BG64506B1 - Хетероарилни сукцинамиди и тяхното приложение като инхибитори на металопротеиназата - Google Patents
Хетероарилни сукцинамиди и тяхното приложение като инхибитори на металопротеиназата Download PDFInfo
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- BG64506B1 BG64506B1 BG103415A BG10341599A BG64506B1 BG 64506 B1 BG64506 B1 BG 64506B1 BG 103415 A BG103415 A BG 103415A BG 10341599 A BG10341599 A BG 10341599A BG 64506 B1 BG64506 B1 BG 64506B1
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- group
- formula
- alkyl
- heteroaryl
- aryl
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- 102000005741 Metalloproteases Human genes 0.000 title claims abstract description 9
- 108010006035 Metalloproteases Proteins 0.000 title claims abstract description 9
- -1 Heteroaryl succinamides Chemical class 0.000 title claims description 474
- 239000003112 inhibitor Substances 0.000 title description 9
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- 230000000694 effects Effects 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 164
- 125000003118 aryl group Chemical group 0.000 claims description 158
- 238000002360 preparation method Methods 0.000 claims description 147
- 125000001072 heteroaryl group Chemical group 0.000 claims description 146
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 138
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 129
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 73
- 239000001257 hydrogen Substances 0.000 claims description 71
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- 239000000651 prodrug Substances 0.000 claims description 52
- 229940002612 prodrug Drugs 0.000 claims description 52
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
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- 239000012453 solvate Substances 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000003277 amino group Chemical group 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
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- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 18
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 18
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 16
- 241000124008 Mammalia Species 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 14
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 14
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
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- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 6
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000004442 acylamino group Chemical group 0.000 claims description 5
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- 230000033115 angiogenesis Effects 0.000 claims description 3
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- 201000011066 hemangioma Diseases 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims description 3
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- 238000004519 manufacturing process Methods 0.000 claims description 2
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- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
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- 238000006243 chemical reaction Methods 0.000 abstract description 107
- 230000005764 inhibitory process Effects 0.000 abstract description 4
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- 235000019439 ethyl acetate Nutrition 0.000 description 111
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- 238000003818 flash chromatography Methods 0.000 description 63
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 41
- 239000000126 substance Substances 0.000 description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 41
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- 238000007327 hydrogenolysis reaction Methods 0.000 description 35
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
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- 235000011152 sodium sulphate Nutrition 0.000 description 32
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- 235000017281 sodium acetate Nutrition 0.000 description 1
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- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 238000011272 standard treatment Methods 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical class CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 125000005881 triazolinyl group Chemical group 0.000 description 1
