JP2011500673A - 代謝調節型グルタミン酸受容体（ｍｇｌｕｒｓ）の調節因子としてのテトラゾール誘導体 - Google Patents
代謝調節型グルタミン酸受容体（ｍｇｌｕｒｓ）の調節因子としてのテトラゾール誘導体 Download PDFInfo
- Publication number
- JP2011500673A JP2011500673A JP2010529900A JP2010529900A JP2011500673A JP 2011500673 A JP2011500673 A JP 2011500673A JP 2010529900 A JP2010529900 A JP 2010529900A JP 2010529900 A JP2010529900 A JP 2010529900A JP 2011500673 A JP2011500673 A JP 2011500673A
- Authority
- JP
- Japan
- Prior art keywords
- disorder
- methyl
- pain
- use according
- triazol
- 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
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title description 32
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title description 32
- 150000003536 tetrazoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 238000011282 treatment Methods 0.000 claims abstract description 36
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 20
- 230000001404 mediated effect Effects 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
- 208000035475 disorder Diseases 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- 206010011224 Cough Diseases 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
- 208000002193 Pain Diseases 0.000 claims description 17
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 15
- -1 3-methylphenyl-2H-tetrazol-5-yl Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 208000019695 Migraine disease Diseases 0.000 claims description 11
- 206010027599 migraine Diseases 0.000 claims description 11
- 230000036407 pain Effects 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 201000006549 dyspepsia Diseases 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 206010012335 Dependence Diseases 0.000 claims description 5
- 206010065390 Inflammatory pain Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 5
- 208000004296 neuralgia Diseases 0.000 claims description 5
- 208000021722 neuropathic pain Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 206010019196 Head injury Diseases 0.000 claims description 4
- 208000013016 Hypoglycemia Diseases 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 4
- 201000001119 neuropathy Diseases 0.000 claims description 4
- 230000007823 neuropathy Effects 0.000 claims description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- MBVZOUHNLPNTLU-UHFFFAOYSA-N 1-[2-(3-methylphenyl)tetrazol-5-yl]ethanone Chemical compound N1=C(C(=O)C)N=NN1C1=CC=CC(C)=C1 MBVZOUHNLPNTLU-UHFFFAOYSA-N 0.000 claims description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 208000030507 AIDS Diseases 0.000 claims description 3
- 208000004998 Abdominal Pain Diseases 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 206010003805 Autism Diseases 0.000 claims description 3
- 208000020706 Autistic disease Diseases 0.000 claims description 3
- 208000008035 Back Pain Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000002881 Colic Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 201000010374 Down Syndrome Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000008930 Low Back Pain Diseases 0.000 claims description 3
- 208000036626 Mental retardation Diseases 0.000 claims description 3
- 206010029148 Nephrolithiasis Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 3
- 208000004550 Postoperative Pain Diseases 0.000 claims description 3
- 108010029485 Protein Isoforms Proteins 0.000 claims description 3
- 102000001708 Protein Isoforms Human genes 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 208000009205 Tinnitus Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 235000019788 craving Nutrition 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000001130 gallstones Diseases 0.000 claims description 3
- 230000005906 menstruation Effects 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 231100000886 tinnitus Toxicity 0.000 claims description 3
