NO313635B1 - Sulfonamid-metalloprotease-inhibitorer, fremgangsmåter for fremstilling og anvendelse derav, og farmasöytiske preparater sominneholder dem - Google Patents

Info

Publication number

NO313635B1

NO313635B1 NO19993587A NO993587A NO313635B1 NO 313635 B1 NO313635 B1 NO 313635B1 NO 19993587 A NO19993587 A NO 19993587A NO 993587 A NO993587 A NO 993587A NO 313635 B1 NO313635 B1 NO 313635B1

Authority

NO

Norway

Prior art keywords

alkyl

phenyl

hydrogen

compound according

sulfonyl

Prior art date

1997-01-23

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims description 36
• 238000002360 preparation method Methods 0.000 title claims description 18
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 14
• 239000003475 metalloproteinase inhibitor Substances 0.000 title description 3
• 229940124530 sulfonamide Drugs 0.000 title 1
• 150000003456 sulfonamides Chemical class 0.000 title 1
• -1 piperidino, thiomorpholino Chemical group 0.000 claims description 336
• 150000001875 compounds Chemical class 0.000 claims description 224
• 239000001257 hydrogen Substances 0.000 claims description 133
• 229910052739 hydrogen Inorganic materials 0.000 claims description 133
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 92
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 79
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
• 125000000217 alkyl group Chemical group 0.000 claims description 64
• 238000006243 chemical reaction Methods 0.000 claims description 62
• 229910052736 halogen Inorganic materials 0.000 claims description 50
• 150000002367 halogens Chemical class 0.000 claims description 50
• 229910052757 nitrogen Inorganic materials 0.000 claims description 42
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 39
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 39
• 125000001424 substituent group Chemical group 0.000 claims description 37
• 125000004429 atom Chemical group 0.000 claims description 35
• 239000000203 mixture Substances 0.000 claims description 34
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 31
• 125000004476 heterocycloamino group Chemical group 0.000 claims description 28
• 125000004432 carbon atom Chemical group C* 0.000 claims description 25
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 17
• 238000011282 treatment Methods 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical group C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 10
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 9
• 125000002252 acyl group Chemical group 0.000 claims description 9
• 239000000654 additive Substances 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 8
• 125000003386 piperidinyl group Chemical group 0.000 claims description 8
• QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 claims description 8
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
• 230000000996 additive effect Effects 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 6
• 201000006417 multiple sclerosis Diseases 0.000 claims description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 5
• 239000002585 base Substances 0.000 claims description 5
• 125000002837 carbocyclic group Chemical group 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 150000002148 esters Chemical class 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 235000019260 propionic acid Nutrition 0.000 claims description 5
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 5
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 206010027476 Metastases Diseases 0.000 claims description 4
• 208000001132 Osteoporosis Diseases 0.000 claims description 4
• 230000001594 aberrant effect Effects 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 230000033115 angiogenesis Effects 0.000 claims description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 208000037803 restenosis Diseases 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• QKIHQFCYDKNBDP-QGZVFWFLSA-N (2r)-4-(dimethylcarbamoyl)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonylpiperazine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C=CC(F)=CC=2)CC1 QKIHQFCYDKNBDP-QGZVFWFLSA-N 0.000 claims description 3
• AVQNLPBUKQGTIW-GFCCVEGCSA-N (2r)-n-hydroxy-1-[4-(4,5,6,7-tetrafluoro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=C(F)C(F)=C(F)C(F)=C3NC=2)CC1 AVQNLPBUKQGTIW-GFCCVEGCSA-N 0.000 claims description 3
• ZUJIVHDUJHBQQG-CYBMUJFWSA-N (3r)-3-n-hydroxy-1-n,1-n-dimethyl-4-[4-(4,5,6,7-tetrafluoro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C3=C(F)C(F)=C(F)C(F)=C3NC=2)CC1 ZUJIVHDUJHBQQG-CYBMUJFWSA-N 0.000 claims description 3
• PMBFZMBLMABGCK-QGZVFWFLSA-N (3r)-4-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C=CC(F)=CC=2)CC1 PMBFZMBLMABGCK-QGZVFWFLSA-N 0.000 claims description 3
• ZGTUJWFPJXGONO-QGZVFWFLSA-N (3r)-4-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 ZGTUJWFPJXGONO-QGZVFWFLSA-N 0.000 claims description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 3
• 239000012964 benzotriazole Substances 0.000 claims description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 230000009401 metastasis Effects 0.000 claims description 3
• 208000028169 periodontal disease Diseases 0.000 claims description 3
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 3
• KRAGHFLTVIWIQP-QGZVFWFLSA-N (2r)-1-[[4-(4-fluoro-3-methylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]piperidine-2-carboxylic acid Chemical compound C1=C(F)C(C)=CC(C=2CCN(CC=2)S(=O)(=O)N2[C@H](CCCC2)C(O)=O)=C1 KRAGHFLTVIWIQP-QGZVFWFLSA-N 0.000 claims description 2
• QITZRWFHDISBIM-MRXNPFEDSA-N (2r)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-4-(2,2,2-trifluoroethyl)piperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(CC(F)(F)F)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 QITZRWFHDISBIM-MRXNPFEDSA-N 0.000 claims description 2
• KCRVQMUGCKXEME-MRXNPFEDSA-N (2r)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 KCRVQMUGCKXEME-MRXNPFEDSA-N 0.000 claims description 2
• ZVVNGVIQKLLPSJ-QGZVFWFLSA-N (3r)-4-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 ZVVNGVIQKLLPSJ-QGZVFWFLSA-N 0.000 claims description 2
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
• 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 2
• UHQKRLCCJFFEMZ-UHFFFAOYSA-N 2-(azepan-1-ylsulfonylazaniumyl)-4-methylpentanoate Chemical compound CC(C)CC(C(O)=O)NS(=O)(=O)N1CCCCCC1 UHQKRLCCJFFEMZ-UHFFFAOYSA-N 0.000 claims description 2
• JZIAAXXKIVZHLH-UHFFFAOYSA-N 2-(sulfamoylamino)acetic acid Chemical compound NS(=O)(=O)NCC(O)=O JZIAAXXKIVZHLH-UHFFFAOYSA-N 0.000 claims description 2
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
• 239000004305 biphenyl Substances 0.000 claims description 2
• 235000010290 biphenyl Nutrition 0.000 claims description 2
• 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 2
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
• 125000005879 dioxolanyl group Chemical group 0.000 claims description 2
• 125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 claims description 2
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
• 239000000651 prodrug Substances 0.000 claims description 2
• 229940002612 prodrug Drugs 0.000 claims description 2
• 125000005554 pyridyloxy group Chemical group 0.000 claims description 2
• 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims description 2
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• 125000001425 triazolyl group Chemical group 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 6
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 6
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 6
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 5
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 5
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 5
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 4
• 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims 3
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims 2
• BMQVWLIVQKJCOL-CQSZACIVSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1OC1=CC=C(Cl)C=N1 BMQVWLIVQKJCOL-CQSZACIVSA-N 0.000 claims 1
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
• 206010064996 Ulcerative keratitis Diseases 0.000 claims 1
• 125000003710 aryl alkyl group Chemical group 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 claims 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical class C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
• 125000001207 fluorophenyl group Chemical group 0.000 claims 1
• 239000012458 free base Substances 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 246
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 169
• 239000011541 reaction mixture Substances 0.000 description 98
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
• 239000000243 solution Substances 0.000 description 92
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 85
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
• 239000007787 solid Substances 0.000 description 51
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• 239000012267 brine Substances 0.000 description 32
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
• 238000003786 synthesis reaction Methods 0.000 description 32
• 230000015572 biosynthetic process Effects 0.000 description 31
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
• 229910004298 SiO 2 Inorganic materials 0.000 description 26
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
• 239000000463 material Substances 0.000 description 25
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 23
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 20
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
• 102000003390 tumor necrosis factor Human genes 0.000 description 20
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 17
• 239000011159 matrix material Substances 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• 238000012360 testing method Methods 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• 239000012074 organic phase Substances 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• 102000008186 Collagen Human genes 0.000 description 12
• 108010035532 Collagen Proteins 0.000 description 12
