JP2006513154A - カリウムチャネルおよび／または皮質ニューロン活性モジュレーターとしての、ｎ−フェニルアントラニル酸および２−ベンズイミダゾロンの誘導体 - Google Patents
カリウムチャネルおよび／または皮質ニューロン活性モジュレーターとしての、ｎ−フェニルアントラニル酸および２−ベンズイミダゾロンの誘導体 Download PDFInfo
- Publication number
- JP2006513154A JP2006513154A JP2004544675A JP2004544675A JP2006513154A JP 2006513154 A JP2006513154 A JP 2006513154A JP 2004544675 A JP2004544675 A JP 2004544675A JP 2004544675 A JP2004544675 A JP 2004544675A JP 2006513154 A JP2006513154 A JP 2006513154A
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- alkyl
- hydrogen
- cycloalkyl
- 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.)
- Pending
Links
- 230000000694 effects Effects 0.000 title claims abstract description 108
- 210000003618 cortical neuron Anatomy 0.000 title claims abstract description 50
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 title claims abstract description 12
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 title claims description 35
- 108020001213 potassium channel Proteins 0.000 title description 30
- 102000004257 Potassium Channel Human genes 0.000 title description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 280
- 238000000034 method Methods 0.000 claims abstract description 79
- 102000003734 Voltage-Gated Potassium Channels Human genes 0.000 claims abstract description 25
- 108090000013 Voltage-Gated Potassium Channels Proteins 0.000 claims abstract description 25
- 230000001603 reducing effect Effects 0.000 claims abstract description 8
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 claims description 143
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 108091006146 Channels Proteins 0.000 claims description 84
- 125000003118 aryl group Chemical group 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- 239000001257 hydrogen Substances 0.000 claims description 72
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
- 150000002431 hydrogen Chemical group 0.000 claims description 58
- 239000008194 pharmaceutical composition Substances 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 51
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 47
- 229910052760 oxygen Inorganic materials 0.000 claims description 47
- 239000001301 oxygen Substances 0.000 claims description 47
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 41
- 229910052717 sulfur Inorganic materials 0.000 claims description 41
- 239000011593 sulfur Substances 0.000 claims description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 229920001515 polyalkylene glycol Chemical group 0.000 claims description 33
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 32
- 108010038888 KCNQ3 Potassium Channel Proteins 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 28
- 125000003827 glycol group Chemical group 0.000 claims description 26
- 239000004480 active ingredient Substances 0.000 claims description 25
- 150000002829 nitrogen Chemical class 0.000 claims description 25
- 208000035475 disorder Diseases 0.000 claims description 23
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
- -1 cyano, nitro, amino Chemical group 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000005190 thiohydroxy group Chemical group 0.000 claims description 21
- 125000004385 trihaloalkyl group Chemical group 0.000 claims description 21
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 19
- 229910052698 phosphorus Inorganic materials 0.000 claims description 19
- 239000011574 phosphorus Substances 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
- 229940125898 compound 5 Drugs 0.000 claims description 13
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 13
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 13
