
- 125000003118 aryl group Chemical group 0.000 claims description 86
- 239000000651 prodrug Substances 0.000 claims description 81
- 229940002612 prodrug Drugs 0.000 claims description 81
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 77
- 239000002253 acid Substances 0.000 claims description 75
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 75
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 67
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 55
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
- 239000012453 solvate Substances 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229920006395 saturated elastomer Polymers 0.000 claims description 34
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 33
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 22
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 14
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 13
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000000962 organic group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 239000011593 sulfur Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- QAEQFMLHOAVLOC-SJLPKXTDSA-N (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-(3-phenylpyrrol-1-yl)butanoic acid Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC=CC=2)=C1 QAEQFMLHOAVLOC-SJLPKXTDSA-N 0.000 claims description 4
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 4
- 208000025865 Ulcer Diseases 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 230000009400 cancer invasion Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 230000036269 ulceration Effects 0.000 claims description 4
- YOTFTGGJVORSJZ-TZIWHRDSSA-N (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-[3-(4-propylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C1=CC(CCC)=CC=C1C1=CN([C@H](CC(O)=O)C(=O)N[C@H](C(=O)NC)C(C)(C)C)C=C1 YOTFTGGJVORSJZ-TZIWHRDSSA-N 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 208000022461 Glomerular disease Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 230000002500 effect on skin Effects 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 208000007565 gingivitis Diseases 0.000 claims description 3
- 231100000852 glomerular disease Toxicity 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 201000001245 periodontitis Diseases 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- RTIHLTBGWBMYRG-FGZHOGPDSA-N (3r)-4-[[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound CC(C)(C)[C@@H](CO)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC(=CC=2)C=2C=CN=CC=2)=C1 RTIHLTBGWBMYRG-FGZHOGPDSA-N 0.000 claims description 2
- SAIXUIBHQBOBSO-UIOOFZCWSA-N (3s)-3-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-[[(1s)-1-(1h-imidazol-2-yl)-3-methylbutyl]amino]-4-oxobutanoic acid Chemical compound C1=C([C@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C=2NC=CN=2)C=CN1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 SAIXUIBHQBOBSO-UIOOFZCWSA-N 0.000 claims description 2
- UARDZWGWRFHLHE-UKILVPOCSA-N (3s)-3-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound C1=C([C@H](CC(O)=O)C(=O)N[C@H](C(=O)NC)C(C)(C)C)C=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 UARDZWGWRFHLHE-UKILVPOCSA-N 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- FRJJYQFPSSQIEI-WIOPSUGQSA-N CC(C)(C)[C@@H](C(=O)NC)NC(=O)C[C@@H](C1=COC(=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C#N)C(=O)O Chemical compound CC(C)(C)[C@@H](C(=O)NC)NC(=O)C[C@@H](C1=COC(=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C#N)C(=O)O FRJJYQFPSSQIEI-WIOPSUGQSA-N 0.000 claims description 2
- 206010010071 Coma Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010064390 Tumour invasion Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 201000011066 hemangioma Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 8
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims 1
- 230000003412 degenerative effect Effects 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 316
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 217
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 170
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 167
- 238000002360 preparation method Methods 0.000 description 160
- 239000007787 solid Substances 0.000 description 141
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 126
- 235000019439 ethyl acetate Nutrition 0.000 description 122
- 239000000203 mixture Substances 0.000 description 121
- 239000000243 solution Substances 0.000 description 109
- 238000006243 chemical reaction Methods 0.000 description 102
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 87
- 238000004458 analytical method Methods 0.000 description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- 238000003818 flash chromatography Methods 0.000 description 70
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 69
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 56
- 238000000746 purification Methods 0.000 description 50
- 239000007858 starting material Substances 0.000 description 50
- 239000003921 oil Substances 0.000 description 45
- 235000019198 oils Nutrition 0.000 description 45
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 42
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
- 235000011152 sodium sulphate Nutrition 0.000 description 42
- 238000001819 mass spectrum Methods 0.000 description 41
- 239000000047 product Substances 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 35
- 239000012044 organic layer Substances 0.000 description 35
- 150000002148 esters Chemical class 0.000 description 34
- 238000010828 elution Methods 0.000 description 30
- 229910004373 HOAc Inorganic materials 0.000 description 28
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 239000010410 layer Substances 0.000 description 28
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 27
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 26
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 150000001412 amines Chemical class 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- 229960000583 acetic acid Drugs 0.000 description 21
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- 235000011054 acetic acid Nutrition 0.000 description 19
- 238000009833 condensation Methods 0.000 description 19
- 239000008363 phosphate buffer Substances 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
- 239000003054 catalyst Substances 0.000 description 18
- 230000005494 condensation Effects 0.000 description 18
- 239000012442 inert solvent Substances 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000012317 TBTU Substances 0.000 description 16
- 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 16
- 230000002829 reductive effect Effects 0.000 description 16
- KAJBMCZQVSQJDE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC(O)=O KAJBMCZQVSQJDE-RXMQYKEDSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 15
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- KMMJMRXVYSYXQC-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-phenylphenyl)oxolane Chemical compound COC1OC(OC)CC1C1=CC=C(C=2C=CC=CC=2)C=C1 KMMJMRXVYSYXQC-UHFFFAOYSA-N 0.000 description 14
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 239000006260 foam Substances 0.000 description 13
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 13
- QBCKMOIFWSLVGJ-GFCCVEGCSA-N (2R)-4-amino-4-oxo-2-(3-phenylpyrrol-1-yl)butanoic acid Chemical compound C1(=CC=CC=C1)C1=CN(C=C1)[C@@H](C(=O)O)CC(=O)N QBCKMOIFWSLVGJ-GFCCVEGCSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000002329 infrared spectrum Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 150000007942 carboxylates Chemical class 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 11
- 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 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 238000010511 deprotection reaction Methods 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 10
- RPTCYRNCIJAUCS-UHFFFAOYSA-N 3-(4-phenylphenyl)furan Chemical compound O1C=CC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 RPTCYRNCIJAUCS-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000000010 aprotic solvent Substances 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 238000010533 azeotropic distillation Methods 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- GFRKDKZNBVTVIS-VIFPVBQESA-N CCC[C@](CC(N)=O)(C(NC)=O)C(O)=O Chemical compound CCC[C@](CC(N)=O)(C(NC)=O)C(O)=O GFRKDKZNBVTVIS-VIFPVBQESA-N 0.000 description 8
- 102000029816 Collagenase Human genes 0.000 description 8
- 108060005980 Collagenase Proteins 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- PAWZTAIETRQIPG-ILBGXUMGSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-(3-phenylpyrrol-1-yl)butanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)N1C=C(C=C1)C=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 PAWZTAIETRQIPG-ILBGXUMGSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 238000001665 trituration Methods 0.000 description 8
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 8
