JP2002526408A - 疼痛および不安の処置のためのｍｇｌｕｒ５アンタゴニスト - Google Patents
疼痛および不安の処置のためのｍｇｌｕｒ５アンタゴニストInfo
- Publication number
- JP2002526408A JP2002526408A JP2000573360A JP2000573360A JP2002526408A JP 2002526408 A JP2002526408 A JP 2002526408A JP 2000573360 A JP2000573360 A JP 2000573360A JP 2000573360 A JP2000573360 A JP 2000573360A JP 2002526408 A JP2002526408 A JP 2002526408A
- Authority
- JP
- Japan
- Prior art keywords
- antagonist
- mglur
- pain
- mglur5
- receptor
- 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
- 239000005557 antagonist Substances 0.000 title claims abstract description 50
- 208000002193 Pain Diseases 0.000 title claims abstract description 33
- 208000019901 Anxiety disease Diseases 0.000 title claims abstract description 17
- 230000036506 anxiety Effects 0.000 title claims abstract description 17
- 101150087728 Grm5 gene Proteins 0.000 title 1
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 title 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract description 43
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract description 43
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims abstract description 37
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims abstract description 37
- 229940124807 mGLUR antagonist Drugs 0.000 claims abstract description 24
- 230000003993 interaction Effects 0.000 claims abstract description 14
- 230000000202 analgesic effect Effects 0.000 claims abstract description 12
- 230000002093 peripheral effect Effects 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 21
- 102000005962 receptors Human genes 0.000 claims description 16
- 108020003175 receptors Proteins 0.000 claims description 16
- 210000003169 central nervous system Anatomy 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 206010065390 Inflammatory pain Diseases 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 2
- 230000004888 barrier function Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 26
- 241000700159 Rattus Species 0.000 description 15
- MTVWFVDWRVYDOR-UHFFFAOYSA-N 3,4-Dihydroxyphenylglycol Chemical compound OCC(O)C1=CC=C(O)C(O)=C1 MTVWFVDWRVYDOR-UHFFFAOYSA-N 0.000 description 10
- 208000004454 Hyperalgesia Diseases 0.000 description 10
- 210000000278 spinal cord Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- -1 cyano, ethynyl Chemical group 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- HOOWCUZPEFNHDT-UHFFFAOYSA-N 2-amino-2-(3,5-dihydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC(O)=CC(O)=C1 HOOWCUZPEFNHDT-UHFFFAOYSA-N 0.000 description 6
- 230000004064 dysfunction Effects 0.000 description 6
- 230000003040 nociceptive effect Effects 0.000 description 6
- 208000035154 Hyperesthesia Diseases 0.000 description 5
- 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 150000003839 salts Chemical group 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 230000004913 activation Effects 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000003070 anti-hyperalgesia Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000012937 correction Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 230000000917 hyperalgesic effect Effects 0.000 description 3
- 230000002631 hypothermal effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000007306 turnover Effects 0.000 description 3
- DDOQBQRIEWHWBT-VKHMYHEASA-N (2S)-2-amino-4-phosphonobutanoic acid Chemical compound OC(=O)[C@@H](N)CCP(O)(O)=O DDOQBQRIEWHWBT-VKHMYHEASA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- GQSLKBHGURRQLG-UHFFFAOYSA-N 2-[2-(3-fluorophenyl)ethynyl]-6-methylpyridine Chemical compound CC1=CC=CC(C#CC=2C=C(F)C=CC=2)=N1 GQSLKBHGURRQLG-UHFFFAOYSA-N 0.000 description 2
- VTAARTQTOOYTES-UHFFFAOYSA-N 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound OC(=O)C1(N)CCC2C(C(O)=O)C12 VTAARTQTOOYTES-UHFFFAOYSA-N 0.000 description 2
- NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-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
- 108091006146 Channels Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000007788 liquid 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
- 239000000463 material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229910052751 metal Chemical group 0.000 description 2
