TWI504395B - Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier - Google Patents
Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier Download PDFInfo
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- TWI504395B TWI504395B TW099106075A TW99106075A TWI504395B TW I504395 B TWI504395 B TW I504395B TW 099106075 A TW099106075 A TW 099106075A TW 99106075 A TW99106075 A TW 99106075A TW I504395 B TWI504395 B TW I504395B
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- carbon atoms
- alkyl
- substituted
- amine
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- WPFIJUWKLJCQOO-UHFFFAOYSA-N 3-amino-1h-quinoline-2-thione Chemical class C1=CC=C2NC(=S)C(N)=CC2=C1 WPFIJUWKLJCQOO-UHFFFAOYSA-N 0.000 title description 18
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 title description 16
- 102000005453 KCNQ2 Potassium Channel Human genes 0.000 title description 16
- 239000003607 modifier Substances 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims description 537
- 125000003277 amino group Chemical group 0.000 claims description 266
- -1 diaminomethylene Chemical group 0.000 claims description 244
- 125000000217 alkyl group Chemical group 0.000 claims description 193
- 125000003118 aryl group Chemical group 0.000 claims description 111
- 125000001072 heteroaryl group Chemical group 0.000 claims description 106
- 229920006395 saturated elastomer Polymers 0.000 claims description 91
- 125000001424 substituent group Chemical group 0.000 claims description 81
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 76
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 76
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 72
- 125000000623 heterocyclic group Chemical group 0.000 claims description 70
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 68
- 229910052801 chlorine Inorganic materials 0.000 claims description 62
- 239000011737 fluorine Substances 0.000 claims description 61
- 229910052731 fluorine Inorganic materials 0.000 claims description 61
- 239000000460 chlorine Substances 0.000 claims description 59
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 58
- 125000003545 alkoxy group Chemical group 0.000 claims description 57
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 57
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 55
- 208000002193 Pain Diseases 0.000 claims description 55
- 229910052794 bromium Inorganic materials 0.000 claims description 53
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 51
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 48
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 46
- 125000002252 acyl group Chemical group 0.000 claims description 45
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 44
- 229910052740 iodine Inorganic materials 0.000 claims description 43
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
- 239000011630 iodine Substances 0.000 claims description 38
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 38
- 125000004429 atom Chemical group 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 36
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000004414 alkyl thio group Chemical group 0.000 claims description 31
- 150000001412 amines Chemical class 0.000 claims description 30
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 30
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 26
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 26
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 150000001721 carbon Chemical group 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 206010046543 Urinary incontinence Diseases 0.000 claims description 11
- 206010015037 epilepsy Diseases 0.000 claims description 11
- 239000002671 adjuvant Substances 0.000 claims description 10
- 125000003172 aldehyde group Chemical group 0.000 claims description 10
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
- 229940100389 Sulfonylurea Drugs 0.000 claims description 9
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 238000006467 substitution reaction Methods 0.000 claims description 9
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 8
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical group OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 8
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 125000005427 anthranyl group Chemical group 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 206010012335 Dependence Diseases 0.000 claims description 6
- 208000012661 Dyskinesia Diseases 0.000 claims description 6
- 208000014094 Dystonic disease Diseases 0.000 claims description 6
