EA005206B1 - Бициклические аминокислоты в качестве фармацевтических агентов - Google Patents

Бициклические аминокислоты в качестве фармацевтических агентов Download PDF

Info

Publication number: EA005206B1
Authority: EA; Eurasian Patent Office
Prior art keywords: acetic acid; aminomethyl; mixture; mmol; effective amount
Prior art date: 1999-10-20

Application number

EA200200293A

Other languages

English (en)

Russian (ru)

Other versions

EA200200293A1 (ru

Inventor

Дейвид Клайв Блейкмор

Жан-Мари Ресевё

Original Assignee

Уорнер-Ламберт Компани

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.)

1999-10-20

Filing date

2000-10-17

Publication date

2004-12-30

2000-10-17 Application filed by Уорнер-Ламберт Компани filed Critical Уорнер-Ламберт Компани

2002-10-31 Publication of EA200200293A1 publication Critical patent/EA200200293A1/ru

2004-12-30 Publication of EA005206B1 publication Critical patent/EA005206B1/ru

Links

-1 Bicyclic amino acids Chemical class 0.000 title abstract description 54
239000008177 pharmaceutical agent Substances 0.000 title 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 181
150000001875 compounds Chemical class 0.000 claims abstract description 96
238000000034 method Methods 0.000 claims abstract description 47
208000002193 Pain Diseases 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 26
241000124008 Mammalia Species 0.000 claims abstract description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
208000035475 disorder Diseases 0.000 claims abstract description 10
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 8
208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
230000036506 anxiety Effects 0.000 claims abstract description 7
206010015037 epilepsy Diseases 0.000 claims abstract description 7
208000004296 neuralgia Diseases 0.000 claims abstract description 7
230000002981 neuropathic effect Effects 0.000 claims abstract description 6
208000021722 neuropathic pain Diseases 0.000 claims abstract description 5
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
239000003937 drug carrier Substances 0.000 claims abstract description 4
NDDZVQRQVFTNSN-UHFFFAOYSA-N 2-[3-(aminomethyl)-3-bicyclo[3.2.0]heptanyl]acetic acid Chemical compound C1C(CN)(CC(O)=O)CC2CCC21 NDDZVQRQVFTNSN-UHFFFAOYSA-N 0.000 claims description 17
150000002148 esters Chemical class 0.000 claims description 16
ONKWZNBXHSMMDK-UHFFFAOYSA-N 2-[2-(aminomethyl)-1,3,3a,4,5,6,7,7a-octahydroinden-2-yl]acetic acid Chemical compound C1CCCC2CC(CN)(CC(O)=O)CC21 ONKWZNBXHSMMDK-UHFFFAOYSA-N 0.000 claims description 15
150000001408 amides Chemical class 0.000 claims description 12
GSBZRDSCOPXLJJ-UHFFFAOYSA-N 2-[2-(aminomethyl)-3,3a,4,5,6,6a-hexahydro-1h-pentalen-2-yl]acetic acid Chemical compound C1CCC2CC(CN)(CC(O)=O)CC21 GSBZRDSCOPXLJJ-UHFFFAOYSA-N 0.000 claims description 9
206010033664 Panic attack Diseases 0.000 claims description 3
208000019906 panic disease Diseases 0.000 claims description 3
239000000651 prodrug Substances 0.000 abstract description 12
229940002612 prodrug Drugs 0.000 abstract description 12
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 abstract 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 167
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 106
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 99
239000000203 mixture Substances 0.000 description 95
239000002904 solvent Substances 0.000 description 73
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 53
239000000047 product Substances 0.000 description 52
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 49
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
230000002829 reductive effect Effects 0.000 description 38
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000003814 drug Substances 0.000 description 26
150000001413 amino acids Chemical class 0.000 description 25
230000015572 biosynthetic process Effects 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
229940079593 drug Drugs 0.000 description 24
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
238000003786 synthesis reaction Methods 0.000 description 24
239000007787 solid Substances 0.000 description 23
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
239000012267 brine Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 21
102100037580 Sesquipedalian-1 Human genes 0.000 description 19
101710169844 Sesquipedalian-1 Proteins 0.000 description 19
241000699670 Mus sp. Species 0.000 description 17
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
238000003756 stirring Methods 0.000 description 16
238000007792 addition Methods 0.000 description 15
239000012230 colorless oil Substances 0.000 description 15
239000010408 film Substances 0.000 description 15
239000010410 layer Substances 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
238000010992 reflux Methods 0.000 description 14
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 14
239000007788 liquid Substances 0.000 description 13
238000002360 preparation method Methods 0.000 description 13
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
235000019198 oils Nutrition 0.000 description 12
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 12
238000012360 testing method Methods 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000002253 acid Substances 0.000 description 11
239000012300 argon atmosphere Substances 0.000 description 11
239000002585 base Substances 0.000 description 11
150000001916 cyano esters Chemical class 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
206010010904 Convulsion Diseases 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
