SK282676B6 - Benzofuránové karboxamidy a tioamidy, farmaceutický prípravok s ich obsahom a ich použitie - Google Patents
Benzofuránové karboxamidy a tioamidy, farmaceutický prípravok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK282676B6 SK282676B6 SK1604-98A SK160498A SK282676B6 SK 282676 B6 SK282676 B6 SK 282676B6 SK 160498 A SK160498 A SK 160498A SK 282676 B6 SK282676 B6 SK 282676B6
- Authority
- SK
- Slovakia
- Prior art keywords
- acetyl
- alkyl
- methoxy
- aryl
- group
- Prior art date
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- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical class C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 title claims description 33
- 230000001225 therapeutic effect Effects 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 101
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 28
- 230000005764 inhibitory process Effects 0.000 claims abstract description 11
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 6
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 80
- -1 heterocyclosulfonyl Chemical group 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 150000003556 thioamides Chemical class 0.000 claims description 24
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 16
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
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- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
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- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 5
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
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- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 4
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- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
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- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
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- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 208000007451 chronic bronchitis Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 3
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 208000024780 Urticaria Diseases 0.000 claims description 2
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
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- 229940124584 antitussives Drugs 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
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- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 230000007794 irritation Effects 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000000552 rheumatic effect Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims 4
- 230000001154 acute effect Effects 0.000 claims 3
- 230000000241 respiratory effect Effects 0.000 claims 3
- 208000011580 syndromic disease Diseases 0.000 claims 3
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 206010012289 Dementia Diseases 0.000 claims 2
- 102100040247 Tumor necrosis factor Human genes 0.000 claims 2
- 210000003979 eosinophil Anatomy 0.000 claims 2
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims 2
- 125000001831 (C6-C10) heteroaryl group Chemical group 0.000 claims 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 208000030507 AIDS Diseases 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000014644 Brain disease Diseases 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims 1
- 206010020649 Hyperkeratosis Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000001126 Keratosis Diseases 0.000 claims 1
- 206010069698 Langerhans' cell histiocytosis Diseases 0.000 claims 1
- 208000000112 Myalgia Diseases 0.000 claims 1
