NO329038B1 - Forbindelser med GLyT-1-transport inhiberende aktivitet, farmasoytisk preparat, anvendelse samt fremgangsmate for fremstilling - Google Patents
Forbindelser med GLyT-1-transport inhiberende aktivitet, farmasoytisk preparat, anvendelse samt fremgangsmate for fremstilling Download PDFInfo
- Publication number
- NO329038B1 NO329038B1 NO20033634A NO20033634A NO329038B1 NO 329038 B1 NO329038 B1 NO 329038B1 NO 20033634 A NO20033634 A NO 20033634A NO 20033634 A NO20033634 A NO 20033634A NO 329038 B1 NO329038 B1 NO 329038B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- thienyl
- sarcosine
- prop
- compound
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 113
- 238000000034 method Methods 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
- 230000002401 inhibitory effect Effects 0.000 title description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000011282 treatment Methods 0.000 claims abstract description 7
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 80
- 108010077895 Sarcosine Proteins 0.000 claims description 40
- 229940043230 sarcosine Drugs 0.000 claims description 40
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims description 23
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- CLNBFFJOAIHNHT-LSCVHKIXSA-N 2-[[(z)-3-[4-(furan-2-yl)phenyl]-3-thiophen-3-ylprop-2-enyl]-methylazaniumyl]acetate Chemical compound C=1C=C(C=2OC=CC=2)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 CLNBFFJOAIHNHT-LSCVHKIXSA-N 0.000 claims description 11
- JJVNEALISXUBNM-MSXFZWOLSA-N 2-[methyl-[(z)-3-[4-(4-propan-2-ylphenyl)phenyl]-3-thiophen-3-ylprop-2-enyl]amino]acetic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CC=C(C(=C\CN(C)CC(O)=O)\C2=CSC=C2)C=C1 JJVNEALISXUBNM-MSXFZWOLSA-N 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- HWZCEKFYJQGDBJ-JJFYIABZSA-N 2-[methyl-[(z)-3-(2-methylphenyl)-3-(4-thiophen-3-ylphenyl)prop-2-enyl]amino]acetic acid Chemical group C=1C=CC=C(C)C=1C(=C/CN(C)CC(O)=O)\C(C=C1)=CC=C1C=1C=CSC=1 HWZCEKFYJQGDBJ-JJFYIABZSA-N 0.000 claims description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- FBKAMCAARSKHRU-YVNNLAQVSA-N 2-[[(z)-3-[4-(3-methoxyphenyl)phenyl]-3-thiophen-3-ylprop-2-enyl]-methylamino]acetic acid Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)C(=C\CN(C)CC(O)=O)\C2=CSC=C2)=C1 FBKAMCAARSKHRU-YVNNLAQVSA-N 0.000 claims description 7
- VZUOXQPNRZLGNJ-YVNNLAQVSA-N 2-[methyl-[(z)-3-[4-(3-methylphenyl)phenyl]-3-thiophen-3-ylprop-2-enyl]amino]acetic acid Chemical compound C=1C=C(C=2C=C(C)C=CC=2)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 VZUOXQPNRZLGNJ-YVNNLAQVSA-N 0.000 claims description 7
- FTQWYMOYJRLUFC-LSCVHKIXSA-N 2-[methyl-[(z)-3-thiophen-2-yl-3-(4-thiophen-3-ylphenyl)prop-2-enyl]amino]acetic acid Chemical compound C=1C=C(C2=CSC=C2)C=CC=1C(=C/CN(C)CC(O)=O)/C1=CC=CS1 FTQWYMOYJRLUFC-LSCVHKIXSA-N 0.000 claims description 7
- VIACDEZYJNEJHA-LSCVHKIXSA-N 2-[methyl-[(z)-3-thiophen-3-yl-3-(4-thiophen-2-ylphenyl)prop-2-enyl]amino]acetic acid Chemical compound C=1C=C(C=2SC=CC=2)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 VIACDEZYJNEJHA-LSCVHKIXSA-N 0.000 claims description 7
- SRUROZLXEFMFKB-SWNXQHNESA-N 2-[methyl-[(z)-3-thiophen-3-yl-3-(4-thiophen-3-ylphenyl)prop-2-enyl]azaniumyl]acetate Chemical compound C=1C=C(C2=CSC=C2)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 SRUROZLXEFMFKB-SWNXQHNESA-N 0.000 claims description 7