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 3
- QFHRESWLTOSUJH-UHFFFAOYSA-N 2-methyl-5-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)pyrazine Chemical compound C1=NC(C)=CN=C1C1=NN=C(S(C)(=O)=O)N1C QFHRESWLTOSUJH-UHFFFAOYSA-N 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
- 125000005638 hydrazono group Chemical group 0.000 claims description 2
- 208000027520 Somatoform disease Diseases 0.000 claims 6
- 208000027753 pain disease Diseases 0.000 claims 6
- 208000019984 Auditory nerve disease Diseases 0.000 claims 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims 2
- 208000017442 Retinal disease Diseases 0.000 claims 2
- 206010038923 Retinopathy Diseases 0.000 claims 2
- 208000034189 Sclerosis Diseases 0.000 claims 2
- 208000037906 ischaemic injury Diseases 0.000 claims 2
- 210000003205 muscle Anatomy 0.000 claims 2
- 230000004766 neurogenesis Effects 0.000 claims 2
- NQBOKVREWGZKJU-MRVPVSSYSA-N (1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethanol Chemical compound N1=C([C@H](O)C)N=NN1C1=CC=CC(C)=C1 NQBOKVREWGZKJU-MRVPVSSYSA-N 0.000 claims 1
- VLDOGHBCDVMKJO-UHFFFAOYSA-N 2-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyrimidine Chemical compound CN1C(SC)=NN=C1C1=NC=CC=N1 VLDOGHBCDVMKJO-UHFFFAOYSA-N 0.000 claims 1
- RVJAQHSUJLBQMF-UHFFFAOYSA-N 2-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)pyrimidine Chemical compound N1=C(S(C)(=O)=O)N(C)C(C=2N=CC=CN=2)=N1 RVJAQHSUJLBQMF-UHFFFAOYSA-N 0.000 claims 1
- OOWUAHYPZKCHLH-GFCCVEGCSA-N 2-[4-methyl-5-[(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyrimidine Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(C)C=CC=1)C(N1C)=NN=C1C1=NC=CC=N1 OOWUAHYPZKCHLH-GFCCVEGCSA-N 0.000 claims 1
- OXWBQROFVREADY-UHFFFAOYSA-N 2-methyl-4-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyridine Chemical compound CN1C(SC)=NN=C1C1=CC=NC(C)=C1 OXWBQROFVREADY-UHFFFAOYSA-N 0.000 claims 1
- ZPVFNNAJFOSGQA-CQSZACIVSA-N 2-methyl-4-[4-methyl-5-[(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(C)C=CC=1)C(N1C)=NN=C1C1=CC=NC(C)=C1 ZPVFNNAJFOSGQA-CQSZACIVSA-N 0.000 claims 1
- UQAZCZQPTDHGBU-UHFFFAOYSA-N 2-methyl-5-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyrazine Chemical compound CN1C(SC)=NN=C1C1=CN=C(C)C=N1 UQAZCZQPTDHGBU-UHFFFAOYSA-N 0.000 claims 1
- OCIUHGHSQQFGAU-CYBMUJFWSA-N 2-methyl-5-[4-methyl-5-[(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyrazine Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(C)C=CC=1)C(N1C)=NN=C1C1=CN=C(C)C=N1 OCIUHGHSQQFGAU-CYBMUJFWSA-N 0.000 claims 1
- YOKDBPXYKWEEFJ-UHFFFAOYSA-N 5-(4-methyl-5-methylsulfanyl-1,2,4-triazol-3-yl)pyrimidine Chemical compound CN1C(SC)=NN=C1C1=CN=CN=C1 YOKDBPXYKWEEFJ-UHFFFAOYSA-N 0.000 claims 1
- YOLMBYXXELXYKV-UHFFFAOYSA-N 5-(4-methyl-5-methylsulfonyl-1,2,4-triazol-3-yl)pyrimidine Chemical compound N1=C(S(C)(=O)=O)N(C)C(C=2C=NC=NC=2)=N1 YOLMBYXXELXYKV-UHFFFAOYSA-N 0.000 claims 1
- WLXQXSOPLQNURC-GFCCVEGCSA-N 5-[4-methyl-5-[(1r)-1-[2-(3-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyrimidine Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(C)C=CC=1)C(N1C)=NN=C1C1=CN=CN=C1 WLXQXSOPLQNURC-GFCCVEGCSA-N 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- MHZNJJVWSPDLCW-UHFFFAOYSA-N ethyl 2-(3-methylphenyl)tetrazole-5-carboxylate Chemical compound N1=C(C(=O)OCC)N=NN1C1=CC=CC(C)=C1 MHZNJJVWSPDLCW-UHFFFAOYSA-N 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 230000004913 activation Effects 0.000 description 18