• 210000000845 cartilage Anatomy 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 229920001436 collagen Polymers 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 102000005741 Metalloproteases Human genes 0.000 description 11
• 108010006035 Metalloproteases Proteins 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 11
• 230000002401 inhibitory effect Effects 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
• 230000015556 catabolic process Effects 0.000 description 10
• 238000002474 experimental method Methods 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000002002 slurry Substances 0.000 description 10
• 102000004190 Enzymes Human genes 0.000 description 9
• 108090000790 Enzymes Proteins 0.000 description 9
• 239000012230 colorless oil Substances 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• UNEIHNMKASENIG-UHFFFAOYSA-N para-chlorophenylpiperazine Chemical compound C1=CC(Cl)=CC=C1N1CCNCC1 UNEIHNMKASENIG-UHFFFAOYSA-N 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 150000002430 hydrocarbons Chemical group 0.000 description 8
• 239000002609 medium Substances 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical group NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 210000001519 tissue Anatomy 0.000 description 8
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• 102000029816 Collagenase Human genes 0.000 description 7
• 108060005980 Collagenase Proteins 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• 239000006260 foam Substances 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 7
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 101150014058 MMP1 gene Proteins 0.000 description 6
• 102100030417 Matrilysin Human genes 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 6
• 230000003197 catalytic effect Effects 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 6
• 108700004333 collagenase 1 Proteins 0.000 description 6
• 238000006731 degradation reaction Methods 0.000 description 6
• 239000002158 endotoxin Substances 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 229920006008 lipopolysaccharide Polymers 0.000 description 6
• 150000007530 organic bases Chemical class 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 6
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 6
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
• 102000016359 Fibronectins Human genes 0.000 description 5
• 108010067306 Fibronectins Proteins 0.000 description 5
• 102000013382 Gelatinases Human genes 0.000 description 5
• 108010026132 Gelatinases Proteins 0.000 description 5
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 5
• 108090000855 Matrilysin Proteins 0.000 description 5
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
• 208000025865 Ulcer Diseases 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 206010003246 arthritis Diseases 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 239000000470 constituent Substances 0.000 description 5
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 229960002591 hydroxyproline Drugs 0.000 description 5
• MLCVNVBFXYHWKF-OAHLLOKOSA-N methyl (2r)-2-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCC1OC1=CC=C(Cl)C=N1 MLCVNVBFXYHWKF-OAHLLOKOSA-N 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 5
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 5
• 230000036269 ulceration Effects 0.000 description 5
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 4
• AMZYBOJPLHNYJD-UHFFFAOYSA-N 5-chloro-2-piperidin-4-yloxypyridine Chemical compound N1=CC(Cl)=CC=C1OC1CCNCC1 AMZYBOJPLHNYJD-UHFFFAOYSA-N 0.000 description 4
• VQFAITGIMWXQQK-UHFFFAOYSA-N 5-fluoro-3-piperidin-4-yl-1h-indole Chemical compound C12=CC(F)=CC=C2NC=C1C1CCNCC1 VQFAITGIMWXQQK-UHFFFAOYSA-N 0.000 description 4
• 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 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• 206010006895 Cachexia Diseases 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
• PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 4
• 102000000589 Interleukin-1 Human genes 0.000 description 4
• 108010002352 Interleukin-1 Proteins 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• VZOVOHRDLOYBJX-UHFFFAOYSA-N benzyl 4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)CCN1C(=O)OCC1=CC=CC=C1 VZOVOHRDLOYBJX-UHFFFAOYSA-N 0.000 description 4
• 210000000988 bone and bone Anatomy 0.000 description 4
• 235000015165 citric acid Nutrition 0.000 description 4
• 210000002808 connective tissue Anatomy 0.000 description 4
• 210000002744 extracellular matrix Anatomy 0.000 description 4
• 210000002950 fibroblast Anatomy 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 108020001507 fusion proteins Proteins 0.000 description 4
• 102000037865 fusion proteins Human genes 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 238000003018 immunoassay Methods 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
• 229960005141 piperazine Drugs 0.000 description 4
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
• 229940080818 propionamide Drugs 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 210000003491 skin Anatomy 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 4
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 229910052725 zinc Inorganic materials 0.000 description 4
• 239000011701 zinc Substances 0.000 description 4
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
• DDCGNGLDLSABLH-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)piperazin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2C=CC(Cl)=CC=2)CC1 DDCGNGLDLSABLH-UHFFFAOYSA-N 0.000 description 3
• WWEDZYDYJJJRQH-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2C=CC(Cl)=CC=2)CC1 WWEDZYDYJJJRQH-UHFFFAOYSA-N 0.000 description 3
• VHXBNTPMXWASHF-UHFFFAOYSA-N 1-[4-(5-hydroxy-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(O)=CC=C3NC=2)CC1 VHXBNTPMXWASHF-UHFFFAOYSA-N 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• KBYPITRKIJKGMD-UHFFFAOYSA-N 4-phenoxypiperidine Chemical compound C1CNCCC1OC1=CC=CC=C1 KBYPITRKIJKGMD-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 241000283690 Bos taurus Species 0.000 description 3
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
• 206010008111 Cerebral haemorrhage Diseases 0.000 description 3
• 102100027995 Collagenase 3 Human genes 0.000 description 3
• KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 description 3
• 108010062466 Enzyme Precursors Proteins 0.000 description 3
• 102000010911 Enzyme Precursors Human genes 0.000 description 3
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
• 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 108030004510 Interstitial collagenases Proteins 0.000 description 3
• 102000007547 Laminin Human genes 0.000 description 3
• 108010085895 Laminin Proteins 0.000 description 3
• 229940124761 MMP inhibitor Drugs 0.000 description 3
• 102100027998 Macrophage metalloelastase Human genes 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 3
• 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 108030001564 Neutrophil collagenases Proteins 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 102000016611 Proteoglycans Human genes 0.000 description 3
• 108010067787 Proteoglycans Proteins 0.000 description 3
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
• 206010064390 Tumour invasion Diseases 0.000 description 3
• 102000044159 Ubiquitin Human genes 0.000 description 3
• 108090000848 Ubiquitin Proteins 0.000 description 3
• 239000000443 aerosol Substances 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• XFBZJXICJOJLNY-UHFFFAOYSA-N benzyl 4-(5-cyano-1-methylsulfonylindol-3-yl)piperidine-1-carboxylate Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)C)C=C1C(CC1)CCN1C(=O)OCC1=CC=CC=C1 XFBZJXICJOJLNY-UHFFFAOYSA-N 0.000 description 3
• ONRNQGZXWCCYHO-UHFFFAOYSA-N benzyl 4-(5-cyano-1h-indol-3-yl)piperidine-1-carboxylate Chemical compound C1CC(C=2C3=CC(=CC=C3NC=2)C#N)CCN1C(=O)OCC1=CC=CC=C1 ONRNQGZXWCCYHO-UHFFFAOYSA-N 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 230000009400 cancer invasion Effects 0.000 description 3
• 239000013522 chelant Substances 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 239000007943 implant Substances 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• AEYVGCPMTAREPR-UHFFFAOYSA-N methyl 1-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2C=CC(Cl)=CC=2)CC1 AEYVGCPMTAREPR-UHFFFAOYSA-N 0.000 description 3
• XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 3
• 239000002245 particle Substances 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
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• RWBKUZKFJDCPKW-OAHLLOKOSA-N (2r)-1-(4-pyridin-4-ylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(SC=2C=CN=CC=2)CC1 RWBKUZKFJDCPKW-OAHLLOKOSA-N 0.000 description 2
• ZLJYKLLZYQNZGV-CQSZACIVSA-N (2r)-1-[4-(1h-pyrrol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C2=CNC=C2)CC1 ZLJYKLLZYQNZGV-CQSZACIVSA-N 0.000 description 2
• PRWJQRAJCLQTON-MRXNPFEDSA-N (2r)-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 PRWJQRAJCLQTON-MRXNPFEDSA-N 0.000 description 2
• OOZZCPLUTVIMEI-JOCHJYFZSA-N (2r)-1-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxy-4-(morpholine-4-carbonyl)piperazine-2-carboxamide Chemical compound C([C@@H](N(CC1)S(=O)(=O)N2CCC(CC2)C=2C3=CC(=CC=C3NC=2)C#N)C(=O)NO)N1C(=O)N1CCOCC1 OOZZCPLUTVIMEI-JOCHJYFZSA-N 0.000 description 2
• AIOLPATZBOCOCC-GOSISDBHSA-N (2r)-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 AIOLPATZBOCOCC-GOSISDBHSA-N 0.000 description 2
• XXHDRAXWDDIELL-JGCGQSQUSA-N (2r)-1-[4-[5-cyano-1-(2-trimethylsilylethylsulfonyl)indol-3-yl]piperidin-1-yl]sulfonyl-4-(dimethylsulfamoyl)-n-phenylmethoxypiperazine-2-carboxamide Chemical compound O=C([C@@H]1N(CCN(C1)S(=O)(=O)N(C)C)S(=O)(=O)N1CCC(CC1)C=1C2=CC(=CC=C2N(C=1)S(=O)(=O)CC[Si](C)(C)C)C#N)NOCC1=CC=CC=C1 XXHDRAXWDDIELL-JGCGQSQUSA-N 0.000 description 2
• HOWRWHAJEKYNFF-OAHLLOKOSA-N (2r)-2-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1OC1=CC=C(Cl)C=C1 HOWRWHAJEKYNFF-OAHLLOKOSA-N 0.000 description 2
• GMLVWNOSEUIYOQ-CQSZACIVSA-N (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C1=CC=C(Cl)C=C1 GMLVWNOSEUIYOQ-CQSZACIVSA-N 0.000 description 2
