CA2139129A1 - Derives peptidyle et leur utilisation comme inhibiteur d'une metalloproteinase - Google Patents

Derives peptidyle et leur utilisation comme inhibiteur d'une metalloproteinase

Info

Publication number: CA2139129A1
Authority: CA; Canada
Prior art keywords: group; optionally substituted; hydrogen atom; formula; compounds
Prior art date: 1993-04-27
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

Application number

CA002139129A

Other languages

English (en)

Inventor

John Richard Morphy

Thomas Andrew Millican

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Celltech R&D Ltd

Original Assignee

Individual

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.)

1993-04-27

Filing date

1994-04-27

Publication date

1994-11-10

1994-04-27 Application filed by Individual filed Critical Individual

1994-11-10 Publication of CA2139129A1 publication Critical patent/CA2139129A1/fr

Status Abandoned legal-status Critical Current

Links

239000003475 metalloproteinase inhibitor Substances 0.000 title abstract description 6
125000001151 peptidyl group Chemical group 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 130
-1 amino, carboxyl Chemical group 0.000 claims abstract description 104
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 40
125000000217 alkyl group Chemical group 0.000 claims abstract description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 37
125000003118 aryl group Chemical group 0.000 claims abstract description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 23
125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 14
125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 13
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 13
229910052799 carbon Inorganic materials 0.000 claims abstract description 10
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
239000000651 prodrug Substances 0.000 claims abstract description 8
229940002612 prodrug Drugs 0.000 claims abstract description 8
125000004429 atom Chemical group 0.000 claims abstract description 7
150000004677 hydrates Chemical class 0.000 claims abstract description 7
125000002252 acyl group Chemical group 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
125000001931 aliphatic group Chemical group 0.000 claims abstract description 5
125000002947 alkylene group Chemical group 0.000 claims abstract description 5
125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 5
125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 4
239000001301 oxygen Substances 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
239000012453 solvate Substances 0.000 claims abstract description 4
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
239000002253 acid Substances 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
150000001412 amines Chemical class 0.000 claims description 9
238000005859 coupling reaction Methods 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
230000008878 coupling Effects 0.000 claims description 2
238000010168 coupling process Methods 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
239000008024 pharmaceutical diluent Substances 0.000 claims 1
125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
238000011282 treatment Methods 0.000 abstract description 12
201000010099 disease Diseases 0.000 abstract description 10
108060005980 Collagenase Proteins 0.000 abstract description 8
102000029816 Collagenase Human genes 0.000 abstract description 8
108010026132 Gelatinases Proteins 0.000 abstract description 8
102000013382 Gelatinases Human genes 0.000 abstract description 8
206010028980 Neoplasm Diseases 0.000 abstract description 8
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 abstract description 7
108091007196 stromelysin Proteins 0.000 abstract description 7
229960002424 collagenase Drugs 0.000 abstract description 6
206010027476 Metastases Diseases 0.000 abstract description 4
238000011321 prophylaxis Methods 0.000 abstract description 4
238000011161 development Methods 0.000 abstract description 3
208000035475 disorder Diseases 0.000 abstract description 3
201000011510 cancer Diseases 0.000 abstract description 2
238000006243 chemical reaction Methods 0.000 description 24
239000000460 chlorine Substances 0.000 description 20
238000000034 method Methods 0.000 description 18
125000001424 substituent group Chemical group 0.000 description 18
239000002904 solvent Substances 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
239000000543 intermediate Substances 0.000 description 11
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 11
239000000243 solution Substances 0.000 description 11
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
150000007513 acids Chemical class 0.000 description 10
229910052739 hydrogen Inorganic materials 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
239000003112 inhibitor Substances 0.000 description 7
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
125000002619 bicyclic group Chemical group 0.000 description 6
150000001721 carbon Chemical group 0.000 description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 5
125000006017 1-propenyl group Chemical group 0.000 description 5
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
238000012360 testing method Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-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
241000699670 Mus sp. Species 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
238000003556 assay Methods 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
230000015556 catabolic process Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
125000004344 phenylpropyl group Chemical group 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
150000001266 acyl halides Chemical class 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
125000005518 carboxamido group Chemical group 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000011521 glass Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
150000002690 malonic acid derivatives Chemical class 0.000 description 3
230000009401 metastasis Effects 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
210000003281 pleural cavity Anatomy 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
125000000168 pyrrolyl group Chemical group 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000000758 substrate Substances 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 2
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
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 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
229930040373 Paraformaldehyde Natural products 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229910006074 SO2NH2 Inorganic materials 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001263 acyl chlorides Chemical class 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
239000003125 aqueous solvent Substances 0.000 description 2
230000002917 arthritic effect Effects 0.000 description 2
125000004659 aryl alkyl thio group Chemical group 0.000 description 2
230000037396 body weight Effects 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
210000002808 connective tissue Anatomy 0.000 description 2
150000004292 cyclic ethers Chemical class 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
150000005690 diesters Chemical class 0.000 description 2
229960001760 dimethyl sulfoxide Drugs 0.000 description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
239000003814 drug Substances 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
210000002744 extracellular matrix Anatomy 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000007789 gas Substances 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
230000009545 invasion Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
208000037841 lung tumor Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 2
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
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239000007800 oxidant agent Substances 0.000 description 2
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229910052763 palladium Inorganic materials 0.000 description 2
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125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
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125000004193 piperazinyl group Chemical group 0.000 description 2
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230000003389 potentiating effect Effects 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Ophthalmology & Optometry (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pyrrole Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)

