UA75114C2 - GlyT-1 INHIBITORS - Google Patents

GlyT-1 INHIBITORS Download PDF

Info

Publication number: UA75114C2
Authority: UA; Ukraine
Prior art keywords: thienyl; phenyl; compound; uprop; sarcosine
Prior art date: 2001-02-16

Application number

UA2003087630A

Other languages

English (en)

Ukrainian (uk)

Inventor

Allen T Hopper

Original Assignee

Allelix Neuroscience Inc

Nps Allelix Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-02-16

Filing date

2002-02-15

Publication date

2006-03-15

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23026417&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=UA75114(C2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2002-02-15 Application filed by Allelix Neuroscience Inc, Nps Allelix Corp filed Critical Allelix Neuroscience Inc

2006-03-15 Publication of UA75114C2 publication Critical patent/UA75114C2/uk

Links

239000003112 inhibitor Substances 0.000 title claims description 10
102100023145 Sodium- and chloride-dependent glycine transporter 1 Human genes 0.000 title 1
101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 131
238000011282 treatment Methods 0.000 claims abstract description 17
150000003839 salts Chemical class 0.000 claims abstract description 11
230000000926 neurological effect Effects 0.000 claims abstract description 4
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 104
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 74
108010077895 Sarcosine Proteins 0.000 claims description 52
229940043230 sarcosine Drugs 0.000 claims description 52
239000004471 Glycine Substances 0.000 claims description 37
RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims description 30
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
239000000203 mixture Substances 0.000 claims description 17
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 16
238000000034 method Methods 0.000 claims description 16
238000012546 transfer Methods 0.000 claims description 16
-1 2-methoxyethoxy Chemical group 0.000 claims description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 9
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 9
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
201000000980 schizophrenia Diseases 0.000 claims description 6
229930192474 thiophene Natural products 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
230000003993 interaction Effects 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
125000001424 substituent group Chemical group 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
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
238000006073 displacement reaction Methods 0.000 claims description 4
235000019253 formic acid Nutrition 0.000 claims description 4
125000001188 haloalkyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
208000010877 cognitive disease Diseases 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
239000012453 solvate Substances 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
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
206010003805 Autism Diseases 0.000 claims description 2
208000020706 Autistic disease Diseases 0.000 claims description 2
206010012289 Dementia Diseases 0.000 claims description 2
208000036353 Rett disease Diseases 0.000 claims description 2
201000007197 atypical autism Diseases 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
125000004438 haloalkoxy group Chemical group 0.000 claims description 2
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 6
125000001544 thienyl group Chemical group 0.000 claims 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 3
125000003158 alcohol group Chemical group 0.000 claims 3
DNEHKUCSURWDGO-UHFFFAOYSA-N aluminum sodium Chemical compound [Na].[Al] DNEHKUCSURWDGO-UHFFFAOYSA-N 0.000 claims 3
239000003054 catalyst Substances 0.000 claims 3
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims 2
239000004327 boric acid Substances 0.000 claims 2
125000001475 halogen functional group Chemical group 0.000 claims 2
230000007062 hydrolysis Effects 0.000 claims 2
238000006460 hydrolysis reaction Methods 0.000 claims 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims 1
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims 1
208000012239 Developmental disease Diseases 0.000 claims 1
150000001543 aryl boronic acids Chemical class 0.000 claims 1
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims 1
125000004185 ester group Chemical group 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 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
238000012876 topography Methods 0.000 claims 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 59
239000000543 intermediate Substances 0.000 description 28
102000005962 receptors Human genes 0.000 description 26
108020003175 receptors Proteins 0.000 description 26
241001465754 Metazoa Species 0.000 description 22
239000003921 oil Substances 0.000 description 20
235000019198 oils Nutrition 0.000 description 20
239000000243 solution Substances 0.000 description 14
238000012360 testing method Methods 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
150000002148 esters Chemical class 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
230000027455 binding Effects 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
210000004027 cell Anatomy 0.000 description 11
239000003446 ligand Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
239000002858 neurotransmitter agent Substances 0.000 description 9
230000000694 effects Effects 0.000 description 8
108010078791 Carrier Proteins Proteins 0.000 description 7
102000011714 Glycine Receptors Human genes 0.000 description 7
108010076533 Glycine Receptors Proteins 0.000 description 7
210000003414 extremity Anatomy 0.000 description 7
