ZA200005848B - 4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. - Google Patents
4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. Download PDFInfo
- Publication number
- ZA200005848B ZA200005848B ZA200005848A ZA200005848A ZA200005848B ZA 200005848 B ZA200005848 B ZA 200005848B ZA 200005848 A ZA200005848 A ZA 200005848A ZA 200005848 A ZA200005848 A ZA 200005848A ZA 200005848 B ZA200005848 B ZA 200005848B
- Authority
- ZA
- South Africa
- Prior art keywords
- benzooxazol
- piperidin
- ethanesulfinyl
- group
- hydrogen
- Prior art date
Links
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 44
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 208000018737 Parkinson disease Diseases 0.000 claims description 13
- -1 aldehyde amine Chemical class 0.000 claims description 13
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 208000002193 Pain Diseases 0.000 claims description 9
- 208000016354 hearing loss disease Diseases 0.000 claims description 9
- 206010010904 Convulsion Diseases 0.000 claims description 8
- 206010011878 Deafness Diseases 0.000 claims description 8
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 8
- 208000006011 Stroke Diseases 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 230000010370 hearing loss Effects 0.000 claims description 8
- 231100000888 hearing loss Toxicity 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 208000000094 Chronic Pain Diseases 0.000 claims description 7
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 206010008118 cerebral infarction Diseases 0.000 claims description 6
- 208000001763 cytomegalovirus retinitis Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 102000005962 receptors Human genes 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 208000009205 Tinnitus Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 230000036461 convulsion Effects 0.000 claims description 5
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 231100000886 tinnitus Toxicity 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 208000013016 Hypoglycemia Diseases 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 claims description 3
- FCBQJNCAKZSIAH-UHFFFAOYSA-N 6-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical group C1=CC(F)=CC=C1CC1CCN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 FCBQJNCAKZSIAH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 4
- 201000007737 Retinal degeneration Diseases 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 2
- 230000004258 retinal degeneration Effects 0.000 claims 2
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims 1
- ZPZRJMIXFBHMFA-UHFFFAOYSA-N 6-[2-(4-benzyl-4-hydroxypiperidin-1-yl)ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CCC1(O)CC1=CC=CC=C1 ZPZRJMIXFBHMFA-UHFFFAOYSA-N 0.000 claims 1
- DWRLXEBQOCRDPS-UHFFFAOYSA-N 6-[2-(4-benzylpiperidin-1-yl)ethylsulfinyl]-5-chloro-3h-1,3-benzoxazol-2-one Chemical compound ClC1=CC=2NC(=O)OC=2C=C1S(=O)CCN(CC1)CCC1CC1=CC=CC=C1 DWRLXEBQOCRDPS-UHFFFAOYSA-N 0.000 claims 1
- ITCUKPJAOPKNPT-UHFFFAOYSA-N 6-[2-[4-[(4-methoxyphenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound C1=CC(OC)=CC=C1CC1CCN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 ITCUKPJAOPKNPT-UHFFFAOYSA-N 0.000 claims 1
- BAOSFSQHJIWEEW-UHFFFAOYSA-N 6-[2-[4-[(4-methylphenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound C1=CC(C)=CC=C1CC1CCN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 BAOSFSQHJIWEEW-UHFFFAOYSA-N 0.000 claims 1
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 125000006286 dichlorobenzyl group Chemical group 0.000 claims 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 claims 1
- 229960004502 levodopa Drugs 0.000 claims 1
- 102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 16
- 230000000694 effects Effects 0.000 description 13
- 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 8