- OHYZEWIWDWQNHJ-NKVSQWTQSA-N 2-[methyl-[(z)-3-thiophen-3-yl-3-[4-[3-(trifluoromethoxy)phenyl]phenyl]prop-2-enyl]amino]acetic acid Chemical compound C=1C=C(C=2C=C(OC(F)(F)F)C=CC=2)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 OHYZEWIWDWQNHJ-NKVSQWTQSA-N 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- OWMNRPVXVPPJAE-AFPJDJCSSA-N 2-[[(z)-3-[4-(3-cyanophenyl)phenyl]-3-thiophen-3-ylprop-2-enyl]-methylamino]acetic acid Chemical compound C=1C=C(C=2C=C(C=CC=2)C#N)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 OWMNRPVXVPPJAE-AFPJDJCSSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- QENGPZGAWFQWCZ-UHFFFAOYSA-N Methylthiophene Natural products CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000036640 Asperger disease Diseases 0.000 claims description 2
- 201000006062 Asperger syndrome Diseases 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 208000020706 Autistic disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 claims description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
- 201000007197 atypical autism Diseases 0.000 claims description 2
- 239000004327 boric acid Substances 0.000 claims description 2
- 208000024825 childhood disintegrative disease Diseases 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 2
- 239000003054 catalyst Substances 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 150000001543 aryl boronic acids Chemical class 0.000 claims 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- MYKMOIQAHCMLIR-UHFFFAOYSA-N tert-butyl 2-(methylamino)acetate Chemical compound CNCC(=O)OC(C)(C)C MYKMOIQAHCMLIR-UHFFFAOYSA-N 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 abstract description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 64
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 58
- 101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 34
- 102100023145 Sodium- and chloride-dependent glycine transporter 1 Human genes 0.000 description 32
- 239000004471 Glycine Substances 0.000 description 30
- 239000000543 intermediate Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 14
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- -1 alkyl radical Chemical class 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 230000032258 transport Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000003446 ligand Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- GLMGKYSZOXAQHP-UUASQNMZSA-N 2-[[(z)-3-(4-bromophenyl)-3-thiophen-3-ylprop-2-enyl]-methylamino]acetic acid Chemical compound C=1C=C(Br)C=CC=1C(=C/CN(C)CC(O)=O)/C=1C=CSC=1 GLMGKYSZOXAQHP-UUASQNMZSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000011714 Glycine Receptors Human genes 0.000 description 9
- 108010076533 Glycine Receptors Proteins 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002858 neurotransmitter agent Substances 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 7
- BPSMTWSSJJLRQR-WDZFZDKYSA-N 2-[[(z)-3-(4-bromophenyl)-3-iodoprop-2-enyl]-methylamino]acetic acid Chemical compound OC(=O)CN(C)C\C=C(/I)C1=CC=C(Br)C=C1 BPSMTWSSJJLRQR-WDZFZDKYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000008351 acetate buffer Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 210000000278 spinal cord Anatomy 0.000 description 6
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 6
- 108010078791 Carrier Proteins Proteins 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 210000003414 extremity Anatomy 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 210000000225 synapse Anatomy 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 101710083167 Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 4
