JP2000511175A - ビフェニルスルホンアミドマトリックスメタロプロテイナーゼ阻害剤 - Google Patents
ビフェニルスルホンアミドマトリックスメタロプロテイナーゼ阻害剤Info
- Publication number
- JP2000511175A JP2000511175A JP09542377A JP54237797A JP2000511175A JP 2000511175 A JP2000511175 A JP 2000511175A JP 09542377 A JP09542377 A JP 09542377A JP 54237797 A JP54237797 A JP 54237797A JP 2000511175 A JP2000511175 A JP 2000511175A
- Authority
- JP
- Japan
- Prior art keywords
- biphenyl
- sulfonylamino
- acid
- alkyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 title description 10
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 4
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 4
- -1 nitro, amino Chemical group 0.000 claims abstract description 57
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims abstract description 12
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims abstract description 12
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 64
- 239000002253 acid Substances 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical group C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- PLCPLXITTDSMSK-INIZCTEOSA-N (2s)-3-methyl-2-[[4-(4-nitrophenyl)phenyl]sulfonylamino]butanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 PLCPLXITTDSMSK-INIZCTEOSA-N 0.000 claims description 2
- ZGWIOFHKEXLJPC-UHFFFAOYSA-N 2-[[4-(4-formylphenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)NC(C(C)C)C(O)=O)=CC=C1C1=CC=C(C=O)C=C1 ZGWIOFHKEXLJPC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 2
- QVNUOLHHXUUNEH-KRWDZBQOSA-N (2s)-2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-4-methylpentanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](CC(C)C)C(O)=O)=CC=C1C1=CC=C(Br)C=C1 QVNUOLHHXUUNEH-KRWDZBQOSA-N 0.000 claims 1
- WOIAZYSLWSXKKC-UHFFFAOYSA-N 2-[[4-[4-(hydroxymethyl)phenyl]phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)NC(C(C)C)C(O)=O)=CC=C1C1=CC=C(CO)C=C1 WOIAZYSLWSXKKC-UHFFFAOYSA-N 0.000 claims 1
- BGKNBDGHNBOSGD-UHFFFAOYSA-N 3-methyl-2-[(4-phenylphenyl)sulfonylamino]butanoic acid Chemical group C1=CC(S(=O)(=O)NC(C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1 BGKNBDGHNBOSGD-UHFFFAOYSA-N 0.000 claims 1
- JGFBQFKZKSSODQ-UHFFFAOYSA-N Isothiocyanatocyclopropane Chemical compound S=C=NC1CC1 JGFBQFKZKSSODQ-UHFFFAOYSA-N 0.000 claims 1
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims 1
- 229940095574 propionic acid Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 210000002808 connective tissue Anatomy 0.000 abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 2
- 241001465754 Metazoa Species 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 239000007787 solid Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000005741 Metalloproteases Human genes 0.000 description 4
- 108010006035 Metalloproteases Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000008273 gelatin Substances 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
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- GJOCABIDMCKCEG-INIZCTEOSA-N (2s)-2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(Br)C=C1 GJOCABIDMCKCEG-INIZCTEOSA-N 0.000 description 2
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- RIOSJKSGNLGONI-UHFFFAOYSA-N 2-phenylbenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 RIOSJKSGNLGONI-UHFFFAOYSA-N 0.000 description 2
- LCDFVKCZAKLTTD-UHFFFAOYSA-N 4-(4-bromophenyl)benzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1C1=CC=C(Br)C=C1 LCDFVKCZAKLTTD-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010026132 Gelatinases Proteins 0.000 description 2
- 102000013382 Gelatinases Human genes 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 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 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 description 2
