JP2000514043A - マトリックスメタロプロテイナーゼ・インヒビター - Google Patents

マトリックスメタロプロテイナーゼ・インヒビター

Info

Publication number: JP2000514043A
Authority: JP; Japan
Prior art keywords: group; methyl; phenyl; substituted; ethyl
Prior art date: 1996-06-27
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.): Pending

Application number

JP10502322A

Other languages

English (en)

Japanese (ja)

Inventor

アルペジアーニ，マルコ

アブラーテ，フランチエスカ

ビツソリーノ，ピエールイギ

パツラデイーノ，マツシミリアーノ

ペローネ，エツトーレ

Original Assignee

フアルマシア・エ・アツプジヨン・エツセ・ピー・アー

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.)

1996-06-27

Filing date

1997-06-20

Publication date

2000-10-24

1997-06-20 Application filed by フアルマシア・エ・アツプジヨン・エツセ・ピー・アー filed Critical フアルマシア・エ・アツプジヨン・エツセ・ピー・アー

2000-10-24 Publication of JP2000514043A publication Critical patent/JP2000514043A/ja

Status Pending legal-status Critical Current

Links

239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 6
229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 6
239000000203 mixture Substances 0.000 claims abstract description 36
238000000034 method Methods 0.000 claims abstract description 35
239000001257 hydrogen Substances 0.000 claims abstract description 29
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
239000003814 drug Substances 0.000 claims abstract description 25
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
229940079593 drug Drugs 0.000 claims abstract description 21
-1 C1~ C6Alkyl Chemical group 0.000 claims description 246
150000001875 compounds Chemical class 0.000 claims description 148
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 68
125000000217 alkyl group Chemical group 0.000 claims description 67
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 58
125000001424 substituent group Chemical group 0.000 claims description 56
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 46
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
125000000623 heterocyclic group Chemical group 0.000 claims description 40
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 35
125000003118 aryl group Chemical group 0.000 claims description 27
150000003839 salts Chemical class 0.000 claims description 26
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
125000001153 fluoro group Chemical group F* 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 20
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
125000001309 chloro group Chemical group Cl* 0.000 claims description 18
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 18
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
150000001412 amines Chemical class 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
125000004043 oxo group Chemical group O=* 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
125000006239 protecting group Chemical group 0.000 claims description 11
125000003282 alkyl amino group Chemical group 0.000 claims description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
239000000651 prodrug Substances 0.000 claims description 9
229940002612 prodrug Drugs 0.000 claims description 9
239000012453 solvate Substances 0.000 claims description 9
125000000335 thiazolyl group Chemical group 0.000 claims description 9
125000001544 thienyl group Chemical group 0.000 claims description 9
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 8
125000001041 indolyl group Chemical group 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 8
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
235000008206 alpha-amino acids Nutrition 0.000 claims description 6
125000000524 functional group Chemical group 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 5
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 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 description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000004442 acylamino group Chemical group 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 4
229940091173 hydantoin Drugs 0.000 claims description 4
150000004677 hydrates Chemical class 0.000 claims description 4
125000006301 indolyl methyl group Chemical group 0.000 claims description 4
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
229960002317 succinimide Drugs 0.000 claims description 4
125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 4
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 4
150000001371 alpha-amino acids Chemical class 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000005493 quinolyl group Chemical group 0.000 claims description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000005504 styryl group Chemical group 0.000 claims description 3
125000003944 tolyl group Chemical group 0.000 claims description 3
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 2
125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 2
RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 claims description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
150000002475 indoles Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims 1
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
241000610375 Sparisoma viride Species 0.000 claims 1
SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical class NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims 1
SWUIQEBPZIHZQS-UHFFFAOYSA-N calone Chemical compound O1CC(=O)COC2=CC(C)=CC=C21 SWUIQEBPZIHZQS-UHFFFAOYSA-N 0.000 claims 1
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 claims 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 29
108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 29
239000003112 inhibitor Substances 0.000 abstract description 25
238000011282 treatment Methods 0.000 abstract description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 12
201000010099 disease Diseases 0.000 abstract description 8
238000004519 manufacturing process Methods 0.000 abstract description 7
108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 5
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract description 5
150000001413 amino acids Chemical class 0.000 abstract description 5
230000002265 prevention Effects 0.000 abstract description 3
125000000962 organic group Chemical group 0.000 abstract 1
JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical class NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
239000002904 solvent Substances 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
239000000843 powder Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
235000019439 ethyl acetate Nutrition 0.000 description 17
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
239000011734 sodium Substances 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
150000002148 esters Chemical class 0.000 description 15
239000007864 aqueous solution Substances 0.000 description 14
210000004027 cell Anatomy 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
239000007787 solid Substances 0.000 description 13
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
102000004190 Enzymes Human genes 0.000 description 12
108090000790 Enzymes Proteins 0.000 description 12
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
229940088598 enzyme Drugs 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
229910052763 palladium Inorganic materials 0.000 description 12
239000012298 atmosphere Substances 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
239000000758 substrate Substances 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
102100026802 72 kDa type IV collagenase Human genes 0.000 description 8
206010028980 Neoplasm Diseases 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000000796 flavoring agent Substances 0.000 description 8
239000000463 material Substances 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 7
102000029816 Collagenase Human genes 0.000 description 7
108060005980 Collagenase Proteins 0.000 description 7
229940124761 MMP inhibitor Drugs 0.000 description 7
239000004480 active ingredient Substances 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
239000012267 brine Substances 0.000 description 7
229960002424 collagenase Drugs 0.000 description 7
239000002609 medium Substances 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 6
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
102100040247 Tumor necrosis factor Human genes 0.000 description 6
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 6
239000007859 condensation product Substances 0.000 description 6
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
108091007196 stromelysin Proteins 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
150000003952 β-lactams Chemical class 0.000 description 6
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 5
239000012317 TBTU Substances 0.000 description 5
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
238000009833 condensation Methods 0.000 description 5
230000005494 condensation Effects 0.000 description 5
235000014113 dietary fatty acids Nutrition 0.000 description 5
239000002532 enzyme inhibitor Substances 0.000 description 5
229940125532 enzyme inhibitor Drugs 0.000 description 5
239000000194 fatty acid Substances 0.000 description 5
229930195729 fatty acid Natural products 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
235000003599 food sweetener Nutrition 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
108090000765 processed proteins & peptides Proteins 0.000 description 5
239000000047 product Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000375 suspending agent Substances 0.000 description 5
239000006188 syrup Substances 0.000 description 5
235000020357 syrup Nutrition 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical group C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 4
HQAPZMWVZNJFCO-SECBINFHSA-N 4-[[(2S)-1-methoxy-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound COC([C@@H](NC(CCC(=O)O)=O)C(C)(C)C)=O HQAPZMWVZNJFCO-SECBINFHSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
102000010911 Enzyme Precursors Human genes 0.000 description 4
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238000004448 titration Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Immunology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Thiazole And Isothizaole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyridine Compounds (AREA)

