UA61906C2 - Hydroxamic acid derivatives useful for treatment of diseases related to connective tissue degradation, and a pharmaceutical composition based thereon - Google Patents
Hydroxamic acid derivatives useful for treatment of diseases related to connective tissue degradation, and a pharmaceutical composition based thereon Download PDFInfo
- Publication number
- UA61906C2 UA61906C2 UA98105283A UA98105283A UA61906C2 UA 61906 C2 UA61906 C2 UA 61906C2 UA 98105283 A UA98105283 A UA 98105283A UA 98105283 A UA98105283 A UA 98105283A UA 61906 C2 UA61906 C2 UA 61906C2
- Authority
- UA
- Ukraine
- Prior art keywords
- oxo
- hydroxy
- methylpropyl
- pyrrolidine
- diacetamide
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 20
- 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 title claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 17
- 201000010099 disease Diseases 0.000 title abstract description 14
- 210000002808 connective tissue Anatomy 0.000 title abstract description 10
- 230000008354 tissue degradation Effects 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 198
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 222
- ZSBDPRIWBYHIAF-UHFFFAOYSA-N N-acetyl-acetamide Natural products CC(=O)NC(C)=O ZSBDPRIWBYHIAF-UHFFFAOYSA-N 0.000 claims description 152
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 94
- -1 heteroaromatic radical Chemical class 0.000 claims description 76
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- BXDSWYZJSRBPGW-UHFFFAOYSA-N 2-[1-(2-amino-2-oxoethyl)-3-hydroxy-2-oxopyrrolidin-3-yl]acetamide Chemical compound NC(=O)CN1CCC(O)(CC(N)=O)C1=O BXDSWYZJSRBPGW-UHFFFAOYSA-N 0.000 claims description 10
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 229940047583 cetamide Drugs 0.000 claims description 7
- 102000005741 Metalloproteases Human genes 0.000 claims description 5
- 108010006035 Metalloproteases Proteins 0.000 claims description 5
- 229910052796 boron Inorganic materials 0.000 claims description 5
- OUZWUKMCLIBBOG-UHFFFAOYSA-N ethoxzolamide Chemical compound CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1 OUZWUKMCLIBBOG-UHFFFAOYSA-N 0.000 claims description 5
- 229950005098 ethoxzolamide Drugs 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- LBTUTDYXOOUODJ-UHFFFAOYSA-N 2-pyrrolidin-1-ylacetamide Chemical compound NC(=O)CN1CCCC1 LBTUTDYXOOUODJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005418 aryl aryl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 claims 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- YPGUAJGTMSMNMY-UHFFFAOYSA-N 4-(1h-indol-2-yl)butanamide Chemical compound C1=CC=C2NC(CCCC(=O)N)=CC2=C1 YPGUAJGTMSMNMY-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- VREVKZLUMZQJRI-UHFFFAOYSA-N [SH2]=N Chemical compound [SH2]=N VREVKZLUMZQJRI-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 10
- 108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 10
- 102000004190 Enzymes Human genes 0.000 abstract description 7
- 108090000790 Enzymes Proteins 0.000 abstract description 7
- 108010026132 Gelatinases Proteins 0.000 abstract description 7
- 102000013382 Gelatinases Human genes 0.000 abstract description 7
- 206010028980 Neoplasm Diseases 0.000 abstract description 7
- 229940088598 enzyme Drugs 0.000 abstract description 7
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 abstract description 6
- 108091007196 stromelysin Proteins 0.000 abstract description 6
- 108060005980 Collagenase Proteins 0.000 abstract description 5
- 102000029816 Collagenase Human genes 0.000 abstract description 5
- 229960002424 collagenase Drugs 0.000 abstract description 5
- 206010053555 Arthritis bacterial Diseases 0.000 abstract description 4
