NO318910B1 - Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat - Google Patents
Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat Download PDFInfo
- Publication number
- NO318910B1 NO318910B1 NO20013124A NO20013124A NO318910B1 NO 318910 B1 NO318910 B1 NO 318910B1 NO 20013124 A NO20013124 A NO 20013124A NO 20013124 A NO20013124 A NO 20013124A NO 318910 B1 NO318910 B1 NO 318910B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- carboxylic acid
- azepan
- amide
- butyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 400
- 230000015572 biosynthetic process Effects 0.000 title claims description 10
- 238000003786 synthesis reaction Methods 0.000 title claims description 10
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 8
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 819
- 201000010099 disease Diseases 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
- 108090000625 Cathepsin K Proteins 0.000 claims abstract description 24
- 239000004365 Protease Substances 0.000 claims abstract description 15
- 108091005804 Peptidases Proteins 0.000 claims abstract description 14
- 239000011159 matrix material Substances 0.000 claims abstract description 12
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 9
- 210000000845 cartilage Anatomy 0.000 claims abstract description 9
- 206010065687 Bone loss Diseases 0.000 claims abstract description 7
- 208000007565 gingivitis Diseases 0.000 claims abstract description 7
- 201000001245 periodontitis Diseases 0.000 claims abstract description 7
- 230000015556 catabolic process Effects 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 6
- 238000006731 degradation reaction Methods 0.000 claims abstract description 5
- 102000004171 Cathepsin K Human genes 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 283
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 199
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 181
- 239000000203 mixture Substances 0.000 claims description 99
- -1 N-methylindoyl Chemical group 0.000 claims description 75
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 65
- 102000005927 Cysteine Proteases Human genes 0.000 claims description 39
- 108010005843 Cysteine Proteases Proteins 0.000 claims description 39
- XZELWEMGWISCTP-UHFFFAOYSA-N 5-methoxy-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=C2OC(C(O)=O)=CC2=C1 XZELWEMGWISCTP-UHFFFAOYSA-N 0.000 claims description 37
- YMZTUCZCQMQFMK-UHFFFAOYSA-N 3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2C(C)=C(C(O)=O)OC2=C1 YMZTUCZCQMQFMK-UHFFFAOYSA-N 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 claims description 26
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000007800 oxidant agent Substances 0.000 claims description 13
- 230000001590 oxidative effect Effects 0.000 claims description 13
- GVZXSZWCZGKLRS-UHFFFAOYSA-N thieno[3,2-b]thiophene-5-carboxylic acid Chemical compound S1C=CC2=C1C=C(C(=O)O)S2 GVZXSZWCZGKLRS-UHFFFAOYSA-N 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 11
- 102000012479 Serine Proteases Human genes 0.000 claims description 10
- 108010022999 Serine Proteases Proteins 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical group [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 241000562429 Jamides Species 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000005425 toluyl group Chemical group 0.000 claims description 4
- FSWZCXHBMVKFCV-GTPINHCMSA-N (2s)-2-amino-n-(1-benzoyl-3-hydroxyazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)C1=CC=CC=C1 FSWZCXHBMVKFCV-GTPINHCMSA-N 0.000 claims description 3
- RIQUIYQTTZIVIZ-AOCRQIFASA-N (2s)-2-amino-n-(1-benzyl-3-hydroxyazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1CC1=CC=CC=C1 RIQUIYQTTZIVIZ-AOCRQIFASA-N 0.000 claims description 3
- QNQSYELXGHSKTE-GTPINHCMSA-N (2s)-2-amino-n-[1-(benzenesulfonyl)-3-hydroxyazepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1 QNQSYELXGHSKTE-GTPINHCMSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- PQSBQHKJPQBLRS-FHERZECASA-N (2s)-2-amino-n-[3-hydroxy-1-(4-methylpentanoyl)azepan-4-yl]-4-methylpentanamide Chemical compound CC(C)CCC(=O)N1CCCC(NC(=O)[C@@H](N)CC(C)C)C(O)C1 PQSBQHKJPQBLRS-FHERZECASA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- ZAIRIKJXUIZRPN-ADKAHSJRSA-N benzyl n-[(2s)-1-[(3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CNCCC1)O)C(=O)OCC1=CC=CC=C1 ZAIRIKJXUIZRPN-ADKAHSJRSA-N 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 14
- 102000035195 Peptidases Human genes 0.000 abstract description 12
- 150000003839 salts Chemical class 0.000 abstract description 6
- 208000024693 gingival disease Diseases 0.000 abstract description 5
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 abstract description 4
- 208000029725 Metabolic bone disease Diseases 0.000 abstract description 4
- 206010003246 arthritis Diseases 0.000 abstract description 4
- QTLLOLTVQMFWDZ-UHFFFAOYSA-N 4-aminoazepan-3-one Chemical compound NC1CCCNCC1=O QTLLOLTVQMFWDZ-UHFFFAOYSA-N 0.000 abstract description 3
- 208000010191 Osteitis Deformans Diseases 0.000 abstract description 2
- 208000027868 Paget disease Diseases 0.000 abstract description 2
- 208000027202 mammary Paget disease Diseases 0.000 abstract description 2
- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 abstract 1
- 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 396
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 313
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 261
- 238000006467 substitution reaction Methods 0.000 description 237
- 239000000243 solution Substances 0.000 description 209
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- 239000007787 solid Substances 0.000 description 162
- 238000005481 NMR spectroscopy Methods 0.000 description 131
- 239000011541 reaction mixture Substances 0.000 description 101
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 85
- 150000001408 amides Chemical class 0.000 description 85
- 238000004440 column chromatography Methods 0.000 description 74
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- 238000005160 1H NMR spectroscopy Methods 0.000 description 59
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 239000000460 chlorine Substances 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 238000010626 work up procedure Methods 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- 238000006243 chemical reaction Methods 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical class C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 description 32
- 239000012044 organic layer Substances 0.000 description 31
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 29
- 238000004458 analytical method Methods 0.000 description 28
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 28
- 239000011734 sodium Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- HYJQWMUBCRPGDS-UHFFFAOYSA-N 1,3-thiazole-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=NC=CS1 HYJQWMUBCRPGDS-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 238000004809 thin layer chromatography Methods 0.000 description 26
- 102100024940 Cathepsin K Human genes 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 23
- 239000003112 inhibitor Substances 0.000 description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- JQJOGAGLBDBMLU-UHFFFAOYSA-N pyridine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=N1 JQJOGAGLBDBMLU-UHFFFAOYSA-N 0.000 description 22
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 229920006395 saturated elastomer Polymers 0.000 description 19
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 18
- QISAUDWTBBNJIR-UHFFFAOYSA-N 2-phenylmethoxyacetyl chloride Chemical compound ClC(=O)COCC1=CC=CC=C1 QISAUDWTBBNJIR-UHFFFAOYSA-N 0.000 description 18
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 18
- MAHAMBLNIDMREX-UHFFFAOYSA-N 1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1 MAHAMBLNIDMREX-UHFFFAOYSA-N 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 16
- 210000000988 bone and bone Anatomy 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- AWGCBUDAZSSMQT-UHFFFAOYSA-N 5,6-dimethoxy-1-benzofuran-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC2=C1OC(C(O)=O)=C2 AWGCBUDAZSSMQT-UHFFFAOYSA-N 0.000 description 15
- UOCNTRAAJNWDND-UHFFFAOYSA-N 7-methoxy-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=CC2=C1OC(C(O)=O)=C2 UOCNTRAAJNWDND-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 235000002639 sodium chloride Nutrition 0.000 description 14
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 13
- BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical class FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 13
- 208000006386 Bone Resorption Diseases 0.000 description 12
- 102000005600 Cathepsins Human genes 0.000 description 12
- 108010084457 Cathepsins Proteins 0.000 description 12
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- 230000024279 bone resorption Effects 0.000 description 12
- FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical class CC(C)CCC(O)=O FGKJLKRYENPLQH-UHFFFAOYSA-N 0.000 description 12
- 210000002997 osteoclast Anatomy 0.000 description 12
- CNMOQCSVUDRKJN-NFOMZHRRSA-N (2s)-2-amino-n-(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 CNMOQCSVUDRKJN-NFOMZHRRSA-N 0.000 description 11
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 11
- NQAYCMBZPAARNO-UHFFFAOYSA-N 2-cyanobenzenesulfonyl chloride Chemical group ClS(=O)(=O)C1=CC=CC=C1C#N NQAYCMBZPAARNO-UHFFFAOYSA-N 0.000 description 11
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- VDVJGIYXDVPQLP-UHFFFAOYSA-N piperonylic acid Chemical class OC(=O)C1=CC=C2OCOC2=C1 VDVJGIYXDVPQLP-UHFFFAOYSA-N 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- JJWBLYNHZXZGIQ-UHFFFAOYSA-N 5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1OCCN1CCOCC1 JJWBLYNHZXZGIQ-UHFFFAOYSA-N 0.000 description 10
- 239000007822 coupling agent Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- QARBMVPHQWIHKH-KHWXYDKHSA-N methanesulfonyl chloride Chemical class C[35S](Cl)(=O)=O QARBMVPHQWIHKH-KHWXYDKHSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 150000002924 oxiranes Chemical class 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 238000000825 ultraviolet detection Methods 0.000 description 10
- FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 description 9
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 9
- ADRFTNFHVKVATK-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C1=CC=CC(C(F)(F)F)=C1 ADRFTNFHVKVATK-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 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 9
- 239000003480 eluent Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000004108 freeze drying Methods 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 9
- 238000000926 separation method Methods 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 8