230000001404 mediated effect Effects 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000008351 acetate buffer Substances 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
239000003814 drug Substances 0.000 description 6
230000006870 function Effects 0.000 description 6
239000012528 membrane Substances 0.000 description 6
210000000278 spinal cord Anatomy 0.000 description 6
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 6
210000004556 brain Anatomy 0.000 description 5
239000012267 brine Substances 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
230000000971 hippocampal effect Effects 0.000 description 5
230000005764 inhibitory process Effects 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
229960005453 strychnine Drugs 0.000 description 5
210000000225 synapse Anatomy 0.000 description 5
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
HVNPFQOMBNYVMB-UHFFFAOYSA-N butyl 2-(methylamino)acetate Chemical compound CCCCOC(=O)CNC HVNPFQOMBNYVMB-UHFFFAOYSA-N 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
230000002401 inhibitory effect Effects 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
102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 3
108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 3
241001279009 Strychnos toxifera Species 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
238000003556 assay Methods 0.000 description 3
230000003542 behavioural effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000005284 excitation Effects 0.000 description 3
230000002964 excitative effect 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
230000002829 reductive effect Effects 0.000 description 3
230000028327 secretion Effects 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
230000005062 synaptic transmission Effects 0.000 description 3
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 3
HTGQCLJTWPSFNL-UHFFFAOYSA-N (2-methylphenoxy)boronic acid Chemical compound CC1=CC=CC=C1OB(O)O HTGQCLJTWPSFNL-UHFFFAOYSA-N 0.000 description 2
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
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 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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
206010008796 Chromaturia Diseases 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 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
241000124008 Mammalia Species 0.000 description 2
241000699660 Mus musculus Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
208000012202 Pervasive developmental disease Diseases 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
206010042008 Stereotypy Diseases 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
208000029560 autism spectrum disease Diseases 0.000 description 2
239000011230 binding agent Substances 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
125000004432 carbon atom Chemical group C* 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
230000034994 death Effects 0.000 description 2
230000006735 deficit Effects 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
208000001780 epistaxis Diseases 0.000 description 2
208000001936 exophthalmos Diseases 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000013604 expression vector Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 2
ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 2
150000002333 glycines Chemical class 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
150000004677 hydrates Chemical class 0.000 description 2
238000011534 incubation Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
230000027928 long-term synaptic potentiation Effects 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
238000010369 molecular cloning Methods 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
230000002093 peripheral effect Effects 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
230000003518 presynaptic effect Effects 0.000 description 2
230000002685 pulmonary effect Effects 0.000 description 2
210000001747 pupil Anatomy 0.000 description 2
238000011084 recovery Methods 0.000 description 2
210000002027 skeletal muscle Anatomy 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000000946 synaptic effect Effects 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
230000032258 transport Effects 0.000 description 2
238000005406 washing Methods 0.000 description 2
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
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
LVPFZXKLROORIK-UHFFFAOYSA-N (4-methylthiophen-3-yl)boronic acid Chemical compound CC1=CSC=C1B(O)O LVPFZXKLROORIK-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
125000000171 (C1-C6) haloalkyl group Chemical group 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
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
206010000117 Abnormal behaviour Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
241000271566 Aves Species 0.000 description 1
208000031872 Body Remains Diseases 0.000 description 1
101150095408 CNMD gene Proteins 0.000 description 1
101100008044 Caenorhabditis elegans cut-1 gene Proteins 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
108010062745 Chloride Channels Proteins 0.000 description 1
102000011045 Chloride Channels Human genes 0.000 description 1
229920001287 Chondroitin sulfate Polymers 0.000 description 1
241000938605 Crocodylia Species 0.000 description 1
206010011703 Cyanosis Diseases 0.000 description 1
206010011953 Decreased activity Diseases 0.000 description 1
206010012559 Developmental delay 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
208000002021 Enophthalmos Diseases 0.000 description 1
241000402754 Erythranthe moschata Species 0.000 description 1
244000089409 Erythrina poeppigiana Species 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
241000233866 Fungi Species 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
241000238631 Hexapoda Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