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 210000000111 lower esophageal sphincter Anatomy 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000012267 brine Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 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 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 229930195712 glutamate Natural products 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 230000001052 transient effect Effects 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 230000005284 excitation Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- MTVWFVDWRVYDOR-UHFFFAOYSA-N 3,4-Dihydroxyphenylglycol Chemical compound OCC(O)C1=CC=C(O)C(O)=C1 MTVWFVDWRVYDOR-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 208000013116 chronic cough Diseases 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HOOWCUZPEFNHDT-UHFFFAOYSA-N DHPG Natural products OC(=O)C(N)C1=CC(O)=CC(O)=C1 HOOWCUZPEFNHDT-UHFFFAOYSA-N 0.000 description 3
- 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 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 108010084311 Novozyme 435 Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102000014384 Type C Phospholipases Human genes 0.000 description 3
- 108010079194 Type C Phospholipases Proteins 0.000 description 3
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000007975 buffered saline Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 210000003238 esophagus Anatomy 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229960000367 inositol Drugs 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000001242 postsynaptic effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000009747 swallowing Effects 0.000 description 3
- NQBOKVREWGZKJU-UHFFFAOYSA-N 1-[2-(3-methylphenyl)tetrazol-5-yl]ethanol Chemical compound N1=C(C(O)C)N=NN1C1=CC=CC(C)=C1 NQBOKVREWGZKJU-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 208000006687 Esophageal Fistula Diseases 0.000 description 2
- 108010000722 Excitatory Amino Acid Transporter 1 Proteins 0.000 description 2
- 102100031563 Excitatory amino acid transporter 1 Human genes 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 201000008197 Laryngitis Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 2
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 206010065835 Oesophageal fistula Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 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 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000008393 encapsulating agent Substances 0.000 description 2
- AQNDVZFJEOKUPX-GXDHUFHOSA-N ethyl (2e)-2-chloro-2-[(3-methylphenyl)hydrazinylidene]acetate Chemical compound CCOC(=O)C(\Cl)=N/NC1=CC=CC(C)=C1 AQNDVZFJEOKUPX-GXDHUFHOSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 206010016165 failure to thrive Diseases 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 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
- 230000007246 mechanism Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 150000003906 phosphoinositides Chemical class 0.000 description 2
- 230000003518 presynaptic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 230000007306 turnover Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 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
- MMWCIQZXVOZEGG-UHFFFAOYSA-N 1,4,5-IP3 Natural products OC1C(O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(O)C1OP(O)(O)=O MMWCIQZXVOZEGG-UHFFFAOYSA-N 0.000 description 1
- SKYYTGUCWARUCL-UHFFFAOYSA-N 1-amino-3-ethylthiourea Chemical compound CCNC(=S)NN SKYYTGUCWARUCL-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonic acid Chemical compound CC1=CC(C)=C(S(O)(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-N 0.000 description 1
- IRLYGRLEBKCYPY-UHFFFAOYSA-N 2,5-dimethylbenzenesulfonic acid Chemical compound CC1=CC=C(C)C(S(O)(=O)=O)=C1 IRLYGRLEBKCYPY-UHFFFAOYSA-N 0.000 description 1
- IKNZBNHVVQIRTO-UHFFFAOYSA-N 2h-tetrazole-5-carboxylic acid Chemical compound OC(=O)C=1N=NNN=1 IKNZBNHVVQIRTO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- IBFMTDRAKYKXQS-UHFFFAOYSA-N 5-methylpyrazine-2-carbohydrazide Chemical compound CC1=CN=C(C(=O)NN)C=N1 IBFMTDRAKYKXQS-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin 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