- YVTQHZDUDUCGRD-UHFFFAOYSA-N 5-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)O1 YVTQHZDUDUCGRD-UHFFFAOYSA-N 0.000 description 8
- YABCPNYCFFUVNM-UHFFFAOYSA-N 5-methyl-2-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)OC(C=2C=CC=CC=2)=N1 YABCPNYCFFUVNM-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- LPNANKDXVBMDKE-UHFFFAOYSA-N 5-bromopent-1-ene Chemical compound BrCCCC=C LPNANKDXVBMDKE-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- USPFMEKVPDBMCG-LBPRGKRZSA-N N-benzyloxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 USPFMEKVPDBMCG-LBPRGKRZSA-N 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 239000011324 bead Substances 0.000 description 7
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 7
- 125000005605 benzo group Chemical group 0.000 description 7
- 230000008878 coupling Effects 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- PRFCZPKFHQCIQA-UHFFFAOYSA-N 4-amino-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(O)C(N)CCCN1S(=O)(=O)C1=CC=CC=N1 PRFCZPKFHQCIQA-UHFFFAOYSA-N 0.000 description 6
- OWFRWTPPOZSWLL-UHFFFAOYSA-N 5,6-difluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=C(F)C=C2OC(C(=O)O)=CC2=C1 OWFRWTPPOZSWLL-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 230000010933 acylation Effects 0.000 description 6
- 238000005917 acylation reaction Methods 0.000 description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
- 229960002433 cysteine Drugs 0.000 description 6
- 235000018417 cysteine Nutrition 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 6
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
- 235000019345 sodium thiosulphate Nutrition 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 5
- XNCYUACPDCATQA-UHFFFAOYSA-N 2-(3-pyridin-2-ylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(C=2N=CC=CC=2)=C1 XNCYUACPDCATQA-UHFFFAOYSA-N 0.000 description 5
- USFXRYVNRUMABJ-UHFFFAOYSA-N 4,5-dibromothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=C(Br)S1 USFXRYVNRUMABJ-UHFFFAOYSA-N 0.000 description 5
- VCNGNQLPFHVODE-UHFFFAOYSA-N 5-methylthiophene-2-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)S1 VCNGNQLPFHVODE-UHFFFAOYSA-N 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 108090000526 Papain Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000001414 amino alcohols Chemical class 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 229940055729 papain Drugs 0.000 description 5
- 235000019834 papain Nutrition 0.000 description 5
- QEKVQYCTJHJBOF-UHFFFAOYSA-L ruthenium(2+);styrene;triphenylphosphane;dichloride Chemical compound Cl[Ru]Cl.C=CC1=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 QEKVQYCTJHJBOF-UHFFFAOYSA-L 0.000 description 5
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 5
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 4
- RSJSYCZYQNJQPY-UHFFFAOYSA-N 3,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OC RSJSYCZYQNJQPY-UHFFFAOYSA-N 0.000 description 4
- IJEUISLJVBUNRE-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C)=C1C(O)=O IJEUISLJVBUNRE-UHFFFAOYSA-N 0.000 description 4
- VZJHGNQXEKXZIF-UHFFFAOYSA-N 5-(2-cyclohexylethoxy)-1-benzofuran-2-carboxylic acid Chemical compound C=1C=C2OC(C(=O)O)=CC2=CC=1OCCC1CCCCC1 VZJHGNQXEKXZIF-UHFFFAOYSA-N 0.000 description 4
- XIPQHWUSDHTXOO-UHFFFAOYSA-N 5-(4-chlorophenyl)furan-2-carboxylic acid Chemical group O1C(C(=O)O)=CC=C1C1=CC=C(Cl)C=C1 XIPQHWUSDHTXOO-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KSPQDMRTZZYQLM-UHFFFAOYSA-N N-(2-furoyl)glycine Chemical compound OC(=O)CNC(=O)C1=CC=CO1 KSPQDMRTZZYQLM-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- HJZLEGIHUQOJBA-UHFFFAOYSA-N cyclohexane propionic acid Chemical compound OC(=O)CCC1CCCCC1 HJZLEGIHUQOJBA-UHFFFAOYSA-N 0.000 description 4
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- BBEWNCUHEJGRNJ-CGZBRXJRSA-N n-[(2s)-1-[(3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC1CCCNCC1O BBEWNCUHEJGRNJ-CGZBRXJRSA-N 0.000 description 4
- 229960003966 nicotinamide Drugs 0.000 description 4
- 239000011570 nicotinamide Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical class O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 4
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 4
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 4
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 4
- RGFSPOGBCIZTRC-MOKVOYLWSA-N tert-butyl n-[(2s)-1-[(3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC(C)C)C(=O)NC1CCCNCC1O RGFSPOGBCIZTRC-MOKVOYLWSA-N 0.000 description 4
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical class CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 3
- ZIOCIQJXEKFHJO-QMMMGPOBSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical class CCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C ZIOCIQJXEKFHJO-QMMMGPOBSA-N 0.000 description 3
- TYMUCBKTMCCTIC-JTQLQIEISA-N (2s)-2-[cyclohexyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid Chemical compound CC(C)(C)OC(=O)N([C@@H](C)C(O)=O)C1CCCCC1 TYMUCBKTMCCTIC-JTQLQIEISA-N 0.000 description 3
- JBVXXGSEMNXAMH-LSLKUGRBSA-N (2s)-2-amino-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound C1C(=O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 JBVXXGSEMNXAMH-LSLKUGRBSA-N 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- QCBZCEKWIGTIMT-UHFFFAOYSA-N 1,3-bis(sulfanyl)propan-2-one Chemical class SCC(=O)CS QCBZCEKWIGTIMT-UHFFFAOYSA-N 0.000 description 3
- DNGLRCHMGDDHNC-UHFFFAOYSA-N 1-benzothiophene-2-carbonyl chloride Chemical compound C1=CC=C2SC(C(=O)Cl)=CC2=C1 DNGLRCHMGDDHNC-UHFFFAOYSA-N 0.000 description 3
- PYCFLCQAJFEELT-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C(F)(F)F)=C(C(=O)O)N=C1C1=CC=CC=C1 PYCFLCQAJFEELT-UHFFFAOYSA-N 0.000 description 3
- VIOBGCWEHLRBEP-UHFFFAOYSA-N 3,4-dimethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1OC VIOBGCWEHLRBEP-UHFFFAOYSA-N 0.000 description 3
- RUWIHZCDWVFWHF-UHFFFAOYSA-N 4-azido-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(C)(C)CC(N=[N+]=[N-])C(O)CN1S(=O)(=O)C1=CC=CC=N1 RUWIHZCDWVFWHF-UHFFFAOYSA-N 0.000 description 3
- IPEIDGXNXFPGBG-UHFFFAOYSA-N 4-methylsulfonylbenzoyl chloride Chemical compound CS(=O)(=O)C1=CC=C(C(Cl)=O)C=C1 IPEIDGXNXFPGBG-UHFFFAOYSA-N 0.000 description 3
- OVKPUHAFRRGFLR-UHFFFAOYSA-N 5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carbaldehyde Chemical compound C=1C=C2OC(C=O)=CC2=CC=1OCCN1CCOCC1 OVKPUHAFRRGFLR-UHFFFAOYSA-N 0.000 description 3
- HITUZQPFDWNUHA-UHFFFAOYSA-N 5-fluoro-1-benzofuran-2-carboxylic acid Chemical compound FC1=CC=C2OC(C(=O)O)=CC2=C1 HITUZQPFDWNUHA-UHFFFAOYSA-N 0.000 description 3
- IODMEDPPCXSFLD-UHFFFAOYSA-N 5-nitrofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)O1 IODMEDPPCXSFLD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 241000222716 Crithidia Species 0.000 description 3
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000037147 Hypercalcaemia Diseases 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical class CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- FHYMLBVGNFVFBT-UHFFFAOYSA-N Picolinic acid N-oxide Chemical group OC(=O)C1=CC=CC=[N+]1[O-] FHYMLBVGNFVFBT-UHFFFAOYSA-N 0.000 description 3
- 241000233872 Pneumocystis carinii Species 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- NPWCONRRHPNUSQ-UHFFFAOYSA-N acetyl acetate;methane Chemical compound C.CC(=O)OC(C)=O NPWCONRRHPNUSQ-UHFFFAOYSA-N 0.000 description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 3
- DWXNKZJQENJPAN-WLXPTCNVSA-N benzyl 4-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-3-hydroxyazepane-1-carboxylate Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1C(=O)OCC1=CC=CC=C1 DWXNKZJQENJPAN-WLXPTCNVSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 3
- 239000002852 cysteine proteinase inhibitor Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- YVHPHQBRUPLYOS-UHFFFAOYSA-N dichloromethane;methane Chemical compound C.ClCCl YVHPHQBRUPLYOS-UHFFFAOYSA-N 0.000 description 3
- 150000001993 dienes Chemical class 0.000 description 3
- 238000006735 epoxidation reaction Methods 0.000 description 3
- 238000003810 ethyl acetate extraction Methods 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000000148 hypercalcaemia Effects 0.000 description 3
- 208000030915 hypercalcemia disease Diseases 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
- 108010052968 leupeptin Proteins 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 201000006938 muscular dystrophy Diseases 0.000 description 3
- QGXDSBYNGPVUNT-ZVAWYAOSSA-N n-[(2s)-1-[[1-(1h-imidazol-2-ylsulfonyl)-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=NC=CN1 QGXDSBYNGPVUNT-ZVAWYAOSSA-N 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 229920005990 polystyrene resin Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- VQMSRUREDGBWKT-UHFFFAOYSA-N quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=NC2=C1 VQMSRUREDGBWKT-UHFFFAOYSA-N 0.000 description 3
- 239000012508 resin bead Substances 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- 201000004409 schistosomiasis Diseases 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- AWARHXCROCWEAK-UHFFFAOYSA-N tert-butyl n-prop-2-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCC=C AWARHXCROCWEAK-UHFFFAOYSA-N 0.000 description 3
- WORJEOGGNQDSOE-ASTXPPQBSA-N trichloro(deuterio)methane;trideuterio(deuteriooxy)methane Chemical compound [2H]C(Cl)(Cl)Cl.[2H]OC([2H])([2H])[2H] WORJEOGGNQDSOE-ASTXPPQBSA-N 0.000 description 3
- 229960000281 trometamol Drugs 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- RKDVHKSQNHKIAB-GTPINHCMSA-N (2S)-2-amino-N-[1-(3-chlorophenyl)sulfonyl-3-hydroxyazepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC(Cl)=C1 RKDVHKSQNHKIAB-GTPINHCMSA-N 0.000 description 2
- IMUSLIHRIYOHEV-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoic acid Chemical class CSCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C IMUSLIHRIYOHEV-ZETCQYMHSA-N 0.000 description 2
- JKJMZAPDLDRHPM-FHERZECASA-N (2s)-2-amino-n-[3-hydroxy-1-(3-methylpyridin-2-yl)sulfonylazepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=NC=CC=C1C JKJMZAPDLDRHPM-FHERZECASA-N 0.000 description 2
- AZVRTPCWBZAVPJ-LQLXLQOXSA-N (2s)-2-amino-n-[3-hydroxy-1-(4-methoxyphenyl)sulfonylazepan-4-yl]-4-methylpentanamide;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1S(=O)(=O)N1CC(O)C(NC(=O)[C@@H](N)CC(C)C)CCC1 AZVRTPCWBZAVPJ-LQLXLQOXSA-N 0.000 description 2
- URRSNGWVZYRZFA-FHERZECASA-N (2s)-2-amino-n-[3-hydroxy-1-(6-methylpyridin-2-yl)sulfonylazepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 URRSNGWVZYRZFA-FHERZECASA-N 0.000 description 2
- XMPFFIJJWCTMLK-JTQLQIEISA-N (2s)-4-methyl-2-[(2-thiophen-2-ylacetyl)amino]pentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CC1=CC=CS1 XMPFFIJJWCTMLK-JTQLQIEISA-N 0.000 description 2
- TVIGDYUWCBMTOI-XBMUEBEBSA-N (2s)-n-(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)-4-methyl-2-(pyridin-2-ylsulfonylamino)pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)S(=O)(=O)C1=CC=CC=N1 TVIGDYUWCBMTOI-XBMUEBEBSA-N 0.000 description 2