206010027646 Miosis Diseases 0.000 description 1
101100521345 Mus musculus Prop1 gene Proteins 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
108010084810 Neurotransmitter Transport Proteins Proteins 0.000 description 1
102000005665 Neurotransmitter Transport Proteins Human genes 0.000 description 1
101150024701 PPH3 gene 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
108700017836 Prophet of Pit-1 Proteins 0.000 description 1
235000009776 Rathbunia alamosensis Nutrition 0.000 description 1
208000037656 Respiratory Sounds Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
206010039424 Salivary hypersecretion Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
206010047853 Waxy flexibility Diseases 0.000 description 1
206010047924 Wheezing Diseases 0.000 description 1
PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 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
JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
230000009471 action 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
150000001412 amines Chemical class 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
239000012300 argon atmosphere Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
239000002585 base Substances 0.000 description 1
238000010009 beating Methods 0.000 description 1
230000006399 behavior 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
230000033228 biological regulation Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000007975 buffered saline Substances 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
235000015218 chewing gum Nutrition 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229940059329 chondroitin sulfate Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
231100000132 chronic toxicity testing Toxicity 0.000 description 1
230000002566 clonic effect Effects 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
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
230000003920 cognitive function Effects 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
239000003179 convulsant agent Substances 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
230000009260 cross reactivity Effects 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
230000010339 dilation Effects 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 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
238000013504 emergency use authorization Methods 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
230000001747 exhibiting effect Effects 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
239000000945 filler Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 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
230000002538 fungal effect Effects 0.000 description 1
PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 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
239000008187 granular material Substances 0.000 description 1
230000012010 growth Effects 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
210000003128 head Anatomy 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
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 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
208000013403 hyperactivity Diseases 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
229910052738 indium Inorganic materials 0.000 description 1
230000009539 inhibitory neurotransmission Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000035992 intercellular communication Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
230000004317 lacrimation Effects 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 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
238000005259 measurement Methods 0.000 description 1
239000000155 melt Substances 0.000 description 1
239000011707 mineral Substances 0.000 description 1
230000003547 miosis Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
210000004498 neuroglial cell Anatomy 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
229910052755 nonmetal Inorganic materials 0.000 description 1
150000002843 nonmetals Chemical class 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
230000005371 pilomotor reflex Effects 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
239000008057 potassium phosphate buffer Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000008569 process Effects 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
125000006239 protecting group Chemical group 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
201000003004 ptosis Diseases 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
208000012802 recumbency Diseases 0.000 description 1
238000010992 reflux 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
230000002441 reversible effect Effects 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
210000003296 saliva Anatomy 0.000 description 1
208000026451 salivation Diseases 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 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
230000002269 spontaneous effect Effects 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
238000003756 stirring Methods 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 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
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003577 thiophenes Chemical class 0.000 description 1
210000003371 toe Anatomy 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
230000000699 topical 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
230000037317 transdermal delivery Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000005199 ultracentrifugation Methods 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
239000013598 vector Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
229910052727 yttrium Inorganic materials 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

Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurology (AREA)
Psychiatry (AREA)
Psychology (AREA)
Pain & Pain Management (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)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Epoxy Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

UA2003087630A 2001-02-16 2002-02-15 GlyT-1 INHIBITORS UA75114C2 (en)

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 (1)

Publication Number	Publication Date
UA75114C2 true UA75114C2 (en)	2006-03-15

Family

ID=23026417

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2003087630A UA75114C2 (en)	2001-02-16	2002-02-15	GlyT-1 INHIBITORS

Country Status (31)

Country	Link
US (1)	US6667336B2 (he)
EP (1)	EP1368336B9 (he)
JP (2)	JP2004523548A (he)
KR (1)	KR100900020B1 (he)
CN (1)	CN1219776C (he)
AT (1)	ATE327986T1 (he)
AU (1)	AU2002235682C1 (he)
BG (1)	BG108164A (he)
BR (1)	BR0207307A (he)
CA (1)	CA2438367A1 (he)
CY (1)	CY1105529T1 (he)
CZ (1)	CZ20032503A3 (he)
DE (1)	DE60211866T2 (he)
DK (1)	DK1368336T3 (he)
EA (1)	EA006636B1 (he)
EE (1)	EE05329B1 (he)
ES (1)	ES2266446T3 (he)
HK (1)	HK1061025A1 (he)
HR (1)	HRP20030696A2 (he)
HU (1)	HUP0303185A3 (he)
IL (1)	IL157194A (he)
MX (1)	MXPA03007309A (he)
NO (1)	NO329038B1 (he)
NZ (1)	NZ527695A (he)
PL (1)	PL365024A1 (he)
PT (1)	PT1368336E (he)
SI (1)	SI1368336T1 (he)
SK (1)	SK287304B6 (he)
UA (1)	UA75114C2 (he)
WO (1)	WO2002066456A2 (he)
ZA (1)	ZA200307201B (he)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
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
CA2590287A1 (en) *	2004-12-16	2006-06-22	Janssen Pharmaceutica N.V.	Combination of a glycine transporter (glyt1) inhibitor and an antipsychotic for the treatment of symptoms of schizophrenia as well as its preparation and use thereof
WO2008040669A2 (en) *	2006-10-02	2008-04-10	Janssen Pharmaceutica N.V.	Novel intermediates for the preparation of a 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)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3010599A1 (de)	1979-03-22	1980-10-09	Continental Pharma	Derivate von glycinamid, deren herstellung und verwendung
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.
DK165692C (da)	1986-01-07	1993-11-08	Novo Nordisk As	Phenylbutenderivater, fremgangsmaade til fremstilling heraf, farmaceutisk praeparat indeholdende disse, samt anvendelse af disse til fremstilling af et medikament nyttigt til inhibering af gaba-optagelse i mennesker
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".
ATE320804T1 (de)	1995-12-07	2006-04-15	Daniel C Javitt	Behandlung negativer und kognitiver symptome der schizophrenie mit antagonisten der glycinaufnahme
ES2270462T3 (es) *	1996-05-31	2007-04-01	Allelix Neuroscience Inc.	Producto farmaceutico para el tratamiento de trastornos neurologicos y neuropsiquiatricos.
US6191165B1 (en)	1996-05-31	2001-02-20	Allelix Neuroscience Inc.	Pharmaceutical for treatment of neurological and neuropsychiatric disorders
EP1184370B1 (en) *	1996-07-22	2005-09-14	Novo Nordisk A/S	Compounds with growth hormone releasing properties
EP1047665B1 (en) *	1998-01-09	2003-10-22	Pfizer Limited	Matrix metalloprotease inhibitors
US6103743A (en) *	1999-08-06	2000-08-15	Allelix Neuroscience, Inc.	Unsaturated amino acid derivatives

2002
- 2002-02-15 UA UA2003087630A patent/UA75114C2/uk unknown
- 2002-02-15 KR KR1020037010609A patent/KR100900020B1/ko not_active IP Right Cessation
- 2002-02-15 CN CNB028050819A patent/CN1219776C/zh not_active Expired - Fee Related
- 2002-02-15 CA CA002438367A patent/CA2438367A1/en not_active Abandoned
- 2002-02-15 DE DE60211866T patent/DE60211866T2/de not_active Expired - Lifetime
- 2002-02-15 DK DK02702186T patent/DK1368336T3/da active
- 2002-02-15 AU AU2002235682A patent/AU2002235682C1/en not_active Ceased
- 2002-02-15 SI SI200230381T patent/SI1368336T1/sl unknown
- 2002-02-15 BR BR0207307-2A patent/BR0207307A/pt not_active IP Right Cessation
- 2002-02-15 PT PT02702186T patent/PT1368336E/pt unknown
- 2002-02-15 PL PL02365024A patent/PL365024A1/xx unknown
- 2002-02-15 EE EEP200300394A patent/EE05329B1/xx not_active IP Right Cessation
- 2002-02-15 SK SK1144-2003A patent/SK287304B6/sk not_active IP Right Cessation
- 2002-02-15 NZ NZ527695A patent/NZ527695A/en unknown
- 2002-02-15 CZ CZ20032503A patent/CZ20032503A3/cs unknown
- 2002-02-15 EP EP02702186A patent/EP1368336B9/en not_active Expired - Lifetime
- 2002-02-15 EA EA200300900A patent/EA006636B1/ru not_active IP Right Cessation
- 2002-02-15 US US10/077,579 patent/US6667336B2/en not_active Expired - Fee Related
- 2002-02-15 HU HU0303185A patent/HUP0303185A3/hu unknown
- 2002-02-15 WO PCT/CA2002/000176 patent/WO2002066456A2/en active IP Right Grant
- 2002-02-15 MX MXPA03007309A patent/MXPA03007309A/es active IP Right Grant
- 2002-02-15 ES ES02702186T patent/ES2266446T3/es not_active Expired - Lifetime
- 2002-02-15 AT AT02702186T patent/ATE327986T1/de not_active IP Right Cessation
- 2002-02-15 JP JP2002565971A patent/JP2004523548A/ja active Pending
2003
- 2003-07-31 IL IL157194A patent/IL157194A/he 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

