BRPI0920342A2 - Uso de um inibidor da proteína vesicular sináptica 2a (sv2a) ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica para melhora da função cognitiva, uso de levitiracetam ou um sal farmaceuticamente aceitável do mesmo, uso de brivaracetam ou um sal farmaceuticamente aceitável do mesmo, uso do seletracetam ou um sal farmaceuticamente aceitável do mesmo - Google Patents

Info

Publication number

BRPI0920342A2

BRPI0920342A2 BRPI0920342-7A BRPI0920342A BRPI0920342A2 BR PI0920342 A2 BRPI0920342 A2 BR PI0920342A2 BR PI0920342 A BRPI0920342 A BR PI0920342A BR PI0920342 A2 BRPI0920342 A2 BR PI0920342A2

Authority

BR

Brazil

Prior art keywords

pharmaceutically acceptable

acceptable salt

methyl

hydrogen

alkyl

Prior art date

2008-10-16

Links

• Espacenet
• Global Dossier
• Discuss

• 150000003839 salts Chemical class 0.000 title claims abstract description 111
• HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 title claims abstract description 66
• 230000003920 cognitive function Effects 0.000 title claims abstract description 40
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
• ANWPENAPCIFDSZ-BQBZGAKWSA-N seletracetam Chemical compound CC[C@@H](C(N)=O)N1C[C@@H](C=C(F)F)CC1=O ANWPENAPCIFDSZ-BQBZGAKWSA-N 0.000 title claims abstract description 10
• 229950000852 seletracetam Drugs 0.000 title claims abstract description 10
• 230000000946 synaptic effect Effects 0.000 title claims abstract description 7
• 239000012268 protein inhibitor Substances 0.000 title abstract description 4
• 229940121649 protein inhibitor Drugs 0.000 title abstract description 4
• 239000003112 inhibitor Substances 0.000 claims abstract description 100
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 69
• 229960004002 levetiracetam Drugs 0.000 claims abstract description 61
• 208000028698 Cognitive impairment Diseases 0.000 claims abstract description 48
• 238000011282 treatment Methods 0.000 claims abstract description 34
• MSYKRHVOOPPJKU-BDAKNGLRSA-N brivaracetam Chemical compound CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1 MSYKRHVOOPPJKU-BDAKNGLRSA-N 0.000 claims abstract description 23
• 229960002161 brivaracetam Drugs 0.000 claims abstract description 22
• 230000007278 cognition impairment Effects 0.000 claims abstract 5
• 239000000203 mixture Substances 0.000 claims description 81
• 239000003814 drug Substances 0.000 claims description 32
• 229940079593 drug Drugs 0.000 claims description 26
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 22
• 229940102566 valproate Drugs 0.000 claims description 20
• 108090000623 proteins and genes Proteins 0.000 claims description 11
• 238000009472 formulation Methods 0.000 claims description 8
• 239000008280 blood Substances 0.000 claims description 6
• 210000004369 blood Anatomy 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 102000004169 proteins and genes Human genes 0.000 claims description 6
• 101710084141 Synaptic vesicle glycoprotein 2A Proteins 0.000 abstract description 92
• 208000027061 mild cognitive impairment Diseases 0.000 abstract description 19
• 230000007000 age related cognitive decline Effects 0.000 abstract description 14
• 208000026139 Memory disease Diseases 0.000 abstract description 8
• 206010027175 memory impairment Diseases 0.000 abstract description 8
• -1 hydroxy, amino Chemical group 0.000 description 686
• 229910052739 hydrogen Inorganic materials 0.000 description 286
• 239000001257 hydrogen Substances 0.000 description 286
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 235
• 125000000217 alkyl group Chemical group 0.000 description 202
• 229910052736 halogen Inorganic materials 0.000 description 176
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 164
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 157
• 150000002367 halogens Chemical class 0.000 description 143
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 137
• 150000001875 compounds Chemical class 0.000 description 117
• 238000012360 testing method Methods 0.000 description 97
• 125000003118 aryl group Chemical group 0.000 description 95
• 102100030701 Synaptic vesicle glycoprotein 2A Human genes 0.000 description 83
• 241000700159 Rattus Species 0.000 description 71
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 70
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 70
• 125000000623 heterocyclic group Chemical group 0.000 description 68
• 238000000034 method Methods 0.000 description 68
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 63
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 63
• 125000001424 substituent group Chemical group 0.000 description 61
• 125000003545 alkoxy group Chemical group 0.000 description 56
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 51
• 125000005843 halogen group Chemical group 0.000 description 43
• 125000002252 acyl group Chemical group 0.000 description 41
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 38
• 229920002472 Starch Polymers 0.000 description 36
• 150000002148 esters Chemical class 0.000 description 36
• 235000019698 starch Nutrition 0.000 description 36
• 125000000753 cycloalkyl group Chemical group 0.000 description 35
• 239000008107 starch Substances 0.000 description 35