• UMINQNLGNYLPIZ-OAHLLOKOSA-N (2r)-2-[[4-(4-fluorophenoxy)piperidin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1OC1=CC=C(F)C=C1 UMINQNLGNYLPIZ-OAHLLOKOSA-N 0.000 description 2
• KJNSEWZWRWBGAZ-CQSZACIVSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(O)=O)CCC1OC1=CC=C(Cl)C=N1 KJNSEWZWRWBGAZ-CQSZACIVSA-N 0.000 description 2
• WSZLRMUWTDAHFS-QGZVFWFLSA-N (2r)-4-(dimethylcarbamoyl)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]piperazine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 WSZLRMUWTDAHFS-QGZVFWFLSA-N 0.000 description 2
• LQSWKVXINKOJEM-HXUWFJFHSA-N (2r)-n-hydroxy-3-methyl-2-[[4-(2-phenyl-1,3-benzoxazol-5-yl)piperazin-1-yl]sulfonylamino]butanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C1=CC=C(OC(=N2)C=3C=CC=CC=3)C2=C1 LQSWKVXINKOJEM-HXUWFJFHSA-N 0.000 description 2
• FSOBGFSGJSCGFE-OAQYLSRUSA-N (2r)-n-hydroxy-3-methyl-2-[[4-(4-phenylmethoxyphenyl)piperazin-1-yl]sulfonylamino]butanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C(C=C1)=CC=C1OCC1=CC=CC=C1 FSOBGFSGJSCGFE-OAQYLSRUSA-N 0.000 description 2
• NJIRVDHXDLPXJR-GOSISDBHSA-N (2r)-n-phenylmethoxy-1-[4-(4,5,6,7-tetrafluoro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperazine-2-carboxamide Chemical compound O=C([C@H]1CNCCN1S(=O)(=O)N1CCC(CC1)C=1C2=C(F)C(F)=C(C(=C2NC=1)F)F)NOCC1=CC=CC=C1 NJIRVDHXDLPXJR-GOSISDBHSA-N 0.000 description 2
• OGAGNRSAVQGTAA-HXUWFJFHSA-N (3r)-1-n,1-n-dimethyl-3-n-phenylmethoxy-4-[4-(4,5,6,7-tetrafluoro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperazine-1,3-dicarboxamide Chemical compound O=C([C@@H]1N(CCN(C1)C(=O)N(C)C)S(=O)(=O)N1CCC(CC1)C=1C2=C(F)C(F)=C(F)C(F)=C2NC=1)NOCC1=CC=CC=C1 OGAGNRSAVQGTAA-HXUWFJFHSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• ZTLOZFLZBKZABP-UHFFFAOYSA-N 1-(5-chloropyridin-2-yl)piperazine Chemical compound N1=CC(Cl)=CC=C1N1CCNCC1 ZTLOZFLZBKZABP-UHFFFAOYSA-N 0.000 description 2
• ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-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
• WWCJISMKYBHASZ-UHFFFAOYSA-N 2-(chlorosulfonylamino)acetic acid Chemical compound OC(=O)CNS(Cl)(=O)=O WWCJISMKYBHASZ-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• WXTZXJVJCXWCHU-UHFFFAOYSA-N 2-[1,1-dioxo-5-[(4-phenylphenyl)methyl]-1,2,5-thiadiazolidin-2-yl]-n-hydroxyacetamide Chemical compound O=S1(=O)N(CC(=O)NO)CCN1CC1=CC=C(C=2C=CC=CC=2)C=C1 WXTZXJVJCXWCHU-UHFFFAOYSA-N 0.000 description 2
• CFZRULATCKWWDS-UHFFFAOYSA-N 2-[1,1-dioxo-5-[(4-phenylphenyl)methyl]-1,2,5-thiadiazolidin-2-yl]acetic acid Chemical compound O=S1(=O)N(CC(=O)O)CCN1CC1=CC=C(C=2C=CC=CC=2)C=C1 CFZRULATCKWWDS-UHFFFAOYSA-N 0.000 description 2
• YMCFWPXQTPNUBN-UHFFFAOYSA-N 3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indol-5-ol Chemical compound C12=CC(O)=CC=C2NC=C1C1=CCNCC1 YMCFWPXQTPNUBN-UHFFFAOYSA-N 0.000 description 2
• ALEJLUQMYJXRFY-UHFFFAOYSA-N 3-piperidin-4-yl-1-(2-trimethylsilylethylsulfonyl)indole-5-carbonitrile Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)CC[Si](C)(C)C)C=C1C1CCNCC1 ALEJLUQMYJXRFY-UHFFFAOYSA-N 0.000 description 2
• XOYQYCDKGORDBS-UHFFFAOYSA-N 3-piperidin-4-yl-1h-indol-5-ol Chemical compound C12=CC(O)=CC=C2NC=C1C1CCNCC1 XOYQYCDKGORDBS-UHFFFAOYSA-N 0.000 description 2
• BLTPAQMLCMLLLT-UHFFFAOYSA-N 4,5,6,7-tetrafluoro-3-piperidin-4-yl-1h-indole Chemical compound C=1NC2=C(F)C(F)=C(F)C(F)=C2C=1C1CCNCC1 BLTPAQMLCMLLLT-UHFFFAOYSA-N 0.000 description 2
• VOQMPZXAFLPTMM-UHFFFAOYSA-N 4-(4-chlorophenoxy)piperidine Chemical compound C1=CC(Cl)=CC=C1OC1CCNCC1 VOQMPZXAFLPTMM-UHFFFAOYSA-N 0.000 description 2
• OEZMPJSEOJYIIJ-UHFFFAOYSA-N 4-(4-chlorophenyl)piperazine-1-sulfonamide Chemical compound C1CN(S(=O)(=O)N)CCN1C1=CC=C(Cl)C=C1 OEZMPJSEOJYIIJ-UHFFFAOYSA-N 0.000 description 2
• MGNCYSGEAVTZGZ-UHFFFAOYSA-N 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine;sulfamoyl chloride Chemical compound NS(Cl)(=O)=O.C1=CC(F)=CC=C1C1=CCNCC1 MGNCYSGEAVTZGZ-UHFFFAOYSA-N 0.000 description 2
• BINPIXWWYPDKPG-UHFFFAOYSA-N 4-acetyl-n-hydroxy-1-[4-(6-methyl-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperazine-2-carboxamide Chemical compound ONC(=O)C1CN(C(=O)C)CCN1S(=O)(=O)N1CCC(C=2C3=CC=C(C)C=C3NC=2)CC1 BINPIXWWYPDKPG-UHFFFAOYSA-N 0.000 description 2
• 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
• 206010048998 Acute phase reaction Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 2
• 102000016942 Elastin Human genes 0.000 description 2
• 108010014258 Elastin Proteins 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 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
• 208000032843 Hemorrhage Diseases 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• 102000004125 Interleukin-1alpha Human genes 0.000 description 2
• 108010082786 Interleukin-1alpha Proteins 0.000 description 2
• 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 2
• 101150101095 Mmp12 gene Proteins 0.000 description 2
• SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
• 102000056189 Neutrophil collagenases Human genes 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 150000001242 acetic acid derivatives Chemical class 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 230000004658 acute-phase response Effects 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 208000026935 allergic disease Diseases 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 150000001413 amino acids Chemical group 0.000 description 2
• 208000022531 anorexia Diseases 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• UIXLFOUEQUCASZ-UHFFFAOYSA-N azanium;4-phenylmethoxycarbonylpiperazine-2-carboxylate Chemical compound [NH4+].C1CNC(C(=O)[O-])CN1C(=O)OCC1=CC=CC=C1 UIXLFOUEQUCASZ-UHFFFAOYSA-N 0.000 description 2
• 210000002469 basement membrane Anatomy 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• AWXIWDSKNDYSSO-UHFFFAOYSA-N benzyl 4-(4,5,6,7-tetrafluoro-1h-indol-3-yl)piperidine-1-carboxylate Chemical compound C=1NC2=C(F)C(F)=C(F)C(F)=C2C=1C(CC1)CCN1C(=O)OCC1=CC=CC=C1 AWXIWDSKNDYSSO-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 239000012320 chlorinating reagent Substances 0.000 description 2
• 230000015271 coagulation Effects 0.000 description 2
• 238000005345 coagulation Methods 0.000 description 2
• 229910052681 coesite Inorganic materials 0.000 description 2
• 229940125904 compound 1 Drugs 0.000 description 2
• 229910052906 cristobalite Inorganic materials 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 206010061428 decreased appetite Diseases 0.000 description 2
• 238000000502 dialysis Methods 0.000 description 2
• 229950001902 dimevamide Drugs 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• 229940088679 drug related substance Drugs 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 229920002549 elastin Polymers 0.000 description 2
• JHHLUTYUARUAJG-UHFFFAOYSA-N ethyl 2-[benzyl(chlorosulfonyl)amino]acetate Chemical compound CCOC(=O)CN(S(Cl)(=O)=O)CC1=CC=CC=C1 JHHLUTYUARUAJG-UHFFFAOYSA-N 0.000 description 2
• 239000012894 fetal calf serum Substances 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 208000006454 hepatitis Diseases 0.000 description 2
• 231100000283 hepatitis Toxicity 0.000 description 2
• 239000008241 heterogeneous mixture Substances 0.000 description 2
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 150000002513 isocyanates Chemical class 0.000 description 2
• 210000002510 keratinocyte Anatomy 0.000 description 2
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 210000002540 macrophage Anatomy 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
• 230000001404 mediated effect Effects 0.000 description 2
• 210000004379 membrane Anatomy 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• UPJSBXQGQXZKHA-OAHLLOKOSA-N methyl (2r)-1-[4-(1h-pyrrol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C2=CNC=C2)CC1 UPJSBXQGQXZKHA-OAHLLOKOSA-N 0.000 description 2
• DZWKSOIUIMKFSI-XMMPIXPASA-N methyl (2r)-1-[4-[1-tri(propan-2-yl)silylpyrrol-3-yl]piperidin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C2=CN(C=C2)[Si](C(C)C)(C(C)C)C(C)C)CC1 DZWKSOIUIMKFSI-XMMPIXPASA-N 0.000 description 2
• CTTWCVAPMBATKM-XMMPIXPASA-N methyl (2r)-2-[[4-(4-bromophenyl)piperidin-1-yl]sulfonyl-(3-pyridin-3-ylpropyl)amino]-3-methylbutanoate Chemical compound C1CC(C=2C=CC(Br)=CC=2)CCN1S(=O)(=O)N([C@H](C(C)C)C(=O)OC)CCCC1=CC=CN=C1 CTTWCVAPMBATKM-XMMPIXPASA-N 0.000 description 2
• QXFDEAKURRXWIW-JOCHJYFZSA-N methyl (2r)-2-[[4-(4-bromophenyl)piperidin-1-yl]sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanoate Chemical compound C1CC(C=2C=CC(Br)=CC=2)CCN1S(=O)(=O)N([C@H](C(C)C)C(=O)OC)CC1=CC=CN=C1 QXFDEAKURRXWIW-JOCHJYFZSA-N 0.000 description 2
• JGHQJEPDGFHHID-MRXNPFEDSA-N methyl (2r)-2-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCC1OC1=CC=C(Cl)C=C1 JGHQJEPDGFHHID-MRXNPFEDSA-N 0.000 description 2
• SHDDNJQRXSPADI-OAHLLOKOSA-N methyl (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCN1C1=CC=C(Cl)C=C1 SHDDNJQRXSPADI-OAHLLOKOSA-N 0.000 description 2
• ZNAOEFHEEKELNF-MRXNPFEDSA-N methyl (2r)-2-[[4-(4-fluorophenoxy)piperidin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCC1OC1=CC=C(F)C=C1 ZNAOEFHEEKELNF-MRXNPFEDSA-N 0.000 description 2
• SZRLGBNAZCAZRK-CQSZACIVSA-N methyl (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCN1C1=CC=C(Cl)C=N1 SZRLGBNAZCAZRK-CQSZACIVSA-N 0.000 description 2
• GKOGEYICOZZVOJ-QGZVFWFLSA-N methyl (2r)-2-[benzyl-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]propanoate Chemical compound C1CN(C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)N([C@H](C)C(=O)OC)CC1=CC=CC=C1 GKOGEYICOZZVOJ-QGZVFWFLSA-N 0.000 description 2
• CEMZBWPSKYISTN-RXMQYKEDSA-N methyl (2r)-2-amino-3-methylbutanoate Chemical compound COC(=O)[C@H](N)C(C)C CEMZBWPSKYISTN-RXMQYKEDSA-N 0.000 description 2
• LCAZZODKOZWQKX-GOSISDBHSA-N methyl (2r)-3-methyl-2-[[4-(5-phenyl-1h-imidazol-2-yl)piperidin-1-yl]sulfonylamino]butanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCC1C1=NC(C=2C=CC=CC=2)=CN1 LCAZZODKOZWQKX-GOSISDBHSA-N 0.000 description 2
• AODDUEAVSOMLPS-UHFFFAOYSA-N methyl 1-(4-phenylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1S(=O)(=O)N1CCC(SC=2C=CC=CC=2)CC1 AODDUEAVSOMLPS-UHFFFAOYSA-N 0.000 description 2