- FSLJYEBPHHVWOV-JNLGVIEDSA-N (2s)-n-[3-hydroxy-1-(4-methoxyphenyl)sulfonylazepan-4-yl]-4-methyl-2-[(2-phenylmethoxyacetyl)amino]pentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)COCC=2C=CC=CC=2)CCC1 FSLJYEBPHHVWOV-JNLGVIEDSA-N 0.000 description 2
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 2
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 2
- SNLMOXFUCILIPL-UHFFFAOYSA-N 1,8-naphthyridine-2-carboxylic acid Chemical compound C1=CC=NC2=NC(C(=O)O)=CC=C21 SNLMOXFUCILIPL-UHFFFAOYSA-N 0.000 description 2
- NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 description 2
- ZJDRDTZQVOCKPI-UHFFFAOYSA-N 1-benzofuran-2-carbonyl chloride Chemical compound C1=CC=C2OC(C(=O)Cl)=CC2=C1 ZJDRDTZQVOCKPI-UHFFFAOYSA-N 0.000 description 2
- KXUGUWTUFUWYRS-UHFFFAOYSA-N 1-methylimidazole-4-sulfonyl chloride Chemical compound CN1C=NC(S(Cl)(=O)=O)=C1 KXUGUWTUFUWYRS-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
- DXSDIWHOOOBQTJ-UHFFFAOYSA-N 2,2-dimethylpent-4-enal Chemical compound O=CC(C)(C)CC=C DXSDIWHOOOBQTJ-UHFFFAOYSA-N 0.000 description 2
- AFHHWATXYNBLAV-ORFBVSJDSA-N 2-[4-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-3-hydroxyazepan-1-yl]sulfonylbenzoic acid Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=C1C(O)=O AFHHWATXYNBLAV-ORFBVSJDSA-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
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 2
- PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 2
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical group OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 2
- BJVDOAAKGRNIJF-UHFFFAOYSA-N 3,3-dimethyl-5-pyridin-2-ylsulfonyl-8-oxa-5-azabicyclo[5.1.0]octane Chemical compound C1C(C)(C)CC2OC2CN1S(=O)(=O)C1=CC=CC=N1 BJVDOAAKGRNIJF-UHFFFAOYSA-N 0.000 description 2
- ZKHLBCVFVQJMBT-UHFFFAOYSA-N 3-benzoylthiophene-2-carboxylic acid Chemical compound S1C=CC(C(=O)C=2C=CC=CC=2)=C1C(=O)O ZKHLBCVFVQJMBT-UHFFFAOYSA-N 0.000 description 2
- XIZXADDGOCJZAL-UHFFFAOYSA-N 3h-dioxole-5-carboxylic acid Chemical compound OC(=O)C1=CCOO1 XIZXADDGOCJZAL-UHFFFAOYSA-N 0.000 description 2
- ZMAILSBNDKAJFT-UHFFFAOYSA-N 4-amino-1-pyridin-2-ylsulfonylazepan-3-one Chemical compound C1C(=O)C(N)CCCN1S(=O)(=O)C1=CC=CC=N1 ZMAILSBNDKAJFT-UHFFFAOYSA-N 0.000 description 2
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical class OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 2
- LIZUZUKHOVUSNS-UHFFFAOYSA-N 5,6-dimethoxy-1-benzothiophene-2-carboxylic acid Chemical group C1=C(OC)C(OC)=CC2=C1SC(C(O)=O)=C2 LIZUZUKHOVUSNS-UHFFFAOYSA-N 0.000 description 2
- VDHPTEJDGMUZKS-UHFFFAOYSA-N 5-[2-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]ethoxy]-1-benzofuran-2-carboxylic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CCOC1=CC=C(OC(=C2)C(O)=O)C2=C1 VDHPTEJDGMUZKS-UHFFFAOYSA-N 0.000 description 2
- SDFAGAYNULBGAX-UHFFFAOYSA-N 5-hydroxy-1-benzofuran-2-carboxylic acid Chemical compound OC1=CC=C2OC(C(=O)O)=CC2=C1 SDFAGAYNULBGAX-UHFFFAOYSA-N 0.000 description 2
- YUWSYDYNEKIQLL-UHFFFAOYSA-N 6-methylpyridine-2-sulfonyl chloride Chemical compound CC1=CC=CC(S(Cl)(=O)=O)=N1 YUWSYDYNEKIQLL-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- APLVMBDQRQBPEF-HSBZDZAISA-N C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=NC=CN1C Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=NC=CN1C APLVMBDQRQBPEF-HSBZDZAISA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 101710177066 Cathepsin O Proteins 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- IDCFCBGBKVDPND-KBWCOIMZSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)NC1=CC=CC=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)NC1=CC=CC=C1 IDCFCBGBKVDPND-KBWCOIMZSA-N 0.000 description 2
- LVZALEJDERSXNN-ORFBVSJDSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)NCC1=CC=CC=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)NCC1=CC=CC=C1 LVZALEJDERSXNN-ORFBVSJDSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- DLIDRYZFMDEANT-KBWCOIMZSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=C(C)OCN1C Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=C(C)OCN1C DLIDRYZFMDEANT-KBWCOIMZSA-N 0.000 description 2
- BWZXLTPVCSVTKU-ORFBVSJDSA-N O=C([C@@H](NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 BWZXLTPVCSVTKU-ORFBVSJDSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 238000005865 alkene metathesis reaction Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
- KOMDBNXFZQHCIS-UHFFFAOYSA-N benzyl 2,3,4,7-tetrahydroazepine-1-carboxylate Chemical compound C1CCC=CCN1C(=O)OCC1=CC=CC=C1 KOMDBNXFZQHCIS-UHFFFAOYSA-N 0.000 description 2
- IQKOEHQRVYPYOH-AOCRQIFASA-N benzyl 4-[[(2s)-2-amino-4-methylpentanoyl]amino]-3-hydroxyazepane-1-carboxylate Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)OCC1=CC=CC=C1 IQKOEHQRVYPYOH-AOCRQIFASA-N 0.000 description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 210000004268 dentin Anatomy 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 2
- XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910003002 lithium salt 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- JQRWCHTUYWKENU-KOENEWCDSA-N methyl 2-[4-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-3-hydroxyazepan-1-yl]sulfonylbenzoate Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)N1CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)C=2OC3=CC=CC=C3C=2)CCC1 JQRWCHTUYWKENU-KOENEWCDSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- FHSKNAZSUUYRPI-UHFFFAOYSA-N n-(methoxymethyl)-5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carboxamide Chemical compound C=1C=C2OC(C(=O)NCOC)=CC2=CC=1OCCN1CCOCC1 FHSKNAZSUUYRPI-UHFFFAOYSA-N 0.000 description 2
- LCFKMNGRVWNQMC-ADKAHSJRSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]thieno[3,2-b]thiophene-5-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 LCFKMNGRVWNQMC-ADKAHSJRSA-N 0.000 description 2
- OLZAWFZNUMNREC-HWELCPFYSA-N n-[(2s)-1-[(3-hydroxy-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CC(C)(C)CN1S(=O)(=O)C1=CC=CC=N1 OLZAWFZNUMNREC-HWELCPFYSA-N 0.000 description 2
- ASWYDHRNGJTCLS-LBAQZLPGSA-N n-[(2s)-1-[[1-(3,4-dimethoxyphenyl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CCC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=C(OC)C(OC)=C1 ASWYDHRNGJTCLS-LBAQZLPGSA-N 0.000 description 2
- VBPPNJCVXGAZDD-ANYOKISRSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 VBPPNJCVXGAZDD-ANYOKISRSA-N 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical group OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- 229940100595 phenylacetaldehyde Drugs 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229940081066 picolinic acid Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- NCNISYUOWMIOPI-UHFFFAOYSA-N propane-1,1-dithiol Chemical compound CCC(S)S NCNISYUOWMIOPI-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- KZVLNAGYSAKYMG-UHFFFAOYSA-N pyridine-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=N1 KZVLNAGYSAKYMG-UHFFFAOYSA-N 0.000 description 2
- VXGYRCVTBHVXMZ-UHFFFAOYSA-N quinoline-6-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CC=C21 VXGYRCVTBHVXMZ-UHFFFAOYSA-N 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VJYJJHQEVLEOFL-UHFFFAOYSA-N thieno[3,2-b]thiophene Chemical compound S1C=CC2=C1C=CS2 VJYJJHQEVLEOFL-UHFFFAOYSA-N 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical class OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- AEZJMSICFGBQJC-BHWOMJMDSA-N (2S)-2-amino-N-(1-benzyl-3-oxoazepan-4-yl)-4-methylpentanamide Chemical compound C1C(=O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1CC1=CC=CC=C1 AEZJMSICFGBQJC-BHWOMJMDSA-N 0.000 description 1
- VCHMKTQVOJUNCV-OXCCAUKLSA-N (2S)-2-amino-N-(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)-3-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)C(C)CC)CCCN1S(=O)(=O)C1=CC=CC=N1 VCHMKTQVOJUNCV-OXCCAUKLSA-N 0.000 description 1
- BJEXMZURBRNDSR-GTPINHCMSA-N (2S)-2-amino-N-[1-(benzenesulfonyl)-3-hydroxyazepan-4-yl]-N-methylpentanamide Chemical compound C1C(O)C(N(C)C(=O)[C@@H](N)CCC)CCCN1S(=O)(=O)C1=CC=CC=C1 BJEXMZURBRNDSR-GTPINHCMSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- MOHLVDJRXGVGOM-SNVBAGLBSA-N (2r)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCC(=O)N1CC1=CC=CC=C1 MOHLVDJRXGVGOM-SNVBAGLBSA-N 0.000 description 1
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical class CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
- MOHLVDJRXGVGOM-JTQLQIEISA-N (2s)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1CC1=CC=CC=C1 MOHLVDJRXGVGOM-JTQLQIEISA-N 0.000 description 1
- QPENHNFPZYEKPX-LBAQZLPGSA-N (2s)-2-(benzylcarbamoylamino)-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)NCC1=CC=CC=C1 QPENHNFPZYEKPX-LBAQZLPGSA-N 0.000 description 1
- INWOAUUPYIXDHN-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical class CCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C INWOAUUPYIXDHN-ZETCQYMHSA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical class OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- DJORAVRVYPXZCE-LBAQZLPGSA-N (2s)-2-[[2-(4-fluorophenoxy)acetyl]amino]-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)COC1=CC=C(F)C=C1 DJORAVRVYPXZCE-LBAQZLPGSA-N 0.000 description 1
- SRCPHYIXPIQMTN-LBPRGKRZSA-N (2s)-2-[[2-(4-fluorophenoxy)acetyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)COC1=CC=C(F)C=C1 SRCPHYIXPIQMTN-LBPRGKRZSA-N 0.000 description 1
- UGIZNFBYGSACQK-RBKXMNCYSA-N (2s)-2-amino-n-[3-hydroxy-1-[2-(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)CC1=CC=CC(C=2N=CC=CC=2)=C1 UGIZNFBYGSACQK-RBKXMNCYSA-N 0.000 description 1
- FRVVRWKZCQMXOM-KHRZNOOSSA-N (2s)-2-amino-n-[3-hydroxy-1-[2-(3-pyridin-2-ylphenyl)ethyl]azepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1CCC1=CC=CC(C=2N=CC=CC=2)=C1 FRVVRWKZCQMXOM-KHRZNOOSSA-N 0.000 description 1
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical class CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 1
- XJODGRWDFZVTKW-LURJTMIESA-N (2s)-4-methyl-2-(methylamino)pentanoic acid Chemical compound CN[C@H](C(O)=O)CC(C)C XJODGRWDFZVTKW-LURJTMIESA-N 0.000 description 1
- HCCYLKNNKOGEKR-AMVUTOCUSA-N (2s)-4-methyl-2-[methyl(naphthalen-2-ylmethyl)amino]-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)pentanamide Chemical compound O=C([C@@H](N(C)CC=1C=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 HCCYLKNNKOGEKR-AMVUTOCUSA-N 0.000 description 1
- RZCNQVJZHKHAJR-ANYOKISRSA-N (2s)-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)-2-(phenylcarbamoylamino)pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)NC1=CC=CC=C1 RZCNQVJZHKHAJR-ANYOKISRSA-N 0.000 description 1
- WPLYAJIBNJKWAC-LBAQZLPGSA-N (2s)-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)-2-(quinolin-8-ylsulfonylamino)pentanamide Chemical compound O=C([C@@H](NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 WPLYAJIBNJKWAC-LBAQZLPGSA-N 0.000 description 1
- BULIPGOJFLOUBF-LBAQZLPGSA-N (2s)-4-methyl-n-(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)-2-[(2-phenoxyacetyl)amino]pentanamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)COC1=CC=CC=C1 BULIPGOJFLOUBF-LBAQZLPGSA-N 0.000 description 1