JP10502322A 1996-06-27 1997-06-20 マトリックスメタロプロテイナーゼ・インヒビター Pending JP2000514043A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB9613547.0		1996-06-27
GBGB9613547.0A GB9613547D0 (en)	1996-06-27	1996-06-27	Matrix metalloproteinase inhibitors
PCT/EP1997/003251 WO1997049674A1 (en)	1996-06-27	1997-06-20	Matrix metalloproteinase inhibitors

Publications (1)

Publication Number	Publication Date
JP2000514043A true JP2000514043A (ja)	2000-10-24

Family

ID=10796022

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP10502322A Pending JP2000514043A (ja)	1996-06-27	1997-06-20	マトリックスメタロプロテイナーゼ・インヒビター

Country Status (18)

Country	Link
EP (1)	EP0920414A1 (pt)
JP (1)	JP2000514043A (pt)
KR (1)	KR20000022534A (pt)
AR (1)	AR008621A1 (pt)
AU (1)	AU733938B2 (pt)
BR (1)	BR9709902A (pt)
CA (1)	CA2257404A1 (pt)
CZ (1)	CZ430398A3 (pt)
EA (1)	EA001432B1 (pt)
GB (1)	GB9613547D0 (pt)
ID (1)	ID17792A (pt)
IL (1)	IL127262A0 (pt)
NO (1)	NO986049L (pt)
NZ (1)	NZ333550A (pt)
PL (1)	PL330897A1 (pt)
TW (1)	TW460441B (pt)
WO (1)	WO1997049674A1 (pt)
ZA (1)	ZA975631B (pt)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20060116552A (ko) *	2005-05-10	2006-11-15	연세대학교 산학협력단	매트릭스 메탈로프로테이나제 저해제로서 엔-포르밀히드록실아민 유도체
JP2013503142A (ja) *	2009-08-26	2013-01-31	コミッサリアアレネルジアトミックエオーエネルジアルターネイティブス	Ｍｍｐインヒビターとしてのシュードジペプチド