- 125000005296 thioaryloxy group Chemical group 0.000 claims description 13
- 229940126214 compound 3 Drugs 0.000 claims description 12
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims description 11
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 11
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 10
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000002723 alicyclic group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 208000004296 neuralgia Diseases 0.000 claims description 9
- 208000021722 neuropathic pain Diseases 0.000 claims description 9
- 150000003017 phosphorus Chemical class 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 206010003591 Ataxia Diseases 0.000 claims description 8
- 208000020925 Bipolar disease Diseases 0.000 claims description 8
- 201000004569 Blindness Diseases 0.000 claims description 8
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 8
- 206010011878 Deafness Diseases 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 8
- 208000026072 Motor neurone disease Diseases 0.000 claims description 8
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical class C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 206010015037 epilepsy Diseases 0.000 claims description 8
- 230000010370 hearing loss Effects 0.000 claims description 8
- 231100000888 hearing loss Toxicity 0.000 claims description 8
- 208000016354 hearing loss disease Diseases 0.000 claims description 8
- 206010027175 memory impairment Diseases 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- 208000005264 motor neuron disease Diseases 0.000 claims description 8
- 208000018198 spasticity Diseases 0.000 claims description 8
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 8
- 208000019022 Mood disease Diseases 0.000 claims description 7
- 239000000872 buffer Substances 0.000 claims description 7
- 239000000945 filler Substances 0.000 claims description 7
- 201000003723 learning disability Diseases 0.000 claims description 7
- 239000005022 packaging material Substances 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 208000020358 Learning disease Diseases 0.000 claims description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
- 239000000739 antihistaminic agent Substances 0.000 claims description 5
- 229940125715 antihistaminic agent Drugs 0.000 claims description 5
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 5
- 239000003443 antiviral agent Substances 0.000 claims description 5
- 229940127089 cytotoxic agent Drugs 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- 239000000829 suppository Substances 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 230000033228 biological regulation Effects 0.000 claims description 4
- 230000007423 decrease Effects 0.000 claims description 4
- 238000007918 intramuscular administration Methods 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 102100034354 Potassium voltage-gated channel subfamily KQT member 2 Human genes 0.000 claims description 3
- 230000005856 abnormality Effects 0.000 claims description 3
- 230000003340 mental effect Effects 0.000 claims description 3
- 210000004877 mucosa Anatomy 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 3
- 206010036790 Productive cough Diseases 0.000 claims 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims 1
- 230000036651 mood Effects 0.000 claims 1
- 210000003802 sputum Anatomy 0.000 claims 1
- 208000024794 sputum Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 33
- 230000004907 flux Effects 0.000 abstract description 4
- 229910001414 potassium ion Inorganic materials 0.000 abstract description 4
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 abstract description 3