- WHLFDVKBOIGELH-BBMPLOMVSA-N (2s)-n-[1-(4-methoxyphenyl)sulfonyl-3-oxoazepan-4-yl]-4-methyl-2-[(2-phenylmethoxyacetyl)amino]pentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1CC(=O)C(NC(=O)[C@H](CC(C)C)NC(=O)COCC=2C=CC=CC=2)CCC1 WHLFDVKBOIGELH-BBMPLOMVSA-N 0.000 description 1
- CMRZBTXIKVDZLB-BOMBAVFCSA-N (2s)-n-butyl-n-(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)-4-methyl-2-[(2-thiophen-2-ylacetyl)amino]pentanamide Chemical class O=C([C@H](CC(C)C)NC(=O)CC=1SC=CC=1)N(CCCC)C(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 CMRZBTXIKVDZLB-BOMBAVFCSA-N 0.000 description 1
- LLHOYOCAAURYRL-RITPCOANSA-N (2s,3r)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical class C[C@@H](O)[C@@H](C(O)=O)NC(=O)OC(C)(C)C LLHOYOCAAURYRL-RITPCOANSA-N 0.000 description 1
- QJCNLJWUIOIMMF-YUMQZZPRSA-N (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C QJCNLJWUIOIMMF-YUMQZZPRSA-N 0.000 description 1
- OLBGTCWFHHTDSS-UHFFFAOYSA-N (3-hydroxyazepan-4-yl)carbamic acid Chemical compound OC1CNCCCC1NC(O)=O OLBGTCWFHHTDSS-UHFFFAOYSA-N 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- OVBFMEVBMNZIBR-UHFFFAOYSA-N -2-Methylpentanoic acid Natural products CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 description 1
- ZRSGZIMDIHBXIN-UHFFFAOYSA-N 1,3-benzodioxole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2OCOC2=C1 ZRSGZIMDIHBXIN-UHFFFAOYSA-N 0.000 description 1
- OZZMWXQJCJUCEJ-UHFFFAOYSA-N 1,6-naphthyridine-2-carboxylic acid Chemical group C1=NC=CC2=NC(C(=O)O)=CC=C21 OZZMWXQJCJUCEJ-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- 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 1
- XWHOMDUCBPDNMI-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid;5-methoxy-1-benzofuran-2-carboxylic acid Chemical class C1=CC=C2SC(C(=O)O)=CC2=C1.COC1=CC=C2OC(C(O)=O)=CC2=C1 XWHOMDUCBPDNMI-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- RWHIKEMYOLGZOC-UHFFFAOYSA-N 1h-imidazole-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=NC=CN1 RWHIKEMYOLGZOC-UHFFFAOYSA-N 0.000 description 1
- SIYWVPMYOGMRDW-UHFFFAOYSA-N 2,1,3-benzoxadiazole-4-sulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=CC2=NON=C12 SIYWVPMYOGMRDW-UHFFFAOYSA-N 0.000 description 1
- YSLXJUQVRQDRFJ-UHFFFAOYSA-N 2,3,4,7-tetrahydroazepine-1-carboxylic acid Chemical compound OC(=O)N1CCCC=CC1 YSLXJUQVRQDRFJ-UHFFFAOYSA-N 0.000 description 1
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 description 1
- AWCMTWJCXINHTH-UHFFFAOYSA-N 2-(2-chlorosulfonylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1S(Cl)(=O)=O AWCMTWJCXINHTH-UHFFFAOYSA-N 0.000 description 1
- OYDTZBTZXLNXOQ-UHFFFAOYSA-N 2-(3-chlorosulfonylphenyl)acetic acid Chemical class OC(=O)CC1=CC=CC(S(Cl)(=O)=O)=C1 OYDTZBTZXLNXOQ-UHFFFAOYSA-N 0.000 description 1
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
- ZBIULCVFFJJYTN-UHFFFAOYSA-N 2-(4-fluorophenoxy)acetic acid Chemical group OC(=O)COC1=CC=C(F)C=C1 ZBIULCVFFJJYTN-UHFFFAOYSA-N 0.000 description 1
- WXWWJUKMWNYILA-UHFFFAOYSA-N 2-(4-methoxy-3-phenylmethoxyphenyl)acetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OCC1=CC=CC=C1 WXWWJUKMWNYILA-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical class CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- PNFVIPIQXAIUAY-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical class CCC(C(O)=O)NC(=O)OC(C)(C)C PNFVIPIQXAIUAY-UHFFFAOYSA-N 0.000 description 1
- CVRGLSNUBFHEQZ-UHFFFAOYSA-N 2-[(2-oxo-2-phenylmethoxyacetyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C(=O)OCC1=CC=CC=C1 CVRGLSNUBFHEQZ-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- BUKCNFAUCKLAPY-LBAQZLPGSA-N 2-[4-[[(2s)-2-(1-benzofuran-2-carbonylamino)-4-methylpentanoyl]amino]-3-oxoazepan-1-yl]sulfonylbenzoic acid Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=C1C(O)=O BUKCNFAUCKLAPY-LBAQZLPGSA-N 0.000 description 1
- ZSZKAQCISWFDCQ-UHFFFAOYSA-N 2-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=CC=C1S(Cl)(=O)=O ZSZKAQCISWFDCQ-UHFFFAOYSA-N 0.000 description 1
- FRWLZBIMKACPAF-UHFFFAOYSA-N 2-tert-butyl-6-methylthieno[3,2-b]thiophene-5-carboxylic acid Chemical group C1=C(C(C)(C)C)SC2=C1SC(C(O)=O)=C2C FRWLZBIMKACPAF-UHFFFAOYSA-N 0.000 description 1
- VPHHJAOJUJHJKD-UHFFFAOYSA-N 3,4-dichlorobenzoic acid Chemical class OC(=O)C1=CC=C(Cl)C(Cl)=C1 VPHHJAOJUJHJKD-UHFFFAOYSA-N 0.000 description 1
- MQSSBVLREFSMDP-UHFFFAOYSA-N 3,4-dihydro-2h-1,5-benzodioxepine-7-carboxylic acid Chemical compound O1CCCOC2=CC(C(=O)O)=CC=C21 MQSSBVLREFSMDP-UHFFFAOYSA-N 0.000 description 1
- CXPVSKUOASPRHM-UHFFFAOYSA-N 3,5-dimethyl-2h-1,3-oxazole-4-sulfonyl chloride Chemical class CN1COC(C)=C1S(Cl)(=O)=O CXPVSKUOASPRHM-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-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
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- OINWZUJVEXUHCC-UHFFFAOYSA-N 3-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(S(Cl)(=O)=O)=C1 OINWZUJVEXUHCC-UHFFFAOYSA-N 0.000 description 1
- GKRRTFCDSZGFSZ-UHFFFAOYSA-N 3-cyclopropyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical class CC(C)(C)OC(=O)NC(C(O)=O)CC1CC1 GKRRTFCDSZGFSZ-UHFFFAOYSA-N 0.000 description 1
- ZYJSTSMEUKNCEV-UHFFFAOYSA-N 3-diazo-1-diazonioprop-1-en-2-olate Chemical class [N-]=[N+]=CC(=O)C=[N+]=[N-] ZYJSTSMEUKNCEV-UHFFFAOYSA-N 0.000 description 1
- JPDAHPLCGNRCEX-UHFFFAOYSA-N 3-hydroxy-4-(4-methylpentanoylamino)azepane-1-carboxylic acid Chemical compound CC(C)CCC(=O)NC1CCCN(C(O)=O)CC1O JPDAHPLCGNRCEX-UHFFFAOYSA-N 0.000 description 1
- JHJKSEKUZNJKGO-UHFFFAOYSA-N 3-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=CC(S(Cl)(=O)=O)=C1 JHJKSEKUZNJKGO-UHFFFAOYSA-N 0.000 description 1
- AQTVZOSWTCMVKN-KEKNWZKVSA-N 3-methyl-n-[(2s)-4-methyl-1-[[1-(3-methylpyridin-2-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=NC=CC=C1C AQTVZOSWTCMVKN-KEKNWZKVSA-N 0.000 description 1
- IATYULMTMJKGFO-KEKNWZKVSA-N 3-methyl-n-[(2s)-4-methyl-1-[[1-(6-methylpyridin-2-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 IATYULMTMJKGFO-KEKNWZKVSA-N 0.000 description 1
- SRYKQBAZBAROTC-UHFFFAOYSA-N 3-methylpyridine-2-sulfonyl chloride Chemical class CC1=CC=CN=C1S(Cl)(=O)=O SRYKQBAZBAROTC-UHFFFAOYSA-N 0.000 description 1
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- OQSUATODAOKSDO-GTPINHCMSA-N 4-[[(2s)-2-aminopentanoyl]-methylamino]-3-hydroxy-n-phenylazepane-1-carboxamide Chemical compound C1C(O)C(N(C)C(=O)[C@@H](N)CCC)CCCN1C(=O)NC1=CC=CC=C1 OQSUATODAOKSDO-GTPINHCMSA-N 0.000 description 1
- ZGYGQMBXYVMHRV-UHFFFAOYSA-N 4-amino-1-(3-methoxyphenyl)sulfonylazepan-3-ol Chemical compound COC1=CC=CC(S(=O)(=O)N2CC(O)C(N)CCC2)=C1 ZGYGQMBXYVMHRV-UHFFFAOYSA-N 0.000 description 1
- VDXDQOKREOXGGP-UHFFFAOYSA-N 4-amino-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-3-ol Chemical compound C1C(C)(C)CC(N)C(O)CN1S(=O)(=O)C1=CC=CC=N1 VDXDQOKREOXGGP-UHFFFAOYSA-N 0.000 description 1
- MGWJXYOBULWIEL-UHFFFAOYSA-N 4-amino-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-3-ol hydrochloride Chemical compound Cl.C1C(C)(C)CC(N)C(O)CN1S(=O)(=O)C1=CC=CC=N1 MGWJXYOBULWIEL-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- BNTCOWFLQLLDSU-UHFFFAOYSA-N 4-azido-3-hydroxyazepane-1-carboxylic acid Chemical compound OC1CN(C(O)=O)CCCC1N=[N+]=[N-] BNTCOWFLQLLDSU-UHFFFAOYSA-N 0.000 description 1
- KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 1
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
- RYAQFHLUEMJOMF-UHFFFAOYSA-N 4-phenoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC=C1 RYAQFHLUEMJOMF-UHFFFAOYSA-N 0.000 description 1
- SXEGUTXRUGXAQR-UHFFFAOYSA-N 5,5-bis(4-methoxyphenyl)pent-4-enoic acid Chemical compound C1=CC(OC)=CC=C1C(=CCCC(O)=O)C1=CC=C(OC)C=C1 SXEGUTXRUGXAQR-UHFFFAOYSA-N 0.000 description 1
- ILDCMWQKEAQZRX-LBAQZLPGSA-N 5,6-dimethoxy-n-[(2s)-4-methyl-1-[[1-(6-methylpyridin-2-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=C(C(=CC=2S1)OC)OC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 ILDCMWQKEAQZRX-LBAQZLPGSA-N 0.000 description 1
- ZLRXPOZMNSZWTH-UHFFFAOYSA-N 5-(2-piperidin-1-ylethoxy)-1-benzofuran-2-carboxylic acid Chemical class C=1C=C2OC(C(=O)O)=CC2=CC=1OCCN1CCCCC1 ZLRXPOZMNSZWTH-UHFFFAOYSA-N 0.000 description 1
- UTKAPAFUQBYNLU-UHFFFAOYSA-N 5-(2-pyrrolidin-1-ylethoxy)-1-benzofuran-2-carboxylic acid Chemical class C=1C=C2OC(C(=O)O)=CC2=CC=1OCCN1CCCC1 UTKAPAFUQBYNLU-UHFFFAOYSA-N 0.000 description 1
- FDQMAYITLCZAQV-KEKNWZKVSA-N 5-(4-chlorophenyl)-n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]furan-2-carboxamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(O1)=CC=C1C1=CC=C(Cl)C=C1 FDQMAYITLCZAQV-KEKNWZKVSA-N 0.000 description 1
- BGPOHJSGSYVQSU-UHFFFAOYSA-N 5-(4-methoxyphenyl)pentanoic acid Chemical compound COC1=CC=C(CCCCC(O)=O)C=C1 BGPOHJSGSYVQSU-UHFFFAOYSA-N 0.000 description 1
- FXZTYDPWMQBTDH-UHFFFAOYSA-N 5-(4-nitrophenyl)furan-2-carboxylic acid Chemical class O1C(C(=O)O)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 FXZTYDPWMQBTDH-UHFFFAOYSA-N 0.000 description 1
- CKOZVEHVVHCMGD-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-n,n-dimethyltetrazole-1-carboxamide Chemical compound CN(C)C(=O)N1N=NN=C1CC1=CC=C(F)C=C1 CKOZVEHVVHCMGD-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- IKTADOGELLIBNN-GPJFCIFZSA-N 5-hydroxy-N-[(2S)-1-[[3-hydroxy-1-(1-methylimidazol-4-yl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=C(O)C=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CN(C)C=N1 IKTADOGELLIBNN-GPJFCIFZSA-N 0.000 description 1
- DSDSNIIFNGMUAZ-GGYWPGCISA-N 5-hydroxy-n-[(2s)-4-methyl-1-[[1-(1-methylimidazol-4-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=C(O)C=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CN(C)C=N1 DSDSNIIFNGMUAZ-GGYWPGCISA-N 0.000 description 1
- NPSSHZYEKWSWCB-KEKNWZKVSA-N 5-methoxy-n-[(2s)-4-methyl-1-[[1-(3-methylpyridin-2-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C=1OC2=CC=C(C=C2C=1)OC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=NC=CC=C1C NPSSHZYEKWSWCB-KEKNWZKVSA-N 0.000 description 1
- FRJRAYQZMBXNPU-LBAQZLPGSA-N 5-methoxy-n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C=1OC2=CC=C(C=C2C=1)OC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 FRJRAYQZMBXNPU-LBAQZLPGSA-N 0.000 description 1
- ONPSEKCXWKJUJN-UHFFFAOYSA-N 5-oxohexanoyl chloride Chemical group CC(=O)CCCC(Cl)=O ONPSEKCXWKJUJN-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical group CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-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
- WPPRWFMUTKRZQO-UHFFFAOYSA-N 8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylic acid Chemical compound C1N(C(=O)O)CCCC2OC21 WPPRWFMUTKRZQO-UHFFFAOYSA-N 0.000 description 1
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 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
- 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
- 108010087765 Antipain Proteins 0.000 description 1