241000700159 Rattus Species 0.000 description 10
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 10
239000012071 phase Substances 0.000 description 10
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
229910017976 MgO 4 Inorganic materials 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
229960003692 gamma aminobutyric acid Drugs 0.000 description 9
150000003951 lactams Chemical class 0.000 description 9
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
238000001816 cooling Methods 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
239000003054 catalyst Substances 0.000 description 7
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 7
229910052759 nickel Inorganic materials 0.000 description 7
239000008096 xylene Substances 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 6
101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
102100030413 Spermidine synthase Human genes 0.000 description 6
208000006011 Stroke Diseases 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
239000002775 capsule Substances 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
230000003197 catalytic effect Effects 0.000 description 6
230000000694 effects Effects 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
229910052697 platinum Inorganic materials 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
239000003826 tablet Substances 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 6
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
238000010521 absorption reaction Methods 0.000 description 5
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
150000001241 acetals Chemical class 0.000 description 5
230000001154 acute effect Effects 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
235000010418 carrageenan Nutrition 0.000 description 5
229920001525 carrageenan Polymers 0.000 description 5
230000006378 damage Effects 0.000 description 5
150000002170 ethers Chemical class 0.000 description 5
229960002870 gabapentin Drugs 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
230000014759 maintenance of location Effects 0.000 description 5
241001515942 marmosets Species 0.000 description 5
230000036651 mood Effects 0.000 description 5
230000003040 nociceptive effect Effects 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
239000000843 powder Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
230000001256 tonic effect Effects 0.000 description 5
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
208000004454 Hyperalgesia Diseases 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
230000001773 anti-convulsant effect Effects 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
229940125904 compound 1 Drugs 0.000 description 4
IBAHLNWTOIHLKE-UHFFFAOYSA-N cyano cyanate Chemical compound N#COC#N IBAHLNWTOIHLKE-UHFFFAOYSA-N 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
229910001623 magnesium bromide Inorganic materials 0.000 description 4
125000002524 organometallic group Chemical group 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
150000003738 xylenes Chemical class 0.000 description 4
SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 3
JKONURJHZJCUAD-UHFFFAOYSA-N 2-[2-(aminomethyl)-3,3a,4,5,6,7,8,8a-octahydro-1h-azulen-2-yl]acetic acid Chemical compound C1CCCCC2CC(CN)(CC(O)=O)CC21 JKONURJHZJCUAD-UHFFFAOYSA-N 0.000 description 3
HZROAXDCVPLQAB-UHFFFAOYSA-N 2-[3-(aminomethyl)-3-bicyclo[3.1.0]hexanyl]acetic acid Chemical compound C1C(CN)(CC(O)=O)CC2CC21 HZROAXDCVPLQAB-UHFFFAOYSA-N 0.000 description 3
MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 3
WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 3
101150072179 ATP1 gene Proteins 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
101100003366 Arabidopsis thaliana ATPA gene Proteins 0.000 description 3
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
102100021649 Elongator complex protein 6 Human genes 0.000 description 3
206010019196 Head injury Diseases 0.000 description 3
101100065219 Homo sapiens ELP6 gene Proteins 0.000 description 3
208000035154 Hyperesthesia Diseases 0.000 description 3
208000006083 Hypokinesia Diseases 0.000 description 3
239000002841 Lewis acid Substances 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
239000001961 anticonvulsive agent Substances 0.000 description 3
229960003965 antiepileptics Drugs 0.000 description 3
101150105046 atpI gene Proteins 0.000 description 3
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
208000002173 dizziness Diseases 0.000 description 3
210000002683 foot Anatomy 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
230000003483 hypokinetic effect Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
208000013433 lightheadedness Diseases 0.000 description 3
239000007937 lozenge Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 3
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
239000011592 zinc chloride Substances 0.000 description 3
235000005074 zinc chloride Nutrition 0.000 description 3
OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
DBZBJLJYSYHKJO-UHFFFAOYSA-N 6-chloro-4-methyl-1,3-benzothiazol-2-amine Chemical compound CC1=CC(Cl)=CC2=C1N=C(N)S2 DBZBJLJYSYHKJO-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
208000001387 Causalgia Diseases 0.000 description 2
208000000094 Chronic Pain Diseases 0.000 description 2
208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
208000020401 Depressive disease Diseases 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
208000007101 Muscle Cramp Diseases 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
208000028389 Nerve injury Diseases 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