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 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 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 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 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710098398 Probable alanine aminotransferase, mitochondrial Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229910052787 antimony Inorganic materials 0.000 description 1
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000002982 auditory neuropathy Diseases 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001669 calcium Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028435 intralipid Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000020796 long term synaptic depression Effects 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000003050 macronutrient Effects 0.000 description 1
- 235000021073 macronutrients Nutrition 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000002609 medium Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000013557 residual solvent Chemical group 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000005586 smoking cessation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 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
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000004462 vestibulo-ocular reflex Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98129407P | 2007-10-19 | 2007-10-19 | |
| PCT/SE2008/051170 WO2009051556A1 (en) | 2007-10-19 | 2008-10-17 | Tetrazole derivatives as modulators of metabotropic glutamate receptors (mglurs) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011500673A true JP2011500673A (ja) | 2011-01-06 |
| JP2011500673A5 JP2011500673A5 (enExample) | 2011-11-24 |
Family
ID=40567640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010529900A Pending JP2011500673A (ja) | 2007-10-19 | 2008-10-17 | 代謝調節型グルタミン酸受容体（ｍｇｌｕｒｓ）の調節因子としてのテトラゾール誘導体 |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US7960422B2 (enExample) |
| EP (1) | EP2231647A4 (enExample) |
| JP (1) | JP2011500673A (enExample) |
| KR (1) | KR20100090777A (enExample) |
| CN (1) | CN101896480A (enExample) |
| AR (1) | AR068921A1 (enExample) |
| AU (1) | AU2008312055A1 (enExample) |
| BR (1) | BRPI0818448A2 (enExample) |
| CA (1) | CA2703425A1 (enExample) |
| CL (1) | CL2008003085A1 (enExample) |
| CO (1) | CO6321281A2 (enExample) |
| CR (1) | CR11376A (enExample) |
| DO (1) | DOP2010000119A (enExample) |
| EA (1) | EA201000654A1 (enExample) |
| IL (1) | IL204958A0 (enExample) |
| MX (1) | MX2010004272A (enExample) |
| PE (1) | PE20090875A1 (enExample) |
| TW (1) | TW200934771A (enExample) |
| UY (1) | UY31403A1 (enExample) |
| WO (1) | WO2009051556A1 (enExample) |
| ZA (1) | ZA201002694B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1847543A1 (de) | 2006-04-19 | 2007-10-24 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dihydrothienopyrimidine zur Behandlung von entzündlichen Erkrankungen |
| RU2500681C2 (ru) | 2007-10-19 | 2013-12-10 | Берингер Ингельхайм Интернациональ Гмбх | Замещенные гетероциклом пиперазинодигидротиенопиримидины |
| SI2610258T1 (sl) | 2007-10-19 | 2014-12-31 | Boehringer Ingelheim International Gmbh | Substituirani piperidino-dihidrotienopirimidini |
| EP2215093B1 (de) | 2007-10-19 | 2011-12-14 | Boehringer Ingelheim International GmbH | Neue piperazino-dihydrothienopyrimidin-derivate |
| MY154000A (en) | 2008-09-22 | 2015-04-30 | Cayman Chem Co | Multiheteroaryl compounds as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases |
| EP2379531A1 (en) * | 2008-12-18 | 2011-10-26 | AstraZeneca AB | Processes for the manufacture of 3-{4-methyl-5- [ (ir) -1- (2- (3-methylphenyl) -2h-tetrazol-5-yl) -ethoxy]-4h- [1,2, 4]triazol-3-yl} -pyridine, 4-methyl-3-methylthio-5- (3- pyridyl)-l,2,4-triazole, and (ir) -1- [2- (3-methylphenyl) -2h- tetrazol-5-yl]ethanol |