- 229920002554 vinyl polymer Polymers 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- WPOMDJXLIZKCKB-UHFFFAOYSA-N 4-[4-(2,5-dimethoxyoxolan-3-yl)phenyl]benzonitrile Chemical compound COC1OC(OC)CC1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 WPOMDJXLIZKCKB-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 102000008186 Collagen Human genes 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 7
- 229920001436 collagen Polymers 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 7
- 150000003233 pyrroles Chemical class 0.000 description 7
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 7
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- 125000000218 acetic acid group Chemical class C(C)(=O)* 0.000 description 6
- 150000001345 alkine derivatives Chemical class 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- ZLSTXEBTAJKDKH-UHFFFAOYSA-N benzyl 4-amino-4-oxobutanoate Chemical compound NC(=O)CCC(=O)OCC1=CC=CC=C1 ZLSTXEBTAJKDKH-UHFFFAOYSA-N 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 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 6
- XPEIJWZLPWNNOK-UHFFFAOYSA-N (4-phenylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=CC=CC=C1 XPEIJWZLPWNNOK-UHFFFAOYSA-N 0.000 description 5
- OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 5
- BNKZAMCRVRPGCU-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-phenylphenyl)-2,5-dihydrofuran Chemical compound COC1OC(OC)C(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 BNKZAMCRVRPGCU-UHFFFAOYSA-N 0.000 description 5
- PUYVVMABQFYDIU-UHFFFAOYSA-N 2-(4-phenylphenyl)furan Chemical compound C1=COC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 PUYVVMABQFYDIU-UHFFFAOYSA-N 0.000 description 5
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 5
- TUAOCHMKNGTVCK-UHFFFAOYSA-N 4-(furan-3-yl)pyridine Chemical compound O1C=CC(C=2C=CN=CC=2)=C1 TUAOCHMKNGTVCK-UHFFFAOYSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- 239000005711 Benzoic acid Substances 0.000 description 5
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001450 anions Chemical class 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
- 210000000845 cartilage Anatomy 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 150000004820 halides Chemical class 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 150000002917 oxazolidines Chemical class 0.000 description 5
- HVAMZGADVCBITI-UHFFFAOYSA-N pent-4-enoic acid Chemical compound OC(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 5
- FKECUBFZCOXSPT-QGZVFWFLSA-N (2R)-4-amino-4-oxo-2-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound N1=CC=C(C=C1)C1=CC=C(C=C1)C1=CN(C=C1)[C@@H](C(=O)O)CC(=O)N FKECUBFZCOXSPT-QGZVFWFLSA-N 0.000 description 4
- KVPHDZMGTLGFQB-AWEZNQCLSA-N (4s)-4-benzyl-3-(2-thiophen-3-ylacetyl)-1,3-oxazolidin-2-one Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CC=1C=CSC=1 KVPHDZMGTLGFQB-AWEZNQCLSA-N 0.000 description 4
- HMFRRTAVCKTQMK-UHFFFAOYSA-N 1-(4-phenylphenyl)pyrrole Chemical compound C1=CC=CN1C1=CC=C(C=2C=CC=CC=2)C=C1 HMFRRTAVCKTQMK-UHFFFAOYSA-N 0.000 description 4
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 4
- FUYICGSJBLULDW-UHFFFAOYSA-N 2,5-dimethoxy-3-phenyloxolane Chemical compound COC1OC(OC)CC1C1=CC=CC=C1 FUYICGSJBLULDW-UHFFFAOYSA-N 0.000 description 4
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 4
- XQWPSKGGXTWBEL-UHFFFAOYSA-N 2-[1-(4-fluorophenyl)pyrrol-3-yl]acetic acid Chemical compound C1=C(CC(=O)O)C=CN1C1=CC=C(F)C=C1 XQWPSKGGXTWBEL-UHFFFAOYSA-N 0.000 description 4
- BPKJNEIOHOEWLO-UHFFFAOYSA-N 2-amino-n,3,3-trimethylbutanamide Chemical compound CNC(=O)C(N)C(C)(C)C BPKJNEIOHOEWLO-UHFFFAOYSA-N 0.000 description 4
- LXWLEQZDXOQZGW-UHFFFAOYSA-N 3-bromofuran Chemical compound BrC=1C=COC=1 LXWLEQZDXOQZGW-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 102100027995 Collagenase 3 Human genes 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 4
- 229940124761 MMP inhibitor Drugs 0.000 description 4
- 101150014058 MMP1 gene Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102000016611 Proteoglycans Human genes 0.000 description 4
- 108010067787 Proteoglycans Proteins 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 4
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 239000000538 analytical sample Substances 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 235000010338 boric acid Nutrition 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229960002424 collagenase Drugs 0.000 description 4
- 108700004333 collagenase 1 Proteins 0.000 description 4
- 125000004663 dialkyl amino group Chemical group 0.000 description 4
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 4
- 210000002744 extracellular matrix Anatomy 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 150000002240 furans Chemical class 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- ADGKSWJGJKONTH-UHFFFAOYSA-N methyl 2-(2,5-dimethoxyoxolan-3-yl)acetate Chemical compound COC1CC(CC(=O)OC)C(OC)O1 ADGKSWJGJKONTH-UHFFFAOYSA-N 0.000 description 4
- SZSIYWCIRQJDCT-UHFFFAOYSA-N methyl 2-[1-(4-fluorophenyl)pyrrol-3-yl]acetate Chemical compound C1=C(CC(=O)OC)C=CN1C1=CC=C(F)C=C1 SZSIYWCIRQJDCT-UHFFFAOYSA-N 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 description 4
- 125000006168 tricyclic group Chemical group 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- BZEHXVRCEIEBAT-GJMOJQLCSA-N (2r)-2-[(3s,5r)-5-(iodomethyl)-2-oxooxolan-3-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)[C@@H]1C[C@H](CI)OC1=O BZEHXVRCEIEBAT-GJMOJQLCSA-N 0.000 description 3
- JBULSURVMXPBNA-RXMQYKEDSA-N (2s)-2-amino-3,3-dimethylbutan-1-ol Chemical compound CC(C)(C)[C@H](N)CO JBULSURVMXPBNA-RXMQYKEDSA-N 0.000 description 3
- XYSSRBMYWOURKE-RRPNLBNLSA-N (3r)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(O)=O)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 XYSSRBMYWOURKE-RRPNLBNLSA-N 0.000 description 3
- JTZFTQQGIJTQND-ZDUSSCGKSA-N (4s)-4-benzyl-3-(2-thiophen-2-ylacetyl)-1,3-oxazolidin-2-one Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CC1=CC=CS1 JTZFTQQGIJTQND-ZDUSSCGKSA-N 0.000 description 3
- PTNXGJACGVBBSF-NDEPHWFRSA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-[1-(4-phenylphenyl)pyrrol-3-yl]ethanone Chemical compound C([C@H]1COC(N1C(=O)CC1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 PTNXGJACGVBBSF-NDEPHWFRSA-N 0.000 description 3
- HZQJSDRVZOVEFS-MHZLTWQESA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-[4-(4-phenylphenyl)pyrazol-1-yl]ethanone Chemical compound C([C@H]1COC(N1C(=O)CN1N=CC(=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 HZQJSDRVZOVEFS-MHZLTWQESA-N 0.000 description 3
- ZMKPCAFWBBLXPL-SANMLTNESA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-[5-(4-phenylphenyl)furan-2-yl]ethanone Chemical compound C([C@H]1COC(N1C(=O)CC=1OC(=CC=1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 ZMKPCAFWBBLXPL-SANMLTNESA-N 0.000 description 3
- SFZJUKUMQATOBW-LBPRGKRZSA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-bromoethanone Chemical compound BrCC(=O)N1C(C)(C)OC[C@@H]1CC1=CC=CC=C1 SFZJUKUMQATOBW-LBPRGKRZSA-N 0.000 description 3
- QSKYSTJFDPMNDS-MBMZGMDYSA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-hydroxy-2-[1-(4-phenylphenyl)pyrrol-3-yl]ethanone Chemical compound C([C@H]1COC(N1C(=O)C(O)C1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 QSKYSTJFDPMNDS-MBMZGMDYSA-N 0.000 description 3
- SQTQVBANJGZKCE-ALLRNTDFSA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-hydroxy-2-[5-(4-phenylphenyl)furan-2-yl]ethanone Chemical compound C([C@H]1COC(N1C(=O)C(O)C=1OC(=CC=1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 SQTQVBANJGZKCE-ALLRNTDFSA-N 0.000 description 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 3
- JRMZMYQBGJJNBQ-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-propylphenyl)-2,5-dihydrofuran Chemical compound C1=CC(CCC)=CC=C1C1=CC(OC)OC1OC JRMZMYQBGJJNBQ-UHFFFAOYSA-N 0.000 description 3
- KTXJYDIPXMUXPL-UHFFFAOYSA-N 2,5-dimethoxy-3-phenyl-2,5-dihydrofuran Chemical compound COC1OC(OC)C(C=2C=CC=CC=2)=C1 KTXJYDIPXMUXPL-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- CNIGPRFUDFXAEK-UHFFFAOYSA-N 2-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]acetic acid Chemical compound C1=C(CC(=O)O)C=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 CNIGPRFUDFXAEK-UHFFFAOYSA-N 0.000 description 3
- AGDWTOMWNATOTH-JTQLQIEISA-N 2-bromo-n-[(2s)-1-hydroxy-3-phenylpropan-2-yl]acetamide Chemical compound BrCC(=O)N[C@H](CO)CC1=CC=CC=C1 AGDWTOMWNATOTH-JTQLQIEISA-N 0.000 description 3
- KEFLZJUCLMFCAR-UHFFFAOYSA-N 3-(1,3-dithian-2-ylidenemethyl)-2,5-dimethoxyoxolane Chemical compound COC1OC(OC)CC1C=C1SCCCS1 KEFLZJUCLMFCAR-UHFFFAOYSA-N 0.000 description 3
- ZEGCRICEWZCPJU-UHFFFAOYSA-N 3-(4-propylphenyl)furan Chemical compound C1=CC(CCC)=CC=C1C1=COC=C1 ZEGCRICEWZCPJU-UHFFFAOYSA-N 0.000 description 3
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- HBNDZJLZMVURSS-UHFFFAOYSA-N 4-(2,5-dimethoxy-2,5-dihydrofuran-3-yl)pyridine Chemical compound COC1OC(OC)C(C=2C=CN=CC=2)=C1 HBNDZJLZMVURSS-UHFFFAOYSA-N 0.000 description 3
- PLAIWDOXCRWTLP-UHFFFAOYSA-N 4-(2,5-dimethoxyoxolan-3-yl)benzonitrile Chemical compound COC1OC(OC)CC1C1=CC=C(C#N)C=C1 PLAIWDOXCRWTLP-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- BHVHKOVPWZKVCC-UHFFFAOYSA-N 4-(4-bromophenyl)benzonitrile Chemical compound C1=CC(Br)=CC=C1C1=CC=C(C#N)C=C1 BHVHKOVPWZKVCC-UHFFFAOYSA-N 0.000 description 3