- 208000015114 central nervous system disease Diseases 0.000 abstract description 2
- 239000004090 neuroprotective agent Substances 0.000 abstract description 2
- 208000027232 peripheral nervous system disease Diseases 0.000 abstract description 2
- XFNUIZJDGZXLIA-UHFFFAOYSA-N 6-amino-6-phenylcyclohexa-2,4-diene-1-carboxylic acid Chemical class C1(=CC=CC=C1)C1(C(C(=O)O)C=CC=C1)N XFNUIZJDGZXLIA-UHFFFAOYSA-N 0.000 abstract 1
- 102000005453 KCNQ2 Potassium Channel Human genes 0.000 description 131
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 78
- 229960003803 meclofenamic acid Drugs 0.000 description 76
- 229940125904 compound 1 Drugs 0.000 description 66
- CXUCKELNYMZTRT-UHFFFAOYSA-N 1-Ethyl-2-benzimidazolinone Chemical compound C1=CC=C2NC(=O)N(CC)C2=C1 CXUCKELNYMZTRT-UHFFFAOYSA-N 0.000 description 47
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 41
- 229940125773 compound 10 Drugs 0.000 description 40
- 230000004913 activation Effects 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 34
- 230000001537 neural effect Effects 0.000 description 32
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 25
- 241000700159 Rattus Species 0.000 description 24
- 229960001259 diclofenac Drugs 0.000 description 23
- 230000009849 deactivation Effects 0.000 description 22
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 21
- 102000015686 KCNQ3 Potassium Channel Human genes 0.000 description 19
- 125000005843 halogen group Chemical group 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 229940125782 compound 2 Drugs 0.000 description 14
- 230000008064 spontaneous neuronal effect Effects 0.000 description 13
- 206010010904 Convulsion Diseases 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- PCOBBVZJEWWZFR-UHFFFAOYSA-N ezogabine Chemical compound C1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 PCOBBVZJEWWZFR-UHFFFAOYSA-N 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 230000036982 action potential Effects 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 11
- 229960003312 retigabine Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 230000002269 spontaneous effect Effects 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000011591 potassium Substances 0.000 description 10
- 229910052700 potassium Inorganic materials 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 0 CC1N(*)c2ccccc2N1 Chemical compound CC1N(*)c2ccccc2N1 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 210000003050 axon Anatomy 0.000 description 8
- 230000000763 evoking effect Effects 0.000 description 8
- 210000002569 neuron Anatomy 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000007704 transition Effects 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- 102000012359 KCNQ Potassium Channels Human genes 0.000 description 6
- 108010022282 KCNQ Potassium Channels Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 6
- OWHMUADMRHFRCJ-UHFFFAOYSA-N CN(CCO)C(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O Chemical compound CN(CCO)C(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O OWHMUADMRHFRCJ-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- RLUNNWGNXYIAMB-UHFFFAOYSA-N COCCOCCOC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O Chemical compound COCCOCCOC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O RLUNNWGNXYIAMB-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 108010011185 KCNQ1 Potassium Channel Proteins 0.000 description 4
- PRWBZDKKXFLKAL-UHFFFAOYSA-N OCCOCCNC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O Chemical compound OCCOCCNC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O PRWBZDKKXFLKAL-UHFFFAOYSA-N 0.000 description 4