206010038669 Respiratory arrest Diseases 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
208000005392 Spasm Diseases 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
208000005298 acute pain Diseases 0.000 description 2
150000001412 amines Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000012223 aqueous fraction Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
230000007177 brain activity Effects 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
208000026106 cerebrovascular disease Diseases 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 2
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
238000001647 drug administration Methods 0.000 description 2
235000013601 eggs Nutrition 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
210000000981 epithelium Anatomy 0.000 description 2
ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
235000013305 food Nutrition 0.000 description 2
210000000548 hind-foot Anatomy 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 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
IJMWREDHKRHWQI-UHFFFAOYSA-M magnesium;ethene;chloride Chemical compound [Mg+2].[Cl-].[CH-]=C IJMWREDHKRHWQI-UHFFFAOYSA-M 0.000 description 2
SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
230000008764 nerve damage Effects 0.000 description 2
230000002232 neuromuscular Effects 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
238000005192 partition Methods 0.000 description 2
210000000578 peripheral nerve Anatomy 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
229910000105 potassium hydride Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
230000001107 psychogenic effect Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
229910052703 rhodium Inorganic materials 0.000 description 2
239000010948 rhodium Substances 0.000 description 2
208000019116 sleep disease Diseases 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical class [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
210000000225 synapse Anatomy 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
PGOLTJPQCISRTO-UHFFFAOYSA-N vinyllithium Chemical compound [Li]C=C PGOLTJPQCISRTO-UHFFFAOYSA-N 0.000 description 2
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
CEIVLWVVDDLERA-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalen-2-ylmethanamine Chemical compound C1CCC2CC(CN)CC21 CEIVLWVVDDLERA-UHFFFAOYSA-N 0.000 description 1
LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
NBINUAYUYGRPPJ-UHFFFAOYSA-N 2-[3-(aminomethyl)-3-bicyclo[3.2.0]heptanyl]acetic acid;hydrochloride Chemical compound Cl.C1C(CN)(CC(O)=O)CC2CCC21 NBINUAYUYGRPPJ-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
208000007848 Alcoholism Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
206010003497 Asphyxia Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
208000037157 Azotemia Diseases 0.000 description 1
208000020925 Bipolar disease Diseases 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
206010058019 Cancer Pain Diseases 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
208000018152 Cerebral disease Diseases 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
206010053398 Clonic convulsion Diseases 0.000 description 1
229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
238000001061 Dunnett's test Methods 0.000 description 1
206010014498 Embolic stroke Diseases 0.000 description 1
208000005189 Embolism Diseases 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
102000020897 Formins Human genes 0.000 description 1
108091022623 Formins Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000037357 HIV infectious disease Diseases 0.000 description 1
206010018985 Haemorrhage intracranial Diseases 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
206010019973 Herpes virus infection Diseases 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
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 1
206010061218 Inflammation Diseases 0.000 description 1
208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
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 1
239000004367 Lipase Substances 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
206010027940 Mood altered Diseases 0.000 description 1
206010028923 Neonatal asphyxia Diseases 0.000 description 1
208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
208000005890 Neuroma Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
206010068106 Occipital neuralgia Diseases 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
208000004983 Phantom Limb Diseases 0.000 description 1
206010056238 Phantom pain Diseases 0.000 description 1
206010035039 Piloerection Diseases 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
206010036618 Premenstrual syndrome Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
206010040007 Sense of oppression Diseases 0.000 description 1
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
206010043994 Tonic convulsion Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
229910052770 Uranium Inorganic materials 0.000 description 1
235000003560 Valerianella locusta Nutrition 0.000 description 1
240000004668 Valerianella locusta Species 0.000 description 1
206010047115 Vasculitis Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
IYGZPNSIEQRRIL-UHFFFAOYSA-M [I-].[Mg+]CC1=CC=CC=C1 Chemical compound [I-].[Mg+]CC1=CC=CC=C1 IYGZPNSIEQRRIL-UHFFFAOYSA-M 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
206010053552 allodynia Diseases 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
238000002266 amputation Methods 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
238000000149 argon plasma sintering Methods 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000001977 ataxic effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