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DE19719817A1 (de) *	1997-05-13	1998-11-19	Hoechst Ag	Substituierte 6- und 7-Aminotetrahydroisochinolincarbonsäuren
KR100352316B1 (ko)	1997-07-31	2002-09-12	더 프록터 앤드 갬블 캄파니	메탈로프로테아제억제제로서사용되는술포닐아미노치환히드록삼산유도체
GB9803005D0 (en) *	1998-02-12	1998-04-08	British Biotech Pharm	Anti-inflammatory agents
GB9804777D0 (en) *	1998-03-07	1998-04-29	British Biotech Pharm	Anti-inflammatory agents
US6335324B1 (en)	1998-06-25	2002-01-01	Bristol-Myers Squibb Co.	Beta lactam compounds and their use as inhibitors of tryptase
GB9901863D0 (en)	1999-01-29	1999-03-17	British Biotech Pharm	Antibacterial agents
PL350340A1 (en)	1999-03-03	2002-12-02	Procter & Gamble	Alkenyl- and alkynyl-containing metalloprotease inhibitors
EP1237862A1 (en) *	1999-12-17	2002-09-11	Versicor, Inc.	Succinate compounds, compositions and methods of use and preparation
GB9930754D0 (en) *	1999-12-29	2000-02-16	Smithkline Beecham Plc	Novel compounds
WO2002006227A1 (en) *	2000-07-18	2002-01-24	Chugai Seiyaku Kabushiki Kaisha	Matrix metalloprotease inhibitors
EP1406893B1 (en)	2001-06-15	2007-04-18	Vicuron Pharmaceuticals, Inc.	Pyrrolidine bicyclic compounds
AR036053A1 (es)	2001-06-15	2004-08-04	Versicor Inc	Compuestos de n-formil-hidroxilamina, un proceso para su preparacion y composiciones farmaceuticas
US20110230479A1 (en) *	2005-04-15	2011-09-22	Longo Frank M	Neurotrophin mimetics and uses thereof
CA2780940C (en)	2009-11-12	2021-08-31	Pharmatrophix, Inc.	Crystalline forms of neurotrophin mimetic compounds and their salts
US10273219B2 (en)	2009-11-12	2019-04-30	Pharmatrophix, Inc.	Crystalline forms of neurotrophin mimetic compounds and their salts
AU2019352741A1 (en)	2018-10-04	2021-05-06	Assistance Publique-Hôpitaux De Paris (Aphp)	EGFR inhibitors for treating keratodermas

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US4599361A (en) *	1985-09-10	1986-07-08	G. D. Searle & Co.	Hydroxamic acid based collagenase inhibitors
DK77487A (da) *	1986-03-11	1987-09-12	Hoffmann La Roche	Hydroxylaminderivater
ATE120182T1 (de) *	1990-12-03	1995-04-15	Celltech Ltd	Peptidylderivate.
CA2058797A1 (en) *	1991-02-01	1992-08-02	Michael John Broadhurst	Amino acid derivatives
EP0520573A1 (en) *	1991-06-27	1992-12-30	Glaxo Inc.	Cyclic imide derivatives

