SK87598A3 - Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases - Google Patents

Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases Download PDF

Info

Publication number: SK87598A3
Authority: SK; Slovakia
Prior art keywords: defined above; derivatives; pharmaceutically acceptable; formula; compound
Prior art date: 1995-12-22

Application number

SK875-98A

Other languages

English (en)

Slovak (sk)

Inventor

Donald J Hupe

Linda L Johnson

Daniel F Ortwine

Claude F Purchase Jr

Andrew D White

Qi-Zhuang Ye

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

1995-12-22

Filing date

1996-11-27

Publication date

1999-04-13

1996-11-27 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

1999-04-13 Publication of SK87598A3 publication Critical patent/SK87598A3/sk

Links

-1 Aromatic keto-acids Chemical class 0.000 title claims abstract description 72
102000002274 Matrix Metalloproteinases Human genes 0.000 title claims abstract description 12
108010000684 Matrix Metalloproteinases Proteins 0.000 title claims abstract description 12
239000003112 inhibitor Substances 0.000 title abstract description 13
238000000034 method Methods 0.000 claims abstract description 30
102000000424 Matrix Metalloproteinase 2 Human genes 0.000 claims abstract description 17
108010016165 Matrix Metalloproteinase 2 Proteins 0.000 claims abstract description 17
238000002360 preparation method Methods 0.000 claims abstract description 16
206010028980 Neoplasm Diseases 0.000 claims abstract description 14
201000011510 cancer Diseases 0.000 claims abstract description 12
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 claims abstract description 11
206010003246 arthritis Diseases 0.000 claims abstract description 11
208000037260 Atherosclerotic Plaque Diseases 0.000 claims abstract description 7
230000001419 dependent effect Effects 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
210000000265 leukocyte Anatomy 0.000 claims abstract description 6
208000037803 restenosis Diseases 0.000 claims abstract description 6
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
208000027866 inflammatory disease Diseases 0.000 claims abstract description 5
206010064996 Ulcerative keratitis Diseases 0.000 claims abstract description 4
230000001363 autoimmune Effects 0.000 claims abstract description 4
208000028169 periodontal disease Diseases 0.000 claims abstract description 4
201000006417 multiple sclerosis Diseases 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 128
150000003839 salts Chemical class 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
238000006243 chemical reaction Methods 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 21
239000003814 drug Substances 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 17
150000004715 keto acids Chemical class 0.000 claims description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 7
206010052428 Wound Diseases 0.000 claims description 6
208000027418 Wounds and injury Diseases 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
230000001684 chronic effect Effects 0.000 claims description 5
230000008569 process Effects 0.000 claims description 5
208000004210 Pressure Ulcer Diseases 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
108091007196 stromelysin Proteins 0.000 claims description 4
229910052727 yttrium Inorganic materials 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 3
208000020446 Cardiac disease Diseases 0.000 claims description 2
239000002841 Lewis acid Substances 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
208000019622 heart disease Diseases 0.000 claims description 2
150000007517 lewis acids Chemical class 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims 5
229910052717 sulfur Chemical group 0.000 claims 4
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 3
229910052760 oxygen Inorganic materials 0.000 claims 3
XOKVBTKTLBLNSW-UHFFFAOYSA-N 4-oxo-4-[4-(4-phenylpiperidin-1-yl)phenyl]butanoic acid Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1N1CCC(C=2C=CC=CC=2)CC1 XOKVBTKTLBLNSW-UHFFFAOYSA-N 0.000 claims 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
125000001475 halogen functional group Chemical group 0.000 claims 2
239000003883 ointment base Substances 0.000 claims 2
239000011593 sulfur Chemical group 0.000 claims 2
LNGVLSZEFFMWIU-OHYPFYFLSA-N (4z)-4-phenylmethoxyimino-4-[4-(4-phenylpiperidin-1-yl)phenyl]butanoic acid Chemical compound C=1C=C(N2CCC(CC2)C=2C=CC=CC=2)C=CC=1C(/CCC(=O)O)=N\OCC1=CC=CC=C1 LNGVLSZEFFMWIU-OHYPFYFLSA-N 0.000 claims 1
PKUGMMYQZAMIDX-UHFFFAOYSA-N 3-methyl-5-oxo-5-[4-(4-phenylpiperidin-1-yl)phenyl]pentanoic acid Chemical compound C1=CC(C(=O)CC(CC(O)=O)C)=CC=C1N1CCC(C=2C=CC=CC=2)CC1 PKUGMMYQZAMIDX-UHFFFAOYSA-N 0.000 claims 1
SGJNBMOXAMANCI-UHFFFAOYSA-N 4-oxo-4-[4-(4-phenylpiperazin-1-yl)phenyl]butanoic acid Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1N1CCN(C=2C=CC=CC=2)CC1 SGJNBMOXAMANCI-UHFFFAOYSA-N 0.000 claims 1
101000737090 Agrotis ipsilon Neuropeptide CCHamide-2 Proteins 0.000 claims 1
208000004196 Heart Aneurysm Diseases 0.000 claims 1
QPYYMFJNZAEBJP-XDOYNYLZSA-N O\N=C(\CCC(=O)O)/C1=CC=C(C=C1)N1CCC(CC1)C1=CC=CC=C1 Chemical compound O\N=C(\CCC(=O)O)/C1=CC=C(C=C1)N1CCC(CC1)C1=CC=CC=C1 QPYYMFJNZAEBJP-XDOYNYLZSA-N 0.000 claims 1