- 239000002184 metal Chemical group 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000005477 standard model Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- AKHBUEMSSQXMIN-UHFFFAOYSA-N 2-amino-2-(2-chloro-3-hydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC=CC(O)=C1Cl AKHBUEMSSQXMIN-UHFFFAOYSA-N 0.000 description 1
- QFKXUDHGSXTPAU-UHFFFAOYSA-N 2-methyl-6-(2-pyridin-3-ylethenyl)pyridine Chemical compound CC1=CC=CC(C=CC=2C=NC=CC=2)=N1 QFKXUDHGSXTPAU-UHFFFAOYSA-N 0.000 description 1
- KYJSGWVPWUBKGL-UHFFFAOYSA-N 2-methyl-6-(2-pyridin-3-ylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=NC=CC=2)=N1 KYJSGWVPWUBKGL-UHFFFAOYSA-N 0.000 description 1
- OONJJBQNBKMFFT-UHFFFAOYSA-N 2-methyl-6-[2-(2,3,5-trichlorophenyl)ethynyl]pyridine Chemical compound CC1=CC=CC(C#CC=2C(=C(Cl)C=C(Cl)C=2)Cl)=N1 OONJJBQNBKMFFT-UHFFFAOYSA-N 0.000 description 1
- VTMJKPGFERYGJF-ZETCQYMHSA-N 4-[(s)-amino(carboxy)methyl]benzoic acid Chemical compound OC(=O)[C@@H](N)C1=CC=C(C(O)=O)C=C1 VTMJKPGFERYGJF-ZETCQYMHSA-N 0.000 description 1
- 206010001497 Agitation Diseases 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
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 206010004663 Biliary colic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- ASNFTDCKZKHJSW-UHFFFAOYSA-N DL-Quisqualic acid Natural products OC(=O)C(N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 102100022197 Glutamate receptor ionotropic, kainate 1 Human genes 0.000 description 1
- 101710112359 Glutamate receptor ionotropic, kainate 1 Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001032845 Homo sapiens Metabotropic glutamate receptor 5 Proteins 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 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
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229920004011 Macrolon® Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
- 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
- 102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 238000011795 OF1 mouse Methods 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 101100219325 Phaseolus vulgaris BA13 gene Proteins 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- ASNFTDCKZKHJSW-REOHCLBHSA-N Quisqualic acid Chemical compound OC(=O)[C@@H](N)CN1OC(=O)NC1=O ASNFTDCKZKHJSW-REOHCLBHSA-N 0.000 description 1
- 101001032838 Rattus norvegicus Metabotropic glutamate receptor 5 Proteins 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010039670 Sciatic nerve injury Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 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
- 208000004760 Tenosynovitis Diseases 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 210000002226 anterior horn cell Anatomy 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000003461 brachial plexus Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 201000011510 cancer Diseases 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- LOCPVWIREQIGNQ-UHFFFAOYSA-N chembl88553 Chemical group CC1=CC=C(O)C(N=NC=2C=CC=CC=2)=N1 LOCPVWIREQIGNQ-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003823 glutamate receptor agonist Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011669 lister hooded rat Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
- 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
- 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 231100000243 mutagenic effect Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003906 phosphoinositides Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000003572 second messenger assay Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- SISOFUCTXZKSOQ-ZHACJKMWSA-N sib-1893 Chemical compound CC1=CC=CC(\C=C\C=2C=CC=CC=2)=N1 SISOFUCTXZKSOQ-ZHACJKMWSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000013519 translation Methods 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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61P25/18—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
- A61P25/24—Antidepressants
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9821503.1A GB9821503D0 (en) | 1998-10-02 | 1998-10-02 | Organic compounds |
| US22081398A | 1998-12-23 | 1998-12-23 | |
| US9821503.1 | 1998-12-23 | ||
| US09/220,813 | 1998-12-23 | ||
| PCT/EP1999/007239 WO2000020001A1 (en) | 1998-10-02 | 1999-09-30 | Mglur5 antagonists for the treatment of pain and anxiety |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002526408A true JP2002526408A (ja) | 2002-08-20 |