1996
- 1996-06-27 GB GBGB9613547.0A patent/GB9613547D0/en active Pending
1997
- 1997-06-18 TW TW086108613A patent/TW460441B/zh active
- 1997-06-20 EA EA199900057A patent/EA001432B1/ru not_active IP Right Cessation
- 1997-06-20 IL IL12726297A patent/IL127262A0/xx unknown
- 1997-06-20 NZ NZ333550A patent/NZ333550A/xx unknown
- 1997-06-20 CA CA002257404A patent/CA2257404A1/en not_active Abandoned
- 1997-06-20 CZ CZ984303A patent/CZ430398A3/cs unknown
- 1997-06-20 AU AU33422/97A patent/AU733938B2/en not_active Ceased
- 1997-06-20 EP EP97929242A patent/EP0920414A1/en not_active Withdrawn
- 1997-06-20 WO PCT/EP1997/003251 patent/WO1997049674A1/en not_active Ceased
- 1997-06-20 BR BR9709902A patent/BR9709902A/pt unknown
- 1997-06-20 JP JP10502322A patent/JP2000514043A/ja active Pending
- 1997-06-20 PL PL97330897A patent/PL330897A1/xx unknown
- 1997-06-20 KR KR1019980710980A patent/KR20000022534A/ko not_active Withdrawn
- 1997-06-25 ZA ZA9705631A patent/ZA975631B/xx unknown
- 1997-06-26 ID IDP972218A patent/ID17792A/id unknown
- 1997-06-26 AR ARP970102813A patent/AR008621A1/es unknown
1998
- 1998-12-22 NO NO986049A patent/NO986049L/no not_active Application Discontinuation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20060116552A (ko) *	2005-05-10	2006-11-15	연세대학교 산학협력단	매트릭스 메탈로프로테이나제 저해제로서 엔-포르밀히드록실아민 유도체
JP2013503142A (ja) *	2009-08-26	2013-01-31	コミッサリアアレネルジアトミックエオーエネルジアルターネイティブス	Ｍｍｐインヒビターとしてのシュードジペプチド

Also Published As

Publication number	Publication date
NO986049L (no)	1999-03-01
CA2257404A1 (en)	1997-12-31
AU733938B2 (en)	2001-05-31
ID17792A (id)	1998-01-29
EP0920414A1 (en)	1999-06-09
TW460441B (en)	2001-10-21
KR20000022534A (ko)	2000-04-25
NO986049D0 (no)	1998-12-22
PL330897A1 (en)	1999-06-07
EA199900057A1 (ru)	1999-06-24
BR9709902A (pt)	1999-08-10
AR008621A1 (es)	2000-02-09
IL127262A0 (en)	1999-09-22
ZA975631B (en)	1998-01-30
GB9613547D0 (en)	1996-08-28
EA001432B1 (ru)	2001-02-26
AU3342297A (en)	1998-01-14
CZ430398A3 (cs)	1999-08-11
WO1997049674A1 (en)	1997-12-31
NZ333550A (en)	2000-07-28

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DE69615058T2 (de)	2002-06-27	Metalloproteinase inhibitoren
JP2001500533A (ja)	2001-01-16	マトリックスメタロプロテイナーゼ・インヒビター
CA2443600A1 (en)	2002-10-31	Heterocyclyldicarbamides as caspase inhibitors
JP2002516336A (ja)	2002-06-04	Ｖｌａ−４アンタゴニスト活性を有するフェニルアラニン誘導体
CA2285405A1 (en)	1998-09-11	Amidoaromatic ring sulfonamide hydroxamic acid compounds
JP2001521504A (ja)	2001-11-06	メタロプロテイナーゼ阻害薬、それらを含有する薬剤組成物および薬剤としてのそれらの使用
JPH11507912A (ja)	1999-07-13	システインプロテアーゼインヒビターとしてのα−（１，３−ジカルボニルエノールエーテル）メチルケトン
JP2001501955A (ja)	2001-02-13	新規のピペリジン―ケトカルボン酸誘導体、その製造および使用
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AU2003297364B2 (en)	2009-07-09	Inhibitors of TACE
JP2856548B2 (ja)	1999-02-10	チオナフタレン誘導体およびその製法並びにそれを含む抗アレルギー剤
EP1493739A1 (fr)	2005-01-05	Dérivés thiophényliques d'aminoacides, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
JPH09507846A (ja)	1997-08-12	フェニルメチルヘキサンアミドおよびその使用
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US6482827B1 (en)	2002-11-19	Matrix metalloproteinase inhibitors
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EP0979816B1 (fr)	2003-05-02	Nouveaux dérivés d'acide hydroxamique, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
DE19748040A1 (de)	1998-05-07	Carbonsäurederivate, Verfahren zu ihrer Herstellung und pharmazeutische Präparate, die diese Verbindungen enthalten
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JP2000514043A - マトリックスメタロプロテイナーゼ・インヒビター - Google Patents

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