229940000635 beta-alanine Drugs 0.000 description 1
239000003613 bile acid Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000003461 brachial plexus Anatomy 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
230000006931 brain damage Effects 0.000 description 1
231100000874 brain damage Toxicity 0.000 description 1
230000003925 brain function Effects 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
239000000872 buffer Substances 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000013172 carotid endarterectomy Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000002585 cerebral angiography Methods 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
HJRJDOWDYGURNY-UHFFFAOYSA-N copper(1+) methylsulfanylmethane Chemical compound [Cu+].CSC HJRJDOWDYGURNY-UHFFFAOYSA-N 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
125000004966 cyanoalkyl group Chemical group 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
235000013365 dairy product Nutrition 0.000 description 1
230000003001 depressive effect Effects 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
ZWWCURLKEXEFQT-UHFFFAOYSA-N dinitrogen pentaoxide Chemical compound [O-][N+](=O)O[N+]([O-])=O ZWWCURLKEXEFQT-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
235000011389 fruit/vegetable juice Nutrition 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
235000003642 hunger Nutrition 0.000 description 1
BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
208000013403 hyperactivity Diseases 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
230000036543 hypotension Effects 0.000 description 1
208000003532 hypothyroidism Diseases 0.000 description 1
230000002989 hypothyroidism Effects 0.000 description 1
238000005286 illumination Methods 0.000 description 1
239000007943 implant Substances 0.000 description 1
UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
238000009434 installation Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
210000004347 intestinal mucosa Anatomy 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
OPLZTPRSJUNYJI-UHFFFAOYSA-N isocyanatosulfanylmethylbenzene Chemical compound O=C=NSCC1=CC=CC=C1 OPLZTPRSJUNYJI-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000011542 limb amputation Methods 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
CYSFUFRXDOAOMP-UHFFFAOYSA-M magnesium;prop-1-ene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C=C CYSFUFRXDOAOMP-UHFFFAOYSA-M 0.000 description 1
238000005259 measurement Methods 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
239000000693 micelle Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000007510 mood change Effects 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
BSIDXUHWUKTRQL-UHFFFAOYSA-N nickel palladium Chemical compound [Ni].[Pd] BSIDXUHWUKTRQL-UHFFFAOYSA-N 0.000 description 1
JCZMXVGQBBATMY-UHFFFAOYSA-N nitro acetate Chemical compound CC(=O)O[N+]([O-])=O JCZMXVGQBBATMY-UHFFFAOYSA-N 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
238000001543 one-way ANOVA Methods 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
235000021542 oral nutrition Nutrition 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
239000006201 parenteral dosage form Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
229960005152 pentetrazol Drugs 0.000 description 1
208000033300 perinatal asphyxia Diseases 0.000 description 1
208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
208000019899 phobic disease Diseases 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000005371 pilomotor reflex Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000008569 process Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000000306 recurrent effect Effects 0.000 description 1
230000011514 reflex Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
235000002020 sage Nutrition 0.000 description 1
UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical compound I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
208000022925 sleep disturbance Diseases 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000003093 somatogenic effect Effects 0.000 description 1
230000005236 sound signal Effects 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000037351 starvation Effects 0.000 description 1
208000005809 status epilepticus Diseases 0.000 description 1
239000010959 steel Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
210000002820 sympathetic nervous system Anatomy 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
239000010409 thin film Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
239000010937 tungsten Substances 0.000 description 1
210000001364 upper extremity Anatomy 0.000 description 1
208000009852 uremia Diseases 0.000 description 1
230000002792 vascular Effects 0.000 description 1
238000007631 vascular surgery Methods 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- 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
- A61P25/08—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
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/28—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and containing rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/18—All rings being cycloaliphatic the ring system containing six carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/20—All rings being cycloaliphatic the ring system containing seven carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/22—All rings being cycloaliphatic the ring system containing eight carbon atoms, e.g. pentalene
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/28—Hydrogenated naphthalenes