- GYJBDJGUNDKZKO-UHFFFAOYSA-N 4-(4-bromophenyl)pyridine Chemical compound C1=CC(Br)=CC=C1C1=CC=NC=C1 GYJBDJGUNDKZKO-UHFFFAOYSA-N 0.000 description 3
- LJQWJKTWCIDGHB-UHFFFAOYSA-N 4-(furan-3-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=COC=C1 LJQWJKTWCIDGHB-UHFFFAOYSA-N 0.000 description 3
- UYDIJJCYXWRBFX-UHFFFAOYSA-N 4-[2-(2,5-dimethoxyoxolan-3-yl)ethynyl]benzonitrile Chemical compound COC1OC(OC)CC1C#CC1=CC=C(C#N)C=C1 UYDIJJCYXWRBFX-UHFFFAOYSA-N 0.000 description 3
- LUQKBMUOJGTCLE-UHFFFAOYSA-N 4-[4-(2,5-dimethoxyoxolan-3-yl)phenyl]pyridine Chemical compound COC1OC(OC)CC1C1=CC=C(C=2C=CN=CC=2)C=C1 LUQKBMUOJGTCLE-UHFFFAOYSA-N 0.000 description 3
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- JOCKMLWSXJMPTN-IFMALSPDSA-N CC(C)(C)[C@@H](C(NC1=CC=NC=C1)=O)NC(C[C@H](C(OCC1=CC=CC=C1)=O)NC(OC(C)(C)C)=O)=O Chemical compound CC(C)(C)[C@@H](C(NC1=CC=NC=C1)=O)NC(C[C@H](C(OCC1=CC=CC=C1)=O)NC(OC(C)(C)C)=O)=O JOCKMLWSXJMPTN-IFMALSPDSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 206010014561 Emphysema Diseases 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 108010026132 Gelatinases Proteins 0.000 description 3
- 102000013382 Gelatinases Human genes 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 102100030417 Matrilysin Human genes 0.000 description 3
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 3
- 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 3
- 101150101095 Mmp12 gene Proteins 0.000 description 3
- LIFJPRWVVBIIPH-UHFFFAOYSA-N N1(C=CC=C1)C(C(=O)O)CC(=O)N Chemical compound N1(C=CC=C1)C(C(=O)O)CC(=O)N LIFJPRWVVBIIPH-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- MLQLNCYNGXVXER-CEBUJLNPSA-N [2-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-oxo-1-[5-(4-phenylphenyl)furan-2-yl]ethyl] acetate Chemical compound C([C@@H]1N(C(OC1)(C)C)C(=O)C(OC(=O)C)C=1OC(=CC=1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MLQLNCYNGXVXER-CEBUJLNPSA-N 0.000 description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 210000002469 basement membrane Anatomy 0.000 description 3
- FYKJKYJYQNAFCQ-UKRRQHHQSA-N benzyl (2r)-2-amino-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoate Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)C[C@@H](N)C(=O)OCC1=CC=CC=C1 FYKJKYJYQNAFCQ-UKRRQHHQSA-N 0.000 description 3
- BXOSNBNCMAIEKS-SJLPKXTDSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](NC(=O)OC(C)(C)C)CC(=O)OCC1=CC=CC=C1 BXOSNBNCMAIEKS-SJLPKXTDSA-N 0.000 description 3
- STAGVTRQQCDPPF-ISKFKSNPSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-(3-pyridin-4-ylpyrrol-1-yl)butanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)N1C=C(C=C1)C=1C=CN=CC=1)C(=O)OCC1=CC=CC=C1 STAGVTRQQCDPPF-ISKFKSNPSA-N 0.000 description 3
- YQHAKZFNCHRNSN-DNQXCXABSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-phenylmethoxycarbonyloxybutan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N[C@H](COC(=O)OCC=1C=CC=CC=1)C(C)(C)C)C(=O)OCC1=CC=CC=C1 YQHAKZFNCHRNSN-DNQXCXABSA-N 0.000 description 3
- VORUWGHMKZREIY-CYBMUJFWSA-N benzyl (4r)-4-(2-hydroxypropan-2-yl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound CC(C)(O)[C@H]1COC(C)(C)N1C(=O)OCC1=CC=CC=C1 VORUWGHMKZREIY-CYBMUJFWSA-N 0.000 description 3
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 3
- 239000012455 biphasic mixture Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- CKEVOWPRILMONE-UHFFFAOYSA-N ethyl 2-[5-(4-phenylphenyl)furan-2-yl]acetate Chemical compound O1C(CC(=O)OCC)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 CKEVOWPRILMONE-UHFFFAOYSA-N 0.000 description 3
- LWXPACBINBXCJI-ZDUSSCGKSA-N ethyl 2-[[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]amino]-2-oxoacetate Chemical compound C1OC(C)(C)N(NC(=O)C(=O)OCC)[C@H]1CC1=CC=CC=C1 LWXPACBINBXCJI-ZDUSSCGKSA-N 0.000 description 3
- FSSXLILAQSXOQH-UHFFFAOYSA-N ethyl 2-acetyloxy-2-[5-(4-phenylphenyl)furan-2-yl]acetate Chemical compound O1C(C(OC(C)=O)C(=O)OCC)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 FSSXLILAQSXOQH-UHFFFAOYSA-N 0.000 description 3
- HNBDOCMQSLZYIH-UHFFFAOYSA-N ethyl 2-hydroxy-2-[5-(4-phenylphenyl)furan-2-yl]acetate Chemical compound O1C(C(O)C(=O)OCC)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 HNBDOCMQSLZYIH-UHFFFAOYSA-N 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 150000003254 radicals Chemical group 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 108091007196 stromelysin Proteins 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000011044 succinic acid Nutrition 0.000 description 3
- 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 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- ZEGBYSBVMJCHEI-ZCFIWIBFSA-N (2r)-2-(butoxycarbonylamino)butanedioic acid Chemical compound CCCCOC(=O)N[C@@H](C(O)=O)CC(O)=O ZEGBYSBVMJCHEI-ZCFIWIBFSA-N 0.000 description 2
- IWJFNYWOFXSKCH-WUFINQPMSA-N (3r)-3-[3-[4-(4-cyanophenyl)phenyl]pyrrol-1-yl]-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(O)=O)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C#N)C1=CC=CC=C1 IWJFNYWOFXSKCH-WUFINQPMSA-N 0.000 description 2
- FTLXLFPMDCOABE-BYPYZUCNSA-N (3r)-3-amino-4,4-dimethyloxolan-2-one Chemical compound CC1(C)COC(=O)[C@@H]1N FTLXLFPMDCOABE-BYPYZUCNSA-N 0.000 description 2
- FANKKTKSSUOWHV-LOSJGSFVSA-N (3r)-4-[[(2s)-1-[methoxy(methyl)amino]-4-methyl-1-oxopentan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoic acid Chemical compound CON(C)C(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 FANKKTKSSUOWHV-LOSJGSFVSA-N 0.000 description 2
- IGJNBEBJECPONG-WUFINQPMSA-N (3r)-4-[[(2s)-1-methoxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C([C@@H](COC)NC(=O)[C@@H](CC(O)=O)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 IGJNBEBJECPONG-WUFINQPMSA-N 0.000 description 2
- KIMPDPYEKZDGEZ-YTUWVCBBSA-N (3s)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)-1,2-dihydropyrrol-3-yl]butanoic acid Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(O)=O)C1(C=CNC1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 KIMPDPYEKZDGEZ-YTUWVCBBSA-N 0.000 description 2
- JOYDUCRIYCOQIJ-FUHWJXTLSA-N (3s)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-3-[1-(4-fluorophenyl)pyrrol-3-yl]-4-oxobutanoic acid Chemical compound C1=C([C@H](CC(O)=O)C(=O)N[C@H](C(=O)NC)C(C)(C)C)C=CN1C1=CC=C(F)C=C1 JOYDUCRIYCOQIJ-FUHWJXTLSA-N 0.000 description 2
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 2
- FEOQILOJSYWPKH-FQEVSTJZSA-N (4s)-4-benzyl-3-[2-[1-(4-fluorophenyl)pyrrol-3-yl]acetyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(F)=CC=C1N1C=C(CC(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)C=C1 FEOQILOJSYWPKH-FQEVSTJZSA-N 0.000 description 2
- BTTUMVHWIAXYPJ-UHFFFAOYSA-N 1,3-dithian-2-yl(trimethyl)silane Chemical compound C[Si](C)(C)C1SCCCS1 BTTUMVHWIAXYPJ-UHFFFAOYSA-N 0.000 description 2
- YUIOPHXTILULQC-UHFFFAOYSA-N 1,4-Dithiane-2,5-diol Chemical compound OC1CSC(O)CS1 YUIOPHXTILULQC-UHFFFAOYSA-N 0.000 description 2
- YBQFSLFZRGIWNY-HNNXBMFYSA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-(4-iodopyrazol-1-yl)ethanone Chemical compound C([C@H]1COC(N1C(=O)CN1N=CC(I)=C1)(C)C)C1=CC=CC=C1 YBQFSLFZRGIWNY-HNNXBMFYSA-N 0.000 description 2
- ODAPOJJDMKTHSJ-MHZLTWQESA-N 1-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-[1-(4-phenylphenyl)pyrrol-3-yl]ethane-1,2-dione Chemical compound C([C@H]1COC(N1C(=O)C(=O)C1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)(C)C)C1=CC=CC=C1 ODAPOJJDMKTHSJ-MHZLTWQESA-N 0.000 description 2
- ZRWCHMFGMKNWEC-UHFFFAOYSA-N 1-iodo-4-propylbenzene Chemical compound CCCC1=CC=C(I)C=C1 ZRWCHMFGMKNWEC-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- WKGLVASMQICNLR-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-propylphenyl)oxolane Chemical compound C1=CC(CCC)=CC=C1C1C(OC)OC(OC)C1 WKGLVASMQICNLR-UHFFFAOYSA-N 0.000 description 2
- QMIGEDXMDGEZSR-UHFFFAOYSA-N 2,5-dimethoxyoxolane-3-carbaldehyde Chemical compound COC1CC(C=O)C(OC)O1 QMIGEDXMDGEZSR-UHFFFAOYSA-N 0.000 description 2
- RPDMSYGUNCULQY-UHFFFAOYSA-N 2-(2-amino-2-oxoethyl)pentanoic acid Chemical compound CCCC(C(O)=O)CC(N)=O RPDMSYGUNCULQY-UHFFFAOYSA-N 0.000 description 2
- KOPAPNLCUNYNON-UHFFFAOYSA-N 2-[5-(4-phenylphenyl)furan-2-yl]acetic acid Chemical compound O1C(CC(=O)O)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 KOPAPNLCUNYNON-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- YOWQWFMSQCOSBA-UHFFFAOYSA-N 2-methoxypropene Chemical compound COC(C)=C YOWQWFMSQCOSBA-UHFFFAOYSA-N 0.000 description 2
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- FGPHREAJQSDGPN-UHFFFAOYSA-N 3-bromo-1-(4-phenylphenyl)pyrrole Chemical compound C1=C(Br)C=CN1C1=CC=C(C=2C=CC=CC=2)C=C1 FGPHREAJQSDGPN-UHFFFAOYSA-N 0.000 description 2
- AZVSIHIBYRHSLB-UHFFFAOYSA-N 3-furaldehyde Chemical compound O=CC=1C=COC=1 AZVSIHIBYRHSLB-UHFFFAOYSA-N 0.000 description 2
- ZZXONYZLJZRERV-UHFFFAOYSA-N 4-(2,5-dimethoxyoxolan-3-yl)pyridine Chemical compound COC1OC(OC)CC1C1=CC=NC=C1 ZZXONYZLJZRERV-UHFFFAOYSA-N 0.000 description 2
- BYUXFTRUIKTAMD-UHFFFAOYSA-N 4-[4-(2,5-dimethoxy-2,5-dihydrofuran-3-yl)phenyl]benzonitrile Chemical compound COC1OC(OC)C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)=C1 BYUXFTRUIKTAMD-UHFFFAOYSA-N 0.000 description 2