125000003710 aryl alkyl group Chemical group 0.000 claims 1
125000004433 nitrogen atom Chemical group N* 0.000 claims 1
QGCNKCCIODANKX-UHFFFAOYSA-M potassium 4-oxo-4-[4-(4-phenylpiperidin-1-yl)phenyl]butanoate Chemical compound [K+].[O-]C(=O)CCC(=O)c1ccc(cc1)N1CCC(CC1)c1ccccc1 QGCNKCCIODANKX-UHFFFAOYSA-M 0.000 claims 1
125000004434 sulfur atom Chemical group 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
108010016160 Matrix Metalloproteinase 3 Proteins 0.000 abstract description 7
208000025865 Ulcer Diseases 0.000 abstract description 7
231100000397 ulcer Toxicity 0.000 abstract description 6
102000013382 Gelatinases Human genes 0.000 abstract description 4
108010026132 Gelatinases Proteins 0.000 abstract description 4
206010019280 Heart failures Diseases 0.000 abstract description 2
230000029663 wound healing Effects 0.000 abstract description 2
230000009545 invasion Effects 0.000 abstract 1
239000002253 acid Substances 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
239000002904 solvent Substances 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
239000000203 mixture Substances 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000004480 active ingredient Substances 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
239000007787 solid Substances 0.000 description 13
238000010992 reflux Methods 0.000 description 12
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000000694 effects Effects 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
108090000765 processed proteins & peptides Proteins 0.000 description 8
238000003756 stirring Methods 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
BTVVEKSXUOEVAY-UHFFFAOYSA-N 4,4-diphenylpiperidine Chemical compound C1CNCCC1(C=1C=CC=CC=1)C1=CC=CC=C1 BTVVEKSXUOEVAY-UHFFFAOYSA-N 0.000 description 6
102000029816 Collagenase Human genes 0.000 description 6
108060005980 Collagenase Proteins 0.000 description 6
229960002424 collagenase Drugs 0.000 description 6
239000003826 tablet Substances 0.000 description 6
210000001519 tissue Anatomy 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000002775 capsule Substances 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
210000002744 extracellular matrix Anatomy 0.000 description 5
230000014509 gene expression Effects 0.000 description 5
150000002576 ketones Chemical class 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229910052744 lithium Inorganic materials 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 4
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
206010027476 Metastases Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
208000007474 aortic aneurysm Diseases 0.000 description 4
230000003683 cardiac damage Effects 0.000 description 4
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LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
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230000002829 reductive effect Effects 0.000 description 4
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235000017550 sodium carbonate Nutrition 0.000 description 4
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150000005691 triesters Chemical class 0.000 description 4
210000004881 tumor cell Anatomy 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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 3
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
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125000004432 carbon atom Chemical group C* 0.000 description 3
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238000010531 catalytic reduction reaction Methods 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
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UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 2
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KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
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CCVKPWUMYBYHCD-UHFFFAOYSA-N oxolane;pyridine Chemical compound C1CCOC1.C1=CC=NC=C1 CCVKPWUMYBYHCD-UHFFFAOYSA-N 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
239000004323 potassium nitrate Substances 0.000 description 1
235000010333 potassium nitrate Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000004892 pyridazines Chemical class 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
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
230000000552 rheumatic effect Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
239000004576 sand Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
230000015590 smooth muscle cell migration Effects 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000005309 thioalkoxy group Chemical group 0.000 description 1
229910000083 tin tetrahydride Inorganic materials 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 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
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
MYMLGBAVNHFRJS-UHFFFAOYSA-N trifluoromethanamine Chemical compound NC(F)(F)F MYMLGBAVNHFRJS-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
238000007805 zymography Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- 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
- A61P27/00—Drugs for disorders of the senses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- 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