• CBDLVRNFICLZDM-UHFFFAOYSA-N methyl 2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl-methylamino]-4-phenylbutanoate Chemical compound C1CN(C=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)N(C)C(C(=O)OC)CCC1=CC=CC=C1 CBDLVRNFICLZDM-UHFFFAOYSA-N 0.000 description 2
• DNIDFDKZHXUOGH-UHFFFAOYSA-N methyl 2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-4-phenylbutanoate Chemical compound C1CN(C=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)NC(C(=O)OC)CCC1=CC=CC=C1 DNIDFDKZHXUOGH-UHFFFAOYSA-N 0.000 description 2
• CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical group COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 2
• 210000002864 mononuclear phagocyte Anatomy 0.000 description 2
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
• RIBBVCBXKCZBSJ-UHFFFAOYSA-N n-hydroxy-1-(4-phenoxypiperidin-1-yl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(OC=2C=CC=CC=2)CC1 RIBBVCBXKCZBSJ-UHFFFAOYSA-N 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• SSUCKKNRCOFUPT-UHFFFAOYSA-N o-[tert-butyl(dimethyl)silyl]hydroxylamine Chemical compound CC(C)(C)[Si](C)(C)ON SSUCKKNRCOFUPT-UHFFFAOYSA-N 0.000 description 2
• KKVUFSINQFSJNK-UHFFFAOYSA-N o-tert-butylhydroxylamine Chemical compound CC(C)(C)ON KKVUFSINQFSJNK-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• BRYCUMKDWMEGMK-UHFFFAOYSA-N piperazine-2-carboxamide Chemical compound NC(=O)C1CNCCN1 BRYCUMKDWMEGMK-UHFFFAOYSA-N 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 238000012746 preparative thin layer chromatography Methods 0.000 description 2
• 108010067415 progelatinase Proteins 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 229910052682 stishovite Inorganic materials 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• CKLQTBZRZXIQRW-UHFFFAOYSA-N sulfamoyl chloride;4,5,6,7-tetrafluoro-3-piperidin-4-yl-1h-indole Chemical compound NS(Cl)(=O)=O.C=1NC2=C(F)C(F)=C(F)C(F)=C2C=1C1CCNCC1 CKLQTBZRZXIQRW-UHFFFAOYSA-N 0.000 description 2
• 238000005694 sulfonylation reaction Methods 0.000 description 2
• 239000013589 supplement Substances 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• QJIDTHNWWRLAGC-XMMPIXPASA-N tert-butyl (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-phenylpropanoate Chemical compound C([C@H](C(=O)OC(C)(C)C)N(C(=O)OC(C)(C)C)S(=O)(=O)N1CCN(CC1)C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 QJIDTHNWWRLAGC-XMMPIXPASA-N 0.000 description 2
• UUXHSLJTFJBZPX-UHFFFAOYSA-N tert-butyl 2-[1,1-dioxo-5-[(4-phenylphenyl)methyl]-1,2,5-thiadiazolidin-2-yl]acetate Chemical compound O=S1(=O)N(CC(=O)OC(C)(C)C)CCN1CC1=CC=C(C=2C=CC=CC=2)C=C1 UUXHSLJTFJBZPX-UHFFFAOYSA-N 0.000 description 2
• QYTJFOBUAJLXAR-UHFFFAOYSA-N tert-butyl 4-(5-fluoro-1h-indol-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CNC2=CC=C(F)C=C12 QYTJFOBUAJLXAR-UHFFFAOYSA-N 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
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 229910052905 tridymite Inorganic materials 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 235000013311 vegetables Nutrition 0.000 description 2
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• GUEHESDOJBMSSE-UHFFFAOYSA-M (2-aminophenyl)mercury(1+);acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1N GUEHESDOJBMSSE-UHFFFAOYSA-M 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• GUFHMBFLDVPMOU-QGZVFWFLSA-N (2r)-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-4-(dimethylsulfamoyl)-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(S(=O)(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 GUFHMBFLDVPMOU-QGZVFWFLSA-N 0.000 description 1
• CYWBUKTUFWLGMY-GOSISDBHSA-N (2r)-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-n-[(2-methylpropan-2-yl)oxy]piperazine-2-carboxamide Chemical compound CC(C)(C)ONC(=O)[C@H]1CNCCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 CYWBUKTUFWLGMY-GOSISDBHSA-N 0.000 description 1
• NZCYDESFDSCXTG-MRXNPFEDSA-N (2r)-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 NZCYDESFDSCXTG-MRXNPFEDSA-N 0.000 description 1
• WKJHULNWMREZBN-QGZVFWFLSA-N (2r)-1-[4-(4-chlorophenyl)piperidin-1-yl]sulfonyl-4-(dimethylcarbamoyl)piperazine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C=CC(Cl)=CC=2)CC1 WKJHULNWMREZBN-QGZVFWFLSA-N 0.000 description 1
• ZOUIBRXIOYYLNH-OEMAIJDKSA-N (2r)-1-[4-(4-chlorophenyl)piperidin-1-yl]sulfonyl-n,4-dihydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CC(O)CCN1S(=O)(=O)N1CCC(C=2C=CC(Cl)=CC=2)CC1 ZOUIBRXIOYYLNH-OEMAIJDKSA-N 0.000 description 1
• OZSSQGXGWHBIGA-MRXNPFEDSA-N (2r)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-n-hydroxy-4-(2,2,2-trifluoroethyl)piperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(CC(F)(F)F)CCN1S(=O)(=O)N1CCC(C=2C=CC(F)=CC=2)CC1 OZSSQGXGWHBIGA-MRXNPFEDSA-N 0.000 description 1
• CDGQVDXCVAPZCN-LJQANCHMSA-N (2r)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-n-hydroxy-4-(morpholine-4-carbonyl)piperazine-2-carboxamide Chemical compound C([C@@H]1C(=O)NO)N(C(=O)N2CCOCC2)CCN1S(=O)(=O)N(CC1)CCC1C1=CC=C(F)C=C1 CDGQVDXCVAPZCN-LJQANCHMSA-N 0.000 description 1
• NORUZOXLVJRPIK-LJQANCHMSA-N (2r)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-n-hydroxy-4-morpholin-4-ylsulfonylpiperazine-2-carboxamide Chemical compound C([C@@H]1C(=O)NO)N(S(=O)(=O)N2CCOCC2)CCN1S(=O)(=O)N(CC1)CCC1C1=CC=C(F)C=C1 NORUZOXLVJRPIK-LJQANCHMSA-N 0.000 description 1
• PBNBKLYZGHYUAZ-MRXNPFEDSA-N (2r)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C=CC(F)=CC=2)CC1 PBNBKLYZGHYUAZ-MRXNPFEDSA-N 0.000 description 1
• IZNBYWSZOOOPAE-HXUWFJFHSA-N (2r)-1-[4-(5-cyano-1-methylsulfonylindol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)C)C=C1C(CC1)CCN1S(=O)(=O)N1CCCC[C@@H]1C(=O)NO IZNBYWSZOOOPAE-HXUWFJFHSA-N 0.000 description 1
• RDEYQKUTZYBPOR-HXUWFJFHSA-N (2r)-1-[4-(5-cyano-1-methylsulfonylindol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)C)C=C1C(CC1)CCN1S(=O)(=O)N1CCCC[C@@H]1C(O)=O RDEYQKUTZYBPOR-HXUWFJFHSA-N 0.000 description 1
• UDMLJMBEQBKXKJ-HXUWFJFHSA-N (2r)-1-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]sulfonyl-4-(dimethylsulfamoyl)-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(S(=O)(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C3=CC(=CC=C3NC=2)C#N)CC1 UDMLJMBEQBKXKJ-HXUWFJFHSA-N 0.000 description 1
• SXQGKDWGOGJLBE-HHHXNRCGSA-N (2r)-1-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]sulfonyl-4-(dimethylsulfamoyl)-n-phenylmethoxypiperazine-2-carboxamide Chemical compound O=C([C@@H]1N(CCN(C1)S(=O)(=O)N(C)C)S(=O)(=O)N1CCC(CC1)C=1C2=CC(=CC=C2NC=1)C#N)NOCC1=CC=CC=C1 SXQGKDWGOGJLBE-HHHXNRCGSA-N 0.000 description 1
• HEARGSJFMNPWOX-LJQANCHMSA-N (2r)-1-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxy-4-(2,2,2-trifluoroethyl)piperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(CC(F)(F)F)CCN1S(=O)(=O)N1CCC(C=2C3=CC(=CC=C3NC=2)C#N)CC1 HEARGSJFMNPWOX-LJQANCHMSA-N 0.000 description 1
• XDCNNKFVXAUJSU-LJQANCHMSA-N (2r)-1-[4-(5-cyano-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(=CC=C3NC=2)C#N)CC1 XDCNNKFVXAUJSU-LJQANCHMSA-N 0.000 description 1
• IAEAVFXRJOKGQD-GOSISDBHSA-N (2r)-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-4-formyl-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(C=O)CCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 IAEAVFXRJOKGQD-GOSISDBHSA-N 0.000 description 1
• JSUUSRQDGRWNKF-LJQANCHMSA-N (2r)-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxy-n-methylpiperidine-2-carboxamide Chemical compound CN(O)C(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 JSUUSRQDGRWNKF-LJQANCHMSA-N 0.000 description 1
• ITMKARKAIFINEE-RUZDIDTESA-N (2r)-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-phenylmethoxypiperidine-2-carboxamide Chemical compound O=C([C@H]1CCCCN1S(=O)(=O)N1CCC(CC1)C1=CNC2=CC=C(C=C21)F)NOCC1=CC=CC=C1 ITMKARKAIFINEE-RUZDIDTESA-N 0.000 description 1
• OBNCQRGXXLLEHY-GOSISDBHSA-N (2r)-1-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC=C(Cl)C=C3NC=2)CC1 OBNCQRGXXLLEHY-GOSISDBHSA-N 0.000 description 1
• KZTPWWSBINJDLM-OAHLLOKOSA-N (2r)-1-[4-(6-fluoro-1,2-benzothiazol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC=C(F)C=C3SN=2)CC1 KZTPWWSBINJDLM-OAHLLOKOSA-N 0.000 description 1
• QRGCSIMLWQGCRC-HXUWFJFHSA-N (2r)-1-[4-[5-(4-chlorophenyl)-1h-pyrrol-2-yl]piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2NC(=CC=2)C=2C=CC(Cl)=CC=2)CC1 QRGCSIMLWQGCRC-HXUWFJFHSA-N 0.000 description 1
• UZCHIJMNFOONOL-MRXNPFEDSA-N (2r)-1-[[4-(3-chloro-4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]piperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1S(=O)(=O)N1CC=C(C=2C=C(Cl)C(F)=CC=2)CC1 UZCHIJMNFOONOL-MRXNPFEDSA-N 0.000 description 1
• YBSSMKSSLFLVLK-QGZVFWFLSA-N (2r)-1-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-4-(dimethylsulfamoyl)piperazine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CN(S(=O)(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(Cl)=CC=2)CC1 YBSSMKSSLFLVLK-QGZVFWFLSA-N 0.000 description 1
• KNRPSOXOQCVYEE-QGZVFWFLSA-N (2r)-1-[[4-(4-fluoro-3-methylphenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxypiperidine-2-carboxamide Chemical compound C1=C(F)C(C)=CC(C=2CCN(CC=2)S(=O)(=O)N2[C@H](CCCC2)C(=O)NO)=C1 KNRPSOXOQCVYEE-QGZVFWFLSA-N 0.000 description 1
• GGFKIIWUVMOESL-LJQANCHMSA-N (2r)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-4-(morpholine-4-carbonyl)piperazine-2-carboxamide Chemical compound C([C@@H]1C(=O)NO)N(C(=O)N2CCOCC2)CCN1S(=O)(=O)N(CC=1)CCC=1C1=CC=C(F)C=C1 GGFKIIWUVMOESL-LJQANCHMSA-N 0.000 description 1
• WKGRZNZXWIPOCT-LJQANCHMSA-N (2r)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-4-morpholin-4-ylsulfonylpiperazine-2-carboxamide Chemical compound C([C@@H]1C(=O)NO)N(S(=O)(=O)N2CCOCC2)CCN1S(=O)(=O)N(CC=1)CCC=1C1=CC=C(F)C=C1 WKGRZNZXWIPOCT-LJQANCHMSA-N 0.000 description 1
• WTECAOZWVGHXGI-GOSISDBHSA-N (2r)-2-(4-fluorophenyl)-2-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonylamino]-n-hydroxyacetamide Chemical compound N([C@@H](C(=O)NO)C=1C=CC(F)=CC=1)S(=O)(=O)N(CC=1)CCC=1C1=CC=C(F)C=C1 WTECAOZWVGHXGI-GOSISDBHSA-N 0.000 description 1
• MTUGUUZQCNGNFX-GOSISDBHSA-N (2r)-2-(4-fluorophenyl)-2-[[4-(4-fluorophenyl)piperidin-1-yl]sulfonylamino]-n-hydroxyacetamide Chemical compound N([C@@H](C(=O)NO)C=1C=CC(F)=CC=1)S(=O)(=O)N(CC1)CCC1C1=CC=C(F)C=C1 MTUGUUZQCNGNFX-GOSISDBHSA-N 0.000 description 1