- 239000005557 antagonist Substances 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- 229930195712 glutamate Natural products 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 102100022645 Glutamate receptor ionotropic, NMDA 1 Human genes 0.000 description 4
- 208000023105 Huntington disease Diseases 0.000 description 4
- 108010054235 NMDA receptor A1 Proteins 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000003492 excitotoxic effect Effects 0.000 description 4
- 231100000063 excitotoxicity Toxicity 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- ABGXADJDTPFFSZ-UHFFFAOYSA-N 4-benzylpiperidine Chemical compound C=1C=CC=CC=1CC1CCNCC1 ABGXADJDTPFFSZ-UHFFFAOYSA-N 0.000 description 3
- 206010019233 Headaches Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 241000269370 Xenopus <genus> Species 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 231100000869 headache Toxicity 0.000 description 3
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 3
- 210000000287 oocyte Anatomy 0.000 description 3
- 230000002207 retinal effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108091006146 Channels Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010027603 Migraine headaches Diseases 0.000 description 2
- 208000000060 Migraine with aura Diseases 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 208000032625 disorder of ear Diseases 0.000 description 2
- 230000002461 excitatory amino acid Effects 0.000 description 2
- 239000003257 excitatory amino acid Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000036963 noncompetitive effect Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 230000001734 parasympathetic effect Effects 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 150000003462 sulfoxides Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical class C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- BHDHBGPHCQNONZ-UHFFFAOYSA-N 6-[2-(4-benzoylpiperidin-1-yl)ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CCC1C(=O)C1=CC=CC=C1 BHDHBGPHCQNONZ-UHFFFAOYSA-N 0.000 description 1
- ISVNVERJTYNQIU-UHFFFAOYSA-N 6-[2-[4-[(2,3-difluorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound FC1=CC=CC(CC2CCN(CCS(=O)C=3C=C4OC(=O)NC4=CC=3)CC2)=C1F ISVNVERJTYNQIU-UHFFFAOYSA-N 0.000 description 1
- DGTHJLGWIBFLAI-UHFFFAOYSA-N 6-[2-[4-[(2,4-dichlorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound ClC1=CC(Cl)=CC=C1CC1CCN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 DGTHJLGWIBFLAI-UHFFFAOYSA-N 0.000 description 1
- GPQLQRXXSSFLBP-UHFFFAOYSA-N 6-[2-[4-[(2-fluorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3h-1,3-benzoxazol-2-one Chemical compound FC1=CC=CC=C1CC1CCN(CCS(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 GPQLQRXXSSFLBP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 208000024255 Audiogenic seizures Diseases 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229940127486 Competitive NMDA Receptor Antagonists Drugs 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 229940123511 Excitatory amino acid receptor antagonist Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 description 1
- 102100022626 Glutamate receptor ionotropic, NMDA 2D Human genes 0.000 description 1
- 101710195184 Glutamate receptor ionotropic, NMDA 2D Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000001393 Lathyrism Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 108010084867 N-methyl D-aspartate receptor subtype 2A Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010030043 Ocular hypertension Diseases 0.000 description 1
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- LPMRCCNDNGONCD-RITPCOANSA-N Selfotel Chemical compound OC(=O)[C@@H]1C[C@H](CP(O)(O)=O)CCN1 LPMRCCNDNGONCD-RITPCOANSA-N 0.000 description 1