| JP2002526408A5 JP2002526408A5 (https=) | 2006-11-24 |
Family
ID=26314451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000573360A Pending JP2002526408A (ja) | 1998-10-02 | 1999-09-30 | 疼痛および不安の処置のためのｍｇｌｕｒ５アンタゴニスト |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1117403B1 (https=) |
| JP (1) | JP2002526408A (https=) |
| KR (1) | KR20010088832A (https=) |
| CN (1) | CN1187048C (https=) |
| AT (1) | ATE255894T1 (https=) |
| AU (1) | AU765644B2 (https=) |
| BR (1) | BR9914215A (https=) |
| CA (1) | CA2345137A1 (https=) |
| DE (1) | DE69913548T2 (https=) |
| DK (1) | DK1117403T3 (https=) |
| ES (1) | ES2213389T3 (https=) |
| HU (1) | HUP0200553A3 (https=) |
| ID (1) | ID29095A (https=) |
| IL (2) | IL142047A0 (https=) |
| NO (1) | NO20011440L (https=) |
| NZ (1) | NZ510743A (https=) |
| PL (1) | PL202906B1 (https=) |
| PT (1) | PT1117403E (https=) |
| RU (1) | RU2232017C2 (https=) |
| SK (1) | SK4382001A3 (https=) |
| WO (1) | WO2000020001A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008533102A (ja) * | 2005-03-18 | 2008-08-21 | ピエール・ファーブル・メディカマン | 平衡障害の治療用薬剤の製造のためのアセチル−ロイシンの使用 |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0005700D0 (en) * | 2000-03-09 | 2000-05-03 | Glaxo Group Ltd | Therapy |
| PT1345609E (pt) | 2000-12-22 | 2005-08-31 | Hoffmann La Roche | Derivados de tetra-hidro-(benzo ou tieno)-azepina-pirazina como antagonistas de mglur 1 |
| GB0128996D0 (en) | 2001-12-04 | 2002-01-23 | Novartis Ag | Organic compounds |
| SE0303418D0 (sv) * | 2003-12-17 | 2003-12-17 | Astrazeneca Ab | New use 1 |
| SE0303419D0 (sv) * | 2003-12-17 | 2003-12-17 | Astrazeneca Ab | New use 11 |
| GB0525068D0 (en) | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| DE102005062985A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte bis(hetero)aromatische N-Ethylpropiolamide und ihre Verwendung zur Herstellung von Arzneimitteln |
| ES2610508T3 (es) | 2006-11-22 | 2017-04-27 | Clinical Research Associates, Llc | Métodos para tratar el síndrome de Down, el síndrome del cromosoma X frágil y el autismo |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| US8586581B2 (en) * | 2009-12-17 | 2013-11-19 | Hoffmann-La Roche Inc | Ethynyl compounds useful for treatment of CNS disorders |
| WO2011092290A1 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| US20130058915A1 (en) | 2010-03-02 | 2013-03-07 | Children's Medica Center Corporation | Methods and compositions for treatment of angelman syndrome and autism spectrum disorders |
| WO2011150380A1 (en) | 2010-05-28 | 2011-12-01 | Xenoport, Inc. | Methods of treatment of fragile x syndrome, down's syndrome, autism and related disorders |
| US20120016021A1 (en) | 2010-07-15 | 2012-01-19 | Xenoport, Inc. | Methods of treating fragile x syndrome, down's syndrome, autism and related disorders |
| WO2012054724A1 (en) | 2010-10-21 | 2012-04-26 | Massachusetts Institute Of Technology | Methods of treating seizure disorders |
| AR086554A1 (es) | 2011-05-27 | 2014-01-08 | Novartis Ag | Derivados de la piperidina 3-espirociclica como agonistas de receptores de la ghrelina |
| EP2557183A1 (de) | 2011-08-12 | 2013-02-13 | Siemens Aktiengesellschaft | Verfahren zum Betrieb einer Konti-Glühe für die Verarbeitung eines Walzguts |
| JP2015525202A (ja) | 2012-05-03 | 2015-09-03 | ノバルティス アーゲー | グレリン受容体アゴニストとしての２，７−ジアザ−スピロ［４，５］デカ−７−イル誘導体のｌ−リンゴ酸塩およびその結晶形態 |
| LT3303316T (lt) | 2015-06-03 | 2020-05-11 | F. Hoffmann-La Roche Ag | Etinilo dariniai |
| CA3066711A1 (en) | 2017-07-31 | 2019-02-07 | Novartis Ag | Use of mavoglurant in the reduction of cocaine use or in preventing relapse into cocaine use |
| EP3459939A1 (en) | 2017-09-26 | 2019-03-27 | Pragma Therapeutics | Novel heterocyclic compounds as modulators of mglur7 |
| KR102027368B1 (ko) * | 2018-05-29 | 2019-10-01 | 서울대학교산학협력단 | 통증의 강도를 측정하는 방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2056983T3 (es) * | 1988-03-21 | 1994-10-16 | Boehringer Ingelheim Pharma | Compuestos para inhibir la biosintesis de metabolitos de acido araquidonico derivados de lipoxigenasa. |
| TW544448B (en) * | 1997-07-11 | 2003-08-01 | Novartis Ag | Pyridine derivatives |
-
1999
- 1999-09-30 EP EP99948905A patent/EP1117403B1/en not_active Revoked
- 1999-09-30 CA CA002345137A patent/CA2345137A1/en not_active Abandoned
- 1999-09-30 ES ES99948905T patent/ES2213389T3/es not_active Expired - Lifetime