• HOVDQRMTFJAOKK-OAHLLOKOSA-N (2r)-2-[(4-benzyl-4-hydroxypiperidin-1-yl)sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1(O)CC1=CC=CC=C1 HOVDQRMTFJAOKK-OAHLLOKOSA-N 0.000 description 1
• QCRKIVZMHYNNBI-MRXNPFEDSA-N (2r)-2-[2-phenylethyl(2-phenylethylsulfamoyl)amino]propanoic acid Chemical compound C=1C=CC=CC=1CCNS(=O)(=O)N([C@H](C)C(O)=O)CCC1=CC=CC=C1 QCRKIVZMHYNNBI-MRXNPFEDSA-N 0.000 description 1
• QCIYDGYJDRMPGI-HSZRJFAPSA-N (2r)-2-[[4-(4-bromophenyl)piperidin-1-yl]sulfonyl-(3-pyridin-3-ylpropyl)amino]-n-hydroxy-3-methylbutanamide Chemical compound C1CC(C=2C=CC(Br)=CC=2)CCN1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CCCC1=CC=CN=C1 QCIYDGYJDRMPGI-HSZRJFAPSA-N 0.000 description 1
• OVGJEFFKRQUBSN-OAQYLSRUSA-N (2r)-2-[[4-(4-bromophenyl)piperidin-1-yl]sulfonyl-(pyridin-3-ylmethyl)amino]-n-hydroxy-3-methylbutanamide Chemical compound C1CC(C=2C=CC(Br)=CC=2)CCN1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CC1=CC=CN=C1 OVGJEFFKRQUBSN-OAQYLSRUSA-N 0.000 description 1
• XLCJBHNKUPHYJQ-OAHLLOKOSA-N (2r)-2-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(O)=O)CCC1C(=O)C1=CC=C(Cl)C=C1 XLCJBHNKUPHYJQ-OAHLLOKOSA-N 0.000 description 1
• KSMABAPTGXILQS-LJQANCHMSA-N (2r)-2-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-n-hydroxy-3-phenylpropanethioamide Chemical compound C([C@H](C(=S)NO)NS(=O)(=O)N1CCC(CC1)C(=O)C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 KSMABAPTGXILQS-LJQANCHMSA-N 0.000 description 1
• FSLMMJYCPSDZPO-OAHLLOKOSA-N (2r)-2-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(O)=O)CCC1OC1=CC=C(Cl)C=C1 FSLMMJYCPSDZPO-OAHLLOKOSA-N 0.000 description 1
• ALPDXZZVWMQAGH-CQSZACIVSA-N (2r)-2-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylamino]-n-hydroxybutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](CC)C(=O)NO)CCC1OC1=CC=C(Cl)C=C1 ALPDXZZVWMQAGH-CQSZACIVSA-N 0.000 description 1
• LJGXPNMDWVGUCD-SNVBAGLBSA-N (2r)-2-[[4-(4-chlorophenoxy)piperidin-1-yl]sulfonylamino]-n-hydroxypropanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCC1OC1=CC=C(Cl)C=C1 LJGXPNMDWVGUCD-SNVBAGLBSA-N 0.000 description 1
• RXHALQFBQHAVEJ-GOSISDBHSA-N (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-3-phenylpropanoic acid Chemical compound C([C@H](C(=O)O)NS(=O)(=O)N1CCN(CC1)C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 RXHALQFBQHAVEJ-GOSISDBHSA-N 0.000 description 1
• ABDKEONHOCKUJZ-AWEZNQCLSA-N (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3,3-dimethylbutanethioamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)(C)C)C(=S)NO)CCN1C1=CC=C(Cl)C=C1 ABDKEONHOCKUJZ-AWEZNQCLSA-N 0.000 description 1
• OSRPJWLCUYFDAR-CQSZACIVSA-N (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxypentanamide Chemical compound C1CN(S(=O)(=O)N[C@H](CCC)C(=O)NO)CCN1C1=CC=C(Cl)C=C1 OSRPJWLCUYFDAR-CQSZACIVSA-N 0.000 description 1
• QGLRLQKPPAPIFH-SNVBAGLBSA-N (2r)-2-[[4-(4-chlorophenyl)piperidin-1-yl]sulfonylamino]propanoic acid Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(O)=O)CCC1C1=CC=C(Cl)C=C1 QGLRLQKPPAPIFH-SNVBAGLBSA-N 0.000 description 1
• OZBXBAUELQCNCH-OAHLLOKOSA-N (2r)-2-[[4-(4-cyanophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C1=CC=C(C#N)C=C1 OZBXBAUELQCNCH-OAHLLOKOSA-N 0.000 description 1
• WELUMSPRUSXHAV-QGZVFWFLSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-2-cyclohexyl-n-hydroxyacetamide Chemical compound N([C@@H](C(=O)NO)C1CCCCC1)S(=O)(=O)N(CC1)CCC1OC1=CC=C(Cl)C=N1 WELUMSPRUSXHAV-QGZVFWFLSA-N 0.000 description 1
• YAZCLYSEGYXPPP-CQSZACIVSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1CN(S(=O)(=O)N[C@H](CC(C)C)C(=O)NO)CCC1OC1=CC=C(Cl)C=N1 YAZCLYSEGYXPPP-CQSZACIVSA-N 0.000 description 1
• DQUDGSFMKNLOAF-GOSISDBHSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl-methylamino]-n-hydroxy-3-phenylmethoxypropanamide Chemical compound C([C@@H](N(C)S(=O)(=O)N1CCN(CC1)C=1N=CC(Cl)=CC=1)C(=O)NO)OCC1=CC=CC=C1 DQUDGSFMKNLOAF-GOSISDBHSA-N 0.000 description 1
• AOFLUZDRKIKYQD-MRXNPFEDSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-(4-hydroxyphenyl)propanamide Chemical compound C([C@H](C(=O)NO)NS(=O)(=O)N1CCN(CC1)C=1N=CC(Cl)=CC=1)C1=CC=C(O)C=C1 AOFLUZDRKIKYQD-MRXNPFEDSA-N 0.000 description 1
• ACXYHWHUHZTNFP-CYBMUJFWSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C1=CC=C(Cl)C=N1 ACXYHWHUHZTNFP-CYBMUJFWSA-N 0.000 description 1
• ATLFQXCHOWOUTO-INIZCTEOSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-phenylsulfanylpropanamide Chemical compound C([C@@H](C(=O)NO)NS(=O)(=O)N1CCN(CC1)C=1N=CC(Cl)=CC=1)SC1=CC=CC=C1 ATLFQXCHOWOUTO-INIZCTEOSA-N 0.000 description 1
• LRQRZFSEFVYJHB-AWEZNQCLSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-n-hydroxy-3-pyridin-2-ylsulfanylpropanamide Chemical compound C([C@@H](C(=O)NO)NS(=O)(=O)N1CCN(CC1)C=1N=CC(Cl)=CC=1)SC1=CC=CC=N1 LRQRZFSEFVYJHB-AWEZNQCLSA-N 0.000 description 1
• CJLHXDNGCYMIRV-GFCCVEGCSA-N (2r)-2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonylamino]-n-hydroxypentanamide Chemical compound C1CN(S(=O)(=O)N[C@H](CCC)C(=O)NO)CCN1C1=CC=C(Cl)C=N1 CJLHXDNGCYMIRV-GFCCVEGCSA-N 0.000 description 1
• QSPQEYANZDGXHR-CQSZACIVSA-N (2r)-2-[[4-(6-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1OC1=CC=CC(Cl)=N1 QSPQEYANZDGXHR-CQSZACIVSA-N 0.000 description 1
• GYNSHUXWOBBRDP-CYBMUJFWSA-N (2r)-2-[[4-(6-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylamino]-n-hydroxy-4,4-dimethylpentanamide Chemical compound C1CN(S(=O)(=O)N[C@H](CC(C)(C)C)C(=O)NO)CCC1OC1=CC=CC(Cl)=N1 GYNSHUXWOBBRDP-CYBMUJFWSA-N 0.000 description 1
• GGRSLHGUASDLKE-GFCCVEGCSA-N (2r)-2-[[4-[2-[(4-chlorophenyl)methylamino]-2-oxoethyl]piperidin-1-yl]sulfonylamino]-n-hydroxypropanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCC1CC(=O)NCC1=CC=C(Cl)C=C1 GGRSLHGUASDLKE-GFCCVEGCSA-N 0.000 description 1
• KIZVKSSRFXPSOF-MRXNPFEDSA-N (2r)-2-[benzyl(piperidin-1-ylsulfonyl)amino]-n-hydroxy-3-methylbutanamide Chemical compound C1CCCCN1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CC1=CC=CC=C1 KIZVKSSRFXPSOF-MRXNPFEDSA-N 0.000 description 1
• JUZWEVXSXSWGTG-MRXNPFEDSA-N (2r)-2-[benzyl-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxypropanamide Chemical compound C1CN(C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)N([C@H](C)C(=O)NO)CC1=CC=CC=C1 JUZWEVXSXSWGTG-MRXNPFEDSA-N 0.000 description 1
• DYLFNYAYUYTGMH-HXUWFJFHSA-N (2r)-3-methyl-2-[[4-[2-(pyridin-4-ylmethoxy)phenyl]piperazin-1-yl]sulfonylamino]butanoic acid Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(O)=O)CCN1C1=CC=CC=C1OCC1=CC=NC=C1 DYLFNYAYUYTGMH-HXUWFJFHSA-N 0.000 description 1
• AFNJYPCPILRYBJ-OAQYLSRUSA-N (2r)-4-(cyclopropylmethyl)-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperazine-2-carboxamide Chemical compound C([C@@H](N(CC1)S(=O)(=O)N2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)C(=O)NO)N1CC1CC1 AFNJYPCPILRYBJ-OAQYLSRUSA-N 0.000 description 1
• JZZBBHDGFCVQOW-OAQYLSRUSA-N (2r)-4-(cyclopropylmethyl)-1-[4-(6-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperazine-2-carboxamide Chemical compound C([C@@H](N(CC1)S(=O)(=O)N2CCC(CC2)C=2C3=CC=C(F)C=C3NC=2)C(=O)NO)N1CC1CC1 JZZBBHDGFCVQOW-OAQYLSRUSA-N 0.000 description 1
• TTWUNHWGMFEVNY-TZHYSIJRSA-N (2r)-4-(dimethylcarbamoyl)-1-[[4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridin-2-yl]sulfonyl]piperazine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)C1NCC=C(C=2C=CC(F)=CC=2)C1 TTWUNHWGMFEVNY-TZHYSIJRSA-N 0.000 description 1
• XTALPRDVMRMKQP-QGZVFWFLSA-N (2r)-4-(dimethylsulfamoyl)-1-[4-(4-fluorophenyl)piperidin-1-yl]sulfonyl-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(S(=O)(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C=CC(F)=CC=2)CC1 XTALPRDVMRMKQP-QGZVFWFLSA-N 0.000 description 1
• HNYFEXVRCNMJLW-QGZVFWFLSA-N (2r)-4-(dimethylsulfamoyl)-1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(S(=O)(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 HNYFEXVRCNMJLW-QGZVFWFLSA-N 0.000 description 1
• DOJSEIHMCAJPCJ-LJQANCHMSA-N (2r)-4-acetyl-1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)C)CCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 DOJSEIHMCAJPCJ-LJQANCHMSA-N 0.000 description 1
• UWGPYFXKUBVUAJ-OAHLLOKOSA-N (2r)-n-hydroxy-1-(4-pyridin-4-ylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(SC=2C=CN=CC=2)CC1 UWGPYFXKUBVUAJ-OAHLLOKOSA-N 0.000 description 1
• SQPWWKOGYATBQV-CQSZACIVSA-N (2r)-n-hydroxy-1-[4-(1h-pyrrol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C2=CNC=C2)CC1 SQPWWKOGYATBQV-CQSZACIVSA-N 0.000 description 1
• CPTYWPKPIQSUCU-SECBINFHSA-N (2r)-n-hydroxy-1-pyrrolidin-1-ylsulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCCC1 CPTYWPKPIQSUCU-SECBINFHSA-N 0.000 description 1
• OBLYYKNCLJUBRK-OAQYLSRUSA-N (2r)-n-hydroxy-3-methyl-2-[(4-phenoxypiperidin-1-yl)sulfonyl-(pyridin-3-ylmethyl)amino]butanamide Chemical compound C1CC(OC=2C=CC=CC=2)CCN1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CC1=CC=CN=C1 OBLYYKNCLJUBRK-OAQYLSRUSA-N 0.000 description 1
• IIYIQOSACFFLRO-QGZVFWFLSA-N (2r)-n-hydroxy-3-methyl-2-[[4-(5-phenyl-1,3-thiazol-2-yl)piperidin-1-yl]sulfonylamino]butanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1C1=NC=C(C=2C=CC=CC=2)S1 IIYIQOSACFFLRO-QGZVFWFLSA-N 0.000 description 1
• KTSCWJXFORNCSL-QGZVFWFLSA-N (2r)-n-hydroxy-3-methyl-2-[[4-(5-phenyl-1h-imidazol-2-yl)piperidin-1-yl]sulfonylamino]butanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCC1C1=NC(C=2C=CC=CC=2)=CN1 KTSCWJXFORNCSL-QGZVFWFLSA-N 0.000 description 1
• OFJVMRCGJWKENF-HXUWFJFHSA-N (2r)-n-hydroxy-3-methyl-2-[[4-[4-(pyridin-4-ylmethoxy)phenyl]piperazin-1-yl]sulfonylamino]butanamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C(C=C1)=CC=C1OCC1=CC=NC=C1 OFJVMRCGJWKENF-HXUWFJFHSA-N 0.000 description 1
• WNSDZBQLMGKPQS-RZFWHQLPSA-N (2r)-piperazine-1,4-diium-2-carboxylic acid;dichloride Chemical compound Cl.Cl.OC(=O)[C@H]1CNCCN1 WNSDZBQLMGKPQS-RZFWHQLPSA-N 0.000 description 1
• DPNBCUQPARXJAN-KLPPUMKISA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(2r)-piperidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCCN1.OC(=O)[C@H](O)[C@@H](O)C(O)=O DPNBCUQPARXJAN-KLPPUMKISA-N 0.000 description 1