CA002139129A 1993-04-27 1994-04-27 Derives peptidyle et leur utilisation comme inhibiteur d'une metalloproteinase Abandoned CA2139129A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB9308695.7		1993-04-27
GB939308695A GB9308695D0 (en)	1993-04-27	1993-04-27	Peptidyl derivatives

Publications (1)

Publication Number	Publication Date
CA2139129A1 true CA2139129A1 (fr)	1994-11-10

Family

ID=10734557

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002139129A Abandoned CA2139129A1 (fr)	1993-04-27	1994-04-27	Derives peptidyle et leur utilisation comme inhibiteur d'une metalloproteinase

Country Status (6)

Country	Link
EP (1)	EP0648206A1 (fr)
JP (1)	JPH08500610A (fr)
AU (1)	AU6575494A (fr)
CA (1)	CA2139129A1 (fr)
GB (1)	GB9308695D0 (fr)
WO (1)	WO1994025435A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6037472A (en)	1993-11-04	2000-03-14	Syntex (U.S.A.) Inc.	Matrix metalloprotease inhibitors
JP3827324B2 (ja) *	1994-01-22	2006-09-27	ブリテッシュバイオテックファーマシューティカルズリミテッド	金属タンパク質分解酵素阻害剤
GB2300188B (en) *	1994-01-22	1998-07-01	British Biotech Pharm	Metalloproteinase inhibitors
AU711047B2 (en) *	1994-01-22	1999-10-07	British Biotech Pharmaceuticals Limited	Metalloproteinase inhibitors
GB9423914D0 (en) *	1994-11-26	1995-01-11	British Biotech Pharm	Polyether derivatives as metalloproteinase inhibitors
US5917090A (en) *	1995-06-30	1999-06-29	British Biotech Pharmaceuticals Ltd.	Matrix metalloproteinase inhibitors
JP2000500761A (ja)	1995-11-23	2000-01-25	ブリティッシュバイオテックファーマシューティカルズリミテッド	金属タンパク質分解酵素阻害剤
DE69633947T2 (de) *	1995-12-08	2005-12-01	Agouron Pharmaceuticals, Inc., San Diego	Zwischenprodukte zur Herstellung von Metallproteinasehemmern
TW424083B (en) *	1996-07-10	2001-03-01	American Cyanamid Co	Mercaptoketones and mercaptoalcohols and a process for their prepartation
US5852213A (en) *	1996-07-10	1998-12-22	American Cyanamid Company	Mercaptoketones and mercaptoalcohols and a process for their preparation
NZ333923A (en)	1996-09-10	2000-11-24	British Biotech Pharm	Cytostatic hydroxamic acid derivatives for inhibiting proliferation of tumour cells
US6462023B1 (en)	1996-09-10	2002-10-08	British Biotech Pharmaceuticals, Ltd.	Cytostatic agents
ZA9818B (en) *	1997-01-07	1998-07-02	Abbott Lab	C-terminal ketone inhibitors of matrix metalloproteinases and tnf alpha secretion
US5985911A (en) *	1997-01-07	1999-11-16	Abbott Laboratories	C-terminal ketone inhibitors of matrix metalloproteinases and TNFα secretion
RU2141483C1 (ru) *	1997-07-04	1999-11-20	Небольсин Владимир Евгеньевич	Производные пептидов или их фармацевтически приемлемые соли, способ их получения, применение и фармацевтическая композиция
EA002971B1 (ru)	1998-01-09	2002-12-26	Пфайзер Инк.	Ингибиторы металлопротеаз матрикса, способы их получения, фармкомпозиция, применение и способ лечения
GB9803005D0 (en)	1998-02-12	1998-04-08	British Biotech Pharm	Anti-inflammatory agents
US6329418B1 (en)	1998-04-14	2001-12-11	The Procter & Gamble Company	Substituted pyrrolidine hydroxamate metalloprotease inhibitors
US6288261B1 (en)	1998-12-18	2001-09-11	Abbott Laboratories	Inhibitors of matrix metalloproteinases
RU2245876C2 (ru)	2000-03-21	2005-02-10	Дзе Проктер Энд Гэмбл Компани	Производные сульфонамидов и фармацевтическая композиция на их основе
CA2401728A1 (fr)	2000-03-21	2001-09-27	The Procter & Gamble Company	Inhibiteurs de metalloproteases d'acide difluorobutyrique
JP2003528850A (ja) *	2000-03-27	2003-09-30	ザ・スクリプス・リサーチ・インステイチユート	血管形成および腫瘍成長の阻害
ATE360014T1 (de)	2001-06-15	2007-05-15	Vicuron Pharm Inc	Bicyclische pyrrolidinverbindungen
AR036053A1 (es)	2001-06-15	2004-08-04	Versicor Inc	Compuestos de n-formil-hidroxilamina, un proceso para su preparacion y composiciones farmaceuticas
RU2217196C2 (ru) *	2002-02-28	2003-11-27	Небольсин Владимир Евгеньевич	Способ индукции дифференцировки клеток
WO2008119176A1 (fr) *	2007-04-02	2008-10-09	Merck Frosst Canada Ltd.	Procédé d'amidation pour la préparation d'inhibiteurs de la cathepsine k