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- 231100000650 Toxic shock syndrome Toxicity 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 238000009825 accumulation Methods 0.000 claims 1
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 208000019664 bone resorption disease Diseases 0.000 claims 1
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 330
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 182
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 45
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- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
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- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
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- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/86—Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
-
- 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
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9610515.0A GB9610515D0 (en) | 1996-05-20 | 1996-05-20 | Novel compounds |
| PCT/GB1996/003012 WO1997020833A1 (en) | 1995-12-05 | 1996-12-05 | Benzofuran carboxamides and sulphonamides |
| GBGB9708070.9A GB9708070D0 (en) | 1997-04-22 | 1997-04-22 | Compounds |
| PCT/GB1997/001361 WO1997044337A1 (en) | 1996-05-20 | 1997-05-20 | Benzofuran carboxamides and their therapeutic use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK160498A3 SK160498A3 (en) | 1999-06-11 |
| SK282676B6 true SK282676B6 (sk) | 2002-11-06 |
Family
ID=26309366
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1604-98A SK282676B6 (sk) | 1996-05-20 | 1997-05-20 | Benzofuránové karboxamidy a tioamidy, farmaceutický prípravok s ich obsahom a ich použitie |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5972936A (enExample) |
| EP (1) | EP0901482B1 (enExample) |
| JP (1) | JP2000510848A (enExample) |
| CN (1) | CN1219171A (enExample) |
| AT (1) | ATE239004T1 (enExample) |
| BR (1) | BR9709113A (enExample) |
| CA (1) | CA2252537A1 (enExample) |
| CZ (1) | CZ371998A3 (enExample) |
| DE (1) | DE69721526T2 (enExample) |
| ES (1) | ES2193376T3 (enExample) |
| HU (1) | HUP0100042A3 (enExample) |
| IL (1) | IL126558A (enExample) |
| NO (1) | NO985375L (enExample) |
| NZ (1) | NZ332340A (enExample) |
| PL (1) | PL329912A1 (enExample) |
| RU (1) | RU2162467C2 (enExample) |
| SK (1) | SK282676B6 (enExample) |
| TR (1) | TR199802386T2 (enExample) |
| WO (1) | WO1997044337A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000501411A (ja) * | 1995-12-05 | 2000-02-08 | ダーウィン・ディスカバリー・リミテッド | ベンゾフランカルボキサミドおよびスルホンアミド |
| ES2188983T4 (es) * | 1996-08-19 | 2004-06-01 | Altana Pharma Ag | Nuevas benzofuran-4-carboxamidas. |
| EP1029860B1 (en) * | 1997-10-01 | 2003-04-16 | Kyowa Hakko Kogyo Co., Ltd. | Benzofuran derivatives |
| AU2529799A (en) * | 1998-02-09 | 1999-08-23 | Darwin Discovery Limited | Benzofuran-4-carboxamides and their therapeutic use |
| ES2196806T3 (es) * | 1998-05-08 | 2003-12-16 | Smithkline Beecham Plc | Derivados de fenilurea y de feniltiourea. |
| TW555759B (en) * | 1998-06-08 | 2003-10-01 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| US7217722B2 (en) | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| GB0003257D0 (en) | 2000-02-11 | 2000-04-05 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| US7112594B2 (en) | 2000-08-09 | 2006-09-26 | Mitsubishi Pharma Corporation | Fused bicyclic amide compounds and medicinal use thereof |
| US6953774B2 (en) | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| MXPA04005782A (es) | 2001-12-14 | 2004-09-13 | Applied Research Systems | Metodos para inducir la ovulacion usando un modulador de nivel camp no polipeptido. |