- RZWGPIPJNPLJLH-UHFFFAOYSA-N 4-[4-(2,5-dimethoxy-2,5-dihydrofuran-3-yl)phenyl]pyridine Chemical compound COC1OC(OC)C(C=2C=CC(=CC=2)C=2C=CN=CC=2)=C1 RZWGPIPJNPLJLH-UHFFFAOYSA-N 0.000 description 2
- XATDMDVXNVEARM-UHFFFAOYSA-N 4-[4-(furan-3-yl)phenyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=C(C2=COC=C2)C=C1 XATDMDVXNVEARM-UHFFFAOYSA-N 0.000 description 2
- ZGFGQOMKFQBTEH-UGGDCYSXSA-N 4-o-benzyl 1-o-tert-butyl (2r)-3-amino-2-[[(2s)-1-methoxy-3-phenylpropan-2-yl]carbamoyl]butanedioate Chemical compound C([C@@H](COC)NC(=O)[C@@H](C(N)C(=O)OCC=1C=CC=CC=1)C(=O)OC(C)(C)C)C1=CC=CC=C1 ZGFGQOMKFQBTEH-UGGDCYSXSA-N 0.000 description 2
- BPMBNLJJRKCCRT-UHFFFAOYSA-N 4-phenylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=CC=C1 BPMBNLJJRKCCRT-UHFFFAOYSA-N 0.000 description 2
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- FYYSQDHBALBGHX-RXMQYKEDSA-N Boc-D-asparagine Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC(N)=O FYYSQDHBALBGHX-RXMQYKEDSA-N 0.000 description 2
- MSBMGFSERLZZMJ-WOJBJXKFSA-N C(C1=CC=CC=C1)OC([C@@H](CC(=O)N[C@H](CO)C1=CC=CC=C1)NC(=O)OC(C)(C)C)=O Chemical compound C(C1=CC=CC=C1)OC([C@@H](CC(=O)N[C@H](CO)C1=CC=CC=C1)NC(=O)OC(C)(C)C)=O MSBMGFSERLZZMJ-WOJBJXKFSA-N 0.000 description 2
- HPXGIXJOOXSCHL-FCHUYYIVSA-N C(C1=CC=CC=C1)OC([C@@H](CC(=O)N[C@H](COC)CC1=CC=CC=C1)NC(=O)OC(C)(C)C)=O Chemical compound C(C1=CC=CC=C1)OC([C@@H](CC(=O)N[C@H](COC)CC1=CC=CC=C1)NC(=O)OC(C)(C)C)=O HPXGIXJOOXSCHL-FCHUYYIVSA-N 0.000 description 2
- HIBHWMUIKMHHDK-KZNAEPCWSA-N CC(C)(C)OC(N[C@H](CC(N[C@H](CCCC1)[C@@H]1O)=O)C(OCC1=CC=CC=C1)=O)=O Chemical compound CC(C)(C)OC(N[C@H](CC(N[C@H](CCCC1)[C@@H]1O)=O)C(OCC1=CC=CC=C1)=O)=O HIBHWMUIKMHHDK-KZNAEPCWSA-N 0.000 description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000016942 Elastin Human genes 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108030004510 Interstitial collagenases Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 2
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 108090000855 Matrilysin Proteins 0.000 description 2
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 102000036436 Metzincins Human genes 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 208000011675 Skin degenerative disease Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 102100030416 Stromelysin-1 Human genes 0.000 description 2
- 102100028847 Stromelysin-3 Human genes 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- UZLFNEJQHFESJD-UFXYQILXSA-N [2-[(4s)-4-benzyl-2,2-dimethyl-1,3-oxazolidin-3-yl]-2-oxo-1-[1-(4-phenylphenyl)pyrrol-3-yl]ethyl] acetate Chemical compound C([C@@H]1N(C(OC1)(C)C)C(=O)C(OC(=O)C)C1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 UZLFNEJQHFESJD-UFXYQILXSA-N 0.000 description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000010640 amide synthesis reaction Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229960004050 aminobenzoic acid Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- GLOKAFJTGJPIED-SJLPKXTDSA-N benzyl (2r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)C[C@@H](NC(=O)OC(C)(C)C)C(=O)OCC1=CC=CC=C1 GLOKAFJTGJPIED-SJLPKXTDSA-N 0.000 description 2
- VNFPRPGXGYMAKL-GFCCVEGCSA-N benzyl (2r)-4-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)N[C@H](CC(N)=O)C(=O)OCC1=CC=CC=C1 VNFPRPGXGYMAKL-GFCCVEGCSA-N 0.000 description 2
- QBJJOAILUQXWRD-OIDHKYIRSA-N benzyl (3r)-3-[3-[4-(4-cyanophenyl)phenyl]pyrrol-1-yl]-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxobutanoate Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(=O)OCC=1C=CC=CC=1)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C#N)C1=CC=CC=C1 QBJJOAILUQXWRD-OIDHKYIRSA-N 0.000 description 2
- IJULCZYYIBZTSX-LEWJYISDSA-N benzyl (3r)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound C([C@@H](NC(=O)OC(C)(C)C)C(=O)N[C@H](CO)CC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 IJULCZYYIBZTSX-LEWJYISDSA-N 0.000 description 2
- PECYCZAUDRMYPZ-SZAHLOSFSA-N benzyl (3r)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoate Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(=O)OCC=1C=CC=CC=1)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 PECYCZAUDRMYPZ-SZAHLOSFSA-N 0.000 description 2
- IQTIUBVCGGJROJ-FCHUYYIVSA-N benzyl (3r)-4-[[(2s)-1-methoxy-3-phenylpropan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound C([C@@H](COC)NC(=O)[C@@H](CC(=O)OCC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 IQTIUBVCGGJROJ-FCHUYYIVSA-N 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- DMVOXQPQNTYEKQ-UHFFFAOYSA-N biphenyl-4-amine Chemical group C1=CC(N)=CC=C1C1=CC=CC=C1 DMVOXQPQNTYEKQ-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 125000005619 boric acid group Chemical class 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 150000001934 cyclohexanes Chemical class 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229920002549 elastin Polymers 0.000 description 2
- 230000003628 erosive effect Effects 0.000 description 2
- CJNCTYVJNJTROC-UHFFFAOYSA-N ethyl 2-oxo-2-[5-(4-phenylphenyl)furan-2-yl]acetate Chemical compound O1C(C(=O)C(=O)OCC)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 CJNCTYVJNJTROC-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 125000005283 haloketone group Chemical group 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 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 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
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 229960002523 mercuric chloride Drugs 0.000 description 2
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- MHAHLZDPOBUSCI-UHFFFAOYSA-N methyl 2-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]acetate Chemical compound C1=C(CC(=O)OC)C=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 MHAHLZDPOBUSCI-UHFFFAOYSA-N 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical class NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- PQMCFTMVQORYJC-PHDIDXHHSA-N (1r,2r)-2-aminocyclohexan-1-ol Chemical compound N[C@@H]1CCCC[C@H]1O PQMCFTMVQORYJC-PHDIDXHHSA-N 0.000 description 1
- LOPKSXMQWBYUOI-BDAKNGLRSA-N (1s,2r)-1-amino-2,3-dihydro-1h-inden-2-ol Chemical compound C1=CC=C2[C@H](N)[C@H](O)CC2=C1 LOPKSXMQWBYUOI-BDAKNGLRSA-N 0.000 description 1
- CZMZRCJPBSNFDE-HTRCEHHLSA-N (2R)-2-amino-4-[[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)C[C@@H](N)C(O)=O CZMZRCJPBSNFDE-HTRCEHHLSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- GQOBNZBUGXBIOA-QMMMGPOBSA-N (2R)-4-(tert-butylamino)-4-oxo-2-thiophen-2-ylbutanoic acid Chemical compound CC(C)(C)NC(=O)C[C@H](C(O)=O)C1=CC=CS1 GQOBNZBUGXBIOA-QMMMGPOBSA-N 0.000 description 1
- PFNZGPJNBGADEY-GSVOUGTGSA-N (2R)-4-amino-2-(hydroxymethyl)-4-oxobutanoic acid Chemical compound NC(=O)C[C@H](CO)C(O)=O PFNZGPJNBGADEY-GSVOUGTGSA-N 0.000 description 1
- FBNDATPFHWZDQL-IEBWSBKVSA-N (2r)-2-[3-(4-cyanophenyl)pyrrol-1-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)C[C@H](C(O)=O)N1C=CC(C=2C=CC(=CC=2)C#N)=C1 FBNDATPFHWZDQL-IEBWSBKVSA-N 0.000 description 1
- XAHDZPZZVHYHHU-PGMHMLKASA-N (2r)-2-amino-3-methylbutane-1,3-diol;hydrochloride Chemical compound Cl.CC(C)(O)[C@H](N)CO XAHDZPZZVHYHHU-PGMHMLKASA-N 0.000 description 1
- CBSVXHQDZYDLKK-QMMMGPOBSA-N (2r)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-thiophen-2-ylbutanoic acid Chemical compound CC(C)(C)OC(=O)C[C@H](C(O)=O)C1=CC=CS1 CBSVXHQDZYDLKK-QMMMGPOBSA-N 0.000 description 1
- XQAZRXKMQMGRKC-SECBINFHSA-N (2r)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-thiophen-3-ylbutanoic acid Chemical compound CC(C)(C)OC(=O)C[C@@H](C(O)=O)C=1C=CSC=1 XQAZRXKMQMGRKC-SECBINFHSA-N 0.000 description 1
- CNTXDOYFHRQVFM-RPWUZVMVSA-N (2r)-4-amino-2-[[1-[(3s)-2-[(2-methylpropan-2-yl)oxycarbonyl]-3,4-dihydro-1h-isoquinoline-3-carbonyl]-4-phenylpiperidine-4-carbonyl]amino]-4-oxobutanoic acid Chemical compound O=C([C@@H]1CC2=CC=CC=C2CN1C(=O)OC(C)(C)C)N(CC1)CCC1(C(=O)N[C@H](CC(N)=O)C(O)=O)C1=CC=CC=C1 CNTXDOYFHRQVFM-RPWUZVMVSA-N 0.000 description 1
- QMYLXQOQZOUTMS-IBGZPJMESA-N (2s)-2-[1-(4-fluorophenyl)pyrrol-3-yl]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound C([C@H](C(=O)O)C1=CN(C=C1)C=1C=CC(F)=CC=1)C(=O)OCC1=CC=CC=C1 QMYLXQOQZOUTMS-IBGZPJMESA-N 0.000 description 1
- LANUPQOFFSPHBM-UKILVPOCSA-N (2s)-2-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound C1=C([C@@H](C(O)=O)CC(=O)N[C@H](C(=O)NC)C(C)(C)C)C=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 LANUPQOFFSPHBM-UKILVPOCSA-N 0.000 description 1
- LGXUPQSFJRPWSS-SANMLTNESA-N (2s)-2-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound C([C@H](C(=O)O)C1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C#N)C(=O)OCC1=CC=CC=C1 LGXUPQSFJRPWSS-SANMLTNESA-N 0.000 description 1
- LIBDTAYIDBPBRN-LURJTMIESA-N (2s)-2-amino-n,4-dimethylpentanamide Chemical compound CNC(=O)[C@@H](N)CC(C)C LIBDTAYIDBPBRN-LURJTMIESA-N 0.000 description 1
- LRFZIPCTFBPFLX-SSDOTTSWSA-N (2s)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C(C)(C)C LRFZIPCTFBPFLX-SSDOTTSWSA-N 0.000 description 1
- ZPVMLTOTVGPJJB-HSZRJFAPSA-N (2s)-n,3,3-trimethyl-2-[[2-[5-(4-phenylphenyl)furan-2-yl]acetyl]amino]butanamide Chemical compound O1C(CC(=O)N[C@H](C(=O)NC)C(C)(C)C)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 ZPVMLTOTVGPJJB-HSZRJFAPSA-N 0.000 description 1