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 2
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 201000001245 periodontitis Diseases 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- AUIVQIHTTVPKFS-FJXQXJEOSA-N tert-butyl (2s)-2-amino-3-methylbutanoate;hydrochloride Chemical compound Cl.CC(C)[C@H](N)C(=O)OC(C)(C)C AUIVQIHTTVPKFS-FJXQXJEOSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- GJOCABIDMCKCEG-MRXNPFEDSA-N (2r)-2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(Br)C=C1 GJOCABIDMCKCEG-MRXNPFEDSA-N 0.000 description 1
- NEOOWKPSCAQYPI-INIZCTEOSA-N (2s)-2-[[4-(3-bromophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC(Br)=C1 NEOOWKPSCAQYPI-INIZCTEOSA-N 0.000 description 1
- WJFKRCVNGHZYFA-INIZCTEOSA-N (2s)-2-[[4-(3-fluorophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC(F)=C1 WJFKRCVNGHZYFA-INIZCTEOSA-N 0.000 description 1
- LKVAANCBUJLQIE-INIZCTEOSA-N (2s)-2-[[4-(4-aminophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(N)C=C1 LKVAANCBUJLQIE-INIZCTEOSA-N 0.000 description 1
- UWHPJOBPMXNVII-INIZCTEOSA-N (2s)-2-[[4-(4-bromo-2-fluorophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(Br)C=C1F UWHPJOBPMXNVII-INIZCTEOSA-N 0.000 description 1
- GSCKLBZEPMMUCA-FQEVSTJZSA-N (2s)-2-[[4-(4-bromophenyl)phenyl]sulfonylamino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NS(=O)(=O)C=1C=CC(=CC=1)C=1C=CC(Br)=CC=1)C1=CC=CC=C1 GSCKLBZEPMMUCA-FQEVSTJZSA-N 0.000 description 1
- PTONAIKVYGVBIS-INIZCTEOSA-N (2s)-2-[[4-(4-chlorophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(Cl)C=C1 PTONAIKVYGVBIS-INIZCTEOSA-N 0.000 description 1
- AGRDSOUIPBKOKQ-KRWDZBQOSA-N (2s)-2-[[4-(4-cyanophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(C#N)C=C1 AGRDSOUIPBKOKQ-KRWDZBQOSA-N 0.000 description 1
- INVXSBCIDABVMG-INIZCTEOSA-N (2s)-2-[[4-(4-fluorophenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(F)C=C1 INVXSBCIDABVMG-INIZCTEOSA-N 0.000 description 1
- MDWFJTBWOFNAQX-KRWDZBQOSA-N (2s)-2-[[4-(4-methoxyphenyl)phenyl]sulfonylamino]-3-methylbutanoic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=C(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)C=C1 MDWFJTBWOFNAQX-KRWDZBQOSA-N 0.000 description 1
- MZIZOOUSSMSGAV-KRWDZBQOSA-N (2s)-3-methyl-2-[[4-(4-methylphenyl)phenyl]sulfonylamino]butanoic acid Chemical compound C1=CC(S(=O)(=O)N[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=C(C)C=C1 MZIZOOUSSMSGAV-KRWDZBQOSA-N 0.000 description 1
- 108010091181 (R)-2-(4'-bromo-biphenyl-4-sulfonyl-amino)-3-methyl-butyric acid Proteins 0.000 description 1
- PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- YWAPUIQWVUXRRW-UHFFFAOYSA-N 2-[[4-(4-bromophenyl)phenyl]sulfonylamino]acetic acid Chemical compound C1=CC(S(=O)(=O)NCC(=O)O)=CC=C1C1=CC=C(Br)C=C1 YWAPUIQWVUXRRW-UHFFFAOYSA-N 0.000 description 1
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- RAXPEBLSVFVDFD-UHFFFAOYSA-N 4-[4-[(1-carboxy-2-methylpropyl)sulfamoyl]phenyl]benzoic acid Chemical compound C1=CC(S(=O)(=O)NC(C(C)C)C(O)=O)=CC=C1C1=CC=C(C(O)=O)C=C1 RAXPEBLSVFVDFD-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- KQZFABSTXSNEQH-UHFFFAOYSA-N 4-iodobenzenesulfonamide Chemical group NS(=O)(=O)C1=CC=C(I)C=C1 KQZFABSTXSNEQH-UHFFFAOYSA-N 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
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 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
- 208000012659 Joint disease Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000004318 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 1
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102000010750 Metalloproteins Human genes 0.000 description 1
- 108010063312 Metalloproteins Proteins 0.000 description 1
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
