JP2002523395A - 新規なアリールスルホンアミド及び類似体 - Google Patents
新規なアリールスルホンアミド及び類似体Info
- Publication number
- JP2002523395A JP2002523395A JP2000566241A JP2000566241A JP2002523395A JP 2002523395 A JP2002523395 A JP 2002523395A JP 2000566241 A JP2000566241 A JP 2000566241A JP 2000566241 A JP2000566241 A JP 2000566241A JP 2002523395 A JP2002523395 A JP 2002523395A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- alkyl
- group
- optionally
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 125000004421 aryl sulphonamide group Chemical group 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 230000002265 prevention Effects 0.000 claims abstract description 5
- 206010019196 Head injury Diseases 0.000 claims abstract description 4
- 208000008238 Muscle Spasticity Diseases 0.000 claims abstract description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 4
- 208000018198 spasticity Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 81
- -1 methylthio, hydroxyl Chemical group 0.000 claims description 61
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 239000000460 chlorine Substances 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- 239000011737 fluorine Substances 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 239000012442 inert solvent Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 230000029936 alkylation Effects 0.000 claims description 7
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 206010008118 cerebral infarction Diseases 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
- 229920001774 Perfluoroether Polymers 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
- 230000002152 alkylating effect Effects 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- 150000003868 ammonium compounds Chemical class 0.000 claims description 4
- 230000001363 autoimmune Effects 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000016285 Movement disease Diseases 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 3
- 208000022531 anorexia Diseases 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 206010061428 decreased appetite Diseases 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 230000008673 vomiting Effects 0.000 claims description 3
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 2
- 206010010904 Convulsion Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
- 206010028813 Nausea Diseases 0.000 claims description 2
- 206010039897 Sedation Diseases 0.000 claims description 2
- QWQONZVLXJGXHV-UHFFFAOYSA-N [chlorosulfonyloxy(dimethyl)silyl]methane Chemical compound C[Si](C)(C)OS(Cl)(=O)=O QWQONZVLXJGXHV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 230000031709 bromination Effects 0.000 claims description 2
- 238000005893 bromination reaction Methods 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 230000036461 convulsion Effects 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- XOVJAYNMQDTIJD-UHFFFAOYSA-N cyclopentobarbital Chemical compound C1CC=CC1C1(CC=C)C(=O)NC(=O)NC1=O XOVJAYNMQDTIJD-UHFFFAOYSA-N 0.000 claims description 2
- 238000001212 derivatisation Methods 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 210000000777 hematopoietic system Anatomy 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 230000008693 nausea Effects 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 230000036280 sedation Effects 0.000 claims description 2
- 210000000697 sensory organ Anatomy 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 229910052785 arsenic Inorganic materials 0.000 claims 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims 1
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims 1
- 239000004020 conductor Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 abstract description 5
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- 230000004770 neurodegeneration Effects 0.000 abstract description 2
- 206010019233 Headaches Diseases 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- 238000012360 testing method Methods 0.000 description 34