- 206010040026 Sensory disturbance Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000009739 binding Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- 230000008344 brain blood flow Effects 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 238000013172 carotid endarterectomy Methods 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 201000005682 chronic closed-angle glaucoma Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000006287 difluorobenzyl group Chemical group 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001400 expression cloning Methods 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 208000027096 gram-negative bacterial infections Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 108091008757 nuclear thyroid hormone receptors Proteins 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229960004851 pergolide Drugs 0.000 description 1
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 201000006366 primary open angle glaucoma Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000016153 withdrawal disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9091498P | 1998-06-26 | 1998-06-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200005848B true ZA200005848B (en) | 2001-12-18 |
Family
ID=22224939
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200005848A ZA200005848B (en) | 1998-06-26 | 2000-10-19 | 4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. |
Country Status (28)
Country | Link |
---|---|
US (1) | US6284774B1 (fr) |
EP (1) | EP1089735B1 (fr) |
JP (1) | JP2002519322A (fr) |
KR (1) | KR20010053170A (fr) |
CN (1) | CN1304307A (fr) |
AP (1) | AP2000001949A0 (fr) |
AT (1) | ATE297207T1 (fr) |
AU (1) | AU769650B2 (fr) |
BG (1) | BG105082A (fr) |
BR (1) | BR9911575A (fr) |
CA (1) | CA2327888A1 (fr) |
DE (1) | DE69925730T2 (fr) |
EA (1) | EA200100058A1 (fr) |
EE (1) | EE200000778A (fr) |
ES (1) | ES2244201T3 (fr) |
HU (1) | HUP0102471A2 (fr) |
ID (1) | ID28005A (fr) |
IL (1) | IL138949A0 (fr) |
IS (1) | IS5667A (fr) |
NO (1) | NO20006482L (fr) |
NZ (1) | NZ508808A (fr) |
OA (1) | OA11570A (fr) |
PE (1) | PE20000728A1 (fr) |
PL (1) | PL345024A1 (fr) |
SK (1) | SK19512000A3 (fr) |
TR (1) | TR200003888T2 (fr) |
WO (1) | WO2000000197A1 (fr) |
ZA (1) | ZA200005848B (fr) |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6476041B1 (en) | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
UA73749C2 (en) * | 1999-11-01 | 2005-09-15 | Diarylenines | |
AU2001255620A1 (en) | 2000-04-26 | 2001-11-07 | Warner-Lambert Company | Cyclohexylamine derivative as subtype selective NMDA receptor antagonists |
MXPA02010863A (es) * | 2000-06-01 | 2003-03-27 | Warner Lambert Co | Derivados de ciclohexilamina como subtipo de antagonistas del receptor nmda selectivo. |
JP5079202B2 (ja) * | 2000-07-18 | 2012-11-21 | 大日本住友製薬株式会社 | セロトニン再取り込み阻害剤 |
IL145584A0 (en) * | 2000-10-02 | 2002-06-30 | Pfizer Prod Inc | Nmda nr2b antagonists for treatment |
HU227197B1 (en) | 2000-10-24 | 2010-10-28 | Richter Gedeon Nyrt | Nmda receptor antagonist carboxylic acid amide derivatives and pharmaceutical compositions containing them |
YU64303A (sh) | 2001-02-23 | 2006-05-25 | Merck & Co.Inc. | N-supstituisani nearil-heterociklični antagonisti nmda/nr2b |
JP2005506292A (ja) * | 2001-03-08 | 2005-03-03 | エモリー ユニバーシティ | pHに依存するNMDAレセプターアンタゴニスト |
US7259157B2 (en) | 2001-04-03 | 2007-08-21 | Merck & Co., Inc. | N-substituted nonaryl-heterocyclo amidyl NMDA/NR2B Antagonists |
CA2381630A1 (fr) * | 2001-04-23 | 2002-10-23 | Leonard Theodore Meltzer | Methode de prevention de la dyskinesie |
EP1409477B1 (fr) | 2001-07-24 | 2008-09-17 | Richter Gedeon NYRT | Derives de piperidine utilises en tant qu'antagonistes du recepteur n-methyl-d-aspartate (nmda) |
CA2459161A1 (fr) | 2001-08-31 | 2003-03-13 | The Rockefeller University | Activite de phosphodiesterase et regulation de la signalisation a mediation par phosphodiesterase 1-b dans le cerveau |
EP2246053B1 (fr) * | 2001-12-11 | 2013-09-18 | University Of Virginia Patent Foundation | Utilisation de pramipexole pour traiter la sclérose latérale amyotrophique |