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
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- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
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- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- C07D401/10—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 carbon chain containing aromatic rings
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- 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
-
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
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- C07K5/06113—Asp- or Asn-amino acid
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- A61K38/00—Medicinal preparations containing peptides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Molecular Biology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Genetics & Genomics (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2911596P | 1996-10-24 | 1996-10-24 | |
| US08/823,962 US6008243A (en) | 1996-10-24 | 1997-03-25 | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
Publications (2)
| Publication Number | Publication Date |
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| BG103415A BG103415A (en) | 2000-07-31 |
| BG64506B1 true BG64506B1 (bg) | 2005-05-31 |
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| BG103415A BG64506B1 (bg) | 1996-10-24 | 1999-05-20 | Хетероарилни сукцинамиди и тяхното приложение като инхибитори на металопротеиназата |
Country Status (25)
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| US (1) | US6008243A (cs) |
| EP (1) | EP0937042A1 (cs) |
| JP (1) | JP2000511201A (cs) |
| KR (1) | KR20000052779A (cs) |
| CN (1) | CN1233237A (cs) |
| AP (1) | AP1360A (cs) |
| AR (1) | AR009124A1 (cs) |
| AU (1) | AU735194C (cs) |
| BG (1) | BG64506B1 (cs) |
| BR (1) | BR9713278A (cs) |
| CA (1) | CA2267879C (cs) |
| CZ (1) | CZ132199A3 (cs) |
| EA (1) | EA003127B1 (cs) |
| EE (1) | EE9900171A (cs) |
| GE (1) | GEP20012578B (cs) |
| IL (1) | IL128914A (cs) |
| IS (1) | IS5000A (cs) |
| NO (1) | NO313281B1 (cs) |
| NZ (1) | NZ334886A (cs) |
| OA (1) | OA11035A (cs) |
| PL (1) | PL332947A1 (cs) |
| SK (1) | SK48499A3 (cs) |
| TR (2) | TR199900874T2 (cs) |
| WO (1) | WO1998017643A1 (cs) |
| YU (1) | YU20199A (cs) |
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| US6576664B1 (en) * | 1997-08-18 | 2003-06-10 | Bristol-Myers Squibb Pharma Company | Inhibitors of aggrecanase and matrix metalloproteinases for the treatment of arthritis |
| WO1999030709A1 (en) * | 1997-12-17 | 1999-06-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| AU745921B2 (en) * | 1998-02-13 | 2002-04-11 | British Biotech Pharmaceuticals Limited | Cytostatic agents |
| US6172064B1 (en) | 1998-08-26 | 2001-01-09 | Glaxo Wellcome Inc. | Formamides as therapeutic agents |
| US6329400B1 (en) | 1998-08-26 | 2001-12-11 | Glaxo Wellcome Inc. | Formamide compounds as therapeutic agents |
| GB9818605D0 (en) | 1998-08-26 | 1998-10-21 | Glaxo Group Ltd | Formamide compounds as therepeutic agents |
| US6934639B1 (en) * | 2000-02-25 | 2005-08-23 | Wyeth | Methods for designing agents that interact with MMP-13 |
| PA8539501A1 (es) | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Compuestos triazolo como inhibidores de mmp |
| PA8539301A1 (es) * | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Inhibidores de la metaloproteinasa de la matriz |
| DOP2002000333A (es) * | 2001-02-14 | 2002-09-30 | Warner Lambert Co | Derivados de acido isoftalico como inhibidores de metaloproteinasas de la matriz |
| EP1368323B1 (en) * | 2001-02-14 | 2010-06-30 | Warner-Lambert Company LLC | Pyrimidine matrix metalloproteinase inhibitors |
| MXPA01013171A (es) | 2001-02-14 | 2004-05-21 | Warner Lambert Co | Inhibidores triciclicos de sulfonamida de metaloproteinasa de matriz. |
| PA8539401A1 (es) * | 2001-02-14 | 2002-10-28 | Warner Lambert Co | Quinazolinas como inhibidores de mmp-13 |
| MXPA01013172A (es) | 2001-02-14 | 2002-08-21 | Warner Lambert Co | Inhibidores sulfonamida de metaloproteinasa de matriz. |
| DOP2002000332A (es) | 2001-02-14 | 2002-08-30 | Warner Lambert Co | Inhibidores de piridina de metaloproteinasas de la matriz |
| MXPA01013326A (es) | 2001-02-14 | 2002-08-26 | Warner Lambert Co | Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz. |
| US6924276B2 (en) * | 2001-09-10 | 2005-08-02 | Warner-Lambert Company | Diacid-substituted heteroaryl derivatives as matrix metalloproteinase inhibitors |