- TYJGETBDTFVKAB-UHFFFAOYSA-N OCCOCCOC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O Chemical compound OCCOCCOC(Cc(cccc1)c1Nc(c(Cl)ccc1)c1Cl)=O TYJGETBDTFVKAB-UHFFFAOYSA-N 0.000 description 4
- 102100037444 Potassium voltage-gated channel subfamily KQT member 1 Human genes 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000001054 cortical effect Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000002102 hyperpolarization Effects 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000028161 membrane depolarization Effects 0.000 description 4
- 210000000287 oocyte Anatomy 0.000 description 4
- 238000012402 patch clamp technique Methods 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 210000001428 peripheral nervous system Anatomy 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000004953 trihalomethyl group Chemical group 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000974726 Homo sapiens Potassium voltage-gated channel subfamily E member 1 Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 102100022755 Potassium voltage-gated channel subfamily E member 1 Human genes 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108091082510 Slo family Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000002999 depolarising effect Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000036390 resting membrane potential Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 230000008925 spontaneous activity Effects 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010001497 Agitation Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical class O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007831 electrophysiology Effects 0.000 description 2
- 238000002001 electrophysiology Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- SBDNJUWAMKYJOX-UHFFFAOYSA-M meclofenamic acid(1-) Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C([O-])=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-M 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 230000004118 muscle contraction Effects 0.000 description 2
- OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 2
- 229950010357 tetrodotoxin Drugs 0.000 description 2
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000008882 Benign Neonatal Epilepsy Diseases 0.000 description 1
- 206010067866 Benign familial neonatal convulsions Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GKFRVYIRSVCZOJ-UHFFFAOYSA-N CC(C(Cl)=CCC1)=C1Nc(cccc1)c1C(NCCOCCO)=O Chemical compound CC(C(Cl)=CCC1)=C1Nc(cccc1)c1C(NCCOCCO)=O GKFRVYIRSVCZOJ-UHFFFAOYSA-N 0.000 description 1
- QSTRDUNXBQQVBI-UHFFFAOYSA-N CC(C1Cl)C=CC(Cl)=C1Nc1c(CC(OCCOCCOC)=O)cccc1 Chemical compound CC(C1Cl)C=CC(Cl)=C1Nc1c(CC(OCCOCCOC)=O)cccc1 QSTRDUNXBQQVBI-UHFFFAOYSA-N 0.000 description 1
- UHXVDXDHPOOHSW-UHFFFAOYSA-N CC(CC=C1)C(C)=C1Nc(cccc1)c1C(NCCOCCO)=O Chemical compound CC(CC=C1)C(C)=C1Nc(cccc1)c1C(NCCOCCO)=O UHXVDXDHPOOHSW-UHFFFAOYSA-N 0.000 description 1
- IYINOXIKOXORQM-UHFFFAOYSA-N CC(c(cccc1)c1Nc1cccc(C(F)(F)F)c1)=O Chemical compound CC(c(cccc1)c1Nc1cccc(C(F)(F)F)c1)=O IYINOXIKOXORQM-UHFFFAOYSA-N 0.000 description 1
- ZFENXOXLOXEJAZ-UHFFFAOYSA-N CC1C(NC2C(Cl)=CC=CC2Cl)=C(CC(OCCOCCOC)=O)C=CC1 Chemical compound CC1C(NC2C(Cl)=CC=CC2Cl)=C(CC(OCCOCCOC)=O)C=CC1 ZFENXOXLOXEJAZ-UHFFFAOYSA-N 0.000 description 1
- OQCZKTSCVWYBJL-UHFFFAOYSA-N CC1C(Nc(cccc2)c2C(CCCCOCCO)=O)=CC=CC1C(F)(F)F Chemical compound CC1C(Nc(cccc2)c2C(CCCCOCCO)=O)=CC=CC1C(F)(F)F OQCZKTSCVWYBJL-UHFFFAOYSA-N 0.000 description 1
- JGLBMPBHFJMUPW-UHFFFAOYSA-N CC1C=CC(Nc(cccc2)c2C(NCCOCCO)=O)=C(C)C1C Chemical compound CC1C=CC(Nc(cccc2)c2C(NCCOCCO)=O)=C(C)C1C JGLBMPBHFJMUPW-UHFFFAOYSA-N 0.000 description 1