US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
US20040082543A1 (en) * | 2002-10-29 | 2004-04-29 | Pharmacia Corporation | Compositions of cyclooxygenase-2 selective inhibitors and NMDA receptor antagonists for the treatment or prevention of neuropathic pain |
US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
US8389578B2 (en) | 2004-11-24 | 2013-03-05 | Adamas Pharmaceuticals, Inc | Composition and method for treating neurological disease |
CA2590997A1 (fr) * | 2004-12-23 | 2006-07-06 | Voyager Pharmaceutical Corporation | Acetate de leuprolide et inhibiteurs de l'acetylcholinesterase ou antagonistes des recepteurs nmda pour le traitement de la maladie d'alzheimer |
ES2334061T3 (es) * | 2005-08-15 | 2010-03-04 | University Of Virginia Patent Foundation | Neurorrestauracion con pramipexol r(+). |
US8518926B2 (en) | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
ATE537826T1 (de) | 2006-05-16 | 2012-01-15 | Knopp Neurosciences Inc | Zusammensetzungen aus r(+)- und s(-)-pramipexol sowie verfahren zu ihrer anwendung |
EP2089383B1 (fr) | 2006-11-09 | 2015-09-16 | Probiodrug AG | Dérivés 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one utiles en tant qu' inhibiteurs de la glutaminyl-cyclase dans le traitement des ulcères, du cancer et d'autres maladies |
ATE554085T1 (de) | 2006-11-30 | 2012-05-15 | Probiodrug Ag | Neue inhibitoren von glutaminylcyclase |
US8524695B2 (en) | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
CA2679446C (fr) | 2007-03-01 | 2016-05-17 | Probiodrug Ag | Nouvelle utilisation d'inhibiteurs de la glutaminyl cyclase |
RU2454409C2 (ru) | 2007-03-14 | 2012-06-27 | Нопп Ньюросайенсиз, Инк. | Синтез хирально очищенных замещенных бензотиазолдиаминов |
EP2142514B1 (fr) | 2007-04-18 | 2014-12-24 | Probiodrug AG | Dérivés de thio-urée utilisés comme inhibiteurs de la glutaminyl cyclase |
CN103497114A (zh) | 2007-06-29 | 2014-01-08 | 埃莫里大学 | 用于神经保护的nmda受体拮抗剂 |
DE102007047737A1 (de) * | 2007-10-05 | 2009-04-30 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
TWI410420B (zh) * | 2008-02-05 | 2013-10-01 | Dainippon Sumitomo Pharma Co | 苄基哌啶化合物 |
WO2009129497A2 (fr) * | 2008-04-18 | 2009-10-22 | Arizona Board Of Regents, A Body Corp. Of The State Of Arizona, Acting For And On Behalf Of The University Of Arizona | Methodes et compositions de traitement de la degenerescence maculaire liee a l’age et d’identification de composes appropries |
EP2334185A4 (fr) | 2008-08-19 | 2011-09-21 | Knopp Neurosciences Inc | Compositions et procédés employant du (r)-pramipexole |
HUP0900130A3 (en) | 2009-03-03 | 2012-02-28 | Richter Gedeon Nyrt | Novel crystalline hydrate, amorphous and polymorphic forms of dihydro-benzoxazole-6-yl-acetamide derivative and processes for their preparation |
AU2010279963A1 (en) | 2009-08-04 | 2012-02-23 | Dainippon Sumitomo Pharma Co., Ltd. | Benzyl piperidine compound |
WO2011016861A2 (fr) | 2009-08-05 | 2011-02-10 | Intra-Cellular Therapies, Inc. | Nouvelles protéines régulatrices et nouveaux inhibiteurs |
CA2772488C (fr) | 2009-09-11 | 2018-04-17 | Probiodrug Ag | Derives heterocycliques en tant qu'inhibiteurs de glutaminyle cyclase |
CN102883601A (zh) | 2009-12-02 | 2013-01-16 | 阿达玛斯医药公司 | 金刚烷胺组合物及其使用方法 |
ES2586231T3 (es) | 2010-03-03 | 2016-10-13 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
EP2545047B9 (fr) | 2010-03-10 | 2015-06-10 | Probiodrug AG | Inhibiteurs hétérocycliques de la glutaminyl cyclase (qc, ec 2.3.2.5) |
US8541596B2 (en) | 2010-04-21 | 2013-09-24 | Probiodrug Ag | Inhibitors |
ES2570167T3 (es) | 2011-03-16 | 2016-05-17 | Probiodrug Ag | Derivados de benzimidazol como inhibidores de glutaminil ciclasa |
CN108042517A (zh) | 2011-11-22 | 2018-05-18 | 加利福尼亚大学董事会 | 用于治疗缺血性损伤的半胱胺和/或胱胺 |
US9512096B2 (en) | 2011-12-22 | 2016-12-06 | Knopp Biosciences, LLP | Synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds |
US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
US10154971B2 (en) | 2013-06-17 | 2018-12-18 | Adamas Pharma, Llc | Methods of administering amantadine |
SI3019167T1 (sl) | 2013-07-12 | 2021-04-30 | Knopp Biosciences Llc | Zdravljenje povišanih ravni eozinofilcev in / ali bazofilcev |
US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
US9642840B2 (en) | 2013-08-13 | 2017-05-09 | Knopp Biosciences, Llc | Compositions and methods for treating plasma cell disorders and B-cell prolymphocytic disorders |
PL3033081T3 (pl) | 2013-08-13 | 2021-08-30 | Knopp Biosciences Llc | Kompozycje i sposoby do leczenia przewlekłej pokrzywki |
WO2016100940A1 (fr) | 2014-12-19 | 2016-06-23 | The Broad Institute, Inc. | Ligands des récepteurs dopaminergiques d2 |
US10752588B2 (en) | 2014-12-19 | 2020-08-25 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
IL272834B1 (en) | 2017-08-24 | 2024-04-01 | Adamas Pharma Llc | Compositions of amantadine, their preparation, and methods of use |
EP3461819B1 (fr) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibiteurs de la glutaminyl-cyclase |
EP3958973A4 (fr) * | 2019-04-26 | 2023-06-07 | Cytosolve, Inc. | Compositions permettant d'améliorer la santé du cerveau et la mémoire |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE792187A (fr) * | 1971-12-03 | 1973-03-30 | Sumitomo Chemical Co | Nouveaux derives d'alkylamines |
DE2845537A1 (de) * | 1978-10-19 | 1980-04-30 | Bayer Ag | Benzimidazolylcarbamidsaeureester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
ZA848275B (en) * | 1983-12-28 | 1985-08-28 | Degussa | New piridine-2-ethers or pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring |
EP0488959A3 (en) | 1990-11-28 | 1992-08-05 | Sandoz Ltd. | New uses of competitive nmda receptor antagonists |
JPH05194505A (ja) * | 1991-08-09 | 1993-08-03 | Yoshitomi Pharmaceut Ind Ltd | チオフェン化合物 |
US5192751A (en) | 1992-07-24 | 1993-03-09 | Eli Lilly And Company | Use of competitive NMDA receptor antagonists in the treatment of urinary incontinence |
JP2959615B2 (ja) * | 1993-06-24 | 1999-10-06 | 吉富製薬株式会社 | 縮合型チオフェン化合物およびその医薬用途 |
ATE174915T1 (de) | 1994-10-31 | 1999-01-15 | Merck Patent Gmbh | Benzylpiperidinderivate mit hoher affinität zu bindungsstellen von aminosäure-rezeptoren |
EP0825984A1 (fr) * | 1995-04-07 | 1998-03-04 | Novo Nordisk A/S | Nouveau procede |
ZA9610741B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
ZA9610745B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
WO1998015550A1 (fr) * | 1996-10-04 | 1998-04-16 | Novo Nordisk A/S | Composes azaheterocycliques n-substitues |
DE19643790A1 (de) | 1996-10-30 | 1998-05-07 | Merck Patent Gmbh | Benzoxazol-Derivat |
-
1999
- 1999-06-24 PE PE1999000567A patent/PE20000728A1/es not_active Application Discontinuation
- 1999-06-25 ID IDW20002514A patent/ID28005A/id unknown
- 1999-06-25 AT AT99931887T patent/ATE297207T1/de not_active IP Right Cessation
- 1999-06-25 OA OA1200000347A patent/OA11570A/en unknown
- 1999-06-25 JP JP2000556782A patent/JP2002519322A/ja active Pending
- 1999-06-25 EP EP99931887A patent/EP1089735B1/fr not_active Expired - Lifetime
- 1999-06-25 CA CA002327888A patent/CA2327888A1/fr not_active Abandoned
- 1999-06-25 PL PL99345024A patent/PL345024A1/xx unknown
- 1999-06-25 WO PCT/US1999/014291 patent/WO2000000197A1/fr active IP Right Grant
- 1999-06-25 KR KR1020007014745A patent/KR20010053170A/ko not_active Application Discontinuation
- 1999-06-25 TR TR2000/03888T patent/TR200003888T2/xx unknown
- 1999-06-25 US US09/674,298 patent/US6284774B1/en not_active Expired - Fee Related
- 1999-06-25 CN CN99807087A patent/CN1304307A/zh active Pending
- 1999-06-25 HU HU0102471A patent/HUP0102471A2/hu unknown
- 1999-06-25 AP APAP/P/2000/001949A patent/AP2000001949A0/en unknown
- 1999-06-25 BR BR9911575-1A patent/BR9911575A/pt not_active Application Discontinuation