| US6962922B2 (en) * | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| MXPA04002537A (es) | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| PE20030701A1 (es) | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| US6667330B2 (en) * | 2002-01-31 | 2003-12-23 | Galileo Pharmaceuticals, Inc. | Furanone derivatives |
| US6894057B2 (en) * | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US20040006077A1 (en) * | 2002-06-25 | 2004-01-08 | Bernard Gaudilliere | Thiazine and oxazine derivatives as MMP-13 inhibitors |
| CA2489722A1 (en) * | 2002-07-17 | 2004-01-22 | William Howard Roark | Combination of an allosteric alkyne inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib |
| AU2003281167A1 (en) * | 2002-07-17 | 2004-02-02 | Warner-Lambert Company Llc | Combination of an allosteric inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib |
| BR0312666A (pt) * | 2002-07-17 | 2005-05-10 | Warner Lambert Co | Combinação de um inibidor alcina alostérico de metaloproteinase-13 de matriz com um inibidor seletivo da cicloxigenase-2 à exceção de celecoxib e do valdecoxib |
| CA2492387A1 (en) * | 2002-07-17 | 2004-01-22 | Warner-Lambert Company Llc | Combination of an allosteric carboxylic of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib |
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| BR0313459A (pt) * | 2002-08-13 | 2005-06-21 | Warner Lambert Co | Derivados monocìclicos como inibidores de metaloproteinases de matriz |
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1997
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- 1997-10-06 YU YU20199A patent/YU20199A/sh unknown
- 1997-10-06 AP APAP/P/1999/001536A patent/AP1360A/en active
- 1997-10-06 JP JP10519394A patent/JP2000511201A/ja not_active Ceased
- 1997-10-06 GE GEAP19974822A patent/GEP20012578B/en unknown
- 1997-10-06 AU AU48060/97A patent/AU735194C/en not_active Ceased
- 1997-10-06 TR TR1999/00874T patent/TR199900874T2/xx unknown
- 1997-10-06 BR BR9713278-0A patent/BR9713278A/pt not_active Application Discontinuation
- 1997-10-06 EA EA199900366A patent/EA003127B1/ru not_active IP Right Cessation
- 1997-10-06 KR KR1019990703591A patent/KR20000052779A/ko not_active Ceased
- 1997-10-06 PL PL97332947A patent/PL332947A1/xx unknown
- 1997-10-06 EE EEP199900171A patent/EE9900171A/xx unknown
- 1997-10-06 CZ CZ991321A patent/CZ132199A3/cs unknown
- 1997-10-06 CN CN97198705A patent/CN1233237A/zh active Pending
- 1997-10-06 CA CA002267879A patent/CA2267879C/en not_active Expired - Fee Related
- 1997-10-06 IL IL12891497A patent/IL128914A/xx not_active IP Right Cessation
- 1997-10-06 SK SK484-99A patent/SK48499A3/sk unknown
- 1997-10-06 TR TR2004/02157T patent/TR200402157T2/xx unknown
- 1997-10-06 EP EP97910770A patent/EP0937042A1/en not_active Withdrawn
- 1997-10-06 WO PCT/US1997/017809 patent/WO1998017643A1/en not_active Application Discontinuation
- 1997-10-06 NZ NZ334886A patent/NZ334886A/xx unknown
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1999
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- 1999-04-16 OA OA9900084A patent/OA11035A/en unknown
- 1999-04-22 NO NO19991922A patent/NO313281B1/no not_active IP Right Cessation
- 1999-05-20 BG BG103415A patent/BG64506B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000052779A (ko) | 2000-08-25 |
| BR9713278A (pt) | 1999-11-03 |
| EE9900171A (et) | 1999-12-15 |
| AP9901536A0 (en) | 1999-06-30 |
| BG103415A (en) | 2000-07-31 |
| YU20199A (sh) | 2001-09-28 |
| GEP20012578B (en) | 2001-11-26 |
| TR199900874T2 (xx) | 1999-07-21 |
| EA003127B1 (ru) | 2003-02-27 |
| US6008243A (en) | 1999-12-28 |
| CN1233237A (zh) | 1999-10-27 |
| AU4806097A (en) | 1998-05-15 |
| NZ334886A (en) | 2000-11-24 |
| IL128914A (en) | 2003-04-10 |
| CA2267879C (en) | 2006-03-14 |
| AR009124A1 (es) | 2000-03-08 |
| NO991922D0 (no) | 1999-04-22 |
| WO1998017643A1 (en) | 1998-04-30 |
| AP1360A (en) | 2005-01-05 |
| OA11035A (en) | 2002-03-06 |
| SK48499A3 (en) | 2000-04-10 |
| JP2000511201A (ja) | 2000-08-29 |
| IS5000A (is) | 1999-03-12 |
| AU735194B2 (en) | 2001-07-05 |
| AU735194C (en) | 2002-08-08 |
| EP0937042A1 (en) | 1999-08-25 |
| TR200402157T2 (tr) | 2005-02-21 |
| EA199900366A1 (ru) | 1999-10-28 |
| NO991922L (no) | 1999-04-22 |
| NO313281B1 (no) | 2002-09-09 |
| PL332947A1 (en) | 1999-10-25 |
| IL128914A0 (en) | 2000-02-17 |
| CA2267879A1 (en) | 1998-04-30 |
| CZ132199A3 (cs) | 1999-09-15 |
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