- 239000004475 Arginine Chemical class 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical class OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- RNJKIGSRWMJMEC-HLIUYOAVSA-N C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)C1=CC=CC=N1 Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)C1=CC=CC=N1 RNJKIGSRWMJMEC-HLIUYOAVSA-N 0.000 description 1
- ZQGAPVKLGLTSTB-FHERZECASA-N C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1F Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1F ZQGAPVKLGLTSTB-FHERZECASA-N 0.000 description 1
- QJPFZBRLROOTNE-KBWCOIMZSA-N C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1CC1=CC=CC=C1 Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1CC1=CC=CC=C1 QJPFZBRLROOTNE-KBWCOIMZSA-N 0.000 description 1
- YYLAOGLQDQHPEF-WLXPTCNVSA-N C1C(O)C(NC(=O)[C@H](CC(C)C)NC)CCCN1C(=O)CC1=CC=CC(C=2N=CC=CC=2)=C1 Chemical compound C1C(O)C(NC(=O)[C@H](CC(C)C)NC)CCCN1C(=O)CC1=CC=CC(C=2N=CC=CC=2)=C1 YYLAOGLQDQHPEF-WLXPTCNVSA-N 0.000 description 1
- AWRFPLLQSFXFAX-HFCFLWKCSA-N CC(C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)=O)=O)NC(=O)C1OCCC1)C Chemical compound CC(C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)=O)=O)NC(=O)C1OCCC1)C AWRFPLLQSFXFAX-HFCFLWKCSA-N 0.000 description 1
- ZLUODTARZGKFHP-JRVPFXOQSA-N CC(C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)O)=O)NC(=O)C1OCCC1)C Chemical compound CC(C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)O)=O)NC(=O)C1OCCC1)C ZLUODTARZGKFHP-JRVPFXOQSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 description 1
- 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 229940094664 Cysteine protease inhibitor Drugs 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 1
- 108091020100 Gingipain Cysteine Endopeptidases Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical class OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Chemical class 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical class OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical class NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical class OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical class OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical class OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical class OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical class CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical class CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical class OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical class C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical class C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical class CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical class CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Chemical class NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Chemical class 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- UCGKXGFWPKIQJB-WCSIJFPASA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CC=2C=CC=CC=2)CCC1)=O)C(=O)C1=CC=C(Cl)C(Cl)=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CC=2C=CC=CC=2)CCC1)=O)C(=O)C1=CC=C(Cl)C(Cl)=C1 UCGKXGFWPKIQJB-WCSIJFPASA-N 0.000 description 1
- RFYCRCPEZWJOKE-WLXPTCNVSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CC=2C=CC=CC=2)CCC1)O)C(=O)C1=CC=C(Cl)C(Cl)=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CC=2C=CC=CC=2)CCC1)O)C(=O)C1=CC=C(Cl)C(Cl)=C1 RFYCRCPEZWJOKE-WLXPTCNVSA-N 0.000 description 1
- XFUVGPMFSDTWND-CPRJBALCSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCC1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCC1 XFUVGPMFSDTWND-CPRJBALCSA-N 0.000 description 1
- AESGWBWISBZFFG-VJPAEBCTSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCC1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCC1 AESGWBWISBZFFG-VJPAEBCTSA-N 0.000 description 1
- RNEKKYQSPNLPHG-GBYJYRDPSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCCC1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCCC1 RNEKKYQSPNLPHG-GBYJYRDPSA-N 0.000 description 1
- VTKHTZRMZFZKCR-KEKNWZKVSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(O1)=CC=C1C1=CC=CC(C(F)(F)F)=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(O1)=CC=C1C1=CC=CC(C(F)(F)F)=C1 VTKHTZRMZFZKCR-KEKNWZKVSA-N 0.000 description 1
- KJYLUUVJGMYWOE-CPRJBALCSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCC1CCCCC1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCC1CCCCC1 KJYLUUVJGMYWOE-CPRJBALCSA-N 0.000 description 1
- QWPPTDREYVXKCO-DJNXLDHESA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C1=CC=CO1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C1=CC=CO1 QWPPTDREYVXKCO-DJNXLDHESA-N 0.000 description 1
- IAZLSEDZQSJOQD-KOENEWCDSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(=C(O1)C)N=C1C1=CC=CC=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(=C(O1)C)N=C1C1=CC=CC=C1 IAZLSEDZQSJOQD-KOENEWCDSA-N 0.000 description 1
- IDKWNCDPMHKQED-KOENEWCDSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=C(Cl)C=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=C(Cl)C=C1 IDKWNCDPMHKQED-KOENEWCDSA-N 0.000 description 1
- KDUIEINJCJUXGT-KOENEWCDSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 KDUIEINJCJUXGT-KOENEWCDSA-N 0.000 description 1
- BLRGMYPMCMDGGT-KOENEWCDSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=CC(C(F)(F)F)=C1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(O1)=CC=C1C1=CC=CC(C(F)(F)F)=C1 BLRGMYPMCMDGGT-KOENEWCDSA-N 0.000 description 1
- WLBJKUHDMNOUGB-VJPAEBCTSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCC1CCCCC1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCC1CCCCC1 WLBJKUHDMNOUGB-VJPAEBCTSA-N 0.000 description 1
- RKOLYQILPLGYCP-CGZBRXJRSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C1=CC=C(Br)O1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C1=CC=C(Br)O1 RKOLYQILPLGYCP-CGZBRXJRSA-N 0.000 description 1
- RPNHPWBATRXXQQ-ADKAHSJRSA-N N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C1=CC=CO1 Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)O)C(=O)C1=CC=CO1 RPNHPWBATRXXQQ-ADKAHSJRSA-N 0.000 description 1
- PHVWCVOQLMKUNM-UHFFFAOYSA-N N-(3-hydroxyazepan-4-yl)-4-methylpentanamide Chemical compound CC(C)CCC(=O)NC1CCCNCC1O PHVWCVOQLMKUNM-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- QOFMQZUHRZQVRE-ANYOKISRSA-N N-[(2S)-1-[(1-benzoyl-3-oxoazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1,3-benzodioxole-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C1OC2=CC=CC=C2O1)CC(C)C)NC(C(C1)=O)CCCN1C(=O)C1=CC=CC=C1 QOFMQZUHRZQVRE-ANYOKISRSA-N 0.000 description 1
- FYVYSZZAXIBUJB-KEKNWZKVSA-N N-[(2S)-1-[(1-benzoyl-3-oxoazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-4-fluorobenzamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)C(=O)C=1C=CC=CC=1)=O)C(=O)C1=CC=C(F)C=C1 FYVYSZZAXIBUJB-KEKNWZKVSA-N 0.000 description 1
- HJQXOHDCOXMLED-NVVYMUDLSA-N N-[(2S)-1-[[3-hydroxy-1-[2-(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]-methylamino]-1-oxopentan-2-yl]quinoline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CCC)N(C)C(C(C1)O)CCCN1C(=O)CC(C=1)=CC=CC=1C1=CC=CC=N1 HJQXOHDCOXMLED-NVVYMUDLSA-N 0.000 description 1
- CYUGUEOQYNFNAL-FSRLHOSWSA-N N-[(2S)-1-[methyl-[3-oxo-1-[2-(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]amino]-1-oxopentan-2-yl]quinoline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CCC)N(C)C(C(C1)=O)CCCN1C(=O)CC(C=1)=CC=CC=1C1=CC=CC=N1 CYUGUEOQYNFNAL-FSRLHOSWSA-N 0.000 description 1
- KFNKUDKUOTWHIR-GTPINHCMSA-N N-[(2S)-2-amino-4-methylpentanoyl]-N-(3-hydroxyazepan-4-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C(=O)[C@@H](N)CC(C)C)C1CCCNCC1O KFNKUDKUOTWHIR-GTPINHCMSA-N 0.000 description 1
- BNSKNQDTDYSOIN-VYRBHSGPSA-N N-[(2S)-2-amino-4-methylpentanoyl]-N-(3-oxoazepan-4-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)N(C(=O)[C@@H](N)CC(C)C)C1CCCNCC1=O BNSKNQDTDYSOIN-VYRBHSGPSA-N 0.000 description 1
- AQWYVGSMFHPOTG-JNLGVIEDSA-N N-[(2S)-3-cyclohexyl-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-1-oxopropan-2-yl]-5-[3-(trifluoromethyl)phenyl]furan-2-carboxamide Chemical compound C1(CCCCC1)C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)O)=O)NC(=O)C=1OC(=CC1)C1=CC(=CC=C1)C(F)(F)F AQWYVGSMFHPOTG-JNLGVIEDSA-N 0.000 description 1
- YPPGNLJNGUHTRD-ANYOKISRSA-N N-[(2S)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 YPPGNLJNGUHTRD-ANYOKISRSA-N 0.000 description 1
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
- NITYFZGHPORMQW-CKHPTIKVSA-N N1=C2C(=NO1)C(=CC=C2)S(=O)(=O)N1CC(C(CCC1)NC(=O)[C@H](CC(C)C)NC(=O)C=1OC2=C(C=1)C=CC=C2)O Chemical class N1=C2C(=NO1)C(=CC=C2)S(=O)(=O)N1CC(C(CCC1)NC(=O)[C@H](CC(C)C)NC(=O)C=1OC2=C(C=1)C=CC=C2)O NITYFZGHPORMQW-CKHPTIKVSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- UADPIJANMQUAHU-QLLQDVQFSA-N O=C([C@@H](N(C)CC=1C=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](N(C)CC=1C=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 UADPIJANMQUAHU-QLLQDVQFSA-N 0.000 description 1
- CTKIZKSPJUNRFY-ADKAHSJRSA-N O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC1CCCNCC1O Chemical compound O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC1CCCNCC1O CTKIZKSPJUNRFY-ADKAHSJRSA-N 0.000 description 1
- LZTGPHQFBCZQAT-ANYOKISRSA-N O=C([C@@H](NC(=O)C1=C(C=2SC(=CC=2S1)C(C)(C)C)C)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C1=C(C=2SC(=CC=2S1)C(C)(C)C)C)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 LZTGPHQFBCZQAT-ANYOKISRSA-N 0.000 description 1
- WFAKQRKOMPBMBS-KEKNWZKVSA-N O=C([C@@H](NC(=O)C=1C2=CC=CC=C2C=CN=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C2=CC=CC=C2C=CN=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 WFAKQRKOMPBMBS-KEKNWZKVSA-N 0.000 description 1
- QDMTYTYLXFEJHT-KOENEWCDSA-N O=C([C@@H](NC(=O)C=1C2=CC=CC=C2C=CN=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C2=CC=CC=C2C=CN=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 QDMTYTYLXFEJHT-KOENEWCDSA-N 0.000 description 1
- QKBFMFHVTGLIBD-WCSIJFPASA-N O=C([C@@H](NC(=O)C=1C2=CC=CC=C2N=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C2=CC=CC=C2N=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 QKBFMFHVTGLIBD-WCSIJFPASA-N 0.000 description 1
- CEKNXXFUXUSIPL-WLXPTCNVSA-N O=C([C@@H](NC(=O)C=1C2=CC=CC=C2N=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C2=CC=CC=C2N=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 CEKNXXFUXUSIPL-WLXPTCNVSA-N 0.000 description 1
- DJAKVHYNHLYHPF-WLXPTCNVSA-N O=C([C@@H](NC(=O)C=1C=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 DJAKVHYNHLYHPF-WLXPTCNVSA-N 0.000 description 1
- XEMZUATYHDORFZ-WLXPTCNVSA-N O=C([C@@H](NC(=O)C=1C=C2C=CC=NC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C=C2C=CC=NC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 XEMZUATYHDORFZ-WLXPTCNVSA-N 0.000 description 1
- MPWJDGQRWASNBF-KEKNWZKVSA-N O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1CC1=CC=CC=C1 Chemical compound O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1CC1=CC=CC=C1 MPWJDGQRWASNBF-KEKNWZKVSA-N 0.000 description 1