- QOIRKKYNSGBNQB-RDJZCZTQSA-N (3R)-4-[[(2S)-1-(3-amino-4-methoxycarbonylphenyl)-4-methyl-1-oxopentan-2-yl]amino]-4-oxo-3-thiophen-2-ylbutanoic acid Chemical compound C1=C(N)C(C(=O)OC)=CC=C1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(O)=O)C1=CC=CS1 QOIRKKYNSGBNQB-RDJZCZTQSA-N 0.000 description 1
- DGLWDMQSOCUIDI-IEBWSBKVSA-N (3r)-3-[3-(4-cyanophenyl)pyrrol-1-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC(=CC=2)C#N)=C1 DGLWDMQSOCUIDI-IEBWSBKVSA-N 0.000 description 1
- FUTRWPCKBFESIA-SSYAZFEXSA-N (3r)-3-[3-[4-(4-carbamoylphenyl)phenyl]pyrrol-1-yl]-4-[(1-hydroxy-3-phenylpropan-2-yl)amino]-4-oxobutanoic acid Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=C(C2=CN(C=C2)[C@H](CC(O)=O)C(=O)NC(CO)CC=2C=CC=CC=2)C=C1 FUTRWPCKBFESIA-SSYAZFEXSA-N 0.000 description 1
- VZSWZKRCJWHREV-DHIUTWEWSA-N (3r)-3-[3-[4-(4-carbamoylphenyl)phenyl]pyrrol-1-yl]-4-[[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC(C)(C)[C@@H](CO)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=O)=C1 VZSWZKRCJWHREV-DHIUTWEWSA-N 0.000 description 1
- SOCISSVUMZUFSG-GOSISDBHSA-N (3r)-4-(methylamino)-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound CNC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CC(=CC=2)C=2C=CN=CC=2)=C1 SOCISSVUMZUFSG-GOSISDBHSA-N 0.000 description 1
- QIEUIUAFWAKWRL-BJKOFHAPSA-N (3r)-4-[[(1s)-1-(1h-imidazol-2-yl)-3-methylbutyl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C=1N([C@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C=2NC=CN=2)C=CC=1C(C=C1)=CC=C1C1=CC=NC=C1 QIEUIUAFWAKWRL-BJKOFHAPSA-N 0.000 description 1
- QTSOAJKHQODCIZ-JWQCQUIFSA-N (3r)-4-[[(1s)-2-hydroxy-1-phenylethyl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C=1N([C@H](CC(O)=O)C(=O)N[C@H](CO)C=2C=CC=CC=2)C=CC=1C(C=C1)=CC=C1C1=CC=NC=C1 QTSOAJKHQODCIZ-JWQCQUIFSA-N 0.000 description 1
- UVTZZMNBZMCLIU-AEFFLSMTSA-N (3r)-4-[[(2s)-1-(3-amino-4-methoxycarbonylphenyl)-4-methyl-1-oxopentan-2-yl]amino]-4-oxo-3-thiophen-3-ylbutanoic acid Chemical compound C1=C(N)C(C(=O)OC)=CC=C1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)C1=CSC=C1 UVTZZMNBZMCLIU-AEFFLSMTSA-N 0.000 description 1
- PLPOXERTYPNNOI-IZZNHLLZSA-N (3r)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[4-(4-phenylphenyl)pyrazol-1-yl]butanoic acid Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(O)=O)N1N=CC(=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 PLPOXERTYPNNOI-IZZNHLLZSA-N 0.000 description 1
- ZKBQYRWUTKTYSH-NVXWUHKLSA-N (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-(3-pyridin-4-ylpyrrol-1-yl)butanoic acid Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@@H](CC(O)=O)N1C=CC(C=2C=CN=CC=2)=C1 ZKBQYRWUTKTYSH-NVXWUHKLSA-N 0.000 description 1
- CAKOZUWLHOSJIL-XNMGPUDCSA-N (3r)-4-[[(2s)-3,3-dimethyl-1-oxo-1-(pyridin-4-ylamino)butan-2-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C=1N([C@H](CC(O)=O)C(=O)N[C@@H](C(C)(C)C)C(=O)NC=2C=CN=CC=2)C=CC=1C(C=C1)=CC=C1C1=CC=NC=C1 CAKOZUWLHOSJIL-XNMGPUDCSA-N 0.000 description 1
- ZGSXZKYHKNDSDE-IFMALSPDSA-N (3r)-4-[[(3s)-4,4-dimethyl-2-oxooxolan-3-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound CC1(C)COC(=O)[C@H]1NC(=O)[C@@H](CC(O)=O)N1C=C(C=2C=CC(=CC=2)C=2C=CN=CC=2)C=C1 ZGSXZKYHKNDSDE-IFMALSPDSA-N 0.000 description 1
- GYKMAWIYKPLMGN-LADGPHEKSA-N (3s)-3-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-[[(3s)-4,4-dimethyl-2-oxooxolan-3-yl]amino]-4-oxobutanoic acid Chemical compound CC1(C)COC(=O)[C@H]1NC(=O)[C@@H](CC(O)=O)C1=CN(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)C=C1 GYKMAWIYKPLMGN-LADGPHEKSA-N 0.000 description 1
- ATTRSQMUDMGABC-FCHUYYIVSA-N (3s)-4-[[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]amino]-4-oxo-3-[1-(4-pyridin-4-ylphenyl)pyrrol-3-yl]butanoic acid Chemical compound C1=C([C@H](CC(O)=O)C(=O)N[C@H](CO)C(C)(C)C)C=CN1C1=CC=C(C=2C=CN=CC=2)C=C1 ATTRSQMUDMGABC-FCHUYYIVSA-N 0.000 description 1
- XIKIFHGSIXHYDE-DQEYMECFSA-N (3s)-4-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[5-(4-phenylphenyl)furan-2-yl]butanoic acid Chemical compound C([C@@H](CO)NC(=O)[C@@H](CC(O)=O)C=1OC(=CC=1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 XIKIFHGSIXHYDE-DQEYMECFSA-N 0.000 description 1
- STVVMTBJNDTZBF-UHFFFAOYSA-N -2-Amino-3-phenyl-1-propanol Natural products OCC(N)CC1=CC=CC=C1 STVVMTBJNDTZBF-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
- KFHQOZXAFUKFNB-UHFFFAOYSA-N 1,3-oxathiolanyl Chemical group [CH]1OCCS1 KFHQOZXAFUKFNB-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- OQGGHIBIFQHTAH-UHFFFAOYSA-N 1-amino-4-phenylcyclohexa-2,4-diene-1-carbonitrile Chemical group C1=CC(N)(C#N)CC=C1C1=CC=CC=C1 OQGGHIBIFQHTAH-UHFFFAOYSA-N 0.000 description 1
- PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- SEYQGVYTVHINPB-UHFFFAOYSA-N 2,3-dimethoxyfuran Chemical compound COC=1C=COC=1OC SEYQGVYTVHINPB-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- DYOSAFQUIFEGSK-UHFFFAOYSA-N 2,5-dimethoxy-2,3-dihydrofuran Chemical class COC1CC=C(OC)O1 DYOSAFQUIFEGSK-UHFFFAOYSA-N 0.000 description 1
- RJLWIJITFAZJFB-UHFFFAOYSA-N 2,5-dimethoxy-2-(4-phenylphenyl)oxolane Chemical compound O1C(OC)CCC1(OC)C1=CC=C(C=2C=CC=CC=2)C=C1 RJLWIJITFAZJFB-UHFFFAOYSA-N 0.000 description 1
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- UYCUMNRCCJNSBR-UHFFFAOYSA-N 2-ethoxy-2-oxoacetic acid;hydrochloride Chemical compound Cl.CCOC(=O)C(O)=O UYCUMNRCCJNSBR-UHFFFAOYSA-N 0.000 description 1
- GYVADCQLHHMYLW-UHFFFAOYSA-N 2-hydroxy-4-methylsulfanylbutanoic acid;3-methyl-2-oxobutanoic acid;3-methyl-2-oxopentanoic acid;4-methyl-2-oxopentanoic acid;2-oxo-3-phenylpropanoic acid Chemical compound CC(C)C(=O)C(O)=O.CCC(C)C(=O)C(O)=O.CSCCC(O)C(O)=O.CC(C)CC(=O)C(O)=O.OC(=O)C(=O)CC1=CC=CC=C1 GYVADCQLHHMYLW-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- AJYXPNIENRLELY-UHFFFAOYSA-N 2-thiophen-2-ylacetyl chloride Chemical compound ClC(=O)CC1=CC=CS1 AJYXPNIENRLELY-UHFFFAOYSA-N 0.000 description 1
- RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 description 1
- KEYWOCXIPDAGCS-UHFFFAOYSA-N 2-thiophen-3-ylacetyl chloride Chemical compound ClC(=O)CC=1C=CSC=1 KEYWOCXIPDAGCS-UHFFFAOYSA-N 0.000 description 1
- XVSIERAKGGMEJZ-UHFFFAOYSA-N 3,3-dimethyl-n-pyridin-4-ylbutanamide Chemical compound CC(C)(C)CC(=O)NC1=CC=NC=C1 XVSIERAKGGMEJZ-UHFFFAOYSA-N 0.000 description 1
- ZOYBHQLJFDFGFH-UHFFFAOYSA-N 3-(2,2-dibromoethenyl)-2,5-dimethoxyoxolane Chemical compound COC1CC(C=C(Br)Br)C(OC)O1 ZOYBHQLJFDFGFH-UHFFFAOYSA-N 0.000 description 1
- LLNARJIUJRDDCW-UHFFFAOYSA-N 3-(4-phenylphenyl)-1H-pyrrole Chemical compound C1(=CC=CC=C1)C1=CC=C(C=C1)C1=CNC=C1 LLNARJIUJRDDCW-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- VLYUGUVEQGQOPH-UHFFFAOYSA-N 3-methyl-2-(pentanoylamino)benzoic acid Chemical compound CCCCC(=O)NC1=C(C)C=CC=C1C(O)=O VLYUGUVEQGQOPH-UHFFFAOYSA-N 0.000 description 1
- FACSZQUJPAJGPA-UHFFFAOYSA-N 4-(2,5-dihydroxy-2,5-dimethoxyfuran-3-yl)benzonitrile Chemical compound COC1(O)OC(O)(OC)C(C=2C=CC(=CC=2)C#N)=C1 FACSZQUJPAJGPA-UHFFFAOYSA-N 0.000 description 1
- XMVZXIVPQCQKPS-UHFFFAOYSA-N 4-(2,5-dimethoxy-2,5-dihydrofuran-3-yl)benzonitrile Chemical compound COC1OC(OC)C(C=2C=CC(=CC=2)C#N)=C1 XMVZXIVPQCQKPS-UHFFFAOYSA-N 0.000 description 1
- GFVMZKFJMYHDNM-UHFFFAOYSA-N 4-(benzylamino)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NCC1=CC=CC=C1 GFVMZKFJMYHDNM-UHFFFAOYSA-N 0.000 description 1
- PCEZZENMFIZLMN-MHZLTWQESA-N 4-[4-[3-[2-[(4s)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-oxoethyl]pyrrol-1-yl]phenyl]benzonitrile Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CC(=C1)C=CN1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 PCEZZENMFIZLMN-MHZLTWQESA-N 0.000 description 1
- FYYSQDHBALBGHX-UHFFFAOYSA-N 4-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC(N)=O FYYSQDHBALBGHX-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 1
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- HVHBTFZQLHOFHA-UHFFFAOYSA-N 4-methyl-4-pentenoic acid Chemical compound CC(=C)CCC(O)=O HVHBTFZQLHOFHA-UHFFFAOYSA-N 0.000 description 1
- GYIZDJRATJDJDZ-UGGDCYSXSA-N 4-o-benzyl 1-o-butyl (2r)-3-amino-2-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]carbamoyl]butanedioate Chemical compound NC([C@@H](C(=O)OCCCC)C(=O)N[C@H](CO)CC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 GYIZDJRATJDJDZ-UGGDCYSXSA-N 0.000 description 1
- PHOJOSOUIAQEDH-UHFFFAOYSA-N 5-hydroxypentanoic acid Chemical compound OCCCCC(O)=O PHOJOSOUIAQEDH-UHFFFAOYSA-N 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 244000003416 Asparagus officinalis Species 0.000 description 1
- 235000005340 Asparagus officinalis Nutrition 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- XXMVJJDHMPSGGJ-GFCCVEGCSA-N C1(=CC=CC=C1)C1=CN(C=C1)[C@@H](C(=O)O)CC(=O)O Chemical compound C1(=CC=CC=C1)C1=CN(C=C1)[C@@H](C(=O)O)CC(=O)O XXMVJJDHMPSGGJ-GFCCVEGCSA-N 0.000 description 1
- RUQWGDKTCFJLRU-IBGZPJMESA-N C1=CC(=CC=C1C#N)C2=CC=C(C=C2)N3C=CC(=C3)[C@H](CC(=O)N)C(=O)O Chemical compound C1=CC(=CC=C1C#N)C2=CC=C(C=C2)N3C=CC(=C3)[C@H](CC(=O)N)C(=O)O RUQWGDKTCFJLRU-IBGZPJMESA-N 0.000 description 1