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8919251D0 (en) *	1989-08-24	1989-10-04	British Bio Technology	Compounds
CA2073510A1 (fr) *	1990-12-03	1992-06-04	Celltech Therapeutics Limited	Derives peptidyles

1993
- 1993-04-27 GB GB939308695A patent/GB9308695D0/en active Pending
1994
- 1994-04-27 EP EP94913710A patent/EP0648206A1/fr not_active Withdrawn
- 1994-04-27 JP JP6524027A patent/JPH08500610A/ja active Pending
- 1994-04-27 CA CA002139129A patent/CA2139129A1/fr not_active Abandoned
- 1994-04-27 WO PCT/GB1994/000896 patent/WO1994025435A1/fr not_active Ceased
- 1994-04-27 AU AU65754/94A patent/AU6575494A/en not_active Abandoned

Also Published As

Publication number	Publication date
EP0648206A1 (fr)	1995-04-19
JPH08500610A (ja)	1996-01-23
AU6575494A (en)	1994-11-21
GB9308695D0 (en)	1993-06-09
WO1994025435A1 (fr)	1994-11-10

Legal Events

Date	Code	Title	Description
1998-04-27	FZDE	Dead

Publication	Publication Date	Title
EP0648205B1 (fr)	1999-07-14	Derives peptidiques inhibiteurs de metalloproteinases
AU652596B2 (en)	1994-09-01	Peptidyl derivatives
WO1994025435A1 (fr)	1994-11-10	Derives peptidiques et leur utilisation comme inhibiteurs de metalloproteases
US5530128A (en)	1996-06-25	N-sulphonylamino derivatives of dipetide compounds as metalloproteinase inhibitors
US5569665A (en)	1996-10-29	Peptidyl derivatives and their use as metalloproteinases inhibitors
US5210266A (en)	1993-05-11	N-substituted mercaptopropanamide derivatives
WO2002048097A1 (fr)	2002-06-20	Composes, compositions et procedes de traitement d'infections parasitaires
US5179125A (en)	1993-01-12	N-substituted mercaptopropanamide derivatives
CA2227466A1 (fr)	1997-02-06	Esters et amides utilises en tant qu'inhibiteurs anti-pla2
HU201005B (en)	1990-09-28	Process for producing new n-substituted mercaptopropaneamide derivatives and pharmaceutical compositions comprising such compounds
US5889058A (en)	1999-03-30	Peptidyl derivatives
US20090012006A1 (en)	2009-01-08	Par-2 Antagonists
IE921610A1 (en)	1992-12-16	Peptidyl derivatives
CA2105309A1 (fr)	1993-07-16	Derives phosphono d'aminoacides, inhibiteurs de la metalloproteinase
PT100558A (pt)	1993-11-30	Derivados de peptidilo, composicoes farmaceuticas que os contem e processo para a preparacao desses derivados