- MYVUXHLOMPAJFJ-KOENEWCDSA-N O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 Chemical compound O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 MYVUXHLOMPAJFJ-KOENEWCDSA-N 0.000 description 1
- QUAKSZAFVCOMLL-GPJFCIFZSA-N O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 QUAKSZAFVCOMLL-GPJFCIFZSA-N 0.000 description 1
- YXMJKMLLJJCLDB-UYYAODIZSA-N O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 YXMJKMLLJJCLDB-UYYAODIZSA-N 0.000 description 1
- SGROJFUWTNAZCB-QKDPSFTKSA-N O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 SGROJFUWTNAZCB-QKDPSFTKSA-N 0.000 description 1
- RNAZQFXLRVHZNG-IRQNMHNUSA-N O=C([C@@H](NC(=O)C=1N=C2N=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1N=C2N=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 RNAZQFXLRVHZNG-IRQNMHNUSA-N 0.000 description 1
- MYJIIWYFUBKZSE-RZMWZJFBSA-N O=C([C@@H](NC(=O)C=1N=CC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1N=CC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 MYJIIWYFUBKZSE-RZMWZJFBSA-N 0.000 description 1
- FIEZIGBOJGIGME-QKDPSFTKSA-N O=C([C@@H](NC(=O)C=1NC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1NC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 FIEZIGBOJGIGME-QKDPSFTKSA-N 0.000 description 1
- DUPLMNJETPXXFV-KBWCOIMZSA-N O=C([C@@H](NC(=O)C=1OC2=CC(F)=C(F)C=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC(F)=C(F)C=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 DUPLMNJETPXXFV-KBWCOIMZSA-N 0.000 description 1
- DRCNICLKXOIEAY-KBWCOIMZSA-N O=C([C@@H](NC(=O)C=1OC2=CC=C(F)C=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=C(F)C=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 DRCNICLKXOIEAY-KBWCOIMZSA-N 0.000 description 1
- ZBICSQFAVPFOLS-ANYOKISRSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=C(C)OCN1C Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=C(C)OCN1C ZBICSQFAVPFOLS-ANYOKISRSA-N 0.000 description 1
- QAZGYBADCWQFJN-KEKNWZKVSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=C(Br)C=C1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=C(Br)C=C1 QAZGYBADCWQFJN-KEKNWZKVSA-N 0.000 description 1
- LHFIKPOLVJQYCY-LBAQZLPGSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 LHFIKPOLVJQYCY-LBAQZLPGSA-N 0.000 description 1
- LAAGXFMUYHRJRJ-ORFBVSJDSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 LAAGXFMUYHRJRJ-ORFBVSJDSA-N 0.000 description 1
- CWQFSGGICVTEBX-KOENEWCDSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=C1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=C1 CWQFSGGICVTEBX-KOENEWCDSA-N 0.000 description 1
- SZALMADOCQFLMP-XBMUEBEBSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=NC=CS1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=NC=CS1 SZALMADOCQFLMP-XBMUEBEBSA-N 0.000 description 1
- IGDSQCLNBXEQPP-KBWCOIMZSA-N O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)N1CN(C)C=C1 Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)N1CN(C)C=C1 IGDSQCLNBXEQPP-KBWCOIMZSA-N 0.000 description 1
- NCROEWHRXUDIAH-WLXPTCNVSA-N O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 Chemical compound O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1CC1=CC=CC=C1 NCROEWHRXUDIAH-WLXPTCNVSA-N 0.000 description 1
- LQFIJPRLIZKTLQ-KBWCOIMZSA-N O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 Chemical compound O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 LQFIJPRLIZKTLQ-KBWCOIMZSA-N 0.000 description 1
- KZNHDLUTOWTSOB-ZVAWYAOSSA-N O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 Chemical compound O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 KZNHDLUTOWTSOB-ZVAWYAOSSA-N 0.000 description 1
- LMBAKNYHQBAJIE-XBMUEBEBSA-N O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 Chemical class O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 LMBAKNYHQBAJIE-XBMUEBEBSA-N 0.000 description 1
- HIVKFAFBQICXED-GPJFCIFZSA-N O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=C(C(=CC=2O1)OC)OC)NC(C(C1)O)CCCN1S(=O)(=O)C1=CN(C)C=N1 Chemical compound O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=C(C(=CC=2O1)OC)OC)NC(C(C1)O)CCCN1S(=O)(=O)C1=CN(C)C=N1 HIVKFAFBQICXED-GPJFCIFZSA-N 0.000 description 1
- FPCNYZUXZOWPGO-LBAQZLPGSA-N O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=CC=C(C=2O1)OC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 Chemical compound O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=CC=C(C=2O1)OC)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 FPCNYZUXZOWPGO-LBAQZLPGSA-N 0.000 description 1
- NIHMTEOPPCGNHX-ORFBVSJDSA-N OC1CN(CCCC1NC([C@H](CC(C)C)NC(COC1=CC=C(C=C1)F)=O)=O)S(=O)(=O)C1=NC=CC=C1 Chemical compound OC1CN(CCCC1NC([C@H](CC(C)C)NC(COC1=CC=C(C=C1)F)=O)=O)S(=O)(=O)C1=NC=CC=C1 NIHMTEOPPCGNHX-ORFBVSJDSA-N 0.000 description 1
- KAODPPZCIXBOSY-ORFBVSJDSA-N OC1CN(CCCC1NC([C@H](CC(C)C)NC(COC1=CC=CC=C1)=O)=O)S(=O)(=O)C1=NC=CC=C1 Chemical compound OC1CN(CCCC1NC([C@H](CC(C)C)NC(COC1=CC=CC=C1)=O)=O)S(=O)(=O)C1=NC=CC=C1 KAODPPZCIXBOSY-ORFBVSJDSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 102100036829 Probable peptidyl-tRNA hydrolase Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical class OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000006270 Proton Pumps Human genes 0.000 description 1
- 108010083204 Proton Pumps Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical class OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical class CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Chemical class 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Chemical class C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical class CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- DHSAJHCZUSAJPD-CGZBRXJRSA-N [(2S)-1-[[1-(3-chlorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamic acid Chemical compound ClC=1C=C(C=CC=1)S(=O)(=O)N1CC(C(CCC1)NC(=O)[C@H](CC(C)C)NC(O)=O)O DHSAJHCZUSAJPD-CGZBRXJRSA-N 0.000 description 1
- VKNQVUCKKFOTDE-ADKAHSJRSA-N [(2S)-3-cyclohexyl-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-1-oxopropan-2-yl]carbamic acid Chemical compound C1(CCCCC1)C[C@@H](C(NC1C(CN(CCC1)S(=O)(=O)C1=NC=CC=C1)O)=O)NC(O)=O VKNQVUCKKFOTDE-ADKAHSJRSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N alpha-Butylen-alpha-carbonsaeure Natural products CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940124325 anabolic agent Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical class OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- NNCCEDFHZVCNMJ-KBWCOIMZSA-N benzyl 3-hydroxy-4-[[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]azepane-1-carboxylate Chemical group C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1C(=O)OCC1=CC=CC=C1 NNCCEDFHZVCNMJ-KBWCOIMZSA-N 0.000 description 1
- DWKDPFXZJQTJHM-UHFFFAOYSA-N benzyl 4-amino-3-hydroxyazepane-1-carboxylate Chemical compound C1C(O)C(N)CCCN1C(=O)OCC1=CC=CC=C1 DWKDPFXZJQTJHM-UHFFFAOYSA-N 0.000 description 1
- MLOQDSPTAWUYJP-UHFFFAOYSA-N benzyl 4-azido-3-hydroxyazepane-1-carboxylate Chemical compound C1CCC(N=[N+]=[N-])C(O)CN1C(=O)OCC1=CC=CC=C1 MLOQDSPTAWUYJP-UHFFFAOYSA-N 0.000 description 1
- WNWUYYZBSLFMHF-UHFFFAOYSA-N benzyl 8-oxa-5-azabicyclo[5.1.0]octane-5-carboxylate Chemical compound C1CCC2OC2CN1C(=O)OCC1=CC=CC=C1 WNWUYYZBSLFMHF-UHFFFAOYSA-N 0.000 description 1
- ZZGDDBWFXDMARY-SVBPBHIXSA-N benzyl n-[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NC1=CC=2OC(=O)C=C(C=2C=C1)C)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 ZZGDDBWFXDMARY-SVBPBHIXSA-N 0.000 description 1
- QJXVROLCYARZCT-KEKPXRHTSA-N benzyl n-[(2s)-4-methyl-1-[4-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-oxoazepan-1-yl]-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)C(=O)[C@H](CC(C)C)NC(=O)OCC=1C=CC=CC=1)=O)C(=O)OCC1=CC=CC=C1 QJXVROLCYARZCT-KEKPXRHTSA-N 0.000 description 1
- YIQIYQACMGRMHN-UHFFFAOYSA-N benzyl n-pent-4-enyl-n-prop-2-enylcarbamate Chemical compound C=CCCCN(CC=C)C(=O)OCC1=CC=CC=C1 YIQIYQACMGRMHN-UHFFFAOYSA-N 0.000 description 1
- OSLGKRDOEMLAJV-UHFFFAOYSA-N benzyl n-prop-2-enylcarbamate Chemical compound C=CCNC(=O)OCC1=CC=CC=C1 OSLGKRDOEMLAJV-UHFFFAOYSA-N 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Chemical class OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000000339 bright-field microscopy Methods 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 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
- 239000004202 carbamide Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 210000003541 chondroclast Anatomy 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 208000035196 congenital hypomyelinating 2 neuropathy Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 108090000711 cruzipain Proteins 0.000 description 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- HGWXXIZVRRTDKT-UHFFFAOYSA-N ethyl 2,2-difluoro-2-iodoacetate Chemical group CCOC(=O)C(F)(F)I HGWXXIZVRRTDKT-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Chemical class OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Chemical class OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Chemical class CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-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
- 239000008101 lactose Substances 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical class SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Chemical class 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- QVDXUKJJGUSGLS-LURJTMIESA-N methyl L-leucinate Chemical compound COC(=O)[C@@H](N)CC(C)C QVDXUKJJGUSGLS-LURJTMIESA-N 0.000 description 1
- XUXJHBAJZQREDB-UHFFFAOYSA-N methylbutylamide Natural products CCC(C)C(N)=O XUXJHBAJZQREDB-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- VUWJYROJTRQGKP-WCSIJFPASA-N n-[(2s)-1-[(1-benzyl-3-oxoazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1CC1=CC=CC=C1 VUWJYROJTRQGKP-WCSIJFPASA-N 0.000 description 1
- AGBNZOPRZFUHGQ-JKGBFCRXSA-N n-[(2s)-1-[(1-benzyl-3-oxoazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]quinoline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1CC1=CC=CC=C1 AGBNZOPRZFUHGQ-JKGBFCRXSA-N 0.000 description 1
- YXWMHLJCEFMYJP-KBWCOIMZSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 YXWMHLJCEFMYJP-KBWCOIMZSA-N 0.000 description 1
- MTROZMLOBPWDML-ORFBVSJDSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-3-methyl-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 MTROZMLOBPWDML-ORFBVSJDSA-N 0.000 description 1
- ITCMEVHWEUFNMX-ORFBVSJDSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-5-methoxy-1-benzofuran-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C=1OC2=CC=C(C=C2C=1)OC)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 ITCMEVHWEUFNMX-ORFBVSJDSA-N 0.000 description 1
- NWXJCYZWUKCSNZ-RZMWZJFBSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]quinoline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 NWXJCYZWUKCSNZ-RZMWZJFBSA-N 0.000 description 1
- CYOFIYHBYSWXMW-KOENEWCDSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]quinoline-8-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C2=NC=CC=C2C=CC=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=N1 CYOFIYHBYSWXMW-KOENEWCDSA-N 0.000 description 1