- YGLUHEDVBBRSCD-TXTZDMIGSA-N CC(C)(C)CC[C@@](C(Cl)(Cl)Cl)(NC(=O)[C@@H]([C@@H]1C[C@@H](OC1=O)CI)NC(=O)OC(C)(C)C)OC(=O)O Chemical compound CC(C)(C)CC[C@@](C(Cl)(Cl)Cl)(NC(=O)[C@@H]([C@@H]1C[C@@H](OC1=O)CI)NC(=O)OC(C)(C)C)OC(=O)O YGLUHEDVBBRSCD-TXTZDMIGSA-N 0.000 description 1
- XTWXNZZGHIAQBE-GMTAPVOTSA-N CC(C)(C)OC(=O)N[C@H](CC(=O)N[C@@H]1CCCC[C@H]1O)C(=O)O Chemical compound CC(C)(C)OC(=O)N[C@H](CC(=O)N[C@@H]1CCCC[C@H]1O)C(=O)O XTWXNZZGHIAQBE-GMTAPVOTSA-N 0.000 description 1
- OKFKJSIBFMWKMP-QMMMGPOBSA-N CC(C)(C)OC(=O)[C@@H](CC(=O)O)C1=CC=CS1 Chemical compound CC(C)(C)OC(=O)[C@@H](CC(=O)O)C1=CC=CS1 OKFKJSIBFMWKMP-QMMMGPOBSA-N 0.000 description 1
- GIJIHCPEDOMDQK-LEWJYISDSA-N CC(C)(C)OC(N([C@@H](CC1=CC=CC=C1)CO)[C@H](CC(OCC1=CC=CC=C1)=O)C(O)=O)=O Chemical compound CC(C)(C)OC(N([C@@H](CC1=CC=CC=C1)CO)[C@H](CC(OCC1=CC=CC=C1)=O)C(O)=O)=O GIJIHCPEDOMDQK-LEWJYISDSA-N 0.000 description 1
- SPVSJQYXIZVZGW-XRKRLSELSA-N CC(C)(C)[C@@H](C(=O)NC1=CC=NC=C1)NC(=O)C[C@H](C(=O)O)N2C=CC(=C2)C3=CC=C(C=C3)C4=CC=C(C=C4)C#N Chemical compound CC(C)(C)[C@@H](C(=O)NC1=CC=NC=C1)NC(=O)C[C@H](C(=O)O)N2C=CC(=C2)C3=CC=C(C=C3)C4=CC=C(C=C4)C#N SPVSJQYXIZVZGW-XRKRLSELSA-N 0.000 description 1
- GQVVXCOKZVCKJC-DHIUTWEWSA-N CC(C)(C)[C@@H](CO)NC(=O)C[C@H](C(=O)O)N1C=CC(=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C(=O)N Chemical compound CC(C)(C)[C@@H](CO)NC(=O)C[C@H](C(=O)O)N1C=CC(=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C(=O)N GQVVXCOKZVCKJC-DHIUTWEWSA-N 0.000 description 1
- TXRSHJUMNAPNBE-QMMMGPOBSA-N CCC[C@](CC(N)=O)(CO)C(O)=O Chemical compound CCC[C@](CC(N)=O)(CO)C(O)=O TXRSHJUMNAPNBE-QMMMGPOBSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 238000003479 Claisen-Ireland rearrangement reaction Methods 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Chemical group 0.000 description 1
- 101000990912 Homo sapiens Matrilysin Proteins 0.000 description 1
- ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108700010340 Leishmanolysins Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 108010076502 Matrix Metalloproteinase 11 Proteins 0.000 description 1
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102220470425 Melanoregulin_H35N_mutation Human genes 0.000 description 1
- 108091007161 Metzincins Proteins 0.000 description 1
- MYHFFGLHTYBHJS-UHFFFAOYSA-N N'-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanediamide Chemical compound C(CCC(=O)N)(=O)NN1C=C(C=C1)C1=CC=C(C=C1)C1=CC=NC=C1 MYHFFGLHTYBHJS-UHFFFAOYSA-N 0.000 description 1
- KAJBMCZQVSQJDE-YFKPBYRVSA-N Nalpha-(tert-butoxycarbonyl)-l-aspartic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC(O)=O KAJBMCZQVSQJDE-YFKPBYRVSA-N 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- 102000056189 Neutrophil collagenases Human genes 0.000 description 1
- 108030001564 Neutrophil collagenases Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- PEKOJNZPHPFAOE-UHFFFAOYSA-N O1C(C(=O)C(=O)O)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 Chemical compound O1C(C(=O)C(=O)O)=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 PEKOJNZPHPFAOE-UHFFFAOYSA-N 0.000 description 1
- UMYOQCLCJJCVSS-SWYZXDRTSA-N OC(=O)C(F)(F)F.CNC(=O)[C@@H](NC(=O)C[C@@H](N)C(=O)OCc1ccccc1)C(C)(C)C Chemical compound OC(=O)C(F)(F)F.CNC(=O)[C@@H](NC(=O)C[C@@H](N)C(=O)OCc1ccccc1)C(C)(C)C UMYOQCLCJJCVSS-SWYZXDRTSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101000933967 Pseudomonas phage KPP25 Major capsid protein Proteins 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 101150108015 STR6 gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- OQIQSTLJSLGHID-WNWIJWBNSA-N aflatoxin B1 Chemical group C=1([C@@H]2C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O OQIQSTLJSLGHID-WNWIJWBNSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- QCXIKIIPOLIKJC-ZWKOTPCHSA-N benzyl (3R)-3-amino-4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-4-oxobutanoate Chemical compound C([C@@H](N)C(=O)N[C@H](CO)CC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 QCXIKIIPOLIKJC-ZWKOTPCHSA-N 0.000 description 1
- NSKCBLPOOHHCRX-BVRKHOPBSA-N benzyl (3r)-3-[3-[4-(4-carbamoylphenyl)phenyl]pyrrol-1-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C(N)=O)C(=O)OCC1=CC=CC=C1 NSKCBLPOOHHCRX-BVRKHOPBSA-N 0.000 description 1
- CVLXVUATEAOWSU-XLJNKUFUSA-N benzyl (3r)-3-[3-[4-(4-cyanophenyl)phenyl]pyrrol-1-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C#N)C(=O)OCC1=CC=CC=C1 CVLXVUATEAOWSU-XLJNKUFUSA-N 0.000 description 1
- UHBAKIIHISSQKG-JFHPUIQFSA-N benzyl (3r)-4-[[(1r,2r)-2-hydroxycyclohexyl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoate Chemical compound O[C@@H]1CCCC[C@H]1NC(=O)[C@H](N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)CC(=O)OCC1=CC=CC=C1 UHBAKIIHISSQKG-JFHPUIQFSA-N 0.000 description 1
- CULMJHICHLACOX-OIDHKYIRSA-N benzyl (3r)-4-[[(2s)-1-methoxy-3-phenylpropan-2-yl]amino]-4-oxo-3-[3-(4-phenylphenyl)pyrrol-1-yl]butanoate Chemical compound C([C@@H](COC)NC(=O)[C@@H](CC(=O)OCC=1C=CC=CC=1)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 CULMJHICHLACOX-OIDHKYIRSA-N 0.000 description 1
- NRTCUKXUKPGPGR-IXCJQBJRSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-[3-(4-propylphenyl)pyrrol-1-yl]butanoate Chemical compound C1=CC(CCC)=CC=C1C1=CN([C@H](CC(=O)OCC=2C=CC=CC=2)C(=O)N[C@H](C(=O)NC)C(C)(C)C)C=C1 NRTCUKXUKPGPGR-IXCJQBJRSA-N 0.000 description 1
- IRHPNQQWVIVQMY-PQHLKRTFSA-N benzyl (3r)-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CN=CC=1)C(=O)OCC1=CC=CC=C1 IRHPNQQWVIVQMY-PQHLKRTFSA-N 0.000 description 1
- BBBXDXCCIQECKQ-LJEWAXOPSA-N benzyl (3r)-4-oxo-4-[[(1s)-1-phenyl-2-phenylmethoxycarbonyloxyethyl]amino]-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoate Chemical compound C([C@@H](NC(=O)[C@@H](CC(=O)OCC=1C=CC=CC=1)N1C=C(C=C1)C=1C=CC(=CC=1)C=1C=CN=CC=1)C=1C=CC=CC=1)OC(=O)OCC1=CC=CC=C1 BBBXDXCCIQECKQ-LJEWAXOPSA-N 0.000 description 1
- SIMXINQNUIZFHP-XDFJSJKPSA-N benzyl (3s)-3-[1-[4-(4-cyanophenyl)phenyl]pyrrol-3-yl]-4-[[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-4-oxobutanoate Chemical compound C([C@H](C(=O)N[C@H](C(=O)NC)C(C)(C)C)C1=CN(C=C1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C#N)C(=O)OCC1=CC=CC=C1 SIMXINQNUIZFHP-XDFJSJKPSA-N 0.000 description 1
- KDYDYIQTXXJXAD-UHFFFAOYSA-N benzyl 3-[3-[4-(4-carbamoylphenyl)phenyl]pyrrol-1-yl]-4-[(1-hydroxy-3-phenylpropan-2-yl)amino]-4-oxobutanoate Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=C(C2=CN(C=C2)C(CC(=O)OCC=2C=CC=CC=2)C(=O)NC(CO)CC=2C=CC=CC=2)C=C1 KDYDYIQTXXJXAD-UHFFFAOYSA-N 0.000 description 1
- GLOKAFJTGJPIED-UHUGOGIASA-N benzyl 4-[[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]amino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound C(C1=CC=CC=C1)OC(C(CC(=O)N[C@@H](C(C)(C)C)C(NC)=O)NC(=O)OC(C)(C)C)=O GLOKAFJTGJPIED-UHUGOGIASA-N 0.000 description 1
- HTJDVAQGUYGUON-UHFFFAOYSA-N benzyl n,n'-di(propan-2-yl)carbamimidate Chemical compound CC(C)NC(=NC(C)C)OCC1=CC=CC=C1 HTJDVAQGUYGUON-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- XNYOSXARXANYPB-UHFFFAOYSA-N dicyclohexylborane Chemical compound C1CCCCC1BC1CCCCC1 XNYOSXARXANYPB-UHFFFAOYSA-N 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- VFNGKCDDZUSWLR-UHFFFAOYSA-N disulfuric acid Chemical class OS(=O)(=O)OS(O)(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000003670 easy-to-clean Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- RZMZBHSKPLVQCP-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate Chemical compound CCOC(=O)C(N)=O RZMZBHSKPLVQCP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 125000003106 haloaryl group Chemical group 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 1
- 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000010954 inorganic particle Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000005184 irreversible process Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 150000004797 ketoamides Chemical class 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- XYIAXCVGMXBIAJ-ICSRJNTNSA-N methyl 2-amino-4-[(2S)-4-methyl-2-[[(2R)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-thiophen-2-ylbutanoyl]amino]pentanoyl]benzoate Chemical compound CC(C)C[C@@H](C(=O)C1=CC(=C(C=C1)C(=O)OC)N)NC(=O)[C@@H](CC(=O)OC(C)(C)C)C2=CC=CS2 XYIAXCVGMXBIAJ-ICSRJNTNSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004784 molecular pathogenesis Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- PWTWOGMXABHJOA-UHFFFAOYSA-N o-[tert-butyl(diphenyl)silyl]hydroxylamine Chemical compound C=1C=CC=CC=1[Si](ON)(C(C)(C)C)C1=CC=CC=C1 PWTWOGMXABHJOA-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000006194 pentinyl group Chemical group 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- HFNGWVXNSWWIGC-UHFFFAOYSA-N phenylmethoxy carbonochloridate Chemical compound ClC(=O)OOCC1=CC=CC=C1 HFNGWVXNSWWIGC-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 150000005375 primary alkyl halides Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102220127451 rs267597943 Human genes 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000011915 stereoselective alkylation Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 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 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical class CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VSXAXPTWWKGHAK-UHFFFAOYSA-N tributyl-[2-(2,5-dimethoxyoxolan-3-yl)ethynyl]stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1CC(OC)OC1OC VSXAXPTWWKGHAK-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- DWAWYEUJUWLESO-UHFFFAOYSA-N trichloromethylsilane Chemical compound [SiH3]C(Cl)(Cl)Cl DWAWYEUJUWLESO-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- 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