- 102100028886 Sodium- and chloride-dependent glycine transporter 2 Human genes 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- YCXWXRCTQHWFAM-UITAMQMPSA-N (z)-3-(4-bromophenyl)-3-iodoprop-2-en-1-ol Chemical compound OC\C=C(/I)C1=CC=C(Br)C=C1 YCXWXRCTQHWFAM-UITAMQMPSA-N 0.000 description 3
- JNDDPQZHJKAPGS-WQRHYEAKSA-N 2-[[(z)-3-(4-bromophenyl)-3-(2-methylphenyl)prop-2-enyl]-methylamino]acetic acid Chemical compound C=1C=CC=C(C)C=1C(=C/CN(C)CC(O)=O)\C1=CC=C(Br)C=C1 JNDDPQZHJKAPGS-WQRHYEAKSA-N 0.000 description 3
- XXVUZDYGEDBOHT-UHFFFAOYSA-N 3-(4-bromophenyl)prop-2-yn-1-ol Chemical compound OCC#CC1=CC=C(Br)C=C1 XXVUZDYGEDBOHT-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 3
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 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 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000027928 long-term synaptic potentiation Effects 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229960005453 strychnine Drugs 0.000 description 3
- 230000005062 synaptic transmission Effects 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 2
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 2
- WCFVCJIDEVPAPU-ZSOIEALJSA-N 2-[[(z)-3-(4-bromophenyl)-3-thiophen-2-ylprop-2-enyl]-methylamino]acetic acid Chemical compound C=1C=C(Br)C=CC=1C(=C/CN(C)CC(O)=O)/C1=CC=CS1 WCFVCJIDEVPAPU-ZSOIEALJSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 101000631937 Homo sapiens Sodium- and chloride-dependent glycine transporter 2 Proteins 0.000 description 2
- 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 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000002740 Muscle Rigidity Diseases 0.000 description 2
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 2
- 208000012202 Pervasive developmental disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 206010042008 Stereotypy 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
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000036982 action potential Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000010338 boric acid Nutrition 0.000 description 2
- 125000005619 boric acid group Chemical class 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010304 firing Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 150000002332 glycine derivatives Chemical class 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000008101 lactose 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
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- HTGQCLJTWPSFNL-UHFFFAOYSA-N (2-methylphenoxy)boronic acid Chemical compound CC1=CC=CC=C1OB(O)O HTGQCLJTWPSFNL-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 1
- KBQNNOCVJFDHSC-UHFFFAOYSA-N (3-methylphenoxy)boronic acid Chemical compound CC1=CC=CC(OB(O)O)=C1 KBQNNOCVJFDHSC-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- MOOOGTOEKZWEJA-UHFFFAOYSA-N (3-methylthiophen-2-yl)boronic acid Chemical compound CC=1C=CSC=1B(O)O MOOOGTOEKZWEJA-UHFFFAOYSA-N 0.000 description 1
- IAEUFBDMVKQCLU-UHFFFAOYSA-N (4-propan-2-ylphenyl)boronic acid Chemical compound CC(C)C1=CC=C(B(O)O)C=C1 IAEUFBDMVKQCLU-UHFFFAOYSA-N 0.000 description 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
- 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 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- JCDPJKRSPNGOTB-UHFFFAOYSA-N 2-[tert-butyl(methyl)amino]acetic acid Chemical compound CC(C)(C)N(C)CC(O)=O JCDPJKRSPNGOTB-UHFFFAOYSA-N 0.000 description 1
- WBSZZKMQWAVIIV-UHFFFAOYSA-N 2-[tert-butyl(methyl)amino]acetic acid;hydrochloride Chemical compound Cl.CC(C)(C)N(C)CC(O)=O WBSZZKMQWAVIIV-UHFFFAOYSA-N 0.000 description 1