- 239000000203 mixture Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 125000004432 carbon atom Chemical group C* 0.000 description 25
- 239000000126 substance Substances 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
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- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 8
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- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/80—Radicals substituted by oxygen atoms
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- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/06—Antiglaucoma agents or miotics
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19837638.3 | 1998-08-19 | ||
| DE19837638A DE19837638A1 (de) | 1998-08-19 | 1998-08-19 | Neue Arylsulfonamide und Analoga |
| PCT/EP1999/005682 WO2000010967A1 (de) | 1998-08-19 | 1999-08-06 | Neue arylsulfonamide und analoga |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002523395A true JP2002523395A (ja) | 2002-07-30 |
| JP2002523395A5 JP2002523395A5 (https=) | 2006-09-28 |
Family
ID=7878035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000566241A Withdrawn JP2002523395A (ja) | 1998-08-19 | 1999-08-06 | 新規なアリールスルホンアミド及び類似体 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6469054B1 (https=) |
| EP (1) | EP1105370B9 (https=) |
| JP (1) | JP2002523395A (https=) |
| AU (1) | AU5420399A (https=) |
| CA (1) | CA2340928A1 (https=) |
| DE (2) | DE19837638A1 (https=) |
| ES (1) | ES2219049T3 (https=) |
| HN (1) | HN1998000027A (https=) |
| WO (1) | WO2000010967A1 (https=) |
Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2318731C (en) * | 1998-01-29 | 2012-05-29 | Tularik Inc. | Ppar-gamma modulators |
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| AU3580001A (en) * | 2000-03-01 | 2001-09-12 | University College London | Modulators of the endocannabinoid uptake and of the vallinoid receptors |
| DE10015866A1 (de) | 2000-03-30 | 2001-10-11 | Bayer Ag | Aryl- und Heteroarylsulfonate |
| WO2001082916A2 (en) * | 2000-05-03 | 2001-11-08 | Tularik Inc. | Combination therapeutic compositions and methods of use |
| CN1322738A (zh) * | 2000-05-09 | 2001-11-21 | 上海博德基因开发有限公司 | 一种新的多肽——人大麻醇受体11和编码这种多肽的多核苷酸 |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| AU2001288325A1 (en) * | 2000-09-22 | 2002-04-02 | Eli Lilly And Company | Pharmaceutical compounds useful as modulators of endocannabinoid-mediated response |
| DE10047486A1 (de) * | 2000-09-26 | 2002-04-11 | Bayer Ag | Phenoxyphenyl Alkansulfonate |
| WO2003007887A2 (en) | 2001-07-20 | 2003-01-30 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| WO2003061699A1 (en) * | 2001-12-27 | 2003-07-31 | Japan Tobacco, Inc. | Remedies for allergic diseases |
| AU2003217961B2 (en) | 2002-03-08 | 2008-02-28 | Signal Pharmaceuticals, Llc | Combination therapy for treating, preventing or managing proliferative disorders and cancers |
| NZ534757A (en) | 2002-03-12 | 2006-07-28 | Merck & Co Inc | Substituted amides |
| EP1490043A4 (en) | 2002-03-26 | 2007-05-30 | Merck & Co Inc | SPIROCYCLIC AMIDS AS CANNABINOID RECEPTOR MODULATORS |
| WO2003082191A2 (en) | 2002-03-28 | 2003-10-09 | Merck & Co., Inc. | Substituted 2,3-diphenyl pyridines |
| EP1499306A4 (en) | 2002-04-12 | 2007-03-28 | Merck & Co Inc | BICYCLIC AMIDE |
| US6825209B2 (en) | 2002-04-15 | 2004-11-30 | Research Triangle Institute | Compounds having unique CB1 receptor binding selectivity and methods for their production and use |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1606019A1 (en) * | 2003-03-07 | 2005-12-21 | The University Court of The University of Aberdeen | Cannabinoid receptor inverse agonists and neutral antagonists as therapeutic agents for the treatment of bone disorders |
| WO2005037286A1 (en) * | 2003-03-25 | 2005-04-28 | Vasopharm Biotech Gmbh | Use of pteridine derivatives for the treatment of increased intracranial pressure and secondary ischemia |
| CA2538291A1 (en) * | 2003-09-18 | 2005-03-31 | Merck & Co., Inc. | Substituted sulfonamides |