- 208000004575 Infectious Arthritis Diseases 0.000 abstract description 4
- 206010027476 Metastases Diseases 0.000 abstract description 4
- 208000001132 Osteoporosis Diseases 0.000 abstract description 4
- 208000007565 gingivitis Diseases 0.000 abstract description 4
- 230000009545 invasion Effects 0.000 abstract description 4
- 239000011159 matrix material Substances 0.000 abstract description 4
- 201000008482 osteoarthritis Diseases 0.000 abstract description 4
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- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 201000001223 septic arthritis Diseases 0.000 abstract description 4
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- 208000025865 Ulcer Diseases 0.000 abstract 3
- 230000036269 ulceration Effects 0.000 abstract 3
- 208000029725 Metabolic bone disease Diseases 0.000 abstract 1
- 230000002500 effect on skin Effects 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 260
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 204
- 239000000203 mixture Substances 0.000 description 139
- 238000002360 preparation method Methods 0.000 description 129
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
- 239000003921 oil Substances 0.000 description 101
- 235000019198 oils Nutrition 0.000 description 101
- 239000002480 mineral oil Substances 0.000 description 73
- 235000010446 mineral oil Nutrition 0.000 description 73
- 239000007787 solid Substances 0.000 description 67
- 238000000034 method Methods 0.000 description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
- 239000000741 silica gel Substances 0.000 description 50
- 229910002027 silica gel Inorganic materials 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 238000000746 purification Methods 0.000 description 48
- 239000007788 liquid Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 42
- 238000003756 stirring Methods 0.000 description 40
- 230000002829 reductive effect Effects 0.000 description 35
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- 239000012298 atmosphere Substances 0.000 description 30
- 239000010410 layer Substances 0.000 description 29
- 238000004587 chromatography analysis Methods 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- 125000000217 alkyl group Chemical group 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 238000007429 general method Methods 0.000 description 21
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 19
- 238000005804 alkylation reaction Methods 0.000 description 19
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- 238000004440 column chromatography Methods 0.000 description 18
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
- 238000013504 emergency use authorization Methods 0.000 description 16
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- 229920006395 saturated elastomer Polymers 0.000 description 15
- 230000029936 alkylation Effects 0.000 description 14
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
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- 239000012230 colorless oil Substances 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 229910052717 sulfur Inorganic materials 0.000 description 12
- 239000011593 sulfur Substances 0.000 description 12
- SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 11
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 9
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- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- 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
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1309896P | 1996-03-08 | 1996-03-08 | |