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Immunology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Dermatology (AREA)
Physical Education & Sports Medicine (AREA)
Urology & Nephrology (AREA)
Ophthalmology & Optometry (AREA)
Vascular Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Hydrogenated Pyridines (AREA)

SK875-98A 1995-12-22 1996-11-27 Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases SK87598A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US948995P	1995-12-22	1995-12-22
PCT/US1996/018925 WO1997023459A1 (en)	1995-12-22	1996-11-27	Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases

Publications (1)

Publication Number	Publication Date
SK87598A3 true SK87598A3 (en)	1999-04-13

Family

ID=21737977

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK875-98A SK87598A3 (en)	1995-12-22	1996-11-27	Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases

Country Status (19)

Country	Link
US (1)	US6008220A (da)
EP (1)	EP0876343B1 (da)
JP (1)	JP2000502343A (da)
AT (1)	ATE214368T1 (da)
AU (1)	AU713174C (da)
BG (1)	BG63461B1 (da)
BR (1)	BR9612188A (da)
CZ (1)	CZ287868B6 (da)
DE (1)	DE69619865T2 (da)
DK (1)	DK0876343T3 (da)
ES (1)	ES2175155T3 (da)
HU (1)	HU222986B1 (da)
NO (1)	NO309470B1 (da)
NZ (1)	NZ323329A (da)
PL (1)	PL327494A1 (da)
PT (1)	PT876343E (da)
SK (1)	SK87598A3 (da)
WO (1)	WO1997023459A1 (da)
ZA (1)	ZA9610722B (da)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2233275T3 (es) *	1995-12-08	2005-06-16	Agouron Pharmaceuticals, Inc.	Intermediarios que sirven para la preparacion de inhibidores de metaloproteinasas.
US6500948B1 (en)	1995-12-08	2002-12-31	Agouron Pharmaceuticals, Inc.	Metalloproteinase inhibitors-compositions, uses preparation and intermediates thereof
US5795985A (en) *	1996-03-05	1998-08-18	Ciba Specialty Chemicals Corporation	Phenyl alkyl ketone substituted by cyclic amine and a process for the preparation thereof
CO4990925A1 (es)	1996-05-15	2000-12-26	Bayer Corp	Acidos oxibutiricos sustituidos como inhibidores de la metaloproteasa de matriz
CO5011061A1 (es)	1996-05-15	2001-02-28	Bayer Corp	Inhibicion de las metaloprotesas de matriz por acidos biariloxobutiricos sustituidos y composiciones farmaceuticas que los contienen
TNSN97086A1 (fr)	1996-05-15	2005-03-15	Bayer Corp	La substitution des acides derivatives 4-albutyrique comme inhibiteurs de la matrice metalloprotease.
US6008243A (en) *	1996-10-24	1999-12-28	Agouron Pharmaceuticals, Inc.	Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use
US6174915B1 (en)	1997-03-25	2001-01-16	Agouron Pharmaceuticals, Inc.	Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses
ES2212142T3 (es)	1996-12-17	2004-07-16	Warner-Lambert Company Llc	Uso de inhibidores de metaloproteinasas de la matriz para promover la curacion de heridas.
SI0946166T1 (en) *	1996-12-17	2004-06-30	Warner-Lambert Company Llc	Use of matrix metalloproteinase inhibitors for promoting wound healing
US5985900A (en) *	1997-04-01	1999-11-16	Agouron Pharmaceuticals, Inc.	Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses
EP1024134A4 (en)	1997-10-09	2003-05-14	Ono Pharmaceutical Co	DERIVATIVES OF AMINOBUTANIC ACID
US6288063B1 (en)	1998-05-27	2001-09-11	Bayer Corporation	Substituted 4-biarylbutyric and 5-biarylpentanoic acid derivatives as matrix metalloprotease inhibitors
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
AU2003300076C1 (en)	2002-12-30	2010-03-04	Angiotech International Ag	Drug delivery from rapid gelling polymer composition
MY150088A (en)	2003-05-19	2013-11-29	Irm Llc	Immunosuppressant compounds and compositions
WO2010011302A1 (en) *	2008-07-22	2010-01-28	Chdi, Inc.	Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
KR20140072037A (ko)	2011-08-30	2014-06-12	씨에이치디아이 파운데이션, 인코포레이티드	키뉴레닌-3-모노옥시게나제 억제제, 약학적 조성물 및 이의 사용 방법
SI2750677T1 (sl)	2011-08-30	2017-10-30	Chdi Foundation, Inc.	Inhibitorji kinurenin-3-monooksigenaze, farmacevtski sestavki in postopki njihove uporabe
AU2015289492B2 (en)	2014-07-17	2020-02-20	Chdi Foundation, Inc.	Methods and compositions for treating HIV-related disorders
EP3191453B1 (en) *	2014-09-09	2019-10-23	Bristol-Myers Squibb Company	Phenyl-(aza)cycloalkyl carboxylic acid gpr120 modulators