| EP2438052A1 (en) * | 2009-06-05 | 2012-04-11 | Oslo University Hospital HF | Azole derivatives as wtn pathway inhibitors |
| CN103429583A (zh) | 2010-12-08 | 2013-12-04 | 奥斯陆大学医院公司 | 作为wnt信号通路抑制剂的三唑衍生物 |
| EA201391348A8 (ru) | 2011-03-18 | 2014-11-28 | Новартис Аг | КОМБИНАЦИИ АКТИВАТОРОВ АЛЬФА-7 НИКОТИНОВОГО АЦЕТИЛХОЛИНОВОГО РЕЦЕПТОРА И АНТАГОНИСТОВ mGluR5, ПРЕДНАЗНАЧЕННЫЕ ДЛЯ ПРИМЕНЕНИЯ ПРИ ВЫЗВАННОЙ ДОПАМИНОМ ДИСКИНЕЗИИ, СВЯЗАННОЙ С БОЛЕЗНЬЮ ПАРКИНСОНА |
| US9802954B2 (en) | 2011-08-24 | 2017-10-31 | Boehringer Ingelheim International Gmbh | Piperidino-dihydrothienopyrimidine sulfoxides and their use for treating COPD and asthma |
| US20130059866A1 (en) | 2011-08-24 | 2013-03-07 | Boehringer Ingelheim International Gmbh | Novel piperidino-dihydrothienopyrimidine sulfoxides and their use for treating copd and asthma |
| CN106032377A (zh) * | 2015-03-12 | 2016-10-19 | 天津药物研究院有限公司 | 四氮唑类urat1抑制剂、制备方法及其在高尿酸血症和痛风治疗上的用途 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005077345A1 (en) * | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
| JP2006503009A (ja) * | 2002-08-09 | 2006-01-26 | アストラゼネカ アクチボラグ | 代謝調節型グルタミン酸受容体−５の調節因子としての１，２，４−オキサジアゾール類 |
| WO2007040982A1 (en) * | 2005-09-29 | 2007-04-12 | Astrazeneca Ab | 5- (phenylisoxazolylethoxy) -triazol- 3 -yl substituted pyridine compounds for the treatment of neurological, psychiatric or pain disorders |
| JP2007523168A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | 追加の複素多環式化合物及びそれらの代謝調節型グルタミン酸受容体アンタゴニストとしての使用 |
| JP2007523178A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | 代謝型グルタメート受容体アンタゴニストとしてのトリアゾール化合物およびそれらの使用 |
| JP2007523182A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | テトラゾール化合物及び代謝共役型グルタミン酸受容体アンタゴニストとしてのそれらの使用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4663332A (en) * | 1985-10-10 | 1987-05-05 | Hoffman-La Roche Inc. | 5-substituted N-alkylated tetrazoles |
| US5492919A (en) | 1991-08-03 | 1996-02-20 | Smithkline Beecham P.L.C. | 5-HT4 receptor antagonists |
| DE10023430A1 (de) | 2000-05-12 | 2001-11-15 | Bayer Ag | Substituierte N-Benzoyl-N'-(tetrazolylphenyl)-harnstoffe |
| GB0115862D0 (en) | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| GB0121033D0 (en) | 2001-08-30 | 2001-10-24 | Novartis Ag | Organic compounds |
| CA2462289C (en) | 2001-10-04 | 2010-02-23 | Nicholas D. Cosford | Heteroaryl substituted tetrazole modulators of metabotropic glutamate receptor-5 |
| EP1485093B1 (en) | 2002-03-12 | 2010-11-03 | Merck Sharp & Dohme Corp. | Di-aryl substituted tetrazole modulators of metabotropic glutamate receptor-5 |
| SG149900A1 (en) | 2004-02-18 | 2009-02-27 | Astrazeneca Ab | Polyheterocyclic compounds and their use as metabotropic glutamate receptor antagonists |
| TW200811157A (en) | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators I |
| TW200811156A (en) | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators IV |
-
2008
- 2008-10-17 BR BRPI0818448 patent/BRPI0818448A2/pt not_active IP Right Cessation
- 2008-10-17 UY UY31403A patent/UY31403A1/es unknown
- 2008-10-17 EA EA201000654A patent/EA201000654A1/ru unknown
- 2008-10-17 MX MX2010004272A patent/MX2010004272A/es not_active Application Discontinuation
- 2008-10-17 TW TW097139967A patent/TW200934771A/zh unknown
- 2008-10-17 EP EP08840285A patent/EP2231647A4/en not_active Withdrawn
- 2008-10-17 CA CA2703425A patent/CA2703425A1/en not_active Abandoned
- 2008-10-17 CL CL2008003085A patent/CL2008003085A1/es unknown
- 2008-10-17 WO PCT/SE2008/051170 patent/WO2009051556A1/en not_active Ceased
- 2008-10-17 PE PE2008001783A patent/PE20090875A1/es not_active Application Discontinuation
- 2008-10-17 AU AU2008312055A patent/AU2008312055A1/en not_active Abandoned
- 2008-10-17 CN CN2008801179810A patent/CN101896480A/zh active Pending