Publication number	Publication date
NZ527695A (en)	2005-05-27
SK11442003A3 (sk)	2004-03-02
IL157194A (he)	2006-12-31
EA200300900A1 (ru)	2004-02-26
EE200300394A (et)	2003-12-15
HUP0303185A3 (en)	2008-12-29
SI1368336T1 (sl)	2006-10-31
EP1368336A2 (en)	2003-12-10
CN1491221A (zh)	2004-04-21
PL365024A1 (en)	2004-12-27
EP1368336B1 (en)	2006-05-31
MXPA03007309A (es)	2004-06-30
AU2002235682B2 (en)	2007-04-26
EE05329B1 (et)	2010-08-16
CZ20032503A3 (cs)	2004-02-18
WO2002066456A2 (en)	2002-08-29
DE60211866T2 (de)	2007-06-14
NO20033634D0 (no)	2003-08-15
ATE327986T1 (de)	2006-06-15
HK1061025A1 (en)	2004-09-03
DK1368336T3 (da)	2006-10-02
SK287304B6 (sk)	2010-06-07
CN1219776C (zh)	2005-09-21
HRP20030696A2 (en)	2005-04-30
BG108164A (en)	2004-07-30
US20030176489A1 (en)	2003-09-18
AU2002235682C1 (en)	2008-12-11
HUP0303185A2 (hu)	2003-12-29
CY1105529T1 (el)	2010-07-28
ES2266446T3 (es)	2007-03-01
US6667336B2 (en)	2003-12-23
PT1368336E (pt)	2006-10-31
DE60211866D1 (de)	2006-07-06
BR0207307A (pt)	2004-08-17
ZA200307201B (en)	2004-07-28
EA006636B1 (ru)	2006-02-24
KR20040028719A (ko)	2004-04-03
JP2004523548A (ja)	2004-08-05
NO329038B1 (no)	2010-08-02
WO2002066456A3 (en)	2002-10-17
NO20033634L (no)	2003-10-08
JP2010059182A (ja)	2010-03-18
EP1368336B9 (en)	2007-02-14
CA2438367A1 (en)	2002-08-29
KR100900020B1 (ko)	2009-06-01

Publication	Publication Date	Title
CN101801949B (zh)	2014-09-24	作为trpm8调节剂的磺酰胺类
ES2438185T3 (es)	2014-01-16	Derivados de sulfonamida farmacéuticamente activos portadores de restos lipófilos e ionizables como inhibidores de proteína quinasas Jun
US20040248957A1 (en)	2004-12-09	Heterocyclic compounds and uses thereof
ZA200500133B (en)	2005-11-01	1H-1,2,4-triazole-3-carboxamide derivatives as ca nnabinoid- CB, receptor ligands.
JPH08508741A (ja)	1996-09-17	虚血および関連疾患の処置におけるヘテロ環誘導体類
NO324792B1 (no)	2007-12-10	Farmasoytisk aktive sulfonamidderivater
DK170332B1 (da)	1995-08-07	Farmakologisk aktive substituerede benzamider, fremgangsmåde til fremstilling deraf og et farmaceutisk præparat heraf
US6525085B2 (en)	2003-02-25	Diaryl-enynes
JP2010059182A (ja)	2010-03-18	ＧｌｙＴ−１阻害剤
AU2002337863B2 (en)	2007-10-11	Carbinols for the treatment of neuropathic dysfunction
JP2010509402A (ja)	2010-03-25	Ａ１アデノシン受容体のアロステリック調節剤
AU2002235682A1 (en)	2003-02-27	Thiophene substituted amine derivatives as GLYT-1 inhibitors
SA05250441A (ar)	2005-12-03	مشتقات داي أريل ميثيل بيبرازين , ومستحضرات منها واستخداماتها
ES2274415T3 (es)	2007-05-16	Derivados de 4-(3'-(sulfonilamino)fenil)-1'-(ciclimetil)piperidin-4-iliden)metil)benzamida como ligandos de receptores de opioides para el tratamiento de dolor, ansiedad y trastorno gastrointestinal funcional.
JP2011519955A (ja)	2011-07-14	Ａ１アデノシン受容体のアロステリックエンハンサー
US20100035929A1 (en)	2010-02-11	Unnatural dispyrin analogues, preparation and uses thereof
AU780922C (en)	2005-10-20	Diaryl-enynes
KR20010033998A (ko)	2001-04-25	신경학적 질병 치료용 1,4-디아자시클로헵탄 유도체
CN102089285A (zh)	2011-06-08	治疗性的n-芳基或n-杂芳基吡唑烷和吡唑烷酮衍生物