- 1999-09-30 HU HU0200553A patent/HUP0200553A3/hu unknown
- 1999-09-30 AU AU61984/99A patent/AU765644B2/en not_active Ceased
- 1999-09-30 SK SK438-2001A patent/SK4382001A3/sk unknown
- 1999-09-30 RU RU2001111868/14A patent/RU2232017C2/ru not_active IP Right Cessation
- 1999-09-30 PL PL346876A patent/PL202906B1/pl not_active IP Right Cessation
- 1999-09-30 ID IDW20010730A patent/ID29095A/id unknown
- 1999-09-30 KR KR1020017004152A patent/KR20010088832A/ko not_active Ceased
- 1999-09-30 BR BR9914215-5A patent/BR9914215A/pt not_active Application Discontinuation
- 1999-09-30 PT PT99948905T patent/PT1117403E/pt unknown
- 1999-09-30 WO PCT/EP1999/007239 patent/WO2000020001A1/en not_active Ceased
- 1999-09-30 DK DK99948905T patent/DK1117403T3/da active
- 1999-09-30 DE DE69913548T patent/DE69913548T2/de not_active Revoked
- 1999-09-30 CN CNB998117110A patent/CN1187048C/zh not_active Expired - Fee Related
- 1999-09-30 JP JP2000573360A patent/JP2002526408A/ja active Pending
- 1999-09-30 IL IL14204799A patent/IL142047A0/xx active IP Right Grant
- 1999-09-30 NZ NZ510743A patent/NZ510743A/en unknown
- 1999-09-30 AT AT99948905T patent/ATE255894T1/de active
-
2001
- 2001-03-15 IL IL142047A patent/IL142047A/en not_active IP Right Cessation
- 2001-03-21 NO NO20011440A patent/NO20011440L/no unknown
Non-Patent Citations (1)
| Title |
|---|
| JPN5001019839, ＦＵＮＤＹＴＵＳ Ｍ Ｅ, ＮＥＵＲＯＲＥＰＯＲＴ, 19980309, Ｖ９Ｎ４, Ｐ７３１−７３５ * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008533102A (ja) * | 2005-03-18 | 2008-08-21 | ピエール・ファーブル・メディカマン | 平衡障害の治療用薬剤の製造のためのアセチル−ロイシンの使用 |
| JP2013173759A (ja) * | 2005-03-18 | 2013-09-05 | Pierre Fabre Medicament | 平衡障害の治療用薬剤の製造のためのアセチル−ロイシンの使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9914215A (pt) | 2001-07-03 |
| CA2345137A1 (en) | 2000-04-13 |
| NZ510743A (en) | 2003-10-31 |
| ES2213389T3 (es) | 2004-08-16 |
| NO20011440D0 (no) | 2001-03-21 |
| KR20010088832A (ko) | 2001-09-28 |
| CN1187048C (zh) | 2005-02-02 |
| NO20011440L (no) | 2001-05-15 |
| EP1117403A1 (en) | 2001-07-25 |
| EP1117403B1 (en) | 2003-12-10 |
| IL142047A0 (en) | 2002-03-10 |
| DE69913548T2 (de) | 2004-09-23 |
| AU6198499A (en) | 2000-04-26 |
| HUP0200553A2 (hu) | 2002-07-29 |
| ID29095A (id) | 2001-07-26 |
| CN1321087A (zh) | 2001-11-07 |
| PL346876A1 (en) | 2002-03-11 |
| SK4382001A3 (en) | 2001-08-06 |
| AU765644B2 (en) | 2003-09-25 |
| PT1117403E (pt) | 2004-04-30 |
| RU2232017C2 (ru) | 2004-07-10 |
| IL142047A (en) | 2007-09-20 |
| DE69913548D1 (de) | 2004-01-22 |
| HUP0200553A3 (en) | 2002-11-28 |
| WO2000020001A1 (en) | 2000-04-13 |
| PL202906B1 (pl) | 2009-08-31 |
| ATE255894T1 (de) | 2003-12-15 |
| DK1117403T3 (da) | 2004-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002526408A (ja) | 疼痛および不安の処置のためのｍｇｌｕｒ５アンタゴニスト | |
| KR20170003527A (ko) | 경구 투여용 펜토산 폴리설페이트 염의 조성물 | |
| JP2003530429A (ja) | αアドレナリン受容体活性を調節するための方法および組成物 | |
| JP2012131829A (ja) | そう痒状態の処置のためのｍｇｌｕｒ５アンタゴニストの使用 | |
| US20010056084A1 (en) | MGluR5 antagonists for the treatment of pain and anxiety | |
| JP3832229B2 (ja) | フェニルエテンスルホンアミド誘導体含有医薬 | |
| KR20190019171A (ko) | 섬유증 치료에서 사용하기 위한 wnt 억제제 | |
| AU2006230674A8 (en) | Methods for the Treatment of Synucleinopathies | |
| AU2008333220B2 (en) | Mequitazine for treating or preventing pathologies involving histamine H4 receptors | |
| RU2212237C2 (ru) | Средство для лечения нейрогенного воспаления | |
| EP2066323A2 (en) | Pharmaceutical compositions comprising combinations of an ampa/kainate antagonistic compound and an inhibitor of a multidrug resistance protein | |
| WO2006050241A1 (en) | Prostaglandin ep4 antagonists | |
| US20130203789A1 (en) | Novel Inhibitors of LYN Kinase and Methods Using Same | |
| JP2005247843A (ja) | 掻痒治療剤 | |
| HK1148667B (en) | Mequitazine for treating or preventing pathologies involving histamine h4 receptors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060927 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060927 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20091117 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100216 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100223 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100312 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100319 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100517 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100720 |