- 208000015592 Involuntary movements Diseases 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 208000010118 dystonia Diseases 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 claims description 6
- 125000005824 oxyalkoxy group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 5
- 125000005138 alkoxysulfonyl group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000005142 aryl oxy sulfonyl group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004149 thio group Chemical group *S* 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 3
- 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 229940127557 pharmaceutical product Drugs 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- UBKWLYPSSIBFGT-UHFFFAOYSA-N n-(2-pentylsulfanylquinolin-3-yl)-2-thiophen-2-ylacetamide Chemical compound CCCCCSC1=NC2=CC=CC=C2C=C1NC(=O)CC1=CC=CS1 UBKWLYPSSIBFGT-UHFFFAOYSA-N 0.000 claims description 2
- IWQRREJPCILBIR-UHFFFAOYSA-N n-[2-ethylsulfanyl-4-methyl-7-(trifluoromethyl)quinolin-3-yl]-2-thiophen-2-ylacetamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1NC(=O)CC1=CC=CS1 IWQRREJPCILBIR-UHFFFAOYSA-N 0.000 claims description 2
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical compound C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 claims 13
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 2
- IYZUJGWVUSWOFH-UHFFFAOYSA-N 2-(3-bicyclo[2.2.1]heptanyl)-n-(2-ethylsulfanylquinolin-3-yl)acetamide Chemical compound C1=CC=C2C=C(NC(=O)CC3C4CCC(C4)C3)C(SCC)=NC2=C1 IYZUJGWVUSWOFH-UHFFFAOYSA-N 0.000 claims 1
- RTIMSYQWCMQUHT-UHFFFAOYSA-N 2-(3-bicyclo[2.2.1]heptanyl)-n-[2-ethylsulfanyl-7-(trifluoromethyl)quinolin-3-yl]acetamide Chemical compound FC(F)(F)C1=CC=C2C=C(NC(=O)CC3C4CCC(C4)C3)C(SCC)=NC2=C1 RTIMSYQWCMQUHT-UHFFFAOYSA-N 0.000 claims 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims 1
- 125000001769 aryl amino group Chemical group 0.000 claims 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims 1
- 239000000243 solution Substances 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000000034 method Methods 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
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- 239000002585 base Substances 0.000 description 16
- 150000002431 hydrogen Chemical class 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
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- 239000000126 substance Substances 0.000 description 14
- 208000000094 Chronic Pain Diseases 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 208000033808 peripheral neuropathy Diseases 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
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- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 8
- 230000004054 inflammatory process Effects 0.000 description 8
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 8
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- 208000000112 Myalgia Diseases 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
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- 125000000304 alkynyl group Chemical group 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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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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- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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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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- 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
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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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- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Addiction (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09003431 | 2009-03-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201036610A TW201036610A (en) | 2010-10-16 |
| TWI504395B true TWI504395B (zh) | 2015-10-21 |
Family
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Family Applications (1)
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| TW099106075A TWI504395B (zh) | 2009-03-10 | 2010-03-03 | Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier |
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| TW (1) | TWI504395B (enExample) |
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI1009428A2 (pt) * | 2009-03-10 | 2016-03-01 | Gruenenthal Gmbh | 3-aminoisoxazolopiridina substituída como moduladores de kcnq2/3 |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI461197B (zh) | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier | |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| RU2595894C2 (ru) | 2010-08-27 | 2016-08-27 | Грюненталь Гмбх | Замещенные 2-окси-хинолин-3-карбоксамиды в качестве модуляторов kcnq2/3 |