- FTRILNDDIJKDRK-UHFFFAOYSA-N CCc(c(Nc(cccc1)c1C(CCCCOCCO)=O)ccc1)c1Cl Chemical compound CCc(c(Nc(cccc1)c1C(CCCCOCCO)=O)ccc1)c1Cl FTRILNDDIJKDRK-UHFFFAOYSA-N 0.000 description 1
- ZAXBUSABMJBBCD-UHFFFAOYSA-N COCCOCCOC(Cc(cccc1)c1NC(C(CC=C1)Cl)=C1Cl)=O Chemical compound COCCOCCOC(Cc(cccc1)c1NC(C(CC=C1)Cl)=C1Cl)=O ZAXBUSABMJBBCD-UHFFFAOYSA-N 0.000 description 1
- 102100023073 Calcium-activated potassium channel subunit alpha-1 Human genes 0.000 description 1
- 101710189782 Calcium-activated potassium channel subunit alpha-1 Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- QHLSGAOYJCOKRL-UHFFFAOYSA-N Cc(c(Nc(cccc1)c1C(CCCC/[O]=C/CO)=O)ccc1)c1Cl Chemical compound Cc(c(Nc(cccc1)c1C(CCCC/[O]=C/CO)=O)ccc1)c1Cl QHLSGAOYJCOKRL-UHFFFAOYSA-N 0.000 description 1
- NHHUMFLVEKQHQU-UHFFFAOYSA-N Cc1c(C)c(Nc(cccc2)c2C(CCCCOCCO)=O)ccc1 Chemical compound Cc1c(C)c(Nc(cccc2)c2C(CCCCOCCO)=O)ccc1 NHHUMFLVEKQHQU-UHFFFAOYSA-N 0.000 description 1
- RMEPCNVWPRKRCW-UHFFFAOYSA-N Cc1c(C)c(Nc(cccc2)c2C(NCCOCCO)=O)ccc1 Chemical compound Cc1c(C)c(Nc(cccc2)c2C(NCCOCCO)=O)ccc1 RMEPCNVWPRKRCW-UHFFFAOYSA-N 0.000 description 1
- CAHZWUWTSFRZET-UHFFFAOYSA-N Cc1cccc(NC2C=CC=CC2C(CCCCOCCO)=O)c1C Chemical compound Cc1cccc(NC2C=CC=CC2C(CCCCOCCO)=O)c1C CAHZWUWTSFRZET-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010052105 Gastrointestinal hypomotility Diseases 0.000 description 1
- 208000003078 Generalized Epilepsy Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 101000745167 Homo sapiens Neuronal acetylcholine receptor subunit alpha-4 Proteins 0.000 description 1
- 101000944004 Homo sapiens Potassium channel subfamily U member 1 Proteins 0.000 description 1
- 101000994667 Homo sapiens Potassium voltage-gated channel subfamily KQT member 2 Proteins 0.000 description 1
- 101000994648 Homo sapiens Potassium voltage-gated channel subfamily KQT member 4 Proteins 0.000 description 1
- 101000994656 Homo sapiens Potassium voltage-gated channel subfamily KQT member 5 Proteins 0.000 description 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
- 102000009855 Inwardly Rectifying Potassium Channels Human genes 0.000 description 1
- 108010009983 Inwardly Rectifying Potassium Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 description 1
- 102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- ABDMQSFNJPYOLA-UHFFFAOYSA-N NS(=O)(=O)[N+]([O-])=O Chemical compound NS(=O)(=O)[N+]([O-])=O ABDMQSFNJPYOLA-UHFFFAOYSA-N 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZPRYEPOJTAZODT-UHFFFAOYSA-N O=C(Cc(cccc1)c1NC1C(Cl)=CC=CC1C1CCC1)OCCOCCC(I)=O Chemical compound O=C(Cc(cccc1)c1NC1C(Cl)=CC=CC1C1CCC1)OCCOCCC(I)=O ZPRYEPOJTAZODT-UHFFFAOYSA-N 0.000 description 1
- DIOTUAAKLOHMAS-UHFFFAOYSA-N O=CCOCCOC(Cc1ccccc1Nc(c(Cl)ccc1)c1Cl)=O Chemical compound O=CCOCCOC(Cc1ccccc1Nc(c(Cl)ccc1)c1Cl)=O DIOTUAAKLOHMAS-UHFFFAOYSA-N 0.000 description 1
- OTMXHYJYSWGBCX-UHFFFAOYSA-N OC(Cc(cccc1)c1NC1C(Cl)=CC=CC1Cl)O Chemical compound OC(Cc(cccc1)c1NC1C(Cl)=CC=CC1Cl)O OTMXHYJYSWGBCX-UHFFFAOYSA-N 0.000 description 1
- UWBQWPVDHHJUSK-UHFFFAOYSA-N OCCOCCCCC(c1ccccc1NC1C=C(C(F)(F)F)C=CC1)=O Chemical compound OCCOCCCCC(c1ccccc1NC1C=C(C(F)(F)F)C=CC1)=O UWBQWPVDHHJUSK-UHFFFAOYSA-N 0.000 description 1
- QTXYZGKGQBGPOH-UHFFFAOYSA-N OCCOCCNC(c(cccc1)c1Nc1cccc(C(F)(F)F)c1)=O Chemical compound OCCOCCNC(c(cccc1)c1Nc1cccc(C(F)(F)F)c1)=O QTXYZGKGQBGPOH-UHFFFAOYSA-N 0.000 description 1
- JOLFMCIXAHKRSQ-UHFFFAOYSA-N OCCOCCOC(Cc(cccc1)c1NC(C(CC=C1)Cl)=C1Cl)O Chemical compound OCCOCCOC(Cc(cccc1)c1NC(C(CC=C1)Cl)=C1Cl)O JOLFMCIXAHKRSQ-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010061334 Partial seizures Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100033525 Potassium channel subfamily U member 1 Human genes 0.000 description 1