| NZ535267A (en) * | 2002-03-28 | 2006-03-31 | Tanabe Seiyaku Co | Benzofuran derivatives as inhibitors of blood coagulation factor X |
| WO2003090357A1 (en) * | 2002-04-19 | 2003-10-30 | Integrated Magnetoelectronics Corporation | Interfaces between semiconductor circuitry and transpinnor-based circuitry |
| ES2195785B1 (es) * | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| DE10238257B4 (de) * | 2002-08-21 | 2007-04-19 | Johannes-Gutenberg-Universität Mainz | Sorbicillacton A und Sorbicillacton-A-Derivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel |
| US20050215626A1 (en) * | 2003-09-25 | 2005-09-29 | Wyeth | Substituted benzofuran oximes |
| TW200524915A (en) * | 2003-09-26 | 2005-08-01 | Tanabe Seiyaku Co | Carbamoyl-type benzofuran derivatives |
| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| US20100130737A1 (en) * | 2005-02-18 | 2010-05-27 | Takeda Pharmaceutical Company Limited | Regulating Agent of GPR34 Receptor Function |
| JP2009506069A (ja) | 2005-08-26 | 2009-02-12 | ブレインセルス，インコーポレイティド | ムスカリン性受容体調節による神経発生 |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| CA2625153A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| CA2625210A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| US7842713B2 (en) * | 2006-04-20 | 2010-11-30 | Pfizer Inc | Fused phenyl amido heterocyclic compounds |
| EP2382975A3 (en) | 2006-05-09 | 2012-02-29 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| JP5682051B2 (ja) | 2006-05-18 | 2015-03-11 | ファーマサイクリックス，インク． | 細胞内キナーゼ阻害剤 |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CN100434426C (zh) * | 2006-10-10 | 2008-11-19 | 中国科学院昆明植物研究所 | 盐肤木内酯a,其制备方法和其在制药中的应用 |
| KR101571654B1 (ko) | 2007-02-28 | 2015-11-25 | 레오 파마 에이/에스 | 신규한 포스포디에스테라제 억제제 |
| ZA200905371B (en) * | 2007-02-28 | 2010-10-27 | Leo Pharma As | Novel phosphodiesterase Inhibitors |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| KR100752613B1 (ko) * | 2007-05-02 | 2007-08-29 | 우석대학교 산학협력단 | 신규 벤조푸란 유도체를 포함하는 부정맥 예방용 식품 |
| CL2008001933A1 (es) | 2007-06-29 | 2009-09-25 | Millennium Pharm Inc | Compuestos derivados de pirimidina, inhibidores de la raf quinasa; compuestos intermediarios; procedimiento de preparacion; composicion farmaceutica; y su uso para tratar trastornos proliferativos, cardiacos, neurodegenerativos, inflamatorios, oseos, inmunologicos enfermedad viral, entre otros. |
| NZ591366A (en) | 2008-09-11 | 2012-05-25 | Pfizer | Heteroaryls amide derivatives and their use as glucokinase activators |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| WO2010103437A1 (en) * | 2009-03-11 | 2010-09-16 | Pfizer Inc. | Benzofuranyl derivatives used as glucokinase inhibitors |
| BR112012032813B1 (pt) * | 2010-06-24 | 2022-02-01 | UNION therapeutics A/S | Composto heterocíclico de benzodioxol ou benzodioxepina, composição farmacêutica, e, uso do composto |
| CN102010405B (zh) * | 2010-11-08 | 2012-07-25 | 湖南大学 | 4-(苯并呋喃-5-基)-2-苄亚氨基噻唑及其作为抗肿瘤药物的应用 |
| EP2804603A1 (en) | 2012-01-10 | 2014-11-26 | President and Fellows of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| US10196372B2 (en) | 2015-01-05 | 2019-02-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | MYC G-quadruplex stabilizing small molecules and their use |
| BR112021021665A2 (pt) * | 2019-06-04 | 2021-12-21 | Nippon Soda Co | Composto, e, herbicida |
| GB202306662D0 (en) | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Dosage regimen |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES8705871A1 (es) * | 1984-12-29 | 1987-05-16 | Kaken Pharma Co Ltd | Un procedimiento para preparar un derivado de benzofurano |
| WO1992003427A1 (fr) * | 1990-08-17 | 1992-03-05 | Yoshitomi Pharmaceutical Industries, Ltd. | Compose de cetone et remede pour l'osteoporose |