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2153031T4 (es) *	1995-04-20	2001-05-16	Pfizer	Derivados del acido arilsulfonil hidroxamico como inhibidores de mmp y tnf.
KR20000057444A (ko) *	1996-12-09	2000-09-15	로즈 암스트롱, 크리스틴 에이. 트러트웨인	심기능부전 및 심실확장의 치료 및 예방 방법
ES2212142T3 (es) *	1996-12-17	2004-07-16	Warner-Lambert Company Llc	Uso de inhibidores de metaloproteinasas de la matriz para promover la curacion de heridas.

1996
- 1996-11-27 NZ NZ323329A patent/NZ323329A/en unknown
- 1996-11-27 CZ CZ19981952A patent/CZ287868B6/cs not_active IP Right Cessation
- 1996-11-27 HU HU9902079A patent/HU222986B1/hu not_active IP Right Cessation
- 1996-11-27 DK DK96940614T patent/DK0876343T3/da active
- 1996-11-27 PT PT96940614T patent/PT876343E/pt unknown
- 1996-11-27 PL PL96327494A patent/PL327494A1/xx unknown
- 1996-11-27 JP JP9523645A patent/JP2000502343A/ja not_active Abandoned
- 1996-11-27 WO PCT/US1996/018925 patent/WO1997023459A1/en not_active Ceased
- 1996-11-27 ES ES96940614T patent/ES2175155T3/es not_active Expired - Lifetime
- 1996-11-27 SK SK875-98A patent/SK87598A3/sk unknown
- 1996-11-27 AU AU10249/97A patent/AU713174C/en not_active Ceased
- 1996-11-27 DE DE69619865T patent/DE69619865T2/de not_active Expired - Fee Related
- 1996-11-27 AT AT96940614T patent/ATE214368T1/de not_active IP Right Cessation
- 1996-11-27 EP EP96940614A patent/EP0876343B1/en not_active Expired - Lifetime
- 1996-11-27 BR BR9612188A patent/BR9612188A/pt not_active Application Discontinuation
- 1996-11-27 US US09/077,715 patent/US6008220A/en not_active Expired - Fee Related
- 1996-12-19 ZA ZA9610722A patent/ZA9610722B/xx unknown
1998
- 1998-05-20 BG BG102471A patent/BG63461B1/bg unknown
- 1998-06-19 NO NO982840A patent/NO309470B1/no unknown