• QRQUOLZRVQUOHM-JTQLQIEISA-N (2s)-2-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-n-hydroxypropanamide Chemical compound C1CN(S(=O)(=O)N[C@@H](C)C(=O)NO)CCC1C(=O)C1=CC=C(Cl)C=C1 QRQUOLZRVQUOHM-JTQLQIEISA-N 0.000 description 1
• UNLZIQMUHYOONF-OAQYLSRUSA-N (3r)-1-n-tert-butyl-4-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-3-n-[(2-methylpropan-2-yl)oxy]piperazine-1,3-dicarboxamide Chemical compound CC(C)(C)ONC(=O)[C@H]1CN(C(=O)NC(C)(C)C)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 UNLZIQMUHYOONF-OAQYLSRUSA-N 0.000 description 1
• ZZLWUOCMYZABGK-OAHLLOKOSA-N (3r)-4-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-3-n-hydroxypiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 ZZLWUOCMYZABGK-OAHLLOKOSA-N 0.000 description 1
• CYDOHTAWDTYEJY-OAHLLOKOSA-N (3r)-4-[4-(4-fluorophenyl)-3-oxopiperazin-1-yl]sulfonyl-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC(=O)N(C=2C=CC(F)=CC=2)CC1 CYDOHTAWDTYEJY-OAHLLOKOSA-N 0.000 description 1
• ZZGJYRGQJRTVQQ-OEMAIJDKSA-N (3r)-4-[4-(4-fluorophenyl)-3-oxopiperidin-1-yl]sulfonyl-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC(=O)C(C=2C=CC(F)=CC=2)CC1 ZZGJYRGQJRTVQQ-OEMAIJDKSA-N 0.000 description 1
• ZMLAWNRVJAIUMJ-LJQANCHMSA-N (3r)-4-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 ZMLAWNRVJAIUMJ-LJQANCHMSA-N 0.000 description 1
• ACNMYGOWLIWCTL-QGZVFWFLSA-N (3r)-4-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-3-n-hydroxy-1-n,1-n-dimethylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(Cl)=CC=2)CC1 ACNMYGOWLIWCTL-QGZVFWFLSA-N 0.000 description 1
• UWUFUHSRKBXDBQ-GOSISDBHSA-N (3r)-4-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-3-n-hydroxy-1-n,1-n,3-n-trimethylpiperazine-1,3-dicarboxamide Chemical compound CN(O)C(=O)[C@H]1CN(C(=O)N(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 UWUFUHSRKBXDBQ-GOSISDBHSA-N 0.000 description 1
• RKNRMLHDLSOXBO-MRXNPFEDSA-N (3r)-4-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-3-n-hydroxy-1-n-methylpiperazine-1,3-dicarboxamide Chemical compound ONC(=O)[C@H]1CN(C(=O)NC)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 RKNRMLHDLSOXBO-MRXNPFEDSA-N 0.000 description 1
• CBKJZNMHIPFWNP-MRXNPFEDSA-N (3r)-4-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide Chemical compound ONC(=O)[C@@H]1C(C)(C)SCCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 CBKJZNMHIPFWNP-MRXNPFEDSA-N 0.000 description 1
• IYGWDOXHCPQXKN-UHFFFAOYSA-N (4-chlorophenyl)-piperidin-4-ylmethanone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1CCNCC1 IYGWDOXHCPQXKN-UHFFFAOYSA-N 0.000 description 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• RDJUHLUBPADHNP-UHFFFAOYSA-N 1,2,3,5-tetrahydroxybenzene Chemical compound OC1=CC(O)=C(O)C(O)=C1 RDJUHLUBPADHNP-UHFFFAOYSA-N 0.000 description 1
• ONEYFZXGNFNRJH-UHFFFAOYSA-N 1-(4-methylphenyl)piperazine Chemical compound C1=CC(C)=CC=C1N1CCNCC1 ONEYFZXGNFNRJH-UHFFFAOYSA-N 0.000 description 1
• DTUWTMSHQXXDCI-UHFFFAOYSA-N 1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-4-formyl-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)C1CN(C=O)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 DTUWTMSHQXXDCI-UHFFFAOYSA-N 0.000 description 1
• UJGOQASANRPBGZ-UHFFFAOYSA-N 1-[4-(4-chlorophenyl)piperidin-1-yl]sulfonyl-n-hydroxy-4-(pyridine-2-carbonyl)piperazine-2-carboxamide Chemical compound ONC(=O)C1CN(C(=O)C=2N=CC=CC=2)CCN1S(=O)(=O)N(CC1)CCC1C1=CC=C(Cl)C=C1 UJGOQASANRPBGZ-UHFFFAOYSA-N 0.000 description 1
• FDDCQPTVVRQNQM-UHFFFAOYSA-N 1-[4-(5-chloro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(Cl)=CC=C3NC=2)CC1 FDDCQPTVVRQNQM-UHFFFAOYSA-N 0.000 description 1
• WBFQRWIUPPQNOY-UHFFFAOYSA-N 1-[4-(5-chlorobenzotriazol-1-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(N2C3=CC=C(Cl)C=C3N=N2)CC1 WBFQRWIUPPQNOY-UHFFFAOYSA-N 0.000 description 1
• PJUKANOMPKVIBK-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(OC=2N=CC(Cl)=CC=2)CC1 PJUKANOMPKVIBK-UHFFFAOYSA-N 0.000 description 1
• PYYGZQGBQSQGCI-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2N=CC(Cl)=CC=2)CC1 PYYGZQGBQSQGCI-UHFFFAOYSA-N 0.000 description 1
• XGBGBUQSUWFZPR-UHFFFAOYSA-N 1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-4-formyl-n-phenylmethoxypiperazine-2-carboxamide Chemical compound C12=CC(F)=CC=C2NC=C1C(CC1)CCN1S(=O)(=O)N1CCN(C=O)CC1C(=O)NOCC1=CC=CC=C1 XGBGBUQSUWFZPR-UHFFFAOYSA-N 0.000 description 1
• VTVPUOBCMBGIIO-UHFFFAOYSA-N 1-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(F)=CC=C3NC=2)CC1 VTVPUOBCMBGIIO-UHFFFAOYSA-N 0.000 description 1
• OHCAEPXKLQXURR-UHFFFAOYSA-N 1-[4-(6-chloro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC=C(Cl)C=C3NC=2)CC1 OHCAEPXKLQXURR-UHFFFAOYSA-N 0.000 description 1
• PTXVUEIRVILTIN-UHFFFAOYSA-N 1-[4-[5-fluoro-1-(2-trimethylsilylethylsulfonyl)indol-3-yl]piperidin-1-yl]sulfonyl-4-phenylmethoxycarbonylpiperazine-2-carboxylic acid Chemical compound C12=CC(F)=CC=C2N(S(=O)(=O)CC[Si](C)(C)C)C=C1C(CC1)CCN1S(=O)(=O)N(C(C1)C(O)=O)CCN1C(=O)OCC1=CC=CC=C1 PTXVUEIRVILTIN-UHFFFAOYSA-N 0.000 description 1
• HMOKTUUFXQHREN-UHFFFAOYSA-N 1-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxypiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CC=C(C=2C=CC(Cl)=CC=2)CC1 HMOKTUUFXQHREN-UHFFFAOYSA-N 0.000 description 1
• AUOTZKPYQJCSKK-UHFFFAOYSA-N 1-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxycyclohexane-1-carboxamide Chemical compound C1CN(C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)NC1(C(=O)NO)CCCCC1 AUOTZKPYQJCSKK-UHFFFAOYSA-N 0.000 description 1
• QITZRWFHDISBIM-UHFFFAOYSA-N 1-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-n-hydroxy-4-(2,2,2-trifluoroethyl)piperazine-2-carboxamide Chemical compound ONC(=O)C1CN(CC(F)(F)F)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 QITZRWFHDISBIM-UHFFFAOYSA-N 0.000 description 1
• OAXSVEFCBLZGCA-UHFFFAOYSA-N 1-chloro-4-(isocyanatomethyl)benzene Chemical compound ClC1=CC=C(CN=C=O)C=C1 OAXSVEFCBLZGCA-UHFFFAOYSA-N 0.000 description 1
• AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
• JCNAJFLKQWCNJT-UHFFFAOYSA-N 1-methylsulfonyl-3-piperidin-4-ylindole-5-carbonitrile Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)C)C=C1C1CCNCC1 JCNAJFLKQWCNJT-UHFFFAOYSA-N 0.000 description 1
• YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 1
• GOIWZZQXWJVDOG-UHFFFAOYSA-N 2,2,2-trifluoroethyl trichloromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(Cl)(Cl)Cl GOIWZZQXWJVDOG-UHFFFAOYSA-N 0.000 description 1
• BSJURRCNZZFQBW-UHFFFAOYSA-N 2-(4-chlorophenyl)-1h-pyrrole Chemical compound C1=CC(Cl)=CC=C1C1=CC=CN1 BSJURRCNZZFQBW-UHFFFAOYSA-N 0.000 description 1
• AOKWNRGVUBURBL-UHFFFAOYSA-N 2-(5-fluoro-3-piperidin-4-ylindol-1-yl)sulfonylethyl-trimethylsilane Chemical compound C12=CC(F)=CC=C2N(S(=O)(=O)CC[Si](C)(C)C)C=C1C1CCNCC1 AOKWNRGVUBURBL-UHFFFAOYSA-N 0.000 description 1
• KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
• ULGHQGXFLWVMHX-UHFFFAOYSA-N 2-[(2-benzyl-4-phenoxypiperidin-1-yl)sulfonylamino]-n-hydroxy-3-methylbutanamide Chemical compound ONC(=O)C(C(C)C)NS(=O)(=O)N1CCC(OC=2C=CC=CC=2)CC1CC1=CC=CC=C1 ULGHQGXFLWVMHX-UHFFFAOYSA-N 0.000 description 1
• BSMMWMSBDKYDRL-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonyl-sulfamoylamino]acetic acid Chemical compound CC(C)(C)OC(=O)N(S(N)(=O)=O)CC(O)=O BSMMWMSBDKYDRL-UHFFFAOYSA-N 0.000 description 1
• HQMYXFUVFFFTMP-UHFFFAOYSA-N 2-[(4-phenylphenyl)methyl]-1,2,5-thiadiazolidine 1,1-dioxide Chemical compound O=S1(=O)NCCN1CC1=CC=C(C=2C=CC=CC=2)C=C1 HQMYXFUVFFFTMP-UHFFFAOYSA-N 0.000 description 1
• MILQSFKOBIXBQL-UHFFFAOYSA-N 2-[1,1-dioxo-5-(4-phenoxybenzoyl)-1,2,5-thiadiazolidin-2-yl]-n-hydroxyacetamide Chemical compound O=S1(=O)N(CC(=O)NO)CCN1C(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 MILQSFKOBIXBQL-UHFFFAOYSA-N 0.000 description 1
• NLOHNWGAOYFTJL-UHFFFAOYSA-N 2-[1,1-dioxo-5-[(4-phenylphenyl)methyl]-1,2,5-thiadiazolidin-2-yl]-n-phenylmethoxyacetamide Chemical compound C=1C=CC=CC=1CONC(=O)CN(S1(=O)=O)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 NLOHNWGAOYFTJL-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• WMYHNHHDWDKNPZ-UHFFFAOYSA-N 2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonyl-methylamino]-n-hydroxyacetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CN(S(=O)(=O)N(CC(=O)NO)C)CCN1C1=CC=C(Cl)C=C1 WMYHNHHDWDKNPZ-UHFFFAOYSA-N 0.000 description 1
• VSUXQUCUXKRYRO-UHFFFAOYSA-N 2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-n-hydroxybutanamide Chemical compound C1CN(S(=O)(=O)NC(CC)C(=O)NO)CCN1C1=CC=C(Cl)C=C1 VSUXQUCUXKRYRO-UHFFFAOYSA-N 0.000 description 1
• IWICKFVFFQTXHA-UHFFFAOYSA-N 2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]propanoic acid Chemical compound C1CN(S(=O)(=O)NC(C)C(O)=O)CCN1C1=CC=C(Cl)C=C1 IWICKFVFFQTXHA-UHFFFAOYSA-N 0.000 description 1
• QAZCEBYKYPYKOF-UHFFFAOYSA-N 2-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl-methylamino]-n-hydroxy-4-phenylbutanamide Chemical compound C1CN(C=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)N(C)C(C(=O)NO)CCC1=CC=CC=C1 QAZCEBYKYPYKOF-UHFFFAOYSA-N 0.000 description 1
• QJXUOXAQRWQCRS-UHFFFAOYSA-N 2-[benzyl(2-phenylethylsulfamoyl)amino]acetic acid Chemical compound C=1C=CC=CC=1CCNS(=O)(=O)N(CC(=O)O)CC1=CC=CC=C1 QJXUOXAQRWQCRS-UHFFFAOYSA-N 0.000 description 1
• FZFJNCHGRAQGNM-UHFFFAOYSA-N 2-[benzyl-(4-chloropiperidin-1-yl)sulfonylamino]-n-hydroxyacetamide Chemical compound C1CC(Cl)CCN1S(=O)(=O)N(CC(=O)NO)CC1=CC=CC=C1 FZFJNCHGRAQGNM-UHFFFAOYSA-N 0.000 description 1
• MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 1
• MFNXWZGIFWJHMI-UHFFFAOYSA-N 2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(O)=O MFNXWZGIFWJHMI-UHFFFAOYSA-N 0.000 description 1
• JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 1
• YHVZEPIEDXIJJT-UHFFFAOYSA-N 2-piperidin-4-yl-1,3-benzoxazole Chemical class C1CNCCC1C1=NC2=CC=CC=C2O1 YHVZEPIEDXIJJT-UHFFFAOYSA-N 0.000 description 1
• BLPMCIWDCRGIJV-UHFFFAOYSA-N 2-trimethylsilylethanesulfonyl chloride Chemical compound C[Si](C)(C)CCS(Cl)(=O)=O BLPMCIWDCRGIJV-UHFFFAOYSA-N 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-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
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• GLULYPZZPZSRAP-UHFFFAOYSA-N 3-phenylsulfanylpropanamide Chemical compound NC(=O)CCSC1=CC=CC=C1 GLULYPZZPZSRAP-UHFFFAOYSA-N 0.000 description 1