| PCT/US1997/002568 WO1997032846A1 (en) | 1996-03-08 | 1997-03-03 | Hydroxamic acid derivatives for use with the treatment of diseases related to connective tissue degradation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA61906C2 true UA61906C2 (en) | 2003-12-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA98105283A UA61906C2 (en) | 1996-03-08 | 1997-03-03 | Hydroxamic acid derivatives useful for treatment of diseases related to connective tissue degradation, and a pharmaceutical composition based thereon |
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| CN (1) | CN1210517A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE231490T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU707180B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR9707947A (cg-RX-API-DMAC7.html) |
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Families Citing this family (50)
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| US5932579A (en) | 1996-06-18 | 1999-08-03 | Affymax Technologies N.V. | Collagenase-1 and stromelysin-1 inhibitors, pharmaceutical compositions comprising same and methods of their use |
| US5830869A (en) * | 1996-06-21 | 1998-11-03 | Mitchell; Mark Allen | Thiadiazole amide MMP inhibitors |
| EP0929519B1 (en) * | 1996-09-27 | 2005-02-23 | PHARMACIA & UPJOHN COMPANY | Beta-sulfonyl hydroxamic acids as matrix metalloproteinases inhibitors |
| GB9702088D0 (en) | 1997-01-31 | 1997-03-19 | Pharmacia & Upjohn Spa | Matrix metalloproteinase inhibitors |
| WO1998039326A1 (en) * | 1997-03-04 | 1998-09-11 | Monsanto Company | Aromatic sulfonyl alpha-hydroxy hydroxamic acid compounds |
| US6566373B2 (en) | 1997-05-06 | 2003-05-20 | Smithkline Beecham Corporation | Protease inhibitors |
| AR013079A1 (es) * | 1997-05-06 | 2000-12-13 | Smithkline Beecham Corp | Derivados sustituidos de tetrahidrofurano-3-onas, de tetrahidropirano-3- onas y tetrahidrotiofen-3-onas, un procedimiento para su preparacion unacomposicion farmaceutica de un medicamento util como inhibidores de proteasas e intermediarios |
| US5883131A (en) * | 1997-07-09 | 1999-03-16 | Pfizer Inc. | Cyclic sulfone derivatives |
| CA2298617A1 (en) | 1997-07-31 | 1999-02-11 | Yetunde Olabisi Taiwo | Acyclic metalloprotease inhibitors |
| DE19741235A1 (de) * | 1997-09-18 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| ZA988967B (en) * | 1997-10-03 | 2000-04-03 | Du Pont Pharm Co | Lactam metalloprotease inhibitors. |
| US6403632B1 (en) | 2000-03-01 | 2002-06-11 | Bristol Myers Squibb Pharma Co | Lactam metalloprotease inhibitors |
| EP1024134A4 (en) * | 1997-10-09 | 2003-05-14 | Ono Pharmaceutical Co | DERIVATIVES OF AMINOBUTANIC ACID |
| DK1004578T3 (da) * | 1998-11-05 | 2004-06-28 | Pfizer Prod Inc | 5-oxo-pyrrolidin-2-carboxylsyrehydroxamidderivater |
| GB9825988D0 (en) * | 1998-11-27 | 1999-01-20 | Pfizer Ltd | Indole derivatives |
| US20040122011A1 (en) * | 1998-12-23 | 2004-06-24 | Pharmacia Corporation | Method of using a COX-2 inhibitor and a TACE inhibitors as a combination therapy |
| RU2001126721A (ru) | 1999-03-03 | 2004-02-20 | Дзе Проктер Энд Гэмбл Компани (US) | Алкенил-и алкинилсодержащие ингибиторы металлопротезы |
| RU2001126719A (ru) | 1999-03-03 | 2004-02-20 | Дзе Проктер Энд Гэмбл Компани (US) | Дигетерозамещенные ингибиторы металлопротеазы |
| CA2361848A1 (en) * | 1999-04-02 | 2000-10-12 | Dupont Pharmaceuticals Company | Novel lactam inhibitors of matrix metalloproteinases, tnf-.alpha., and aggrecanase |
| US6797820B2 (en) | 1999-12-17 | 2004-09-28 | Vicuron Pharmaceuticals Inc. | Succinate compounds, compositions and methods of use and preparation |
| WO2002028829A2 (en) * | 2000-09-25 | 2002-04-11 | Questcor Pharmaceuticals, Inc. | Peptide deformylase inhibitors |