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Diabetes (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Endocrinology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Hematology (AREA)
Psychiatry (AREA)
Epidemiology (AREA)
Anesthesiology (AREA)
Psychology (AREA)
Pulmonology (AREA)
Vascular Medicine (AREA)
Dermatology (AREA)
Reproductive Health (AREA)
Immunology (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Emergency Medicine (AREA)
Obesity (AREA)

EA200200293A 1999-10-20 2000-10-17 Бициклические аминокислоты в качестве фармацевтических агентов EA005206B1 (ru)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US16072599P	1999-10-20	1999-10-20
PCT/US2000/028687 WO2001028978A1 (en)	1999-10-20	2000-10-17	Bicyclic amino acids as pharmaceutical agents

Publications (2)

Publication Number	Publication Date
EA200200293A1 EA200200293A1 (ru)	2002-10-31
EA005206B1 true EA005206B1 (ru)	2004-12-30

Family

ID=22578159

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EA200200293A EA005206B1 (ru)	1999-10-20	2000-10-17	Бициклические аминокислоты в качестве фармацевтических агентов

Country Status (50)

Country	Link
US (2)	US6689906B1 (2)
EP (2)	EP1506955B1 (2)
JP (2)	JP3632191B2 (2)
KR (2)	KR100593349B1 (2)
CN (1)	CN1165518C (2)
AP (2)	AP2004003186A0 (2)
AR (2)	AR026087A1 (2)
AT (2)	ATE358116T1 (2)
AU (2)	AU778871B2 (2)
BG (2)	BG108860A (2)
BR (1)	BR0014972B1 (2)
CA (1)	CA2386297C (2)
CO (1)	CO5280060A1 (2)
CR (1)	CR6620A (2)
CU (1)	CU23112A3 (2)
CZ (1)	CZ295960B6 (2)
DE (2)	DE60034157T2 (2)
DO (1)	DOP2000000083A (2)
DZ (1)	DZ3197A1 (2)
EA (1)	EA005206B1 (2)
EC (1)	ECSP045393A (2)
EE (1)	EE200200211A (2)
ES (2)	ES2237464T3 (2)
GE (1)	GEP20043297B (2)
GT (2)	GT200000183AA (2)
HK (1)	HK1049826B (2)
HN (1)	HN2000000224A (2)
HR (2)	HRP20040709A2 (2)
HU (1)	HUP0203325A3 (2)
IL (3)	IL149143A0 (2)
IS (2)	IS6348A (2)
MA (1)	MA26842A1 (2)
MX (1)	MXPA02003229A (2)
MY (1)	MY127678A (2)
NO (2)	NO20021780D0 (2)
NZ (1)	NZ517961A (2)
OA (1)	OA12070A (2)
PA (1)	PA8505201A1 (2)
PE (1)	PE20010740A1 (2)
PL (1)	PL354607A1 (2)
PT (1)	PT1226110E (2)
SI (1)	SI1226110T1 (2)
SK (1)	SK5232002A3 (2)
SV (1)	SV2001000188A (2)
TR (2)	TR200201094T2 (2)
TW (2)	TWI225855B (2)
UA (1)	UA72931C2 (2)
WO (1)	WO2001028978A1 (2)
YU (2)	YU73004A (2)
ZA (1)	ZA200202543B (2)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7164034B2 (en)	1999-06-10	2007-01-16	Pfizer Inc.	Alpha2delta ligands for fibromyalgia and other disorders
PL359872A1 (en) *	2000-06-26	2004-09-06	Warner-Lambert Company	Gabapentin analogues for sleep disorders
US6620829B2 (en)	2000-10-17	2003-09-16	Warner-Lambert Company	Method of treating noninflammatory cartilage damage
EP1226820A1 (en)	2001-01-26	2002-07-31	Warner-Lambert Company	Use of bicyclic amino acids for preventing and treating visceral pain and gastrointestinal disorders