• RUGIEMXPGXHGET-UHFFFAOYSA-N 3-piperidin-4-yl-1,2-benzothiazole Chemical class C1CNCCC1C1=NSC2=CC=CC=C12 RUGIEMXPGXHGET-UHFFFAOYSA-N 0.000 description 1
• NXXBDKOYTAXAKM-UHFFFAOYSA-N 3-piperidin-4-yl-2h-indazole Chemical class C1CNCCC1C1=C2C=CC=CC2=NN1 NXXBDKOYTAXAKM-UHFFFAOYSA-N 0.000 description 1
• ZUGAIMFLQLPTKB-UHFFFAOYSA-N 3-pyridin-3-ylpropan-1-ol Chemical compound OCCCC1=CC=CN=C1 ZUGAIMFLQLPTKB-UHFFFAOYSA-N 0.000 description 1
• MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 1
• DTNBMVQXEVNTLO-UHFFFAOYSA-N 4,5,6,7-tetrafluoro-1h-indole Chemical compound FC1=C(F)C(F)=C2NC=CC2=C1F DTNBMVQXEVNTLO-UHFFFAOYSA-N 0.000 description 1
• QUPXFCLFBNUVGX-UHFFFAOYSA-N 4-(4-fluorophenoxy)piperidine Chemical compound C1=CC(F)=CC=C1OC1CCNCC1 QUPXFCLFBNUVGX-UHFFFAOYSA-N 0.000 description 1
• MVXXCFMHLWEWHY-UHFFFAOYSA-N 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine Chemical compound C1=CC(F)=CC=C1C1=CCNCC1 MVXXCFMHLWEWHY-UHFFFAOYSA-N 0.000 description 1
• UGXFHAXYVZFRKS-UHFFFAOYSA-N 4-(5-cyano-1-methylsulfonylindol-3-yl)piperidine-1-sulfonyl chloride Chemical compound C12=CC(C#N)=CC=C2N(S(=O)(=O)C)C=C1C1CCN(S(Cl)(=O)=O)CC1 UGXFHAXYVZFRKS-UHFFFAOYSA-N 0.000 description 1
• QJRQTWKTKQULMZ-UHFFFAOYSA-N 4-(5-phenyl-1h-imidazol-2-yl)piperidine Chemical compound C1CNCCC1C1=NC(C=2C=CC=CC=2)=CN1 QJRQTWKTKQULMZ-UHFFFAOYSA-N 0.000 description 1
• QKZGATFNTZAGLK-OAHLLOKOSA-N 4-[[(2r)-1-(hydroxyamino)-1-oxopropan-2-yl]sulfamoyl]-n-(4-phenoxyphenyl)piperazine-1-carboxamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCN1C(=O)NC(C=C1)=CC=C1OC1=CC=CC=C1 QKZGATFNTZAGLK-OAHLLOKOSA-N 0.000 description 1
• NAISXGLNTNHXFK-UHFFFAOYSA-N 4-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-n-[(2-methylpropan-2-yl)oxy]piperidine-4-carboxamide Chemical compound C1CC(C(=O)C=2C=CC(Cl)=CC=2)CCN1S(=O)(=O)NC1(C(=O)NOC(C)(C)C)CCNCC1 NAISXGLNTNHXFK-UHFFFAOYSA-N 0.000 description 1
• RJGOALDGOVFVEW-UHFFFAOYSA-N 4-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-n-hydroxy-1-methylsulfonylpiperidine-4-carboxamide Chemical compound C1CN(S(=O)(=O)C)CCC1(C(=O)NO)NS(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 RJGOALDGOVFVEW-UHFFFAOYSA-N 0.000 description 1
• PHQJDKMZFNBREY-UHFFFAOYSA-N 4-acetyl-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonyl-n-hydroxypiperazine-2-carboxamide Chemical compound ONC(=O)C1CN(C(=O)C)CCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 PHQJDKMZFNBREY-UHFFFAOYSA-N 0.000 description 1
• QAZLRRMYUONDHH-UHFFFAOYSA-N 4-aminopiperidine-4-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C1(N)CCNCC1 QAZLRRMYUONDHH-UHFFFAOYSA-N 0.000 description 1
• RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
• ZEYSHALLPAKUHG-UHFFFAOYSA-N 4-methoxypiperidine Chemical compound COC1CCNCC1 ZEYSHALLPAKUHG-UHFFFAOYSA-N 0.000 description 1
• CMFUYNUDGNDTGC-UHFFFAOYSA-N 4-phenylsulfanylpiperidine Chemical compound C1CNCCC1SC1=CC=CC=C1 CMFUYNUDGNDTGC-UHFFFAOYSA-N 0.000 description 1
• YWBZWMIDALGFRN-UHFFFAOYSA-N 4-piperidin-4-ylsulfanylpyridine Chemical compound C1CNCCC1SC1=CC=NC=C1 YWBZWMIDALGFRN-UHFFFAOYSA-N 0.000 description 1
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical group O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
• HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 description 1
• NOBJPJHWOFGLFA-UHFFFAOYSA-N 5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indole Chemical compound C12=CC(F)=CC=C2NC=C1C1=CCNCC1 NOBJPJHWOFGLFA-UHFFFAOYSA-N 0.000 description 1
• LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
• MRMGJMGHPJZSAE-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C1CCNCC1 MRMGJMGHPJZSAE-UHFFFAOYSA-N 0.000 description 1
• 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 240000002470 Amphicarpaea bracteata Species 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 229930182831 D-valine Natural products 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 102000005593 Endopeptidases Human genes 0.000 description 1
• 108010059378 Endopeptidases Proteins 0.000 description 1
• 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
• 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
• 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 1
• 101000990912 Homo sapiens Matrilysin Proteins 0.000 description 1
• 101000990908 Homo sapiens Neutrophil collagenase Proteins 0.000 description 1
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 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
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 description 1
• 102100020880 Kit ligand Human genes 0.000 description 1
• 101710177504 Kit ligand Proteins 0.000 description 1
• 108010092694 L-Selectin Proteins 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
• 102100033467 L-selectin Human genes 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound 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
• 101710187853 Macrophage metalloelastase Proteins 0.000 description 1
• 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
• 108010076501 Matrix Metalloproteinase 12 Proteins 0.000 description 1
• 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
• 101710170181 Metalloproteinase inhibitor Proteins 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 241000750002 Nestor Species 0.000 description 1
• 102100030411 Neutrophil collagenase Human genes 0.000 description 1
• 101710118230 Neutrophil collagenase Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 101001011905 Rattus norvegicus Collagenase 3 Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• LDUIXRSNYVPIEF-UHFFFAOYSA-N S(N)(=O)(=O)Cl.ClC1=CC=C(OC2CCNCC2)C=C1 Chemical compound S(N)(=O)(=O)Cl.ClC1=CC=C(OC2CCNCC2)C=C1 LDUIXRSNYVPIEF-UHFFFAOYSA-N 0.000 description 1
• 206010040943 Skin Ulcer Diseases 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
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 235000011941 Tilia x europaea Nutrition 0.000 description 1
• 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
• 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
• 239000007997 Tricine buffer Substances 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
• 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 208000002223 abdominal aortic aneurysm Diseases 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
• 125000004450 alkenylene group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
• 235000008206 alpha-amino acids Nutrition 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• VMPVEPPRYRXYNP-UHFFFAOYSA-I antimony(5+);pentachloride Chemical compound Cl[Sb](Cl)(Cl)(Cl)Cl VMPVEPPRYRXYNP-UHFFFAOYSA-I 0.000 description 1
• 208000007474 aortic aneurysm Diseases 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000012300 argon atmosphere Substances 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
• JHAOIPVMSVZEBP-UHFFFAOYSA-N azanium;piperazine-1-carboxylate Chemical compound [NH4+].[O-]C(=O)N1CCNCC1 JHAOIPVMSVZEBP-UHFFFAOYSA-N 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• UMAYIHNSFYJRFH-UHFFFAOYSA-N benzyl 4-[4-(5-fluoro-1h-indol-3-yl)piperidin-1-yl]sulfonyl-3-(hydroxycarbamoyl)piperazine-1-carboxylate Chemical compound C1CN(S(=O)(=O)N2CCC(CC2)C=2C3=CC(F)=CC=C3NC=2)C(C(=O)NO)CN1C(=O)OCC1=CC=CC=C1 UMAYIHNSFYJRFH-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• JRBQXZHOEDXQPR-JOCHJYFZSA-N benzyl n-[(5r)-5-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]-6-(hydroxyamino)-6-oxohexyl]carbamate Chemical compound C([C@H](C(=O)NO)NS(=O)(=O)N1CCN(CC1)C=1C=CC(Cl)=CC=1)CCCNC(=O)OCC1=CC=CC=C1 JRBQXZHOEDXQPR-JOCHJYFZSA-N 0.000 description 1
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
• 238000005574 benzylation reaction Methods 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000007963 capsule composition Substances 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 150000001722 carbon compounds Chemical class 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 210000001612 chondrocyte Anatomy 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 230000036569 collagen breakdown Effects 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125890 compound Ia Drugs 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• BTJKBSZNARYPDV-UHFFFAOYSA-N dibenzyl piperazine-1,2-dicarboxylate Chemical compound C1NCCN(C(=O)OCC=2C=CC=CC=2)C1C(=O)OCC1=CC=CC=C1 BTJKBSZNARYPDV-UHFFFAOYSA-N 0.000 description 1
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical class ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• JFAYAEGMEBRSLN-UHFFFAOYSA-N ethyl 1-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound CCOC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 JFAYAEGMEBRSLN-UHFFFAOYSA-N 0.000 description 1
• HNMFNMXPRLMNND-UHFFFAOYSA-N ethyl 2-[(2-benzyl-4-phenoxypiperidin-1-yl)sulfonylamino]acetate Chemical compound CCOC(=O)CNS(=O)(=O)N1CCC(OC=2C=CC=CC=2)CC1CC1=CC=CC=C1 HNMFNMXPRLMNND-UHFFFAOYSA-N 0.000 description 1
• QCCOBVWWCFEMBB-UHFFFAOYSA-N ethyl 2-[benzyl(2-phenylethylsulfamoyl)amino]acetate Chemical compound C=1C=CC=CC=1CCNS(=O)(=O)N(CC(=O)OCC)CC1=CC=CC=C1 QCCOBVWWCFEMBB-UHFFFAOYSA-N 0.000 description 1
• OREDGCHFKFQQCU-UHFFFAOYSA-N ethyl 2-[benzyl(morpholin-4-ylsulfonyl)amino]acetate Chemical compound C1COCCN1S(=O)(=O)N(CC(=O)OCC)CC1=CC=CC=C1 OREDGCHFKFQQCU-UHFFFAOYSA-N 0.000 description 1
• FUIDOYSRGNYYPJ-UHFFFAOYSA-N ethyl 2-[benzyl-(4-methoxypiperidin-1-yl)sulfonylamino]acetate Chemical compound C1CC(OC)CCN1S(=O)(=O)N(CC(=O)OCC)CC1=CC=CC=C1 FUIDOYSRGNYYPJ-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-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
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• SZIKRGHFZTYTIT-UHFFFAOYSA-N ethyl piperidine-2-carboxylate Chemical compound CCOC(=O)C1CCCCN1 SZIKRGHFZTYTIT-UHFFFAOYSA-N 0.000 description 1
• LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 235000013312 flour Nutrition 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 229960002518 gentamicin Drugs 0.000 description 1
• FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
• 239000000174 gluconic acid Chemical group 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000004220 glutamic acid Chemical group 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 150000002440 hydroxy compounds Chemical class 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