• 238000012549 training Methods 0.000 description 35
• 125000003342 alkenyl group Chemical group 0.000 description 34
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 33
• 125000004432 carbon atom Chemical group C* 0.000 description 33
• 239000003795 chemical substances by application Substances 0.000 description 33
• 125000004093 cyano group Chemical group *C#N 0.000 description 33
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 32
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 30
• NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 29
• 125000000304 alkynyl group Chemical group 0.000 description 28
• 239000000460 chlorine Substances 0.000 description 28
• 229910052801 chlorine Inorganic materials 0.000 description 27
• 125000004361 3,4,5-trifluorophenyl group Chemical group [H]C1=C(F)C(F)=C(F)C([H])=C1* 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• 125000004414 alkyl thio group Chemical group 0.000 description 26
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 25
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 25
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 24
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 24
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 23
• OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 23
• 125000003431 oxalo group Chemical group 0.000 description 23
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 22
• 230000015654 memory Effects 0.000 description 20
• 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 description 19
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 19
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 19
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 18
• 150000003573 thiols Chemical class 0.000 description 18
• 241001465754 Metazoa Species 0.000 description 17
• 229910052794 bromium Inorganic materials 0.000 description 17
• 230000014759 maintenance of location Effects 0.000 description 17
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 17
• 125000004076 pyridyl group Chemical group 0.000 description 17
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 17
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 16
• 125000002541 furyl group Chemical group 0.000 description 16
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 16
• 125000002947 alkylene group Chemical group 0.000 description 15
• RFMQOHXWHFHOJF-UHFFFAOYSA-N cyano thiocyanate Chemical group N#CSC#N RFMQOHXWHFHOJF-UHFFFAOYSA-N 0.000 description 15
• 229910052760 oxygen Inorganic materials 0.000 description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 14
• 238000012347 Morris Water Maze Methods 0.000 description 14
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 14
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
• 230000001771 impaired effect Effects 0.000 description 14
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 14
• 239000012453 solvate Substances 0.000 description 14
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 14
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 13
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 13
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 12
• 239000011575 calcium Substances 0.000 description 12
• 229910052731 fluorine Inorganic materials 0.000 description 12
• 125000001544 thienyl group Chemical group 0.000 description 12
• 229960000604 valproic acid Drugs 0.000 description 12
• 239000003981 vehicle Substances 0.000 description 12
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 11
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 11
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
• 150000001540 azides Chemical class 0.000 description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 11
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 11
• 239000000523 sample Substances 0.000 description 11
• 125000000335 thiazolyl group Chemical group 0.000 description 11
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 10
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 10
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 10
• 241000282412 Homo Species 0.000 description 10
• 230000032683 aging Effects 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 125000004104 aryloxy group Chemical group 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
• 125000000168 pyrrolyl group Chemical group 0.000 description 10
• 229940124530 sulfonamide Drugs 0.000 description 10
• 150000003456 sulfonamides Chemical class 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• 125000003831 tetrazolyl group Chemical group 0.000 description 10
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 9
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 9
• 239000004215 Carbon black (E152) Substances 0.000 description 9
• 125000004122 cyclic group Chemical group 0.000 description 9
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 9
• 229930195733 hydrocarbon Natural products 0.000 description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
• 125000001624 naphthyl group Chemical group 0.000 description 9
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 9