- 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
- 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
- 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
- A61P9/10—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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D401/10—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 carbon chain containing aromatic rings
-
- 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
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Rheumatology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2911596P | 1996-10-24 | 1996-10-24 | |
| US08/823,962 US6008243A (en) | 1996-10-24 | 1997-03-25 | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
| PCT/US1997/017809 WO1998017643A1 (en) | 1996-10-24 | 1997-10-06 | Heteroaryl succinamides and their use as metalloproteinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK48499A3 true SK48499A3 (en) | 2000-04-10 |
Family
ID=26704557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK484-99A SK48499A3 (en) | 1996-10-24 | 1997-10-06 | Heteroaryl succinamides and their use as metalloproteinase inhibitors |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6008243A (cs) |
| EP (1) | EP0937042A1 (cs) |
| JP (1) | JP2000511201A (cs) |
| KR (1) | KR20000052779A (cs) |
| CN (1) | CN1233237A (cs) |
| AP (1) | AP1360A (cs) |
| AR (1) | AR009124A1 (cs) |
| AU (1) | AU735194C (cs) |
| BG (1) | BG64506B1 (cs) |
| BR (1) | BR9713278A (cs) |
| CA (1) | CA2267879C (cs) |
| CZ (1) | CZ132199A3 (cs) |
| EA (1) | EA003127B1 (cs) |
| EE (1) | EE9900171A (cs) |
| GE (1) | GEP20012578B (cs) |
| IL (1) | IL128914A (cs) |
| IS (1) | IS5000A (cs) |
| NO (1) | NO313281B1 (cs) |
| NZ (1) | NZ334886A (cs) |
| OA (1) | OA11035A (cs) |
| PL (1) | PL332947A1 (cs) |
| SK (1) | SK48499A3 (cs) |
| TR (2) | TR199900874T2 (cs) |
| WO (1) | WO1998017643A1 (cs) |
| YU (1) | YU20199A (cs) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6576664B1 (en) * | 1997-08-18 | 2003-06-10 | Bristol-Myers Squibb Pharma Company | Inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis |
| WO1999030709A1 (en) * | 1997-12-17 | 1999-06-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| AU745921B2 (en) * | 1998-02-13 | 2002-04-11 | British Biotech Pharmaceuticals Limited | Cytostatic agents |
| US6172064B1 (en) | 1998-08-26 | 2001-01-09 | Glaxo Wellcome Inc. | Formamides as therapeutic agents |
| US6329400B1 (en) | 1998-08-26 | 2001-12-11 | Glaxo Wellcome Inc. | Formamide compounds as therapeutic agents |
| GB9818605D0 (en) | 1998-08-26 | 1998-10-21 | Glaxo Group Ltd | Formamide compounds as therepeutic agents |
| US6934639B1 (en) * | 2000-02-25 | 2005-08-23 | Wyeth | Methods for designing agents that interact with MMP-13 |
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| PA8539301A1 (es) * | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Inhibidores de la metaloproteinasa de la matriz |
| DOP2002000333A (es) * | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Derivados de acido isoftalico como inhibidores de metaloproteinasas de la matriz |
| EP1368323B1 (en) * | 2001-02-14 | 2010-06-30 | Warner-Lambert Company LLC | Pyrimidine matrix metalloproteinase inhibitors |
| MXPA01013171A (es) | 2001-02-14 | 2004-05-21 | Warner Lambert Co | Inhibidores triciclicos de sulfonamida de metaloproteinasa de matriz. |
| PA8539401A1 (es) * | 2001-02-14 | 2002-10-28 | Warner Lambert Co | Quinazolinas como inhibidores de mmp-13 |
| MXPA01013172A (es) | 2001-02-14 | 2002-08-21 | Warner Lambert Co | Inhibidores sulfonamida de metaloproteinasa de matriz. |
| DOP2002000332A (es) | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Inhibidores de piridina de metaloproteinasas de la matriz |
| MXPA01013326A (es) | 2001-02-14 | 2002-08-26 | Warner Lambert Co | Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz. |
| US6924276B2 (en) * | 2001-09-10 | 2005-08-02 | Warner-Lambert Company | Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors |
| US6962922B2 (en) * | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| MXPA04002537A (es) | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| US6667330B2 (en) * | 2002-01-31 | 2003-12-23 | Galileo Pharmaceuticals, Inc. | Furanone derivatives |
| US6894057B2 (en) * | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US20040006077A1 (en) * | 2002-06-25 | 2004-01-08 | Bernard Gaudilliere | Thiazine and oxazine derivatives as MMP-13 inhibitors |
| CA2489722A1 (en) * | 2002-07-17 | 2004-01-22 | William Howard Roark | Combination of an allosteric alkyne inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib |
| AU2003281167A1 (en) * | 2002-07-17 | 2004-02-02 | Warner-Lambert Company Llc | Combination of an allosteric inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib |
| BR0312666A (pt) * | 2002-07-17 | 2005-05-10 | Warner Lambert Co | Combinação de um inibidor alcina alostérico de metaloproteinase-13 de matriz com um inibidor seletivo da cicloxigenase-2 à exceção de celecoxib e do valdecoxib |
| CA2492387A1 (en) * | 2002-07-17 | 2004-01-22 | Warner-Lambert Company Llc | Combination of an allosteric carboxylic of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib |
| PA8578101A1 (es) * | 2002-08-13 | 2004-05-07 | Warner Lambert Co | Derivados de heterobiarilo como inhibidores de metaloproteinasa de la matriz |
| BR0313459A (pt) * | 2002-08-13 | 2005-06-21 | Warner Lambert Co | Derivados monocìclicos como inibidores de metaloproteinases de matriz |
| AU2003250470A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidinone fused bicyclic metalloproteinase inhibitors |
| MXPA05001785A (es) * | 2002-08-13 | 2005-04-25 | Warner Lambert Co | Derivados de cromona como inhibidores de las metaloproteinasas de matriz. |
| AU2003249540A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused bicyclic metalloproteinase inhibitors |
| AU2003249539A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
| AU2003253186A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Fused tetrahydropyridine derivatives as matrix metalloproteinase inhibitors |
| WO2004014908A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Heterobicylcic metalloproteinase inhibitors |
| EP1539163A1 (en) * | 2002-08-13 | 2005-06-15 | Warner-Lambert Company LLC | 4-hydroxyquinoline derivatives as matrix metalloproteinase inhibitors |
| CA2497656A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Pyrimidine-2,4-dione derivatives as matrix metalloproteinase inhibitors |
| MXPA05001786A (es) * | 2002-08-13 | 2005-04-25 | Warner Lambert Co | Derivados de azaisoquinolina como inhibidores de la metaloproteinasa de matriz. |
| EP1394159A1 (fr) * | 2002-08-13 | 2004-03-03 | Warner-Lambert Company LLC | Nouveaux dérivés de thiophène, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent |
| WO2004014378A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | 3-isoquinolinone derivatives as matrix metalloproteinase inhiitors |
| US20040142950A1 (en) * | 2003-01-17 | 2004-07-22 | Bunker Amy Mae | Amide and ester matrix metalloproteinase inhibitors |
| WO2005016926A1 (en) * | 2003-08-19 | 2005-02-24 | Warner-Lambert Company Llc | Pyrido [3,4-d] pyrimidine derivatives as matrix metalloproteinase-13 inhibitors |
| US20060247231A1 (en) * | 2003-12-18 | 2006-11-02 | Warner-Lambert Company Llc | Amide and ester matrix metalloproteinase inhibitors |
| US7884079B2 (en) * | 2004-12-27 | 2011-02-08 | Miller Landon C G | 4-aminopyridine and a pharmaceutical composition for treatment of neuronal disorders |
| US8691835B2 (en) * | 2004-12-27 | 2014-04-08 | Landon C. G. Miller | 4 aminopyridine and a pharmaceutical composition for treatment of neuronal disorders |
| US20110009435A1 (en) * | 2007-06-05 | 2011-01-13 | Pfizer, Inc. | Hetero bicyclic carboxamide derivatives and their pharmaceutical use and compositions |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| US8604069B2 (en) * | 2011-04-28 | 2013-12-10 | Japan Tobacco Inc. | Amide compound and medicinal use thereof |
| WO2015107139A1 (en) | 2014-01-17 | 2015-07-23 | Proyecto De Biomedicina Cima, S.L. | Compounds for use as antifibrinolytic agents |
| CN104926707B (zh) * | 2015-05-12 | 2017-10-27 | 江苏福瑞生物医药有限公司 | 一种药物中间体的合成方法 |
| CN106749128A (zh) * | 2017-01-13 | 2017-05-31 | 滕州市悟通香料有限责任公司 | 一种制备2‑甲基‑3‑巯基呋喃的方法 |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4032639A (en) * | 1976-03-22 | 1977-06-28 | American Home Products Corporation | 2,3,4,4A-Tetrahydro-1H-pyrazino[1,2-a,]quinoxalin-5(6H)-ones and derivatives thereof for relieving hypertension |
| ZW23187A1 (en) * | 1986-12-15 | 1988-06-29 | Hoffmann La Roche | Phosphinic acid derivatives |
| GB9000846D0 (en) * | 1990-01-15 | 1990-03-14 | Beecham Group Plc | Novel compounds |