- LPWVUDLZUVBQGP-DHZHZOJOSA-N 3-[(e)-2-carboxy-2-phenylethenyl]-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1/C=C(C(=O)O)\C1=CC=CC=C1 LPWVUDLZUVBQGP-DHZHZOJOSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 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
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000031872 Body Remains Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 102000011045 Chloride Channels Human genes 0.000 description 1
- 108010062745 Chloride Channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 206010008796 Chromaturia Diseases 0.000 description 1
- 208000034657 Convalescence Diseases 0.000 description 1
- 206010011703 Cyanosis Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 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 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000684936 Homo sapiens Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027646 Miosis Diseases 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000011644 Neurologic Gait disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102000005665 Neurotransmitter Transport Proteins Human genes 0.000 description 1
- 108010084810 Neurotransmitter Transport Proteins Proteins 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 206010035039 Piloerection Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- UWDFWVLAHRQSKK-UHFFFAOYSA-N [3-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(OC(F)(F)F)=C1 UWDFWVLAHRQSKK-UHFFFAOYSA-N 0.000 description 1
- WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
- QOKMIHKIMQNRES-UHFFFAOYSA-L [Cl-].[Cl-].[Cr++]Cc1ccccc1 Chemical compound [Cl-].[Cl-].[Cr++]Cc1ccccc1 QOKMIHKIMQNRES-UHFFFAOYSA-L 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- HVNPFQOMBNYVMB-UHFFFAOYSA-N butyl 2-(methylamino)acetate Chemical compound CCCCOC(=O)CNC HVNPFQOMBNYVMB-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 208000001936 exophthalmos Diseases 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000009539 inhibitory neurotransmission Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000005371 pilomotor reflex Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000012501 relaxation of skeletal muscle Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 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
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 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
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- A61P25/14—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
- A61P25/18—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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Epoxy Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26924101P | 2001-02-16 | 2001-02-16 | |
| PCT/CA2002/000176 WO2002066456A2 (en) | 2001-02-16 | 2002-02-15 | Thiophene substituted amine derivatives as glyt-1 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20033634D0 NO20033634D0 (no) | 2003-08-15 |
| NO20033634L NO20033634L (no) | 2003-10-08 |
| NO329038B1 true NO329038B1 (no) | 2010-08-02 |
Family
ID=23026417
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20033634A NO329038B1 (no) | 2001-02-16 | 2003-08-15 | Forbindelser med GLyT-1-transport inhiberende aktivitet, farmasoytisk preparat, anvendelse samt fremgangsmate for fremstilling |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US6667336B2 (sk) |
| EP (1) | EP1368336B9 (sk) |
| JP (2) | JP2004523548A (sk) |
| KR (1) | KR100900020B1 (sk) |
| CN (1) | CN1219776C (sk) |
| AT (1) | ATE327986T1 (sk) |
| AU (1) | AU2002235682C1 (sk) |