• 125000003386 piperidinyl group Chemical group 0.000 description 9
• 150000003254 radicals Chemical class 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 229910052717 sulfur Inorganic materials 0.000 description 9
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 9
• 229920002554 vinyl polymer Polymers 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 8
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• 241000699670 Mus sp. Species 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 125000003282 alkyl amino group Chemical group 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 125000002837 carbocyclic group Chemical group 0.000 description 8
• 230000007423 decrease Effects 0.000 description 8
• 235000013305 food Nutrition 0.000 description 8
• 125000002883 imidazolyl group Chemical group 0.000 description 8
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 8
• 230000013016 learning Effects 0.000 description 8
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 8
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 8
• 125000002971 oxazolyl group Chemical group 0.000 description 8
• 239000001301 oxygen Substances 0.000 description 8
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 8
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 8
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 7
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 7
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 7
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 7
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
• 241000699666 Mus <mouse, genus> Species 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• 125000004423 acyloxy group Chemical group 0.000 description 7
• 125000005110 aryl thio group Chemical group 0.000 description 7
• 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 7
• 239000011737 fluorine Substances 0.000 description 7
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
• 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 7
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 7
• 125000001425 triazolyl group Chemical group 0.000 description 7
• JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 6
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 6
• 125000004780 2-chloro-2,2-difluoroethyl group Chemical group [H]C([H])(*)C(F)(F)Cl 0.000 description 6
• 239000005977 Ethylene Substances 0.000 description 6
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 230000001149 cognitive effect Effects 0.000 description 6
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 6
• 238000013265 extended release Methods 0.000 description 6
• 125000001153 fluoro group Chemical group F* 0.000 description 6
• 230000014509 gene expression Effects 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 6
• 125000002757 morpholinyl group Chemical group 0.000 description 6
• 125000004193 piperazinyl group Chemical group 0.000 description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 description 6
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• MSTWYMAKOBGMBF-UHFFFAOYSA-N 1-(imidazol-1-ylmethyl)-4-phenylpyrrolidin-2-one Chemical compound O=C1CC(C=2C=CC=CC=2)CN1CN1C=CN=C1 MSTWYMAKOBGMBF-UHFFFAOYSA-N 0.000 description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 5
• 206010012289 Dementia Diseases 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 5
• 125000005135 aryl sulfinyl group Chemical group 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• 230000003542 behavioural effect Effects 0.000 description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
• 230000006872 improvement Effects 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 125000004430 oxygen atom Chemical group O* 0.000 description 5
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• 239000011780 sodium chloride Substances 0.000 description 5
• 230000006886 spatial memory Effects 0.000 description 5
• 235000000346 sugar Nutrition 0.000 description 5
• 125000004434 sulfur atom Chemical group 0.000 description 5
• 230000009182 swimming Effects 0.000 description 5
• 230000003977 synaptic function Effects 0.000 description 5
• 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 5
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 4
• 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 4
• 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 description 4
• DHSHMTXXPHLFOX-UHFFFAOYSA-N 1-(imidazol-1-ylmethyl)-4-propylpyrrolidin-2-one Chemical compound O=C1CC(CCC)CN1CN1C=NC=C1 DHSHMTXXPHLFOX-UHFFFAOYSA-N 0.000 description 4
• 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 4
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 4
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 4
• 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 4
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• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 125000005236 alkanoylamino group Chemical group 0.000 description 4
• 238000000540 analysis of variance Methods 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 125000003725 azepanyl group Chemical group 0.000 description 4
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
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