CA2475069A1 - Derives amine utilises comme inhibiteurs de protease - Google Patents
Derives amine utilises comme inhibiteurs de protease Download PDFInfo
- Publication number
- CA2475069A1 CA2475069A1 CA002475069A CA2475069A CA2475069A1 CA 2475069 A1 CA2475069 A1 CA 2475069A1 CA 002475069 A CA002475069 A CA 002475069A CA 2475069 A CA2475069 A CA 2475069A CA 2475069 A1 CA2475069 A1 CA 2475069A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- halo
- substituted
- benzooxazol
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001412 amines Chemical class 0.000 title description 5
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 187
- 125000004429 atom Chemical group 0.000 claims abstract description 66
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 547
- 150000001875 compounds Chemical class 0.000 claims description 483
- -1 benzoxazol-2-yl Chemical group 0.000 claims description 400
- 229910052739 hydrogen Inorganic materials 0.000 claims description 209
- 239000001257 hydrogen Substances 0.000 claims description 208
- 125000003118 aryl group Chemical group 0.000 claims description 178
- 239000000203 mixture Substances 0.000 claims description 163
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 114
- 125000005843 halogen group Chemical group 0.000 claims description 106
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 103
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 80
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 71
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
- 201000010099 disease Diseases 0.000 claims description 37
- 125000001118 alkylidene group Chemical group 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
- ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 claims description 31
- 150000002431 hydrogen Chemical group 0.000 claims description 25
- 125000002723 alicyclic group Chemical group 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 208000006673 asthma Diseases 0.000 claims description 21
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 12
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 11
- 201000011152 Pemphigus Diseases 0.000 claims description 11
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 11
- 201000006417 multiple sclerosis Diseases 0.000 claims description 11
- 210000000056 organ Anatomy 0.000 claims description 11
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 11
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 10
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 206010006451 bronchitis Diseases 0.000 claims description 10
- 201000010251 cutis laxa Diseases 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229940080818 propionamide Drugs 0.000 claims description 10
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 9
- 206010052779 Transplant rejections Diseases 0.000 claims description 9
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 9
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 9
- 206010006448 Bronchiolitis Diseases 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 8
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 7
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 7
- 206010035664 Pneumonia Diseases 0.000 claims description 7
- 206010035742 Pneumonitis Diseases 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004976 cyclobutylene group Chemical group 0.000 claims description 6
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003431 oxalo group Chemical group 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000004979 cyclopentylene group Chemical group 0.000 claims description 4
- 229960003966 nicotinamide Drugs 0.000 claims description 4
- 239000011570 nicotinamide Substances 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 3
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 3
- WMUIZUWOEIQJEH-UHFFFAOYSA-N benzo[e][1,3]benzoxazole Chemical group C1=CC=C2C(N=CO3)=C3C=CC2=C1 WMUIZUWOEIQJEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000001721 carboxyacetyl group Chemical group 0.000 claims description 3
- 235000005152 nicotinamide Nutrition 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- DGOYLVBDCVINQZ-UHFFFAOYSA-N oxane-4-carboxamide Chemical compound NC(=O)C1CCOCC1 DGOYLVBDCVINQZ-UHFFFAOYSA-N 0.000 claims description 2
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 46
- 125000004178 (C1-C4) alkyl group Chemical class 0.000 claims 23
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical group C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 24
- 125000004122 cyclic group Chemical group 0.000 abstract description 8
- 239000002852 cysteine proteinase inhibitor Substances 0.000 abstract description 3
- 229940124597 therapeutic agent Drugs 0.000 abstract description 3
- 125000000623 heterocyclic group Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 134
- 239000000243 solution Substances 0.000 description 128
- 238000005481 NMR spectroscopy Methods 0.000 description 107
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 102
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 75
- 239000002253 acid Substances 0.000 description 73
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 59
- 101150041968 CDC13 gene Proteins 0.000 description 54
- 229940093499 ethyl acetate Drugs 0.000 description 53
- 235000019439 ethyl acetate Nutrition 0.000 description 53
- 150000003254 radicals Chemical class 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000007787 solid Substances 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 125000004043 oxo group Chemical group O=* 0.000 description 26
- 125000006239 protecting group Chemical group 0.000 description 26
- 150000001721 carbon Chemical group 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 21
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 239000000651 prodrug Substances 0.000 description 14
- 229940002612 prodrug Drugs 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000012131 assay buffer Substances 0.000 description 12
- 229960004132 diethyl ether Drugs 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 12
- 229960002572 phenprobamate Drugs 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000007170 pathology Effects 0.000 description 10
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 9
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108090000613 Cathepsin S Proteins 0.000 description 8
- 102000005927 Cysteine Proteases Human genes 0.000 description 8
- 108010005843 Cysteine Proteases Proteins 0.000 description 8
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 8
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 8
- 229940037201 oris Drugs 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
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- 102100035654 Cathepsin S Human genes 0.000 description 7
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
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- 210000004072 lung Anatomy 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical compound CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 6
- 230000001590 oxidative effect Effects 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 108090000712 Cathepsin B Proteins 0.000 description 5
- 102000004225 Cathepsin B Human genes 0.000 description 5
- 102000005600 Cathepsins Human genes 0.000 description 5
- 108010084457 Cathepsins Proteins 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000001624 naphthyl group Chemical group 0.000 description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 5
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 5
- 235000019345 sodium thiosulphate Nutrition 0.000 description 5
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- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12442199P | 1999-03-15 | 1999-03-15 | |
US60/124,421 | 1999-03-15 | ||
CA002367352A CA2367352A1 (fr) | 1999-03-15 | 2000-03-15 | Derives amine utilises comme inhibiteurs de protease |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002367352A Division CA2367352A1 (fr) | 1999-03-15 | 2000-03-15 | Derives amine utilises comme inhibiteurs de protease |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2475069A1 true CA2475069A1 (fr) | 2000-09-21 |
Family
ID=32991601
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002475069A Abandoned CA2475069A1 (fr) | 1999-03-15 | 2000-03-15 | Derives amine utilises comme inhibiteurs de protease |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2475069A1 (fr) |
-
2000
- 2000-03-15 CA CA002475069A patent/CA2475069A1/fr not_active Abandoned
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