- 102100034363 Potassium voltage-gated channel subfamily KQT member 4 Human genes 0.000 description 1
- 102100034365 Potassium voltage-gated channel subfamily KQT member 5 Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 125000005631 S-sulfonamido group Chemical group 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 201000003452 benign familial neonatal epilepsy Diseases 0.000 description 1
- 201000010295 benign neonatal seizures Diseases 0.000 description 1
- JSYBAZQQYCNZJE-UHFFFAOYSA-N benzene-1,2,4-triamine Chemical class NC1=CC=C(N)C(N)=C1 JSYBAZQQYCNZJE-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 201000005108 complex partial epilepsy Diseases 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008202 granule composition Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 201000001993 idiopathic generalized epilepsy Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 230000008062 neuronal firing Effects 0.000 description 1
- 230000010353 neuronal integration Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000036278 prepulse Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical class NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 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
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000004346 regulation of heart rate Effects 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 230000019100 sperm motility Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical class NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 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
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000005423 trihalomethanesulfonamido group Chemical group 0.000 description 1
- 125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41952502P | 2002-10-21 | 2002-10-21 | |
| PCT/IL2003/000855 WO2004035037A2 (en) | 2002-10-21 | 2003-10-21 | Derivatives of n-phenylanthranilic acid and 2-benzimidazolon as potassium channel and/or cortical neuron activity modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006513154A true JP2006513154A (ja) | 2006-04-20 |
| JP2006513154A5 JP2006513154A5 (https=) | 2006-12-07 |
Family
ID=32108098
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004544675A Pending JP2006513154A (ja) | 2002-10-21 | 2003-10-21 | カリウムチャネルおよび／または皮質ニューロン活性モジュレーターとしての、ｎ−フェニルアントラニル酸および２−ベンズイミダゾロンの誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1553932A2 (https=) |
| JP (1) | JP2006513154A (https=) |
| KR (1) | KR20050074493A (https=) |
| AU (1) | AU2003272068A1 (https=) |
| CA (1) | CA2503075A1 (https=) |
| WO (1) | WO2004035037A2 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011529037A (ja) * | 2008-07-22 | 2011-12-01 | ラモット アット テル アビブ ユニバーシティ リミテッド | カリウムイオンチャネル調節剤およびその使用 |
| JP2020536875A (ja) * | 2017-10-09 | 2020-12-17 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッドＲａｍｏｔ Ａｔ Ｔｅｌ Ａｖｉｖ Ｕｎｉｖｅｒｓｉｔｙ Ｌｔｄ． | カリウムイオンチャネル及びｔｒｐｖ１チャネルのモジュレーター、並びにその使用 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7632866B2 (en) | 2002-10-21 | 2009-12-15 | Ramot At Tel Aviv University | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
| US8765815B2 (en) | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
| GB0723794D0 (en) | 2007-12-05 | 2008-01-16 | Lectus Therapeutics Ltd | Potassium ion channel modulators and uses thereof |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5032189A (https=) * | 1973-07-20 | 1975-03-28 | ||
| JPS5095285A (https=) * | 1973-12-26 | 1975-07-29 | ||
| JPH05132431A (ja) * | 1990-03-28 | 1993-05-28 | Nippon Oil & Fats Co Ltd | 高分子化薬剤およびその製造法 |