| BG (1) | BG108164A (sk) |
| BR (1) | BR0207307A (sk) |
| CA (1) | CA2438367A1 (sk) |
| CY (1) | CY1105529T1 (sk) |
| CZ (1) | CZ20032503A3 (sk) |
| DE (1) | DE60211866T2 (sk) |
| DK (1) | DK1368336T3 (sk) |
| EA (1) | EA006636B1 (sk) |
| EE (1) | EE05329B1 (sk) |
| ES (1) | ES2266446T3 (sk) |
| HK (1) | HK1061025A1 (sk) |
| HR (1) | HRP20030696A2 (sk) |
| HU (1) | HUP0303185A3 (sk) |
| IL (1) | IL157194A (sk) |
| MX (1) | MXPA03007309A (sk) |
| NO (1) | NO329038B1 (sk) |
| NZ (1) | NZ527695A (sk) |
| PL (1) | PL365024A1 (sk) |
| PT (1) | PT1368336E (sk) |
| SI (1) | SI1368336T1 (sk) |
| SK (1) | SK287304B6 (sk) |
| UA (1) | UA75114C2 (sk) |
| WO (1) | WO2002066456A2 (sk) |
| ZA (1) | ZA200307201B (sk) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6191165B1 (en) * | 1996-05-31 | 2001-02-20 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| DK1830833T3 (da) * | 2004-12-16 | 2010-05-17 | Janssen Pharmaceutica Nv | Kombination af en glycintransportør (GLyT1) inhibitor og et antipsykotikum til behandling af symptomer på schizofreni samt dens fremstilling og anvendelse deraf |
| US20090253918A1 (en) * | 2006-10-02 | 2009-10-08 | Janssen Pharmaceuticals, N.V. | Novel intermediate for glyt1 inhibitor |
| WO2008065500A2 (en) * | 2006-11-30 | 2008-06-05 | Pfizer Products Inc. | Heteroaryl amides as type i glycine transport inhibitors |
| CN103374057B (zh) * | 2012-04-16 | 2015-08-19 | 中国医药集团总公司四川抗菌素工业研究所 | 一种对甘氨酸转运子具有抑制活性的化合物 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3050800C2 (sk) | 1979-03-22 | 1989-06-22 | Continental Pharma Inc., Bruessel/Bruxelles, Be | |
| BE885303A (fr) | 1980-09-19 | 1981-03-19 | Continental Pharma | Glycinamides |
| US4383999A (en) | 1981-05-26 | 1983-05-17 | Smithkline Beckman Corporation | Inhibition of GABA uptake by N-substituted azaheterocyclic carboxylic acids and their esters |
| AU552050B2 (en) | 1981-05-26 | 1986-05-22 | Smithkline Beckman Corporation | N-substituted azeheterocyclic carboxylic acids and their esters |
| US4514414A (en) | 1982-10-25 | 1985-04-30 | Smithkline Beckman Corporation | N-Substituted pyrrolidineacetic acids and their esters |
| DK288385D0 (da) | 1985-06-26 | 1985-06-26 | Novo Industri As | Aminosyrederivater |
| US4772615A (en) | 1985-11-08 | 1988-09-20 | Warner-Lambert Company | Various N-substituted 3-piperidine carboxylic acids or N-substituted 3-pyridinecarboxylic acids and derivatives thereof |
| FI864246A (fi) | 1985-11-08 | 1987-05-09 | Warner Lambert Co | N-substituerade 3-piperidin- eller 3-pyridinkarboxylsyror samt deras derivat. |
| EP0231996B1 (en) | 1986-01-07 | 1993-10-06 | Novo Nordisk A/S | Novel amino acid derivatives |
| JPH02129158A (ja) | 1988-11-07 | 1990-05-17 | Nippon Steel Corp | 光学活性なグリシン誘導体及びその製造方法 |
| IE913279A1 (en) * | 1990-09-26 | 1992-04-08 | Astra Ab | (2-Thienyl)alkylamine Derivatives Having Neuroprotective¹Properties |
| ES2036926B1 (es) | 1991-08-08 | 1994-01-16 | Uriach & Cia Sa J | "procedimiento para la obtencion de derivados de la (2-alquil-3-piridil)metilpiperazina". |
| DK0871440T3 (da) | 1995-12-07 | 2006-07-10 | Daniel C Javitt | Behandling af negative og kognitive symptomer på skizofreni med glycinoptagelsesantagonister |
| SK285854B6 (sk) * | 1996-05-31 | 2007-09-06 | Allelix Neuroscience Inc. | Substituovaný amín, spôsoby jeho prípravy a použitie, farmaceutický prostriedok a jeho použitie |
| US6191165B1 (en) | 1996-05-31 | 2001-02-20 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
| DE69734215T2 (de) * | 1996-07-22 | 2006-06-29 | Novo Nordisk A/S | Verbindungen mit Wachstumshormon-freisetzenden Eigenschaften |