- 102000056189 Neutrophil collagenases Human genes 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune 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
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- XUPYJHCZDLZNFP-UHFFFAOYSA-N butyl ester butanoic acid Natural products CCCCOC(=O)CCC XUPYJHCZDLZNFP-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 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
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000001054 red pigment Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VFMGXRFRRDTHNX-UHFFFAOYSA-N tert-butyl 2-[(4-bromophenyl)sulfonylamino]-3-methylbutanoate Chemical compound CC(C)(C)OC(=O)C(C(C)C)NS(=O)(=O)C1=CC=C(Br)C=C1 VFMGXRFRRDTHNX-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008354 tissue degradation Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/42—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1746096P | 1996-05-17 | 1996-05-17 | |
| US60/017,460 | 1996-05-17 | ||
| PCT/US1997/006801 WO1997044315A1 (en) | 1996-05-17 | 1997-04-24 | Biphenylsulfonamide matrix metalloproteinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000511175A true JP2000511175A (ja) | 2000-08-29 |
| JP2000511175A5 JP2000511175A5 (enExample) | 2005-01-13 |
Family
ID=21782716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP09542377A Abandoned JP2000511175A (ja) | 1996-05-17 | 1997-04-24 | ビフェニルスルホンアミドマトリックスメタロプロテイナーゼ阻害剤 |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0901466B1 (enExample) |
| JP (1) | JP2000511175A (enExample) |
| KR (1) | KR20000011095A (enExample) |
| CN (1) | CN1077885C (enExample) |
| AT (1) | ATE207891T1 (enExample) |
| BG (1) | BG63940B1 (enExample) |
| BR (1) | BR9710841A (enExample) |
| CA (1) | CA2253342A1 (enExample) |
| CZ (1) | CZ294063B6 (enExample) |
| DE (1) | DE69707865T2 (enExample) |
| DK (1) | DK0901466T3 (enExample) |
| EA (1) | EA001561B1 (enExample) |
| EE (1) | EE03965B1 (enExample) |
| ES (1) | ES2167733T3 (enExample) |
| IL (1) | IL126832A0 (enExample) |
| NO (1) | NO312510B1 (enExample) |
| NZ (1) | NZ332711A (enExample) |
| PL (1) | PL186416B1 (enExample) |
| PT (1) | PT901466E (enExample) |
| SK (1) | SK282863B6 (enExample) |
| WO (1) | WO1997044315A1 (enExample) |
| ZA (1) | ZA974223B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007506664A (ja) * | 2003-06-20 | 2007-03-22 | グラクソ グループ リミテッド | マトリックスメタロプロテイナーゼの阻害剤 |
| JP4750272B2 (ja) * | 1998-02-04 | 2011-08-17 | ノバルティス アーゲー | マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU690703B2 (en) * | 1994-06-22 | 1998-04-30 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
| US6124333A (en) * | 1995-06-22 | 2000-09-26 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
| MXPA99001974A (es) * | 1996-12-09 | 2002-03-27 | Warner Lambert Co | Metodo para tratar y prevenir fallas cardiacas y dilatacion ventricular. |
| EP1366765A1 (en) * | 1996-12-17 | 2003-12-03 | Warner-Lambert Company Llc | Use of matrix metalloproteinase inhibitors for treating neurological disorders and promoting wound healing |
| BR9714142A (pt) * | 1996-12-17 | 2000-02-29 | Warner Lambert Co | Uso de inibidores de metaloproteìnases matriciais para tratamento de distúrbios neurológicos e promoção de cicatrização de feridas |
| GB9706255D0 (en) * | 1997-03-26 | 1997-05-14 | Smithkline Beecham Plc | Novel compounds |
| DE19719621A1 (de) * | 1997-05-09 | 1998-11-12 | Hoechst Ag | Sulfonylaminocarbonsäuren |
| ID24105A (id) | 1997-07-22 | 2000-07-06 | Shionogi & Co | Komposisi untuk mengobati atau mencegah glomerulopati |
| BR9814422A (pt) * | 1997-12-23 | 2000-10-10 | Warner Lambert Co | Combinações de inibidor de ace - inibidor de mmp |
| US6410580B1 (en) | 1998-02-04 | 2002-06-25 | Novartis Ag | Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases |
| JP2002506818A (ja) * | 1998-03-17 | 2002-03-05 | ワーナー−ランバート・カンパニー | スタチン−マトリックスメタロプロテイナーゼ阻害剤組み合わせ物 |
| EP0967201A1 (en) * | 1998-05-20 | 1999-12-29 | Roche Diagnostics GmbH | Pharmaceutical agents containing sulfonamids as matrix metalloproteinase inhibitors |
| EP1097159B1 (de) | 1998-07-16 | 2002-11-06 | Aventis Pharma Deutschland GmbH | Phosphin- und phosphonsäurederivate als arzneimittel |
| OA11584A (en) * | 1998-07-21 | 2004-07-20 | Warner Lambert Co | Coadministration of ACAT and MMP inhibitors for the treatment of atherosclerotic lesions. |
| DE19851184A1 (de) | 1998-11-06 | 2000-05-11 | Aventis Pharma Gmbh | N-Arylsulfonyl-aminosäure-omega-amide |
| US6858598B1 (en) | 1998-12-23 | 2005-02-22 | G. D. Searle & Co. | Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| PL351374A1 (en) * | 1999-04-19 | 2003-04-07 | Shionogi & Co | Sulfonamide derivatives having oxadiazole rings |
| GB9918684D0 (en) | 1999-08-09 | 1999-10-13 | Novartis Ag | Organic compounds |
| WO2001037826A1 (en) | 1999-11-26 | 2001-05-31 | Shionogi & Co., Ltd. | Npyy5 antagonists |
| EP1331224A4 (en) * | 2000-09-29 | 2004-03-17 | Shionogi & Co | THIAZOLE AND OXAZOLE DERIVATIVES |
| GB0103303D0 (en) | 2001-02-09 | 2001-03-28 | Novartis Ag | Organic compounds |
| MXPA01013326A (es) | 2001-02-14 | 2002-08-26 | Warner Lambert Co | Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz. |
| WO2003035610A1 (en) * | 2001-10-26 | 2003-05-01 | Shionogi & Co., Ltd. | Sulfonamide derivative having mmp inhibitory activity |
| BR0318625A (pt) | 2003-12-04 | 2006-10-31 | Wyeth Corp | biaril sulfonamidas e métodos para usar as mesmas |
| CN101001834B (zh) * | 2004-03-22 | 2011-06-29 | 南方研究院 | 基质金属蛋白酶的非肽抑制剂 |
| CN101279956B (zh) * | 2008-04-25 | 2011-06-15 | 南昌大学 | 一种基质金属蛋白酶抑制剂及合成方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5506242A (en) * | 1993-01-06 | 1996-04-09 | Ciba-Geigy Corporation | Arylsufonamido-substituted hydroxamic acids |
| AU690703B2 (en) * | 1994-06-22 | 1998-04-30 | British Biotech Pharmaceuticals Limited | Metalloproteinase inhibitors |
-
1997
- 1997-04-24 CZ CZ19983668A patent/CZ294063B6/cs not_active IP Right Cessation
- 1997-04-24 ES ES97918788T patent/ES2167733T3/es not_active Expired - Lifetime
- 1997-04-24 KR KR1019980709253A patent/KR20000011095A/ko not_active Ceased
- 1997-04-24 EP EP97918788A patent/EP0901466B1/en not_active Expired - Lifetime
- 1997-04-24 NZ NZ332711A patent/NZ332711A/en unknown
- 1997-04-24 BR BR9710841A patent/BR9710841A/pt not_active IP Right Cessation
- 1997-04-24 CN CN97194719A patent/CN1077885C/zh not_active Expired - Fee Related
- 1997-04-24 WO PCT/US1997/006801 patent/WO1997044315A1/en not_active Ceased
- 1997-04-24 EA EA199800988A patent/EA001561B1/ru not_active IP Right Cessation
- 1997-04-24 DK DK97918788T patent/DK0901466T3/da active
- 1997-04-24 JP JP09542377A patent/JP2000511175A/ja not_active Abandoned
- 1997-04-24 DE DE69707865T patent/DE69707865T2/de not_active Expired - Fee Related
- 1997-04-24 EE EE9800397A patent/EE03965B1/xx not_active IP Right Cessation
- 1997-04-24 IL IL12683297A patent/IL126832A0/xx unknown
- 1997-04-24 CA CA002253342A patent/CA2253342A1/en not_active Abandoned
- 1997-04-24 AT AT97918788T patent/ATE207891T1/de not_active IP Right Cessation
- 1997-04-24 PT PT97918788T patent/PT901466E/pt unknown
- 1997-04-24 SK SK1577-98A patent/SK282863B6/sk unknown
- 1997-04-24 PL PL97329929A patent/PL186416B1/pl not_active IP Right Cessation
- 1997-05-15 ZA ZA9704223A patent/ZA974223B/xx unknown
-
1998
- 1998-11-12 BG BG102918A patent/BG63940B1/bg unknown
- 1998-11-16 NO NO19985326A patent/NO312510B1/no not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4750272B2 (ja) * | 1998-02-04 | 2011-08-17 | ノバルティス アーゲー | マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体 |