| WO1998020864A2 (en) * | 1996-11-13 | 1998-05-22 | Universita' Degli Studi Di Brescia - Dipartimento Di Scienze Biomediche | Use of selected non-steroidal antiinflammatory compounds for the prevention and the treatment of neurodegenerative diseases |
| WO2001019406A2 (en) * | 1999-09-13 | 2001-03-22 | Nobex Corporation | Amphiphilic prodrugs |
| WO2001047562A2 (en) * | 1999-12-23 | 2001-07-05 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly(ethylene glycol) |
| WO2001078721A1 (en) * | 2000-04-13 | 2001-10-25 | Mayo Foundation For Medical Education And Research | Aβ42 LOWERING AGENTS |
| JP2002509536A (ja) * | 1997-07-01 | 2002-03-26 | ワーナー−ランバート・カンパニー | ２−（４−ブロモ又は４−ヨードフェニルアミノ）安息香酸誘導体及びｍｅｋ阻害物質としてのそれらの使用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5565483A (en) * | 1995-06-07 | 1996-10-15 | Bristol-Myers Squibb Company | 3-substituted oxindole derivatives as potassium channel modulators |
| US6291442B1 (en) * | 1998-02-03 | 2001-09-18 | The General Hospital Corporation | Pharmacological modulators of voltage-gated potassium ion channels |
| EP1144387A1 (en) * | 1998-12-04 | 2001-10-17 | Neurosearch A/S | New benzimidazolone-, benzoxazolone-, or benzothiazolone derivatives as ion channel modulating agents |
| US6472165B1 (en) * | 1999-08-03 | 2002-10-29 | Arzneimittelwerk Dresden Gmbh | Modulatory binding site in potassium channels for screening and finding new active ingredients |
| US6429223B1 (en) * | 2000-06-23 | 2002-08-06 | Medinox, Inc. | Modified forms of pharmacologically active agents and uses therefor |
| TWI287984B (en) * | 2000-10-17 | 2007-10-11 | Wyeth Corp | Pharmaceutical composition for modulating bladder function |
| GB0026838D0 (en) * | 2000-11-02 | 2000-12-20 | Glaxo Group Ltd | Treatment method |
| US6593349B2 (en) * | 2001-03-19 | 2003-07-15 | Icagen, Inc. | Bisarylamines as potassium channel openers |
| US8765815B2 (en) * | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
-
2003
- 2003-10-21 KR KR1020057006856A patent/KR20050074493A/ko not_active Ceased
- 2003-10-21 JP JP2004544675A patent/JP2006513154A/ja active Pending
- 2003-10-21 WO PCT/IL2003/000855 patent/WO2004035037A2/en not_active Ceased
- 2003-10-21 EP EP03753909A patent/EP1553932A2/en not_active Withdrawn
- 2003-10-21 CA CA002503075A patent/CA2503075A1/en not_active Abandoned
- 2003-10-21 AU AU2003272068A patent/AU2003272068A1/en not_active Abandoned
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5032189A (https=) * | 1973-07-20 | 1975-03-28 | ||
| JPS5095285A (https=) * | 1973-12-26 | 1975-07-29 | ||
| JPH05132431A (ja) * | 1990-03-28 | 1993-05-28 | Nippon Oil & Fats Co Ltd | 高分子化薬剤およびその製造法 |
| WO1998020864A2 (en) * | 1996-11-13 | 1998-05-22 | Universita' Degli Studi Di Brescia - Dipartimento Di Scienze Biomediche | Use of selected non-steroidal antiinflammatory compounds for the prevention and the treatment of neurodegenerative diseases |
| JP2002509536A (ja) * | 1997-07-01 | 2002-03-26 | ワーナー−ランバート・カンパニー | ２−（４−ブロモ又は４−ヨードフェニルアミノ）安息香酸誘導体及びｍｅｋ阻害物質としてのそれらの使用 |
| WO2001019406A2 (en) * | 1999-09-13 | 2001-03-22 | Nobex Corporation | Amphiphilic prodrugs |
| WO2001047562A2 (en) * | 1999-12-23 | 2001-07-05 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly(ethylene glycol) |
| WO2001078721A1 (en) * | 2000-04-13 | 2001-10-25 | Mayo Foundation For Medical Education And Research | Aβ42 LOWERING AGENTS |
Non-Patent Citations (2)
| Title |
|---|
| KALGUTKAR,A.S. ET AL: "Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 12, no. 4, JPN6010030974, 25 February 2002 (2002-02-25), pages 521 - 524, XP002319950, ISSN: 0001640397, DOI: 10.1016/S0960-894X(01)00792-2 * |