| AU2004274309B2 (en) | 2003-09-22 | 2010-04-08 | Msd K.K. | Novel piperidine derivative |
| US7223761B2 (en) * | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| TW200522944A (en) | 2003-12-23 | 2005-07-16 | Lilly Co Eli | CB1 modulator compounds |
| US20050250820A1 (en) * | 2004-03-08 | 2005-11-10 | Amgen Inc. | Therapeutic modulation of PPARgamma activity |
| WO2005123053A2 (en) * | 2004-06-22 | 2005-12-29 | Pharmos Limited | Use of cb2 receptors agonists for the treatment of huntington’s disease |
| WO2006039334A1 (en) * | 2004-09-29 | 2006-04-13 | Schering Corporation | Combinations of substituted azetidonones and cb1 antagonists |
| EP2286840A3 (en) | 2004-11-01 | 2013-09-04 | Amylin Pharmaceuticals, LLC | Treatment of obesity and related diseases |
| US8394765B2 (en) * | 2004-11-01 | 2013-03-12 | Amylin Pharmaceuticals Llc | Methods of treating obesity with two different anti-obesity agents |
| US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| CA2609388C (en) | 2005-05-30 | 2013-08-06 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivative |
| CA2613678A1 (en) | 2005-06-02 | 2006-12-07 | Glenmark Pharmaceuticals S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
| US7923465B2 (en) | 2005-06-02 | 2011-04-12 | Glenmark Pharmaceuticals S.A. | Cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
| JPWO2007018248A1 (ja) | 2005-08-10 | 2009-02-19 | 萬有製薬株式会社 | ピリドン化合物 |
| BRPI0614649A2 (pt) | 2005-08-11 | 2011-04-12 | Amylin Pharmaceuticals Inc | polipeptìdeos hìbridos com propriedades selecionáveis |
| EP2330124B1 (en) | 2005-08-11 | 2015-02-25 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| EP1921065B1 (en) | 2005-08-24 | 2010-10-20 | Banyu Pharmaceutical Co., Ltd. | Phenylpyridone derivative |
| WO2007029847A1 (ja) | 2005-09-07 | 2007-03-15 | Banyu Pharmaceutical Co., Ltd. | 二環性芳香族置換ピリドン誘導体 |
| BRPI0616463A2 (pt) | 2005-09-29 | 2011-06-21 | Merck & Co Inc | composto, composição farmacêutica, e, uso de um composto |
| AU2006307046A1 (en) | 2005-10-27 | 2007-05-03 | Msd K.K. | Novel benzoxathiin derivative |
| US8158791B2 (en) | 2005-11-10 | 2012-04-17 | Msd K.K. | Aza-substituted spiro derivatives |
| JP5489333B2 (ja) | 2006-09-22 | 2014-05-14 | メルク・シャープ・アンド・ドーム・コーポレーション | 脂肪酸合成阻害剤を用いた治療の方法 |
| AU2007301126A1 (en) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | Diaryl ketimine derivative |
| GB0702862D0 (en) * | 2007-02-14 | 2007-03-28 | Univ Aberdeen | Therapeutic compounds |
| CA2682727C (en) | 2007-04-02 | 2016-03-22 | Banyu Pharmaceutical Co., Ltd. | Indoledione derivative |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2527360B1 (en) | 2007-06-04 | 2015-10-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| KR20100098628A (ko) * | 2007-11-14 | 2010-09-08 | 아밀린 파마슈티칼스, 인크. | 비만 및 비만 관련 질환 및 장애의 치료 방법 |
| US20110015181A1 (en) | 2008-03-06 | 2011-01-20 | Makoto Ando | Alkylaminopyridine derivative |
| EP2272841A1 (en) | 2008-03-28 | 2011-01-12 | Banyu Pharmaceutical Co., Ltd. | Diarylmethylamide derivative having antagonistic activity on melanin-concentrating hormone receptor |
| EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009261248A1 (en) | 2008-06-19 | 2009-12-23 | Banyu Pharmaceutical Co., Ltd. | Spirodiamine-diarylketoxime derivative |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| WO2010013595A1 (ja) | 2008-07-30 | 2010-02-04 | 萬有製薬株式会社 | ５員－５員又は５員－６員縮環シクロアルキルアミン誘導体 |
| WO2010047982A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| JP5635991B2 (ja) | 2008-10-30 | 2014-12-03 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | イソニコチンアミドオレキシン受容体アンタゴニスト |
| JP5557845B2 (ja) | 2008-10-31 | 2014-07-23 | メルク・シャープ・アンド・ドーム・コーポレーション | 糖尿病用剤として有用な新規環状ベンゾイミダゾール誘導体 |
| WO2010075069A1 (en) | 2008-12-16 | 2010-07-01 | Schering Corporation | Bicyclic pyranone derivatives as nicotinic acid receptor agonists |