- BCTIAUKTRYCCLC-ORFBVSJDSA-N n-[(2s)-1-[(3-hydroxy-1-pyridin-3-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CN=C1 BCTIAUKTRYCCLC-ORFBVSJDSA-N 0.000 description 1
- JCTWFUJBPUAVGX-BGERDNNASA-N n-[(2s)-1-[(6,6-dimethyl-3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CC(C)(C)CN1S(=O)(=O)C1=CC=CC=N1 JCTWFUJBPUAVGX-BGERDNNASA-N 0.000 description 1
- ZZXXQUIBBQDMJY-ORFBVSJDSA-N n-[(2s)-1-[[1-(2-fluorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC=C1F ZZXXQUIBBQDMJY-ORFBVSJDSA-N 0.000 description 1
- QYJOFFZWADPFOO-ORFBVSJDSA-N n-[(2s)-1-[[1-(3,4-dimethoxyphenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CCC)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=C(OC)C(OC)=C1 QYJOFFZWADPFOO-ORFBVSJDSA-N 0.000 description 1
- VCMHNZQMADRZNP-KOENEWCDSA-N n-[(2s)-1-[[1-(3-chlorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(Cl)=C1 VCMHNZQMADRZNP-KOENEWCDSA-N 0.000 description 1
- BTUDCAFYLPDYLP-KOENEWCDSA-N n-[(2s)-1-[[1-(4-chlorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 BTUDCAFYLPDYLP-KOENEWCDSA-N 0.000 description 1
- YBVQTSMBIKMQFP-KEKNWZKVSA-N n-[(2s)-1-[[1-(4-chlorophenyl)sulfonyl-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=C(Cl)C=C1 YBVQTSMBIKMQFP-KEKNWZKVSA-N 0.000 description 1
- GLLGPTPNNNBTGH-KEKNWZKVSA-N n-[(2s)-1-[[1-(benzenesulfonyl)-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=C1 GLLGPTPNNNBTGH-KEKNWZKVSA-N 0.000 description 1
- YROCWTBUPGWUAD-WCSIJFPASA-N n-[(2s)-1-[[1-(benzenesulfonyl)-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1h-indole-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1NC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=C1 YROCWTBUPGWUAD-WCSIJFPASA-N 0.000 description 1
- MXBXSJBLEDMZMU-XIJSCUBXSA-N n-[(2s)-1-[[1-(benzenesulfonyl)-3-oxoazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-5-(2-piperidin-1-ylethoxy)-1-benzofuran-2-carboxamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1C=CC=CC=1)=O)C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCCCC1 MXBXSJBLEDMZMU-XIJSCUBXSA-N 0.000 description 1
- KDSLNCYBKBWMSE-WLXPTCNVSA-N n-[(2s)-1-[[3-hydroxy-1-(3-methoxyphenyl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound COC1=CC=CC(S(=O)(=O)N2CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)C=3OC4=CC=CC=C4C=3)CCC2)=C1 KDSLNCYBKBWMSE-WLXPTCNVSA-N 0.000 description 1
- PNLLJKQDZAMOOU-XBMUEBEBSA-N n-[(2s)-1-[[3-hydroxy-1-(3-methylpyridin-2-yl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]thieno[3,2-b]thiophene-5-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=NC=CC=C1C PNLLJKQDZAMOOU-XBMUEBEBSA-N 0.000 description 1
- YNAUPNWUUYQLQO-KOENEWCDSA-N n-[(2s)-1-[[3-hydroxy-1-(6-methylpyridin-2-yl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-3-methyl-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C1=C(C2=CC=CC=C2O1)C)CC(C)C)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 YNAUPNWUUYQLQO-KOENEWCDSA-N 0.000 description 1
- MQOPIRWIGRHTEX-ORFBVSJDSA-N n-[(2s)-1-[[3-hydroxy-1-(6-methylpyridin-2-yl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-5,6-dimethoxy-1-benzothiophene-2-carboxamide Chemical compound O=C([C@H](CC(C)C)NC(=O)C1=CC=2C=C(C(=CC=2S1)OC)OC)NC(C(C1)O)CCCN1S(=O)(=O)C1=CC=CC(C)=N1 MQOPIRWIGRHTEX-ORFBVSJDSA-N 0.000 description 1
- QBAUVZVXFGGTNQ-GGYWPGCISA-N n-[(2s)-4-methyl-1-[[1-(1-methylimidazol-4-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CN(C)C=N1 QBAUVZVXFGGTNQ-GGYWPGCISA-N 0.000 description 1
- JMDMVRFBMTYQKK-ZVAWYAOSSA-N n-[(2s)-4-methyl-1-[[1-(3-methylpyridin-2-yl)sulfonyl-3-oxoazepan-4-yl]amino]-1-oxopentan-2-yl]thieno[3,2-b]thiophene-5-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1SC=2C=CSC=2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=NC=CC=C1C JMDMVRFBMTYQKK-ZVAWYAOSSA-N 0.000 description 1
- OANYTQNMSAUWHY-GGYWPGCISA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1,3-benzodioxole-5-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C=C2OCOC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 OANYTQNMSAUWHY-GGYWPGCISA-N 0.000 description 1
- SHACANFSVRUECR-QWAKEFERSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1,8-naphthyridine-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2N=CC=CC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 SHACANFSVRUECR-QWAKEFERSA-N 0.000 description 1
- JJPNYWRFPJDAOT-ANYOKISRSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1-benzothiophene-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1SC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 JJPNYWRFPJDAOT-ANYOKISRSA-N 0.000 description 1
- PZWBJZVNTRLYSD-IAXKEJLGSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1h-indole-6-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C=C2NC=CC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 PZWBJZVNTRLYSD-IAXKEJLGSA-N 0.000 description 1
- MAKIECPXJZPRFD-KEKNWZKVSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-5-(4-nitrophenyl)furan-2-carboxamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C(O1)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 MAKIECPXJZPRFD-KEKNWZKVSA-N 0.000 description 1
- CNPDOFZBJGECAY-LYKKTTPLSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-5-nitrofuran-2-carboxamide Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)S(=O)(=O)C=1N=CC=CC=1)=O)C(=O)C1=CC=C([N+]([O-])=O)O1 CNPDOFZBJGECAY-LYKKTTPLSA-N 0.000 description 1
- JNSFSCKSTYXIAM-YANBTOMASA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]isoquinoline-3-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=CC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 JNSFSCKSTYXIAM-YANBTOMASA-N 0.000 description 1
- LFKWIZQIKIHFJP-YANBTOMASA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]quinoline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 LFKWIZQIKIHFJP-YANBTOMASA-N 0.000 description 1
- SFBABLMJYIFBRW-WCSIJFPASA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]quinoline-3-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 SFBABLMJYIFBRW-WCSIJFPASA-N 0.000 description 1
- ULISHQZUABJOEO-WCSIJFPASA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]quinoline-6-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C=C2C=CC=NC2=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 ULISHQZUABJOEO-WCSIJFPASA-N 0.000 description 1
- OZNGVEHEJAXJKC-KEKNWZKVSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]quinoline-8-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1C2=NC=CC=C2C=CC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 OZNGVEHEJAXJKC-KEKNWZKVSA-N 0.000 description 1
- XERCYXLBBKTDLV-LBAQZLPGSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-2-ylsulfonylazepan-4-yl)amino]pentan-2-yl]quinoxaline-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1N=C2C=CC=CC2=NC=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CC=N1 XERCYXLBBKTDLV-LBAQZLPGSA-N 0.000 description 1
- SFPXQLDUGVEXIZ-LBAQZLPGSA-N n-[(2s)-4-methyl-1-oxo-1-[(3-oxo-1-pyridin-3-ylsulfonylazepan-4-yl)amino]pentan-2-yl]-1-benzofuran-2-carboxamide Chemical compound O=C([C@@H](NC(=O)C=1OC2=CC=CC=C2C=1)CC(C)C)NC(C(C1)=O)CCCN1S(=O)(=O)C1=CC=CN=C1 SFPXQLDUGVEXIZ-LBAQZLPGSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 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
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000008506 pathogenesis 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
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical class OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 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
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- CDRNYKLYADJTMN-UHFFFAOYSA-N pyridine-3-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CN=C1 CDRNYKLYADJTMN-UHFFFAOYSA-N 0.000 description 1
- YBBJKCMMCRQZMA-UHFFFAOYSA-N pyrithione Chemical compound ON1C=CC=CC1=S YBBJKCMMCRQZMA-UHFFFAOYSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical class C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000022932 ruffle assembly Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 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
- 238000003860 storage Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LVTDUCPTYSLNGR-KBWCOIMZSA-N tert-butyl 3-hydroxy-4-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]azepane-1-carboxylate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CN(CCC1)C(=O)OC(C)(C)C)O)C(=O)OCC1=CC=CC=C1 LVTDUCPTYSLNGR-KBWCOIMZSA-N 0.000 description 1
- NUHXKEOHSGKGDR-HSBZDZAISA-N tert-butyl 4-[[(2s)-2-amino-4-methylpentanoyl]amino]-3-hydroxyazepane-1-carboxylate Chemical compound CC(C)C[C@H](N)C(=O)NC1CCCN(C(=O)OC(C)(C)C)CC1O NUHXKEOHSGKGDR-HSBZDZAISA-N 0.000 description 1
- YLLLNYLAZHPCNH-UHFFFAOYSA-N tert-butyl 4-amino-3-hydroxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C(O)C1 YLLLNYLAZHPCNH-UHFFFAOYSA-N 0.000 description 1
- ANEIXTRXVJNLMG-JNLGVIEDSA-N tert-butyl N-[(2S)-1-[[3-hydroxy-1-[2-(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1C(=O)CC1=CC=CC(C=2N=CC=CC=2)=C1 ANEIXTRXVJNLMG-JNLGVIEDSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- ZWSSVKROZKLBMB-UHFFFAOYSA-N tert-butyl n-(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)carbamate Chemical compound C1C(O)C(NC(=O)OC(C)(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 ZWSSVKROZKLBMB-UHFFFAOYSA-N 0.000 description 1
- QIRGSPUWJKPBLG-XBMUEBEBSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-n-methylcarbamate Chemical compound C1C(O)C(NC(=O)[C@@H](N(C)C(=O)OC(C)(C)C)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=N1 QIRGSPUWJKPBLG-XBMUEBEBSA-N 0.000 description 1
- HRAKBUBNYAGJMU-VIQWUECVSA-N tert-butyl n-[(2s)-1-[(3-hydroxy-6,6-dimethyl-1-pyridin-2-ylsulfonylazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CC(C)(C)CN1S(=O)(=O)C1=CC=CC=N1 HRAKBUBNYAGJMU-VIQWUECVSA-N 0.000 description 1
- QBYKFPXMXWDLRJ-SLTAFYQDSA-N tert-butyl n-[(2s)-1-[(3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](CC(C)C)C(=O)NC1CCCNCC1O QBYKFPXMXWDLRJ-SLTAFYQDSA-N 0.000 description 1
- SYNUZGXGRZTRSR-XBMUEBEBSA-N tert-butyl n-[(2s)-1-[[1-(2-fluorophenyl)sulfonyl-3-hydroxyazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1F SYNUZGXGRZTRSR-XBMUEBEBSA-N 0.000 description 1
- WOHVMJJLQPVEJY-KBWCOIMZSA-N tert-butyl n-[(2s)-1-[[3-hydroxy-1-(3-methoxyphenyl)sulfonylazepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC1=CC=CC(S(=O)(=O)N2CC(O)C(NC(=O)[C@H](CC(C)C)NC(=O)OC(C)(C)C)CCC2)=C1 WOHVMJJLQPVEJY-KBWCOIMZSA-N 0.000 description 1
- NGQNFRPEXIIKAF-AVAKVYKDSA-N tert-butyl n-[(2s)-1-[[3-hydroxy-1-(pyridine-2-carbonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1C(O)C(NC(=O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)CCCN1C(=O)C1=CC=CC=N1 NGQNFRPEXIIKAF-AVAKVYKDSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical group ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical group ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical class OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11363698P | 1998-12-23 | 1998-12-23 | |