| DE69819206T2 (de) * | 1998-01-09 | 2004-04-15 | Pfizer Inc. | Matrixmetalloproteinaseinhibitoren |
| US6103743A (en) * | 1999-08-06 | 2000-08-15 | Allelix Neuroscience, Inc. | Unsaturated amino acid derivatives |
-
2002
- 2002-02-15 CZ CZ20032503A patent/CZ20032503A3/cs unknown
- 2002-02-15 PL PL02365024A patent/PL365024A1/xx unknown
- 2002-02-15 PT PT02702186T patent/PT1368336E/pt unknown
- 2002-02-15 MX MXPA03007309A patent/MXPA03007309A/es active IP Right Grant
- 2002-02-15 KR KR1020037010609A patent/KR100900020B1/ko not_active IP Right Cessation
- 2002-02-15 US US10/077,579 patent/US6667336B2/en not_active Expired - Fee Related
- 2002-02-15 AT AT02702186T patent/ATE327986T1/de not_active IP Right Cessation
- 2002-02-15 SI SI200230381T patent/SI1368336T1/sl unknown
- 2002-02-15 ES ES02702186T patent/ES2266446T3/es not_active Expired - Lifetime
- 2002-02-15 JP JP2002565971A patent/JP2004523548A/ja active Pending
- 2002-02-15 CN CNB028050819A patent/CN1219776C/zh not_active Expired - Fee Related
- 2002-02-15 AU AU2002235682A patent/AU2002235682C1/en not_active Ceased
- 2002-02-15 NZ NZ527695A patent/NZ527695A/en unknown
- 2002-02-15 BR BR0207307-2A patent/BR0207307A/pt not_active IP Right Cessation
- 2002-02-15 DE DE60211866T patent/DE60211866T2/de not_active Expired - Lifetime
- 2002-02-15 SK SK1144-2003A patent/SK287304B6/sk not_active IP Right Cessation
- 2002-02-15 CA CA002438367A patent/CA2438367A1/en not_active Abandoned
- 2002-02-15 WO PCT/CA2002/000176 patent/WO2002066456A2/en active IP Right Grant
- 2002-02-15 EP EP02702186A patent/EP1368336B9/en not_active Expired - Lifetime
- 2002-02-15 EE EEP200300394A patent/EE05329B1/xx not_active IP Right Cessation
- 2002-02-15 HU HU0303185A patent/HUP0303185A3/hu unknown
- 2002-02-15 EA EA200300900A patent/EA006636B1/ru not_active IP Right Cessation
- 2002-02-15 UA UA2003087630A patent/UA75114C2/uk unknown
- 2002-02-15 DK DK02702186T patent/DK1368336T3/da active
-
2003
- 2003-07-31 IL IL157194A patent/IL157194A/en not_active IP Right Cessation
- 2003-08-15 NO NO20033634A patent/NO329038B1/no not_active IP Right Cessation
- 2003-09-01 HR HR20030696A patent/HRP20030696A2/xx not_active Application Discontinuation
- 2003-09-09 BG BG108164A patent/BG108164A/xx unknown
- 2003-09-15 ZA ZA200307201A patent/ZA200307201B/en unknown
-
2004
- 2004-06-08 HK HK04104072A patent/HK1061025A1/xx not_active IP Right Cessation
-
2006
- 2006-08-22 CY CY20061101160T patent/CY1105529T1/el unknown
-
2009
- 2009-11-09 JP JP2009255663A patent/JP2010059182A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2438185T3 (es) | Derivados de sulfonamida farmacéuticamente activos portadores de restos lipófilos e ionizables como inhibidores de proteína quinasas Jun | |
| US6525085B2 (en) | Diaryl-enynes | |
| WO2001081308A2 (en) | Aminopiperidines for use as glyt-1 inhibitors | |
| NO324792B1 (no) | Farmasoytisk aktive sulfonamidderivater | |
| DK170332B1 (da) | Farmakologisk aktive substituerede benzamider, fremgangsmåde til fremstilling deraf og et farmaceutisk præparat heraf | |
| JP2010059182A (ja) | ＧｌｙＴ−１阻害剤 | |
| US7652064B2 (en) | AMPA receptor potentiators | |
| AU2002235682A1 (en) | Thiophene substituted amine derivatives as GLYT-1 inhibitors | |
| AU780922C (en) | Diaryl-enynes | |
| CZ272599A3 (cs) | Sulfonamidové deriváty |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CREP | Change of representative |
Representative=s name: ZACCO NORWAY AS, POSTBOKS 2003 VIKA, 0125 OSLO, NO |
|
| MM1K | Lapsed by not paying the annual fees |