| LEGRAND,L. ET AL: "Heterocyclic sulfur compounds. 1,2-Dihydro-3,1,2λ5- benzothiazaphosphinine-2,4-dithiones. A new syn", PHOSPHORUS AND SULFUR AND THE RELATED ELEMENTS, vol. 26, no. 1, JPN6010030975, 1986, pages 111 - 17, ISSN: 0001640398 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011529037A (ja) * | 2008-07-22 | 2011-12-01 | ラモット アット テル アビブ ユニバーシティ リミテッド | カリウムイオンチャネル調節剤およびその使用 |
| US9464052B2 (en) | 2008-07-22 | 2016-10-11 | Ramot At Tel-Aviv University Ltd. | Potassium ion channel modulators and uses thereof |
| US9675567B2 (en) | 2008-07-22 | 2017-06-13 | Ramot At Tel-Aviv University Ltd. | Potassium ion channel modulators and uses thereof |
| JP2020536875A (ja) * | 2017-10-09 | 2020-12-17 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッドＲａｍｏｔ Ａｔ Ｔｅｌ Ａｖｉｖ Ｕｎｉｖｅｒｓｉｔｙ Ｌｔｄ． | カリウムイオンチャネル及びｔｒｐｖ１チャネルのモジュレーター、並びにその使用 |
| JP7448472B2 (ja) | 2017-10-09 | 2024-03-12 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | カリウムイオンチャネル及びｔｒｐｖ１チャネルのモジュレーター、並びにその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004035037A2 (en) | 2004-04-29 |
| CA2503075A1 (en) | 2004-04-29 |
| KR20050074493A (ko) | 2005-07-18 |
| AU2003272068A1 (en) | 2004-05-04 |
| AU2003272068A8 (en) | 2004-05-04 |
| WO2004035037A3 (en) | 2004-06-03 |
| EP1553932A2 (en) | 2005-07-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8618169B2 (en) | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators | |
| ES2564352T3 (es) | Derivados de tranilcipromina como inhibidores de la histona-desmetilasa LSD1 y/o LSD2 | |
| ES2729424T3 (es) | Inhibidores de Rho cinasa | |
| ES2250377T5 (es) | Moleculas organicas pequeñas reguladoras de la proliferacion celular. | |
| ES2338539T3 (es) | Pirazolamidas para uso en el tratamiento del dolor. | |
| KR101599661B1 (ko) | 글루타메이트에 의한 시냅스 반응을 향상시키기 위한 이치환된 아미드 화합물 | |
| WO2018204765A1 (en) | Methods of treating epilepsy and kcnq2 related conditions | |
| KR100252605B1 (ko) | 세포 유착저해제인 3-알킬옥시-, 아릴옥시-, 또는 아릴알킬옥시벤조(b)티오펜-2-카르복스아미드류 | |
| US20040034069A1 (en) | Nitrogen-containing compounds and their use as glycine transport inhibitors | |
| EP2681209B1 (en) | Compounds and methods for the treatment of pain and other disorders | |
| BR112019020252A2 (pt) | compostos úteis como inibidores de alcat 1 | |
| DE69919349T2 (de) | Piperidinyl- und n-amidinopiperidinyl-derivate | |
| JP2006513154A (ja) | カリウムチャネルおよび／または皮質ニューロン活性モジュレーターとしての、ｎ−フェニルアントラニル酸および２−ベンズイミダゾロンの誘導体 | |
| ES2238316T3 (es) | Uso de derivados de carbonilamino contra trastornos del snc. | |
| US8530453B2 (en) | Compounds and methods for the treatment of pain and other diseases | |
| KR20070085973A (ko) | 수면 장애 예방 또는 치료제 | |
| ES2288803B1 (es) | Derivados de benzo(d)isotiazoles como inhibidores de las histonas desacetilasas. | |
| JP2003192660A (ja) | 尿素誘導体 | |
| ES2258406B1 (es) | Uso de compuestos heterociclicos como agentes neurogenicos. | |
| AU2005201685B2 (en) | Derivatives of N-Phenylanthranilic Acid and 2-Benzimidazolon as Potassium Channel and/or Cortical Neuron Activity Modulators | |
| US20120238526A1 (en) | Aconitine compounds, compositions, uses, and preparation thereof | |
| US6962930B1 (en) | Compounds, compositions and method suitable for amelioration of withdrawal syndromes and withdrawal-induced brain damage | |
| EP4351574B1 (en) | Inhibitors of ttbk1 | |
| ES2389271T3 (es) | Amidas novedosas que actúan sobre los receptores de adenosina | |
| EP1777219A1 (en) | 1,2-Substituted naphthalene derivatives with antiglutamatergic properties and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061018 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061018 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100608 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101105 |