US16458199P | 1999-11-10 | 1999-11-10 | |
PCT/US1999/030730 WO2000038687A1 (en) | 1998-12-23 | 1999-12-21 | Protease inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20013124D0 NO20013124D0 (no) | 2001-06-22 |
NO20013124L NO20013124L (no) | 2001-06-22 |
NO318910B1 true NO318910B1 (no) | 2005-05-23 |
Family
ID=26811293
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20013124A NO318910B1 (no) | 1998-12-23 | 2001-06-22 | Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat |
Country Status (24)
Country | Link |
---|---|
US (2) | US20020147188A1 (es) |
EP (1) | EP1158986A4 (es) |
JP (1) | JP2002533397A (es) |
KR (1) | KR100630986B1 (es) |
CN (1) | CN1253441C (es) |
AT (1) | ATE411294T1 (es) |
AU (1) | AU768565B2 (es) |
BR (1) | BR9916488A (es) |
CA (1) | CA2356671A1 (es) |
CZ (1) | CZ20012277A3 (es) |
DE (1) | DE69939752D1 (es) |
DZ (1) | DZ2977A1 (es) |
ES (1) | ES2315456T3 (es) |
GC (1) | GC0000178A (es) |
HK (1) | HK1043536A1 (es) |
HU (1) | HUP0104768A3 (es) |
IL (2) | IL143142A0 (es) |
NO (1) | NO318910B1 (es) |
NZ (1) | NZ511710A (es) |
PE (1) | PE20001340A1 (es) |
PL (1) | PL350132A1 (es) |
TR (1) | TR200101869T2 (es) |
UY (1) | UY25874A1 (es) |
WO (1) | WO2000038687A1 (es) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030144175A1 (en) | 1998-12-23 | 2003-07-31 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034599A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
EP1229914A4 (en) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
WO2001034600A1 (en) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513928A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
JP2003513922A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
AU1474601A (en) * | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
EP1231922A4 (en) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
JP2003513926A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
JP2003533432A (ja) * | 1999-11-10 | 2003-11-11 | スミスクライン・ビーチャム・コーポレイション | プロテア−ゼ阻害剤 |
WO2001034153A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034157A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
EP1235577A4 (en) * | 1999-11-10 | 2003-04-09 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
NZ520588A (en) | 2000-03-21 | 2004-06-25 | Smithkline Beecham Corp | Protease inhibitors |
CO5280093A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Metodos de tratamiento |
CO5280088A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Inhibidores de proteasa |
WO2001095911A1 (en) * | 2000-06-14 | 2001-12-20 | Smithkline Beecham Corporation | Protease inhibitors |
EP1320370A4 (en) * | 2000-09-01 | 2008-10-22 | Smithkline Beecham Corp | TREATMENT METHOD |
HUP0301964A3 (en) * | 2000-11-22 | 2007-09-28 | Smithkline Beecham Corp | Protease inhibitors |
PT1370260E (pt) | 2001-02-20 | 2011-02-01 | Chugai Pharmaceutical Co Ltd | Azóis como inibidores da malonil-coa-descarboxilase úteis como moduladores metabólicos |
US7709510B2 (en) | 2001-02-20 | 2010-05-04 | Chugai Seiyaku Kabushiki Kaisha | Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators |
EP1401453A4 (en) * | 2001-05-17 | 2005-04-06 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
US6982263B2 (en) | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
EP1511745A4 (en) * | 2002-05-22 | 2006-11-15 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
EP1534292A4 (en) * | 2002-05-22 | 2008-04-02 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
KR100962972B1 (ko) | 2002-07-26 | 2010-06-09 | 주식회사유한양행 | 1-페닐피페리딘-3-온 유도체 및 그의 제조방법 |
WO2004033445A1 (en) * | 2002-10-08 | 2004-04-22 | Merck Frosst Canada & Co. | 4-amino-azepan-3-one compounds as cathepsin k inhibitors useful in the treatment of osteoporosis |
SI3345895T1 (sl) | 2003-04-11 | 2020-03-31 | Ptc Therapeutics, Inc. | Spojina 1,2,4-oksadiazol benzojske kisline in njena uporaba za supresijo nesmiselne in zdravljenje bolezni |
CA2533749C (en) | 2003-08-01 | 2012-07-10 | Chugai Seiyaku Kabushiki Kaisha | Piperidine compounds useful as malonyl-coa decarboxylase inhibitors |
EP1653944B1 (en) | 2003-08-01 | 2010-11-10 | Chugai Seiyaku Kabushiki Kaisha | Heterocyclic compounds useful as malonyl-coa decarboxylase inhibitors |
EP1658071B1 (en) | 2003-08-01 | 2008-09-10 | Chugai Seiyaku Kabushiki Kaisha | Cyanoguanidine-based azole compounds useful as malonyl-coa decarboxylase inhibitors |
CN1910175A (zh) * | 2004-01-08 | 2007-02-07 | 默克弗罗斯特加拿大有限公司 | 组织蛋白酶半胱氨酸蛋白酶抑制剂 |
EP1796793A4 (en) * | 2004-09-07 | 2009-08-05 | Smithkline Beecham Corp | NEW CONNECTIONS |
EP1909784A4 (en) * | 2005-07-26 | 2010-04-21 | Merck Frosst Canada Ltd | CYSTEIN PROTEASE HEMMER OF THE PAPAIN FAMILY FOR THE TREATMENT OF PARASITIC ILLNESSES |
EP2387995A1 (en) | 2006-03-30 | 2011-11-23 | PTC Therapeutics, Inc. | Methods for the production of functional protein from DNA having a nonsense mutation and the treatment of disorders associated therewith |
US9943522B2 (en) | 2011-05-16 | 2018-04-17 | Bayer Intellectual Property Gmbh | Use of cathepsin K inhibition for the treatment and/or prophylaxis of pulmonary hypertension and/or heart failure |
CN103275070A (zh) * | 2013-05-10 | 2013-09-04 | 郑彪 | 调节单核细胞增殖的四环化合物及其应用 |
CA2942147C (en) | 2014-03-06 | 2022-12-13 | Ptc Therapeutics, Inc. | Pharmaceutical compositions and salts of a 1,2,4-oxadiazole benzoic acid |
AR106530A1 (es) | 2015-10-30 | 2018-01-24 | Ptc Therapeutics Inc | Métodos para tratar epilepsia |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1195287B (it) * | 1981-11-05 | 1988-10-12 | Ausonia Farma Srl | Derivato tiazolico,procedimento per la sua preparazione e relative composizioni farmaceutiche |
JPH05140063A (ja) * | 1991-11-19 | 1993-06-08 | Suntory Ltd | ジペプチド誘導体及びそれを有効成分とする骨疾患の予防及び治療剤 |
CA2111930A1 (en) * | 1992-12-25 | 1994-06-26 | Ryoichi Ando | Aminoketone derivatives |
DK0603769T3 (da) * | 1992-12-25 | 1999-06-14 | Mitsubishi Chem Corp | Alfa-aminoketonderivater |
JPH06199850A (ja) * | 1992-12-28 | 1994-07-19 | Tanabe Seiyaku Co Ltd | インドール含有ペプチド及びその製法 |
WO1997021694A1 (fr) * | 1995-12-12 | 1997-06-19 | Taiho Pharmaceutical Co., Ltd. | Derives d'epoxysuccinamides ou sels de ces derives, et medicaments les contenant |
US5902882A (en) * | 1996-04-17 | 1999-05-11 | Hoffmann-La Roche Inc. | Assymetric synthesis of azepines |
DZ2285A1 (fr) * | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
US6107291A (en) * | 1997-12-19 | 2000-08-22 | Amgen Inc. | Azepine or larger medium ring derivatives and methods of use |
JP2003533432A (ja) * | 1999-11-10 | 2003-11-11 | スミスクライン・ビーチャム・コーポレイション | プロテア−ゼ阻害剤 |
JP2003513922A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
AU1474601A (en) * | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513928A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
WO2001034599A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034153A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034600A1 (en) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Protease inhibitors |
EP1229914A4 (en) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
EP1235577A4 (en) * | 1999-11-10 | 2003-04-09 | Smithkline Beecham Corp | PROTEASE INHIBITORS |
JP2003513926A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
NL1013996C2 (nl) * | 1999-12-30 | 2001-07-03 | Innas Free Piston Bv | Vrijezuiger aggregaat voor opwekken van hydraulische energie. |
-
1999
- 1999-12-21 HU HU0104768A patent/HUP0104768A3/hu unknown
- 1999-12-21 KR KR1020017007989A patent/KR100630986B1/ko not_active IP Right Cessation
- 1999-12-21 WO PCT/US1999/030730 patent/WO2000038687A1/en active IP Right Grant
- 1999-12-21 JP JP2000590640A patent/JP2002533397A/ja active Pending
- 1999-12-21 AU AU19411/00A patent/AU768565B2/en not_active Ceased
- 1999-12-21 CN CNB998150932A patent/CN1253441C/zh not_active Expired - Fee Related
- 1999-12-21 CZ CZ20012277A patent/CZ20012277A3/cs unknown
- 1999-12-21 ES ES03076211T patent/ES2315456T3/es not_active Expired - Lifetime
- 1999-12-21 PL PL99350132A patent/PL350132A1/xx not_active Application Discontinuation
- 1999-12-21 CA CA002356671A patent/CA2356671A1/en not_active Abandoned
- 1999-12-21 NZ NZ511710A patent/NZ511710A/en unknown
- 1999-12-21 TR TR2001/01869T patent/TR200101869T2/xx unknown
- 1999-12-21 DE DE69939752T patent/DE69939752D1/de not_active Expired - Lifetime
- 1999-12-21 AT AT03076211T patent/ATE411294T1/de not_active IP Right Cessation
- 1999-12-21 BR BR9916488-4A patent/BR9916488A/pt not_active IP Right Cessation
- 1999-12-21 EP EP99963112A patent/EP1158986A4/en not_active Withdrawn
- 1999-12-21 IL IL14314299A patent/IL143142A0/xx active IP Right Grant
- 1999-12-22 GC GCP1999461 patent/GC0000178A/en active
- 1999-12-22 DZ DZ990277A patent/DZ2977A1/xx active
- 1999-12-22 UY UY25874A patent/UY25874A1/es not_active Application Discontinuation
- 1999-12-23 PE PE1999001312A patent/PE20001340A1/es not_active Application Discontinuation
-
2001
- 2001-05-14 IL IL143142A patent/IL143142A/en not_active IP Right Cessation
- 2001-06-22 NO NO20013124A patent/NO318910B1/no unknown
-
2002
- 2002-02-13 US US10/074,940 patent/US20020147188A1/en not_active Abandoned
- 2002-05-13 HK HK02103610.2A patent/HK1043536A1/zh unknown
-
2003
- 2003-04-01 US US10/404,142 patent/US20030225061A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU1941100A (en) | 2000-07-31 |
HUP0104768A2 (hu) | 2002-04-29 |
DZ2977A1 (fr) | 2004-03-15 |
CN1350458A (zh) | 2002-05-22 |
CA2356671A1 (en) | 2000-07-06 |
HUP0104768A3 (en) | 2002-05-28 |
IL143142A0 (en) | 2002-04-21 |
CZ20012277A3 (cs) | 2001-11-14 |
AU768565B2 (en) | 2003-12-18 |
US20020147188A1 (en) | 2002-10-10 |
CN1253441C (zh) | 2006-04-26 |
EP1158986A1 (en) | 2001-12-05 |
ATE411294T1 (de) | 2008-10-15 |
EP1158986A4 (en) | 2002-03-27 |
PL350132A1 (en) | 2002-11-04 |
WO2000038687A1 (en) | 2000-07-06 |
KR20010089677A (ko) | 2001-10-08 |
NO20013124D0 (no) | 2001-06-22 |
JP2002533397A (ja) | 2002-10-08 |
BR9916488A (pt) | 2001-10-09 |
KR100630986B1 (ko) | 2006-10-09 |
NZ511710A (en) | 2003-12-19 |
TR200101869T2 (tr) | 2002-01-21 |
US20030225061A1 (en) | 2003-12-04 |
NO20013124L (no) | 2001-06-22 |
ES2315456T3 (es) | 2009-04-01 |
IL143142A (en) | 2006-08-20 |
HK1043536A1 (zh) | 2002-09-20 |
UY25874A1 (es) | 2001-08-27 |
GC0000178A (en) | 2006-03-29 |
PE20001340A1 (es) | 2001-01-28 |
DE69939752D1 (de) | 2008-11-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO318910B1 (no) | Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat | |
AU2001243441B2 (en) | Protease inhibitors | |
AU2001243441A1 (en) | Protease inhibitors | |
US7405209B2 (en) | Protease inhibitors | |
BG107327A (bg) | Инхибитори на протеаза | |
EP1401453A2 (en) | Protease inhibitors | |
EP1384713A1 (en) | 4-amino-azepan-3-one derivatives as protease inhibitors | |
AU2003261482B2 (en) | Protease inhibitors | |
KR20040004445A (ko) | 프로테아제 억제제 | |
MXPA01006613A (es) | Inhibidores de proteasa |