Also Published As

Publication number	Publication date
NZ323329A (en)	1999-02-25
CZ287868B6 (en)	2001-02-14
WO1997023459A1 (en)	1997-07-03
AU1024997A (en)	1997-07-17
HUP9902079A2 (hu)	1999-10-28
AU713174C (en)	2002-05-02
ZA9610722B (en)	1997-06-27
BG63461B1 (bg)	2002-02-28
AU713174B2 (en)	1999-11-25
BG102471A (en)	1999-08-31
DE69619865T2 (de)	2002-11-07
EP0876343A1 (en)	1998-11-11
EP0876343B1 (en)	2002-03-13
US6008220A (en)	1999-12-28
ATE214368T1 (de)	2002-03-15
DK0876343T3 (da)	2002-07-01
NO982840D0 (no)	1998-06-19
NO982840L (no)	1998-06-19
PL327494A1 (en)	1998-12-21
HU222986B1 (hu)	2004-01-28
DE69619865D1 (de)	2002-04-18
NO309470B1 (no)	2001-02-05
HUP9902079A3 (en)	2000-06-28
PT876343E (pt)	2002-08-30
CZ195298A3 (cs)	1998-09-16
MX9803315A (es)	1998-09-30
JP2000502343A (ja)	2000-02-29
BR9612188A (pt)	1999-07-13
ES2175155T3 (es)	2002-11-16

Publication	Publication Date	Title
SK87598A3 (en)	1999-04-13	Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases
SK282833B6 (sk)	2002-12-03	Sulfónamidové inhibítory matricových metaloproteináz a farmaceutická kompozícia obsahujúca tieto inhibítory
US6307089B2 (en)	2001-10-23	Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases
ES2216614T3 (es)	2004-10-16	Sulfonamidas triciclicas y sus derivados como inhibidores de metaloproteinasas de matriz.
CA2581730C (en)	2012-10-30	New histone deacetylases inhibitors
SK157798A3 (en)	1999-04-13	Biphenylsulfonamide matrix metalloproteinase inhibitors
US6541521B1 (en)	2003-04-01	Benzene butyric acids and their derivatives as inhibitors of matrix metalloproteinases
HRP970474A2 (en)	1998-12-31	Compounds for and a method of inhibiting matrix metalloproteinases
MXPA01013324A (es)	2002-07-02	Compuestos de acido hidroxamico utiles como inhibidores de metaloproteinasa de matriz.
CA2356053A1 (en)	2000-07-13	Use of substituted 4-biarylbutyric and 5-biarylpentanoic acid derivatives as matrix metalloprotease inhibitors for the treatment of respiratory diseases
KR19990022171A (ko)	1999-03-25	매트릭스 메탈로프로테이나제의 트리시클릭 저해제
JP2003321424A (ja)	2003-11-11	エステル化合物及びその医薬用途
US6624177B1 (en)	2003-09-23	Matrix metalloproteinase inhibitors and their therapeutic uses
CA2233560C (en)	2005-12-20	Sulfonamide inhibitors of matrix metalloproteinases
MXPA98003315A (en)	1998-11-16	Queto aromatic acids and their derivatives as inhibitors of metaloproteinases mat
CA2236096A1 (en)	1997-07-03	Aromatic keto-acids and their derivatives as inhibitors of matrix metalloproteinases
CZ2001302A3 (cs)	2001-07-11	Tricyklické sulfonamidy a jejich deriváty jako inhibitory matricových metaloproteináz
MXPA98009871A (en)	1999-04-27	Matrix metalloproteinase inhibitors and their therapeutic uses