| CA2434205A1 (en) | 2001-01-11 | 2002-07-18 | Dupont Pharmaceuticals Company | 1,1-disubstituted cyclic inhibitors of matrix metalloprotease and tnf-.alpha. |
| US6642255B2 (en) | 2001-01-11 | 2003-11-04 | Bristol-Myers Squibb Pharma Company | 1,2,-Disubstituted cyclic inhibitors of matrix metalloproteases and TNF-alpha |
| EP1363623B1 (en) * | 2001-03-01 | 2005-11-16 | Smithkline Beecham Corporation | Peptide deformylase inhibitors |
| AR036053A1 (es) | 2001-06-15 | 2004-08-04 | Versicor Inc | Compuestos de n-formil-hidroxilamina, un proceso para su preparacion y composiciones farmaceuticas |
| EP1406893B1 (en) * | 2001-06-15 | 2007-04-18 | Vicuron Pharmaceuticals, Inc. | Pyrrolidine bicyclic compounds |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| TWI294778B (en) * | 2002-03-13 | 2008-03-21 | Smithkline Beecham Corp | Peptide deformylase inhibitors |
| US7622117B2 (en) * | 2002-04-17 | 2009-11-24 | Dynamis Therapeutics, Inc. | 3-deoxyglucosone and skin |
| PL374117A1 (en) * | 2002-05-29 | 2005-10-03 | Merck & Co, Inc. | Compounds useful in the treatment of anthrax and inhibiting lethal factor |
| US20050176686A1 (en) * | 2002-07-23 | 2005-08-11 | 4Sc Ag | Novel compounds as histone deacetylase inhibitors |
| WO2004101523A1 (en) * | 2003-05-17 | 2004-11-25 | Korea Research Institute Of Bioscience And Biotechnology | Novel 2-oxo-heterocyclic compounds and the pharmaceutical compositions comprising the same |
| US7122560B2 (en) | 2003-06-18 | 2006-10-17 | Bristol-Myers Squibb Company | Lactam derivatives as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme |
| EP1663201A4 (en) * | 2003-07-15 | 2009-10-28 | Korea Res Inst Of Bioscience | USE OF NOVEL 2-OXO-HETEROCYCLIC COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME |
| RU2368390C2 (ru) * | 2003-07-23 | 2009-09-27 | Новартис Аг | Применение кальцитонина при остеоартрите |
| JP2007537256A (ja) * | 2004-05-11 | 2007-12-20 | メルク エンド カムパニー インコーポレーテッド | Ｎ−スルホン化アミノ酸誘導体調製のためのプロセス |
| US20100003276A1 (en) * | 2004-12-07 | 2010-01-07 | Hermes Jeffery D | Methods for treating anthrax and inhibiting lethal factor |
| DE102004060229A1 (de) * | 2004-12-15 | 2006-06-29 | Sanofi-Aventis Deutschland Gmbh | Neue zyklische Harnstoffe als Inhibitoren von Metallproteasen |
| US20080287516A1 (en) * | 2005-01-28 | 2008-11-20 | Irm Llc | Phenyl-Substituted Pyrrolidones |
| GB0811643D0 (en) | 2008-06-25 | 2008-07-30 | Cancer Rec Tech Ltd | New therapeutic agents |
| FR2947268B1 (fr) * | 2009-06-30 | 2011-08-26 | Galderma Res & Dev | Nouveaux composes benzene-sulfonamides, leur procede de synthese et leur utilisation en medecine ainsi qu'en cosmetique |
| WO2012031298A2 (en) | 2010-09-03 | 2012-03-08 | Duke University | Ethynylbenzene derivatives |
| US20140081017A1 (en) * | 2012-09-14 | 2014-03-20 | Methylgene Inc. | Histone Deacetylase Inhibitors for Enhancing Activity of Antifungal Agents |
| US9908851B2 (en) | 2013-08-16 | 2018-03-06 | Duke University | 2-piperidinyl substituted N,3-dihydroxybutanamides |
| EP3041354A4 (en) | 2013-08-16 | 2017-06-14 | Duke University | Substituted hydroxamic acid compounds |
| US10189786B2 (en) | 2013-08-16 | 2019-01-29 | Duke University | Antibacterial compounds |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| GB201704966D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201704965D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1360583A (en) * | 1918-02-18 | 1920-11-30 | Great Lakes Dredge And Dock Co | Car-dumper |
| EP0042100A1 (de) * | 1980-06-13 | 1981-12-23 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Pyrazolopyridazin-Derivate, Zwischenprodukte und Verfahren zu deren Herstellung, sowie diese enthaltende Arzneimittel |