• 238000005184 irreversible process Methods 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
• 229940011051 isopropyl acetate Drugs 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000000629 knee joint Anatomy 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 238000011694 lewis rat Methods 0.000 description 1
• 239000004571 lime Substances 0.000 description 1
• 230000000670 limiting effect Effects 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
• 229920002521 macromolecule Polymers 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
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000023881 membrane protein ectodomain proteolysis Effects 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229940126170 metalloproteinase inhibitor Drugs 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 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
• ZQTKCQFWPNRGJV-MRXNPFEDSA-N methyl (2r)-1-(4-pyridin-4-ylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(SC=2C=CN=CC=2)CC1 ZQTKCQFWPNRGJV-MRXNPFEDSA-N 0.000 description 1
• MEMKIQMQYQFGRS-QGZVFWFLSA-N methyl (2r)-1-[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C(=O)C=2C=CC(Cl)=CC=2)CC1 MEMKIQMQYQFGRS-QGZVFWFLSA-N 0.000 description 1
• JYYSWRLSVCRGTM-OAQYLSRUSA-N methyl (2r)-1-[4-[5-(4-chlorophenyl)-1h-pyrrol-2-yl]piperidin-1-yl]sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1S(=O)(=O)N1CCC(C=2NC(=CC=2)C=2C=CC(Cl)=CC=2)CC1 JYYSWRLSVCRGTM-OAQYLSRUSA-N 0.000 description 1
• LFUIOAXMANYSCA-GFCCVEGCSA-N methyl (2r)-2-(benzylamino)-3-methylbutanoate Chemical compound COC(=O)[C@@H](C(C)C)NCC1=CC=CC=C1 LFUIOAXMANYSCA-GFCCVEGCSA-N 0.000 description 1
• HOLKVLIXMKHADD-SSDOTTSWSA-N methyl (2r)-2-(piperazin-1-ylsulfonylamino)propanoate Chemical compound COC(=O)[C@@H](C)NS(=O)(=O)N1CCNCC1 HOLKVLIXMKHADD-SSDOTTSWSA-N 0.000 description 1
• YOWYAEJEAJRPRU-LLVKDONJSA-N methyl (2r)-2-[[4-(4-chlorophenyl)piperazin-1-yl]sulfonylamino]propanoate Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)OC)CCN1C1=CC=C(Cl)C=C1 YOWYAEJEAJRPRU-LLVKDONJSA-N 0.000 description 1
• YBQBWYUONUIEOA-LJQANCHMSA-N methyl (2r)-2-[[4-[2-[(4-chlorophenyl)methylamino]-2-oxoethyl]piperidin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCC1CC(=O)NCC1=CC=C(Cl)C=C1 YBQBWYUONUIEOA-LJQANCHMSA-N 0.000 description 1
• FXMUJRQONPISFH-CYBMUJFWSA-N methyl (2r)-2-[[4-[2-[(4-chlorophenyl)methylamino]-2-oxoethyl]piperidin-1-yl]sulfonylamino]propanoate Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)OC)CCC1CC(=O)NCC1=CC=C(Cl)C=C1 FXMUJRQONPISFH-CYBMUJFWSA-N 0.000 description 1
• CJBGFLHKSNNFRU-CYBMUJFWSA-N methyl (2r)-2-[benzyl(methylsulfamoyl)amino]-3-methylbutanoate Chemical compound COC(=O)[C@@H](C(C)C)N(S(=O)(=O)NC)CC1=CC=CC=C1 CJBGFLHKSNNFRU-CYBMUJFWSA-N 0.000 description 1
• DWKPPFQULDPWHX-GSVOUGTGSA-N methyl (2r)-2-aminopropanoate Chemical compound COC(=O)[C@@H](C)N DWKPPFQULDPWHX-GSVOUGTGSA-N 0.000 description 1
• BUSHUDRNCYRQLU-OAQYLSRUSA-N methyl (2r)-3-methyl-2-[[4-(2-phenyl-1,3-benzoxazol-5-yl)piperazin-1-yl]sulfonylamino]butanoate Chemical compound C1CN(S(=O)(=O)N[C@@H](C(=O)OC)C(C)C)CCN1C1=CC=C(OC(=N2)C=3C=CC=CC=3)C2=C1 BUSHUDRNCYRQLU-OAQYLSRUSA-N 0.000 description 1
• SBKXKLUMMLYTNN-UHFFFAOYSA-N methyl 1-(4-phenoxypiperidin-1-yl)sulfonylpiperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1S(=O)(=O)N1CCC(OC=2C=CC=CC=2)CC1 SBKXKLUMMLYTNN-UHFFFAOYSA-N 0.000 description 1
• XMQAUMYWZUQSRR-UHFFFAOYSA-N methyl 1-(chlorosulfonylamino)cyclohexane-1-carboxylate Chemical compound COC(=O)C1(NS(Cl)(=O)=O)CCCCC1 XMQAUMYWZUQSRR-UHFFFAOYSA-N 0.000 description 1
• MTPXRXOMKRLUMU-UHFFFAOYSA-N methyl 1-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(N)CCCCC1 MTPXRXOMKRLUMU-UHFFFAOYSA-N 0.000 description 1
• KPUOPKBSCQDGRO-UHFFFAOYSA-N methyl 2-(sulfamoylamino)acetate Chemical compound COC(=O)CNS(N)(=O)=O KPUOPKBSCQDGRO-UHFFFAOYSA-N 0.000 description 1
• 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• APCHKWZTSCBBJX-UHFFFAOYSA-N methyl piperidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1CCCCN1 APCHKWZTSCBBJX-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
• JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
• KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
• YPLBOTUMKFAEHG-LLVKDONJSA-N n-(4-chlorobenzoyl)-4-[[(2r)-1-(hydroxyamino)-1-oxopropan-2-yl]sulfamoyl]-n-methylpiperazine-1-carboxamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCN1C(=O)N(C)C(=O)C1=CC=C(Cl)C=C1 YPLBOTUMKFAEHG-LLVKDONJSA-N 0.000 description 1
• FEVHZEQPVAADEP-SNVBAGLBSA-N n-(4-chlorophenyl)-4-[[(2r)-1-(hydroxyamino)-1-oxopropan-2-yl]sulfamoyl]piperazine-1-carboxamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCN1C(=O)NC1=CC=C(Cl)C=C1 FEVHZEQPVAADEP-SNVBAGLBSA-N 0.000 description 1
• KOCUHZAYIXUHIT-CQSZACIVSA-N n-(4-chlorophenyl)-4-[[(2r)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]sulfamoyl]piperazine-1-carboxamide Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)NO)CCN1C(=O)NC1=CC=C(Cl)C=C1 KOCUHZAYIXUHIT-CQSZACIVSA-N 0.000 description 1
• RBMBUFMMNAPTJP-UHFFFAOYSA-N n-(dimethylamino)sulfamoyl chloride Chemical compound CN(C)NS(Cl)(=O)=O RBMBUFMMNAPTJP-UHFFFAOYSA-N 0.000 description 1
• GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
• NBBNHGNCVGVVOG-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-2-piperidin-4-ylacetamide Chemical compound C1=CC(Cl)=CC=C1CNC(=O)CC1CCNCC1 NBBNHGNCVGVVOG-UHFFFAOYSA-N 0.000 description 1
• IEXLEKMIOFYSNQ-LLVKDONJSA-N n-[(4-chlorophenyl)methyl]-4-[[(2r)-1-(hydroxyamino)-1-oxopropan-2-yl]sulfamoyl]piperazine-1-carboxamide Chemical compound C1CN(S(=O)(=O)N[C@H](C)C(=O)NO)CCN1C(=O)NCC1=CC=C(Cl)C=C1 IEXLEKMIOFYSNQ-LLVKDONJSA-N 0.000 description 1
• SHYZIYOXWYYERV-UHFFFAOYSA-N n-[tert-butyl(dimethyl)silyl]oxy-1-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylpiperidine-2-carboxamide Chemical compound CC(C)(C)[Si](C)(C)ONC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2C=CC(Cl)=CC=2)CC1 SHYZIYOXWYYERV-UHFFFAOYSA-N 0.000 description 1
• UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
• WWZZKBDPWJGHQE-UHFFFAOYSA-N n-hydroxy-1-(4-phenylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(SC=2C=CC=CC=2)CC1 WWZZKBDPWJGHQE-UHFFFAOYSA-N 0.000 description 1
• AGYNYDKOTQBWNJ-UHFFFAOYSA-N n-hydroxy-1-(4-pyridin-2-ylpiperazin-1-yl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCN(C=2N=CC=CC=2)CC1 AGYNYDKOTQBWNJ-UHFFFAOYSA-N 0.000 description 1
• IKBGWRSASGRBHW-UHFFFAOYSA-N n-hydroxy-1-(4-pyridin-2-ylsulfanylpiperidin-1-yl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(SC=2N=CC=CC=2)CC1 IKBGWRSASGRBHW-UHFFFAOYSA-N 0.000 description 1
• PADAVHRTWLNXKY-UHFFFAOYSA-N n-hydroxy-1-[(4-phenoxypiperidin-1-yl)sulfonylamino]cyclopentane-1-carboxamide Chemical compound C1CC(OC=2C=CC=CC=2)CCN1S(=O)(=O)NC1(C(=O)NO)CCCC1 PADAVHRTWLNXKY-UHFFFAOYSA-N 0.000 description 1
• VAUIJJUXSNDBMJ-UHFFFAOYSA-N n-hydroxy-1-[4-(5-hydroxy-1h-indol-3-yl)piperidin-1-yl]sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)C1CCCCN1S(=O)(=O)N1CCC(C=2C3=CC(O)=CC=C3NC=2)CC1 VAUIJJUXSNDBMJ-UHFFFAOYSA-N 0.000 description 1
• ZYLAMVINHRDLDU-UHFFFAOYSA-N n-hydroxy-2-[[4-(4-methylphenyl)piperazin-1-yl]sulfonylamino]acetamide Chemical compound C1=CC(C)=CC=C1N1CCN(S(=O)(=O)NCC(=O)NO)CC1 ZYLAMVINHRDLDU-UHFFFAOYSA-N 0.000 description 1
• RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
• CPQCSJYYDADLCZ-UHFFFAOYSA-N n-methylhydroxylamine Chemical compound CNO CPQCSJYYDADLCZ-UHFFFAOYSA-N 0.000 description 1
• UJJUEJRWNWVHCM-UHFFFAOYSA-N n-methylsulfamoyl chloride Chemical compound CNS(Cl)(=O)=O UJJUEJRWNWVHCM-UHFFFAOYSA-N 0.000 description 1
• RBVFKMBFVHRPCU-UHFFFAOYSA-N n-trimethylsilylhydroxylamine Chemical compound C[Si](C)(C)NO RBVFKMBFVHRPCU-UHFFFAOYSA-N 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 210000002184 nasal cartilage Anatomy 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
• 150000004885 piperazines Chemical class 0.000 description 1
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical class OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
• 108010048738 promatrilysin Proteins 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000004252 protein component Nutrition 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 150000003233 pyrroles Chemical class 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 210000004872 soft tissue Anatomy 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 230000003595 spectral effect Effects 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
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 229960002317 succinimide Drugs 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 230000006103 sulfonylation Effects 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• YIAOLJLRDLQEEA-GOSISDBHSA-N tert-butyl (2r)-2-[[4-(4-chlorobenzoyl)piperidin-1-yl]sulfonylamino]-3-methylbutanoate Chemical compound C1CN(S(=O)(=O)N[C@H](C(C)C)C(=O)OC(C)(C)C)CCC1C(=O)C1=CC=C(Cl)C=C1 YIAOLJLRDLQEEA-GOSISDBHSA-N 0.000 description 1
• DNSORJCEYPEAJT-GOSISDBHSA-N tert-butyl (3r)-4-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]sulfonyl]-3-(hydroxycarbamoyl)piperazine-1-carboxylate Chemical compound ONC(=O)[C@H]1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)N1CC=C(C=2C=CC(F)=CC=2)CC1 DNSORJCEYPEAJT-GOSISDBHSA-N 0.000 description 1
• KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
• PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
• BSSUYVGTTHYWOF-UHFFFAOYSA-N tert-butyl n-[4-(4-chlorophenyl)piperazin-1-yl]sulfonylcarbamate Chemical compound C1CN(S(=O)(=O)NC(=O)OC(C)(C)C)CCN1C1=CC=C(Cl)C=C1 BSSUYVGTTHYWOF-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 230000007838 tissue remodeling Effects 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• FBQURXLBJJNDBX-UHFFFAOYSA-N tri(propan-2-yl)-pyrrol-1-ylsilane Chemical compound CC(C)[Si](C(C)C)(C(C)C)N1C=CC=C1 FBQURXLBJJNDBX-UHFFFAOYSA-N 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000002993 trophoblast Anatomy 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 210000004325 uterine smooth muscle cell Anatomy 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1