| JP2007506664A (ja) * | 2003-06-20 | 2007-03-22 | グラクソ グループ リミテッド | マトリックスメタロプロテイナーゼの阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| PL186416B1 (pl) | 2004-01-30 |
| CA2253342A1 (en) | 1997-11-27 |
| PT901466E (pt) | 2002-04-29 |
| EP0901466A1 (en) | 1999-03-17 |
| NO312510B1 (no) | 2002-05-21 |
| ZA974223B (en) | 1997-12-10 |
| KR20000011095A (ko) | 2000-02-25 |
| SK157798A3 (en) | 1999-04-13 |
| AU713286B2 (en) | 1999-11-25 |
| ES2167733T3 (es) | 2002-05-16 |
| NZ332711A (en) | 2000-06-23 |
| EP0901466B1 (en) | 2001-10-31 |
| CN1219166A (zh) | 1999-06-09 |
| HK1019585A1 (en) | 2000-02-18 |
| WO1997044315A1 (en) | 1997-11-27 |
| SK282863B6 (sk) | 2002-12-03 |
| PL329929A1 (en) | 1999-04-26 |
| CZ294063B6 (cs) | 2004-09-15 |
| DE69707865D1 (de) | 2001-12-06 |
| ATE207891T1 (de) | 2001-11-15 |
| CZ366898A3 (cs) | 1999-02-17 |
| EA001561B1 (ru) | 2001-04-23 |
| IL126832A0 (en) | 1999-08-17 |
| AU2680397A (en) | 1997-12-09 |
| BR9710841A (pt) | 1999-08-17 |
| BG63940B1 (bg) | 2003-07-31 |
| EE03965B1 (et) | 2003-02-17 |
| EA199800988A1 (ru) | 1999-04-29 |
| DK0901466T3 (da) | 2002-02-18 |
| NO985326L (no) | 1999-01-14 |
| NO985326D0 (no) | 1998-11-16 |
| EE9800397A (et) | 1999-06-15 |
| BG102918A (en) | 1999-09-30 |
| DE69707865T2 (de) | 2002-05-02 |
| CN1077885C (zh) | 2002-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0901466B1 (en) | Biphenylsulfonamide matrix metalloproteinase inhibitors | |
| EP0934267B1 (en) | Alpha-amino sulfonyl hydroxamic acids as matrix metalloproteinase inhibitors | |
| EP0489577B1 (en) | Peptidyl derivatives | |
| HU183085B (en) | Process for preparing new phenoxy-alkyl-carboxylic acid derivatives and pharmaceutical compositions containing thereof | |
| JPH09512798A (ja) | 消炎、鎮痛および抗血栓活性を有するニトロ化合物およびそれらの組成物 | |
| JPH09505041A (ja) | ペプチジル化合物および金属プロテイナーゼのインヒビターとしてのその治療的使用 | |
| US5756545A (en) | Biphenysulfonamide matrix metal alloproteinase inhibitors | |
| EP0274453A2 (fr) | Nouveaux composés à activité d'inhibiteurs de collagénase, procédé pour les préparer et compositions pharmaceutiques contenant ces composés | |
| JP2003534312A (ja) | 薬剤として有用な環状アミノ酸誘導体 | |
| US8846760B2 (en) | Dihydronaphthalene and naphthalene derivatives as N-formyl peptide receptor like-1 (FPRL-1) receptor modulators | |
| JP2000510103A (ja) | Ｍｍｐおよびｔｎｆ放出抑制活性を有するペプチジル化合物 | |
| FR2500825A1 (fr) | Nouveau carboxylate de 4-amidino-phenyle substitue, son procede de preparation et agent anti-complement en comprenant | |
| JPH11501288A (ja) | 金属タンパク質分解酵素阻害剤 | |
| US4999345A (en) | Sulfonamide derivatives and drugs obtained therefrom | |
| FR2532647A1 (fr) | Thioesters d'acide acetylsalicylique, procede pour les preparer et compositions pharmaceutiques qui en renferment | |
| JP4390460B2 (ja) | オキサゾール誘導体 | |
| JPS6323857A (ja) | チオエステル、その製造方法およびチオエステルを有効成分とする虚血およびリパ−フュ−ジョン症候群の治療薬 | |
| JP2003321424A (ja) | エステル化合物及びその医薬用途 | |
| JP2000516607A (ja) | 酪酸マトリックスメタロプロテイナーゼ阻害剤 | |
| JPS60226857A (ja) | エンケフアリナーゼ抑制剤 | |
| AU713286C (en) | Biphenylsulfonamide matrix metalloproteinase inhibitors | |
| JP2000508639A (ja) | Ｍｍｐおよびｔｎｆ抑制活性を有するペプチジル化合物 | |
| KR101096427B1 (ko) | 신규한 4-아릴-4-옥소부탄산 아미드 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 약학적 조성물 | |
| JP2002080445A (ja) | ヒドロキサム酸誘導体化合物、その製造方法及びその化合物を有効成分とする医薬 | |
| MXPA98009083A (en) | Metaloproteinase inhibitors with bifenilsulfonam matrix |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040422 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040422 |
|
| A72 | Notification of change in name of applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A721 Effective date: 20060317 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20060317 |