| TW201211007A (en) | 2010-08-27 | 2012-03-16 | Gruenenthal Gmbh | Substituted 2-amino-quinoline-3-carboxamides as KCNQ2/3 modulators |
| HUE024870T2 (en) | 2010-08-27 | 2016-02-29 | Gruenenthal Gmbh | Substituted 2-oxo and 2-thioxo-dihydroquinoline-3-carboxamides as modulators of KCNQ2 / 3 |
| MX2013002295A (es) | 2010-09-01 | 2013-05-09 | Gruenenthal Gmbh | 1-oxo-dihidroisoquinolin-3-carboxamidas sustituidas como moduladores de kcnq2/3. |
| DE102018212006B3 (de) * | 2018-07-18 | 2019-10-31 | Universität Greifswald | Thioether als Modulatoren von Kv7.2/Kv7.3-Kanälen |
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| WO2007057447A1 (en) * | 2005-11-18 | 2007-05-24 | Neurosearch A/S | Novel quinazoline derivatives and their medical use |
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| DE4032147A1 (de) | 1990-10-10 | 1992-04-16 | Bayer Ag | Verwendung von substituierten 2-mercaptonicotinsaeurederivaten zur bekaempfung von endoparasiten, neue substituierte 2-mercaptonicotinsaeurederivate und verfahren zu ihrer herstellung |
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| EP0716077A1 (de) | 1994-12-08 | 1996-06-12 | Ciba-Geigy Ag | Aromatisch substituierte Omega-Aminoalkansäureamide und Alkansäurediamide und ihre Verwendung als Renininhibitoren |
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- 2010-03-09 NZ NZ595569A patent/NZ595569A/xx not_active IP Right Cessation
- 2010-03-09 PL PL10708503T patent/PL2406228T3/pl unknown
- 2010-03-09 WO PCT/EP2010/001449 patent/WO2010102779A1/de not_active Ceased
- 2010-03-09 CN CN2010800109786A patent/CN102341374A/zh active Pending
- 2010-03-09 MX MX2011009338A patent/MX2011009338A/es active IP Right Grant
- 2010-03-09 CA CA2754943A patent/CA2754943A1/en not_active Abandoned
- 2010-03-09 ES ES10708503T patent/ES2436365T3/es active Active
- 2010-03-09 RU RU2011140701/04A patent/RU2011140701A/ru not_active Application Discontinuation
- 2010-03-09 AU AU2010223556A patent/AU2010223556B2/en not_active Ceased
- 2010-03-09 EP EP10708503.7A patent/EP2406228B1/de not_active Not-in-force
- 2010-03-09 KR KR1020117023698A patent/KR20110130461A/ko not_active Withdrawn
- 2010-03-09 PE PE2011001564A patent/PE20120535A1/es not_active Application Discontinuation
- 2010-03-09 BR BRPI1009519A patent/BRPI1009519A2/pt not_active IP Right Cessation
- 2010-03-09 JP JP2011553339A patent/JP5727945B2/ja not_active Expired - Fee Related
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- 2010-03-10 AR ARP100100719A patent/AR075730A1/es not_active Application Discontinuation
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2011
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- 2011-09-02 CL CL2011002160A patent/CL2011002160A1/es unknown
- 2011-09-04 IL IL214944A patent/IL214944A0/en unknown
- 2011-09-23 EC EC2011011346A patent/ECSP11011346A/es unknown
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| WO2007057447A1 (en) * | 2005-11-18 | 2007-05-24 | Neurosearch A/S | Novel quinazoline derivatives and their medical use |
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| KWANG HO YOO, EUN BOK CHOI, HYEON KYU LEE, GUY HWAN YEON, HEE CHEOL YANG, CHWANG SIEK PAK: "Beckmann Rearrangement Using Indium(III) Chloride: Synthesis of Substituted Oxazoloquinolines from the Corresponding Ketoximes of 3-Acyl-1H-quinolin-4-ones" SYNTHESIS, Nr. 10, 27. April 2006 (2006-04-27), Seiten 1599-1612. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CO6410291A2 (es) | 2012-03-30 |
| ZA201107370B (en) | 2012-07-25 |
| ES2436365T3 (es) | 2013-12-30 |
| BRPI1009519A2 (pt) | 2016-03-15 |
| EP2406228B1 (de) | 2013-09-18 |
| CL2011002160A1 (es) | 2012-08-17 |
| IL214944A0 (en) | 2011-11-30 |
| PE20120535A1 (es) | 2012-05-09 |
| TW201036610A (en) | 2010-10-16 |
| AU2010223556B2 (en) | 2015-01-29 |
| CN102341374A (zh) | 2012-02-01 |
| PL2406228T3 (pl) | 2014-02-28 |
| RU2011140701A (ru) | 2013-04-20 |
| JP5727945B2 (ja) | 2015-06-03 |
| WO2010102779A1 (de) | 2010-09-16 |
| CA2754943A1 (en) | 2010-09-16 |
| ECSP11011346A (es) | 2011-10-31 |
| US20100234421A1 (en) | 2010-09-16 |
| EP2406228A1 (de) | 2012-01-18 |
| AR075730A1 (es) | 2011-04-20 |
| KR20110130461A (ko) | 2011-12-05 |
| JP2012521966A (ja) | 2012-09-20 |
| AU2010223556A1 (en) | 2011-11-03 |
| US8207342B2 (en) | 2012-06-26 |
| NZ595569A (en) | 2012-11-30 |
| MX2011009338A (es) | 2011-09-27 |
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