- 2008-10-17 JP JP2010529900A patent/JP2011500673A/ja active Pending
- 2008-10-17 AR ARP080104548A patent/AR068921A1/es unknown
- 2008-10-17 US US12/285,988 patent/US7960422B2/en not_active Expired - Fee Related
- 2008-10-17 KR KR1020107010834A patent/KR20100090777A/ko not_active Withdrawn
-
2010
- 2010-04-08 IL IL204958A patent/IL204958A0/en unknown
- 2010-04-16 ZA ZA2010/02694A patent/ZA201002694B/en unknown
- 2010-04-19 CR CR11376A patent/CR11376A/es not_active Application Discontinuation
- 2010-04-19 DO DO2010000119A patent/DOP2010000119A/es unknown
- 2010-04-28 CO CO10050285A patent/CO6321281A2/es not_active Application Discontinuation
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006503009A (ja) * | 2002-08-09 | 2006-01-26 | アストラゼネカ アクチボラグ | 代謝調節型グルタミン酸受容体−５の調節因子としての１，２，４−オキサジアゾール類 |
| WO2005077345A1 (en) * | 2004-02-03 | 2005-08-25 | Astrazeneca Ab | Compounds for the treatment of gastro-esophageal reflux disease |
| JP2007523168A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | 追加の複素多環式化合物及びそれらの代謝調節型グルタミン酸受容体アンタゴニストとしての使用 |
| JP2007523178A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | 代謝型グルタメート受容体アンタゴニストとしてのトリアゾール化合物およびそれらの使用 |
| JP2007523182A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | テトラゾール化合物及び代謝共役型グルタミン酸受容体アンタゴニストとしてのそれらの使用 |
| WO2007040982A1 (en) * | 2005-09-29 | 2007-04-12 | Astrazeneca Ab | 5- (phenylisoxazolylethoxy) -triazol- 3 -yl substituted pyridine compounds for the treatment of neurological, psychiatric or pain disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| UY31403A1 (es) | 2009-05-29 |
| EP2231647A4 (en) | 2011-08-31 |
| AR068921A1 (es) | 2009-12-16 |
| PE20090875A1 (es) | 2009-08-08 |
| TW200934771A (en) | 2009-08-16 |
| DOP2010000119A (es) | 2010-05-31 |
| BRPI0818448A2 (pt) | 2015-05-12 |
| AU2008312055A1 (en) | 2009-04-23 |
| CR11376A (es) | 2010-07-19 |
| EA201000654A1 (ru) | 2010-12-30 |
| US20090131454A1 (en) | 2009-05-21 |
| ZA201002694B (en) | 2011-03-30 |
| EP2231647A1 (en) | 2010-09-29 |
| CN101896480A (zh) | 2010-11-24 |
| MX2010004272A (es) | 2010-04-30 |
| CO6321281A2 (es) | 2011-09-20 |
| IL204958A0 (en) | 2010-11-30 |
| KR20100090777A (ko) | 2010-08-17 |
| US7960422B2 (en) | 2011-06-14 |
| WO2009051556A1 (en) | 2009-04-23 |
| CL2008003085A1 (es) | 2009-10-09 |
| CA2703425A1 (en) | 2009-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7476684B2 (en) | Compounds for the treatment of neurological, psychiatric or pain disorders | |
| US7960422B2 (en) | Pharmaceutically active compounds containing tetrazolyl and triazolyl rings | |
| US7772235B2 (en) | mGluR5 modulators | |
| US20110166155A1 (en) | Substituted Isoindolones and Their Use as Metabotropic Glutamate Receptor Potentiators | |
| JP2009536211A (ja) | Ｍｇｌｕｒ５モジュレーターｉｉｉ | |
| KR20090009952A (ko) | Ｍｇｌｕｒ５ 조절제 ｉ | |
| JP2009536214A (ja) | 縮合複素環化合物及びｍｇｌｕｒ５モジュレーターとしてのその使用 | |
| US20090111824A1 (en) | Amide linked heteroaromatic derivatives as modulators of mglur5 | |
| JP2009536212A (ja) | 多環式複素環化合物及び代謝調節型グルタミン酸５受容体の調節剤としてのその使用 | |
| JP2009536213A (ja) | 縮合複素環化合物及びｍｇｌｕｒ５モジュレーターとしてのその使用 | |
| JP2009536210A (ja) | Ｍｇｌｕｒ５モジュレーターｉｉ | |
| US20090048303A1 (en) | Indole-2-carboxamidine derivatives as nmda receptor antago | |
| JP2011500798A (ja) | ｍＧｌｕＲ５のモジュレーターとしてのアミノ１，２，４−トリアゾール誘導体 | |
| HU226977B1 (en) | Kynurenic acid amide derivatives, pharmaceutical compositions containing them and process for producing them | |
| US20090111822A1 (en) | 1,2,3-triazole pyrrolidine derivatives as modulators of mglur5 | |
| US20100273805A1 (en) | Sulphide bridged derivatives as modulators of mglur5 733 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111007 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111007 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130820 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140311 |