| DE3420193A1 (de) * | 1984-05-30 | 1985-12-05 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue substituierte pyrrolidinone, verfahren zu ihrer herstellung und arzneimittel |
| EP0639982A1 (en) * | 1992-05-01 | 1995-03-01 | British Biotech Pharmaceuticals Limited | Use of mmp inhibitors |
| US5318964A (en) * | 1992-06-11 | 1994-06-07 | Hoffmann-La Roche Inc. | Hydroxamic derivatives and pharmaceutical compositions |
| ATE195117T1 (de) * | 1993-03-31 | 2000-08-15 | Searle & Co | 1-amdinophenyl-pyrrolidone/piperidinone als blutblättchen-aggregations inhibitoren |
| DE69415159T2 (de) * | 1993-08-02 | 1999-07-22 | Celltech Therapeutics Ltd., Slough, Berkshire | Succinamid-derivate, verfahren zu ihrer herstellung und ihre verwendung als gelatinase- und collagenase- inhibitoren |
| GB9320660D0 (en) * | 1993-10-07 | 1993-11-24 | British Bio Technology | Inhibition of cytokine production |
| US5403952A (en) * | 1993-10-08 | 1995-04-04 | Merck & Co., Inc. | Substituted cyclic derivatives as novel antidegenerative agents |
-
1997
- 1997-02-21 TW TW086102076A patent/TW448172B/zh not_active IP Right Cessation
- 1997-03-03 AU AU20525/97A patent/AU707180B2/en not_active Ceased
- 1997-03-03 UA UA98105283A patent/UA61906C2/uk unknown
- 1997-03-03 DE DE69718634T patent/DE69718634T2/de not_active Expired - Fee Related
- 1997-03-03 WO PCT/US1997/002568 patent/WO1997032846A1/en not_active Ceased
- 1997-03-03 KR KR1019980707039A patent/KR19990087597A/ko not_active Abandoned
- 1997-03-03 RU RU98118372/04A patent/RU2168497C2/ru not_active IP Right Cessation
- 1997-03-03 NZ NZ330922A patent/NZ330922A/xx unknown
- 1997-03-03 JP JP9531784A patent/JP2000506163A/ja not_active Withdrawn
- 1997-03-03 AT AT97908674T patent/ATE231490T1/de not_active IP Right Cessation
- 1997-03-03 PL PL97328693A patent/PL328693A1/xx unknown
- 1997-03-03 PT PT97908674T patent/PT898562E/pt unknown
- 1997-03-03 BR BR9707947A patent/BR9707947A/pt active Search and Examination
- 1997-03-03 EP EP97908674A patent/EP0898562B1/en not_active Expired - Lifetime
- 1997-03-03 DK DK97908674T patent/DK0898562T3/da active
- 1997-03-03 ES ES97908674T patent/ES2191823T3/es not_active Expired - Lifetime
- 1997-03-03 CN CN97192171A patent/CN1210517A/zh active Pending
- 1997-03-04 PE PE1997000155A patent/PE55698A1/es not_active Application Discontinuation
- 1997-03-04 US US08/811,821 patent/US5712300A/en not_active Expired - Fee Related
- 1997-03-05 ZA ZA971902A patent/ZA971902B/xx unknown
- 1997-03-06 ID IDP970713A patent/ID16144A/id unknown
- 1997-03-07 MY MYPI97000965A patent/MY117762A/en unknown
-
1998
- 1998-09-07 NO NO19984112A patent/NO312956B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO984112L (no) | 1998-11-06 |
| PE55698A1 (es) | 1998-09-16 |
| CN1210517A (zh) | 1999-03-10 |
| EP0898562B1 (en) | 2003-01-22 |
| ATE231490T1 (de) | 2003-02-15 |
| RU2168497C2 (ru) | 2001-06-10 |
| NO312956B1 (no) | 2002-07-22 |
| DE69718634D1 (de) | 2003-02-27 |
| NO984112D0 (no) | 1998-09-07 |
| AU2052597A (en) | 1997-09-22 |
| PL328693A1 (en) | 1999-02-15 |
| KR19990087597A (ko) | 1999-12-27 |
| WO1997032846A1 (en) | 1997-09-12 |
| US5712300A (en) | 1998-01-27 |
| ES2191823T3 (es) | 2003-09-16 |
| DK0898562T3 (da) | 2003-05-12 |
| PT898562E (pt) | 2003-06-30 |
| ZA971902B (en) | 1998-09-07 |
| JP2000506163A (ja) | 2000-05-23 |
| MY117762A (en) | 2004-08-30 |
| BR9707947A (pt) | 1999-07-27 |
| TW448172B (en) | 2001-08-01 |
| AU707180B2 (en) | 1999-07-01 |
| ID16144A (id) | 1997-09-04 |
| NZ330922A (en) | 2000-01-28 |
| DE69718634T2 (de) | 2003-10-30 |
| EP0898562A1 (en) | 1999-03-03 |
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