| GB9022117D0 (en) * | 1990-10-11 | 1990-11-21 | Beecham Group Plc | Novel compounds |
| US5189178A (en) * | 1990-11-21 | 1993-02-23 | Galardy Richard E | Matrix metalloprotease inhibitors |
| US5239078A (en) * | 1990-11-21 | 1993-08-24 | Glycomed Incorporated | Matrix metalloprotease inhibitors |
| US5183900A (en) * | 1990-11-21 | 1993-02-02 | Galardy Richard E | Matrix metalloprotease inhibitors |
| CA2073513A1 (en) * | 1990-12-03 | 1992-06-04 | John Robert Porter | Peptidyl derivatives |
| CA2102890A1 (en) * | 1991-05-28 | 1992-11-29 | Soumya P. Sahoo | Substituted n-carboxyalkylpeptidyl derivatives as antidegenerative active agents |
| US5256657A (en) * | 1991-08-19 | 1993-10-26 | Sterling Winthrop, Inc. | Succinamide derivative matrix-metalloprotease inhibitors |
| GB9211706D0 (en) * | 1992-06-03 | 1992-07-15 | Celltech Ltd | Peptidyl derivatives |
| GB9211707D0 (en) * | 1992-06-03 | 1992-07-15 | Celltech Ltd | Peptidyl derivatives |
| US5376664A (en) * | 1992-07-27 | 1994-12-27 | The Du Pont Merck Pharmaceutical Company | Unsymmetrical mono-3-nitro bis-naphthalimides as anticancer agents |
| JPH08503475A (ja) * | 1992-11-25 | 1996-04-16 | メルク エンド カンパニー インコーポレーテッド | 抗変性活性剤としてのカルボキシ−ペプチジル誘導体 |
| US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5506242A (en) * | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| US5552419A (en) * | 1993-01-06 | 1996-09-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| GB9307956D0 (en) * | 1993-04-17 | 1993-06-02 | Walls Alan J | Hydroxamic acid derivatives |
| AU6575394A (en) * | 1993-04-27 | 1994-11-21 | Celltech Therapeutics Limited | Peptidyl derivatives as metalloproteinase inhibitors |
| US6013792A (en) * | 1993-08-05 | 2000-01-11 | Syntex (U.S.A.), Inc. | Matrix metalloprotease inhibitors |
| BR9407217A (pt) * | 1993-08-05 | 1996-09-17 | Syntex Inc | Inibidores de metaloprotease de matriz |
| UA48121C2 (uk) * | 1993-11-04 | 2002-08-15 | Сінтекс (С.Ш.А.) Інк. | Інгібітори матричних металопротеаз і фармацетична композиція на їх основі |
| US6037472A (en) * | 1993-11-04 | 2000-03-14 | Syntex (U.S.A.) Inc. | Matrix metalloprotease inhibitors |
| KR970700652A (ko) * | 1994-01-22 | 1997-02-12 | 포올 리틀우드 | 금속단백질 분해효소 억제제 |
| US5514716A (en) * | 1994-02-25 | 1996-05-07 | Sterling Winthrop, Inc. | Hydroxamic acid and carboxylic acid derivatives, process for their preparation and use thereof |
| AU2572295A (en) * | 1994-05-28 | 1995-12-21 | British Biotech Pharmaceuticals Limited | Succinyl hydroxamic acid, n-formyl-n-hydroxy amino carboxylic acid and succinic acid amide derivatives as metalloprotease inhibitors |
| JPH10501806A (ja) * | 1994-06-22 | 1998-02-17 | ブリティッシュ バイオテック ファーマシューティカルズ リミテッド | 金属タンパク質分解酵素阻害剤 |
| GB9416897D0 (en) * | 1994-08-20 | 1994-10-12 | British Biotech Pharm | Metalloproteinase inhibitors |
| GB9423914D0 (en) * | 1994-11-26 | 1995-01-11 | British Biotech Pharm | Polyether derivatives as metalloproteinase inhibitors |
| US5863949A (en) * | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| JP3053222B2 (ja) * | 1995-04-20 | 2000-06-19 | ファイザー・インコーポレーテッド | Mmpおよびtnf抑制剤としてのアリールスルホニルヒドロキサム酸誘導体 |
| KR980009238A (ko) * | 1995-07-28 | 1998-04-30 | 우에노 도시오 | 설포닐아미노산 유도체 |
| ATE226936T1 (de) * | 1995-08-08 | 2002-11-15 | Ono Pharmaceutical Co | Hydroxamsäurederivate verwendbar zur hemmung von gelatinase |
| KR19990072009A (ko) * | 1995-08-12 | 1999-09-27 | 게리 이. 프리드만 | 메탈로프로티나제 방해제, 그를 포함하는 약제 조성물 및 약제로서의 용도, 그리고 그의 제조방법 및 제조에 유용한 중간체 |
| WO1997018194A1 (de) * | 1995-11-13 | 1997-05-22 | Hoechst Aktiengesellschaft | CYCLISCHE UND HETEROCYCLISCHE N-SUBSTITUIERTE α-IMINOHYDROXAM- UND CARBONSÄUREN |
| DE19542189A1 (de) * | 1995-11-13 | 1997-05-15 | Hoechst Ag | Cyclische N-substituierte alpha-Iminohydroxamsäuren |
| ATE225779T1 (de) * | 1995-11-17 | 2002-10-15 | Warner Lambert Co | Sulfonamidinhibitoren von matrix metalloproteinasen |
| TW453995B (en) * | 1995-12-15 | 2001-09-11 | Novartis Ag | Certain alpha-substituted arylsulfonamido acetohydroxamic acids |
| DK0876343T3 (da) * | 1995-12-22 | 2002-07-01 | Warner Lambert Co | Aromatiske ketosyrer og derivater deraf som inhibitorer af matrixmetalloproteinaser |
| US5837224A (en) * | 1996-01-19 | 1998-11-17 | The Regents Of The University Of Michigan | Method of inhibiting photoaging of skin |
| EP0950656B1 (en) * | 1996-01-23 | 2007-04-11 | Shionogi & Co., Ltd. | Sulfonated amino acid derivatives and metalloproteinase inhibitors containing the same |
| EA199900139A1 (ru) * | 1996-08-23 | 1999-08-26 | Пфайзер, Инк. | Производные арилсульфониламиногидроксамовой кислоты |
| KR100339296B1 (ko) * | 1996-08-28 | 2002-06-03 | 데이비드 엠 모이어 | 헤테로고리성 메탈로프로테아제 억제제 |
| CZ63199A3 (cs) * | 1996-08-28 | 1999-08-11 | The Procter & Gamble Company | Sloučeniny typu substituovaných cyklických aminů jako inhibitory metaloproteáz, způsob jejich přípravy a použití jako léčiv |
-
1997
- 1997-03-25 US US08/823,962 patent/US6008243A/en not_active Expired - Fee Related
- 1997-10-06 YU YU20199A patent/YU20199A/sh unknown
- 1997-10-06 AP APAP/P/1999/001536A patent/AP1360A/en active
- 1997-10-06 JP JP10519394A patent/JP2000511201A/ja not_active Ceased
- 1997-10-06 GE GEAP19974822A patent/GEP20012578B/en unknown
- 1997-10-06 AU AU48060/97A patent/AU735194C/en not_active Ceased
- 1997-10-06 TR TR1999/00874T patent/TR199900874T2/xx unknown
- 1997-10-06 BR BR9713278-0A patent/BR9713278A/pt not_active Application Discontinuation
- 1997-10-06 EA EA199900366A patent/EA003127B1/ru not_active IP Right Cessation
- 1997-10-06 KR KR1019990703591A patent/KR20000052779A/ko not_active Ceased
- 1997-10-06 PL PL97332947A patent/PL332947A1/xx unknown
- 1997-10-06 EE EEP199900171A patent/EE9900171A/xx unknown
- 1997-10-06 CZ CZ991321A patent/CZ132199A3/cs unknown
- 1997-10-06 CN CN97198705A patent/CN1233237A/zh active Pending
- 1997-10-06 CA CA002267879A patent/CA2267879C/en not_active Expired - Fee Related
- 1997-10-06 IL IL12891497A patent/IL128914A/xx not_active IP Right Cessation
- 1997-10-06 SK SK484-99A patent/SK48499A3/sk unknown
- 1997-10-06 TR TR2004/02157T patent/TR200402157T2/xx unknown
- 1997-10-06 EP EP97910770A patent/EP0937042A1/en not_active Withdrawn
- 1997-10-06 WO PCT/US1997/017809 patent/WO1998017643A1/en not_active Application Discontinuation
- 1997-10-06 NZ NZ334886A patent/NZ334886A/xx unknown
- 1997-10-23 AR ARP970104894A patent/AR009124A1/es unknown
-
1999
- 1999-03-12 IS IS5000A patent/IS5000A/is unknown
- 1999-04-16 OA OA9900084A patent/OA11035A/en unknown
- 1999-04-22 NO NO19991922A patent/NO313281B1/no not_active IP Right Cessation
- 1999-05-20 BG BG103415A patent/BG64506B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000052779A (ko) | 2000-08-25 |
| BR9713278A (pt) | 1999-11-03 |
| BG64506B1 (bg) | 2005-05-31 |
| EE9900171A (et) | 1999-12-15 |
| AP9901536A0 (en) | 1999-06-30 |
| BG103415A (en) | 2000-07-31 |
| YU20199A (sh) | 2001-09-28 |
| GEP20012578B (en) | 2001-11-26 |
| TR199900874T2 (xx) | 1999-07-21 |
| EA003127B1 (ru) | 2003-02-27 |
| US6008243A (en) | 1999-12-28 |
| CN1233237A (zh) | 1999-10-27 |
| AU4806097A (en) | 1998-05-15 |
| NZ334886A (en) | 2000-11-24 |
| IL128914A (en) | 2003-04-10 |
| CA2267879C (en) | 2006-03-14 |
| AR009124A1 (es) | 2000-03-08 |
| NO991922D0 (no) | 1999-04-22 |
| WO1998017643A1 (en) | 1998-04-30 |
| AP1360A (en) | 2005-01-05 |
| OA11035A (en) | 2002-03-06 |
| JP2000511201A (ja) | 2000-08-29 |
| IS5000A (is) | 1999-03-12 |
| AU735194B2 (en) | 2001-07-05 |
| AU735194C (en) | 2002-08-08 |
| EP0937042A1 (en) | 1999-08-25 |
| TR200402157T2 (tr) | 2005-02-21 |
| EA199900366A1 (ru) | 1999-10-28 |
| NO991922L (no) | 1999-04-22 |
| NO313281B1 (no) | 2002-09-09 |
| PL332947A1 (en) | 1999-10-25 |
| IL128914A0 (en) | 2000-02-17 |
| CA2267879A1 (en) | 1998-04-30 |
| CZ132199A3 (cs) | 1999-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK48499A3 (en) | Heteroaryl succinamides and their use as metalloproteinase inhibitors | |
| CZ296915B6 (cs) | Slouceniny inhibující proteázy retroviru | |
| KR20090033912A (ko) | 화학적 화합물 | |
| KR100403687B1 (ko) | 관절염질환및골다공증치료에유용한브릿지된인돌 | |
| KR20010020391A (ko) | 프로테아제 억제제 | |
| EP0769498A1 (en) | Sulfonamide derivatives with elastase inhibiting activity | |
| KR20100060012A (ko) | 옥시토신 길항제로서의 치환된 디케토피페라진 | |
| US5459131A (en) | Renin inhibitors | |
| US6306892B1 (en) | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use | |
| EP0964851A1 (en) | C-terminal ketone hydroxamic acid inhibitors of matrix metalloproteinases and tnfa secretion | |
| EP1283825B1 (en) | N-substituted peptidyl nitriles as cysteine cathepsin inhibitors | |
| NO832601L (no) | Fremgangsmaate for fremstilling av et amid-derivat | |
| JP3490441B2 (ja) | レニン阻害剤としてのn−(ヒドロキシエチル)ブタンジアミド誘導体 | |
| EP0975612A1 (en) | Protease inhibitors | |
| AU763835B2 (en) | Heteroaryl succinamides and their use as metalloproteinase inhibitors | |
| WO1996014296A1 (en) | Novel pyrrolinone-based compounds | |
| JP2881688B2 (ja) | スルホンアミド誘導体 | |
| AU2003216554A1 (en) | Peptide deformylase inhibitors | |
| JP2936324B2 (ja) | スルホンアミド誘導体 | |
| MXPA99003730A (en) | Heteroaryl succinamides and their use as metalloproteinase inhibitors |