- 1999-06-25 AU AU48303/99A patent/AU769650B2/en not_active Ceased
- 1999-06-25 IL IL13894999A patent/IL138949A0/xx unknown
- 1999-06-25 NZ NZ508808A patent/NZ508808A/xx unknown
- 1999-06-25 SK SK1951-2000A patent/SK19512000A3/sk unknown
- 1999-06-25 DE DE69925730T patent/DE69925730T2/de not_active Expired - Fee Related
- 1999-06-25 ES ES99931887T patent/ES2244201T3/es not_active Expired - Lifetime
- 1999-06-25 EA EA200100058A patent/EA200100058A1/ru unknown
- 1999-06-25 EE EEP200000778A patent/EE200000778A/xx unknown
-
2000
- 2000-10-16 IS IS5667A patent/IS5667A/is unknown
- 2000-10-19 ZA ZA200005848A patent/ZA200005848B/en unknown
- 2000-12-19 NO NO20006482A patent/NO20006482L/no not_active Application Discontinuation
- 2000-12-21 BG BG105082A patent/BG105082A/xx unknown
Also Published As
Publication number | Publication date |
---|---|
KR20010053170A (ko) | 2001-06-25 |
BR9911575A (pt) | 2001-03-20 |
CN1304307A (zh) | 2001-07-18 |
US6284774B1 (en) | 2001-09-04 |
ATE297207T1 (de) | 2005-06-15 |
NZ508808A (en) | 2002-12-20 |
IS5667A (is) | 2000-10-16 |
BG105082A (en) | 2001-09-28 |
PL345024A1 (en) | 2001-11-19 |
ID28005A (id) | 2001-05-03 |
AP2000001949A0 (en) | 2000-12-31 |
OA11570A (en) | 2004-07-01 |
JP2002519322A (ja) | 2002-07-02 |
EE200000778A (et) | 2002-04-15 |
DE69925730D1 (de) | 2005-07-14 |
HUP0102471A2 (hu) | 2002-05-29 |
NO20006482D0 (no) | 2000-12-19 |
IL138949A0 (en) | 2001-11-25 |
EP1089735A1 (fr) | 2001-04-11 |
NO20006482L (no) | 2000-12-19 |
PE20000728A1 (es) | 2000-08-21 |
AU769650B2 (en) | 2004-01-29 |
DE69925730T2 (de) | 2006-03-23 |
ES2244201T3 (es) | 2005-12-01 |
EP1089735B1 (fr) | 2005-06-08 |
TR200003888T2 (tr) | 2001-06-21 |
CA2327888A1 (fr) | 2000-01-06 |
EA200100058A1 (ru) | 2001-08-27 |
WO2000000197A1 (fr) | 2000-01-06 |
SK19512000A3 (sk) | 2001-08-06 |
AU4830399A (en) | 2000-01-17 |
EP1089735A4 (fr) | 2002-12-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200005848B (en) | 4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists. | |
EP0869792B1 (fr) | Analogues de piperidine a substitution en position 4 et utilisation de ces derniers en tant qu'antagonistes selectivement actifs contre les sous-types du recepteur de nmda | |
DE69628035T2 (de) | In 4-stellung substituierte piperidin-analoge und ihre verwendung als subtyp-selektive nmda rezeptor antagonisten | |
US6410792B1 (en) | Amide derivatives and methods for using the same as selective neuropeptide Y receptor antagonists | |
US6534525B1 (en) | 2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists | |
US8420667B2 (en) | Isoquinolinone derivatives as NK3 antagonists | |
ZA200510044B (en) | Substituted 1,4-di-piperidin-4-yl-piperazine derivative combined with an opioid analgesic and their use for the treatment of pain and side-effects associated with opioid-based treatments | |
JP2011057700A (ja) | 神経変性を処置するためのα2Bまたは2B/2Cアドレナリン受容体アゴニスト | |
ZA200700329B (en) | New heterocyclic carboxylic acid amide derivatives | |
US20160058771A1 (en) | Alpha-2 adrenoceptor and sigma receptor ligand combinations | |
MXPA05009290A (es) | Derivados heterociclicos que contienen nitrogeno que tienen estirilo 2,6-disustituido. | |
US8680279B2 (en) | Compounds for the treatment of neurological disorders | |
MXPA00010169A (en) | 4-benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective nmda receptor antagonists | |
CZ20004725A3 (cs) | 4-Benzylpiperidinové alkylsulfoxidové heterocykly a jejich použití jako subtypověselektivních antagonistů NMDA receptorů | |
US20140275060A1 (en) | Compounds for the treatment of neurologic disorders | |
AU2021349680A1 (en) | Use of sphingosine-1-phosphate receptor agonist | |
WO2006060190A2 (fr) | Derives d'imidazole | |
WO2006132432A1 (fr) | Agent thérapeutique contre la douleur neurogène | |
EP1227859A2 (fr) | Ligands de la neurophiline pour traitement de troubles oculaires |