| US20110245209A1 (en) | 2008-12-16 | 2011-10-06 | Schering Corporation | Pyridopyrimidine derivatives and methods of use thereof |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| BR112013021236B1 (pt) | 2011-02-25 | 2021-05-25 | Merck Sharp & Dohme Corp | composto derivado de benzimidazol, e, composição |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| CA2866910A1 (en) | 2012-03-20 | 2013-09-26 | Adamed Sp. Z O.O. | Sulphonamide derivatives of benzylamine for the treatment of cns diseases |
| US9527875B2 (en) | 2012-08-02 | 2016-12-27 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| RU2015140066A (ru) | 2013-02-22 | 2017-03-30 | Мерк Шарп И Доум Корп. | Противодиабетические бициклические соединения |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| CA2905438A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| SI3004138T1 (sl) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Limited | Ultra čisti agonisti gvanilat ciklaze C, postopek za njihovo pripravo in uporabo |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| KR102431436B1 (ko) | 2014-08-29 | 2022-08-10 | 테스 파마 에스.알.엘. | α-아미노-β-카복시뮤콘산 세미알데히드 데카복실라제의 억제제 |
| US9585867B2 (en) | 2015-08-06 | 2017-03-07 | Charles Everett Ankner | Cannabinod formulation for the sedation of a human or animal |
| AR109950A1 (es) | 2016-10-14 | 2019-02-06 | Tes Pharma S R L | INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA |
| US11072602B2 (en) | 2016-12-06 | 2021-07-27 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| AR117122A1 (es) | 2018-11-20 | 2021-07-14 | Tes Pharma S R L | INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA |
| WO2020167701A1 (en) | 2019-02-13 | 2020-08-20 | Merck Sharp & Dohme Corp. | Pyrrolidine orexin receptor agonists |
| US11098029B2 (en) | 2019-02-13 | 2021-08-24 | Merck Sharp & Dohme Corp. | 5-alkyl pyrrolidine orexin receptor agonists |
| US12312332B2 (en) | 2019-08-08 | 2025-05-27 | Merck Sharp & Dohme Llc | Heteroaryl pyrrolidine and piperidine orexin receptor agonists |
| BR112023002957A2 (pt) | 2020-08-18 | 2023-04-04 | Merck Sharp & Dohme Llc | Composto, composição farmacêutica, e, métodos para tratar narcolepsia e para tratar hipersonia em um sujeito mamífero |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58124758A (ja) * | 1982-01-20 | 1983-07-25 | Fujisawa Pharmaceut Co Ltd | ベンゼンスルホンアミド誘導体 |
| US5532237A (en) * | 1995-02-15 | 1996-07-02 | Merck Frosst Canada, Inc. | Indole derivatives with affinity for the cannabinoid receptor |
| DE19740785A1 (de) | 1997-02-21 | 1998-08-27 | Bayer Ag | Arylsulfonamide und Analoga |
| AR015733A1 (es) | 1998-03-25 | 2001-05-16 | Otsuka Pharma Co Ltd | DERIVADO DE PIRIDINA, EL PRODUCTO Y LA COMPOSICIoN FARMACEUTICA QUE CONTIENE DICHO DERIVADO. |
-
1998
- 1998-02-04 HN HN1998000027A patent/HN1998000027A/es unknown
- 1998-08-19 DE DE19837638A patent/DE19837638A1/de not_active Withdrawn
-
1999
- 1999-08-06 ES ES99940157T patent/ES2219049T3/es not_active Expired - Lifetime
- 1999-08-06 CA CA002340928A patent/CA2340928A1/en not_active Abandoned
- 1999-08-06 EP EP99940157A patent/EP1105370B9/de not_active Expired - Lifetime
- 1999-08-06 US US09/763,215 patent/US6469054B1/en not_active Expired - Fee Related
- 1999-08-06 JP JP2000566241A patent/JP2002523395A/ja not_active Withdrawn
- 1999-08-06 WO PCT/EP1999/005682 patent/WO2000010967A1/de not_active Ceased
- 1999-08-06 DE DE59909250T patent/DE59909250D1/de not_active Expired - Fee Related
- 1999-08-06 AU AU54203/99A patent/AU5420399A/en not_active Abandoned
-
2002
- 2002-08-21 US US10/225,823 patent/US6727279B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2219049T3 (es) | 2004-11-16 |
| EP1105370B9 (de) | 2005-01-12 |
| DE19837638A1 (de) | 2000-02-24 |
| EP1105370B1 (de) | 2004-04-21 |
| AU5420399A (en) | 2000-03-14 |
| US6469054B1 (en) | 2002-10-22 |
| US20030073727A1 (en) | 2003-04-17 |
| HN1998000027A (es) | 1999-06-02 |
| CA2340928A1 (en) | 2000-03-02 |
| DE59909250D1 (de) | 2004-05-27 |
| EP1105370A1 (de) | 2001-06-13 |
| WO2000010967A1 (de) | 2000-03-02 |
| US6727279B2 (en) | 2004-04-27 |
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