| JPH08502484A (ja) * | 1992-10-14 | 1996-03-19 | メルク エンド カンパニー インコーポレーテッド | フィブリノゲンリセプタ拮抗剤 |
| GB9309324D0 (en) * | 1993-05-06 | 1993-06-16 | Bayer Ag | Venzofuranyl-and-thiophenyl-alkanecarboxyclic acids derivatives |
| ES2132284T3 (es) * | 1993-08-05 | 1999-08-16 | Hoechst Marion Roussel Inc | Derivados de carbamato de 2-(piperidin-4-il, piridin-4-il y tetrahidropiridin-4-il)-benzofurano-7, su preparacion y su uso como inhibidores de acetilcolinesterasa. |
| ES2127966T3 (es) * | 1994-05-31 | 1999-05-01 | Bayer Ag | Derivados de amino-benzofurilo y -benzotienilo. |
| ES2152414T3 (es) * | 1994-07-22 | 2001-02-01 | Byk Gulden Lomberg Chem Fab | Dihidrobenzofuranos. |
| WO1996036624A1 (en) * | 1995-05-19 | 1996-11-21 | Kyowa Hakko Kogyo Co., Ltd. | Oxygen-containing heterocyclic compounds |
| JPH10147585A (ja) * | 1996-11-19 | 1998-06-02 | Kyowa Hakko Kogyo Co Ltd | 含酸素複素環化合物 |
| AU5772196A (en) * | 1995-05-19 | 1996-11-29 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| WO1996036595A1 (en) * | 1995-05-19 | 1996-11-21 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| AU5772396A (en) * | 1995-05-19 | 1996-11-29 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| JP2000501411A (ja) * | 1995-12-05 | 2000-02-08 | ダーウィン・ディスカバリー・リミテッド | ベンゾフランカルボキサミドおよびスルホンアミド |
| ES2188983T4 (es) * | 1996-08-19 | 2004-06-01 | Altana Pharma Ag | Nuevas benzofuran-4-carboxamidas. |
-
1997
- 1997-05-20 US US08/859,510 patent/US5972936A/en not_active Expired - Fee Related
- 1997-05-20 IL IL12655897A patent/IL126558A/en not_active IP Right Cessation
- 1997-05-20 ES ES97923193T patent/ES2193376T3/es not_active Expired - Lifetime
- 1997-05-20 WO PCT/GB1997/001361 patent/WO1997044337A1/en not_active Ceased
- 1997-05-20 HU HU0100042A patent/HUP0100042A3/hu unknown
- 1997-05-20 AT AT97923193T patent/ATE239004T1/de not_active IP Right Cessation
- 1997-05-20 CZ CZ983719A patent/CZ371998A3/cs unknown
- 1997-05-20 NZ NZ332340A patent/NZ332340A/xx unknown
- 1997-05-20 SK SK1604-98A patent/SK282676B6/sk unknown
- 1997-05-20 TR TR1998/02386T patent/TR199802386T2/xx unknown
- 1997-05-20 DE DE69721526T patent/DE69721526T2/de not_active Expired - Fee Related
- 1997-05-20 CN CN97194736A patent/CN1219171A/zh active Pending
- 1997-05-20 EP EP97923193A patent/EP0901482B1/en not_active Expired - Lifetime
- 1997-05-20 JP JP09541240A patent/JP2000510848A/ja not_active Ceased
- 1997-05-20 BR BR9709113A patent/BR9709113A/pt active Search and Examination
- 1997-05-20 CA CA002252537A patent/CA2252537A1/en not_active Abandoned
- 1997-05-20 US US08/859,509 patent/US5925636A/en not_active Expired - Fee Related
- 1997-05-20 RU RU98123097/04A patent/RU2162467C2/ru not_active IP Right Cessation
- 1997-05-20 PL PL97329912A patent/PL329912A1/xx unknown
-
1998
- 1998-11-19 NO NO985375A patent/NO985375L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997044337A1 (en) | 1997-11-27 |
| NO985375D0 (no) | 1998-11-19 |
| CZ371998A3 (cs) | 1999-03-17 |
| EP0901482B1 (en) | 2003-05-02 |
| IL126558A0 (en) | 1999-08-17 |
| ES2193376T3 (es) | 2003-11-01 |
| NO985375L (no) | 1998-11-19 |
| NZ332340A (en) | 2000-04-28 |
| IL126558A (en) | 2002-07-25 |
| HUP0100042A2 (hu) | 2002-01-28 |
| JP2000510848A (ja) | 2000-08-22 |
| ATE239004T1 (de) | 2003-05-15 |
| TR199802386T2 (xx) | 1999-02-22 |
| SK160498A3 (en) | 1999-06-11 |
| EP0901482A1 (en) | 1999-03-17 |
| DE69721526T2 (de) | 2004-04-08 |
| DE69721526D1 (de) | 2003-06-05 |
| CA2252537A1 (en) | 1997-11-27 |
| US5972936A (en) | 1999-10-26 |
| US5925636A (en) | 1999-07-20 |
| PL329912A1 (en) | 1999-04-26 |
| BR9709113A (pt) | 1999-08-03 |
| RU2162467C2 (ru) | 2001-01-27 |
| CN1219171A (zh) | 1999-06-09 |
| HUP0100042A3 (en) | 2003-01-28 |
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