BR0208922A (pt) *	2001-04-19	2004-04-20	Warner Lambert Co	Aminoácidos bicìclicos ou tricìclicos fundidos
GB2375108A (en) *	2001-05-04	2002-11-06	Warner Lambert Co	Production of a bicycloheptanone
GB2375109A (en) *	2001-05-04	2002-11-06	Warner Lambert Co	Process for preparing bicyclic amino acid
CA2449729C (en) *	2001-06-11	2009-11-03	Xenoport, Inc.	Prodrugs of gaba analogs, compositions and uses thereof
US6818787B2 (en)	2001-06-11	2004-11-16	Xenoport, Inc.	Prodrugs of GABA analogs, compositions and uses thereof
US7232924B2 (en)	2001-06-11	2007-06-19	Xenoport, Inc.	Methods for synthesis of acyloxyalkyl derivatives of GABA analogs
US7186855B2 (en)	2001-06-11	2007-03-06	Xenoport, Inc.	Prodrugs of GABA analogs, compositions and uses thereof
US8048917B2 (en)	2005-04-06	2011-11-01	Xenoport, Inc.	Prodrugs of GABA analogs, compositions and uses thereof
CN1625393A (zh)	2002-01-31	2005-06-08	沃纳-兰伯特公司	治疗耳鸣的α2δ配体
PL372210A1 (en) *	2002-02-22	2005-07-11	Warner-Lambert Company Llc	Combinations of an alpha-2-delta ligand with a selective inhibitor of cyclooxygenase-2
WO2004002462A2 (en) *	2002-06-27	2004-01-08	Warner-Lambert Company Llc	Use of an alpha2delta ligand such as gabapentin or pregabalin for treating ttention deficit hyperactivity disorder
GB0219024D0 (en) *	2002-08-15	2002-09-25	Pfizer Ltd	Synergistic combinations
US7419981B2 (en)	2002-08-15	2008-09-02	Pfizer Inc.	Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor
JP2005539092A (ja) *	2002-08-15	2005-12-22	ファイザー・インク	縮合二環式または三環式アミノ酸の治療における使用
GB0223072D0 (en)	2002-10-04	2002-11-13	Pfizer Ltd	Cyclic nitromethyl acetic acid derivatives
US7018818B2 (en)	2002-10-04	2006-03-28	Pfizer Inc.	Intermediates in the preparation of therapeutic fused bicyclic amino acids
US7060727B2 (en)	2002-12-11	2006-06-13	Xenoport, Inc.	Prodrugs of fused GABA analogs, pharmaceutical compositions and uses thereof
CA2451267A1 (en)	2002-12-13	2004-06-13	Warner-Lambert Company Llc	Pharmaceutical uses for alpha2delta ligands
AU2003303041B2 (en)	2002-12-13	2008-07-24	Warner-Lambert Company Llc	Alpha-2-delta ligand to treat lower urinary tract symptoms
NZ540591A (en)	2002-12-13	2008-03-28	Warner Lambert Co	Pregabalin derivatives for the treatment of fibromyalgia and other disorders
AU2004271800A1 (en)	2003-09-12	2005-03-24	Pfizer Inc.	Combinations comprising alpha-2-delta ligands and serotonin / noradrenaline re-uptake inhibitors
WO2006092692A1 (en) *	2005-03-01	2006-09-08	Pfizer Limited	Use of combinations of pde7 inhibitors and alpha-2-delty ligands for the treatment of neuropathic pain
AR061728A1 (es) *	2006-06-30	2008-09-17	Pfizer Prod Inc	Composicion para tratamiento usando compuestos selectivos alfa-2-delta-1
CA2673545A1 (en)	2006-12-22	2008-07-03	Recordati Ireland Limited	Combination therapy of lower urinary tract disorders with .alpha.2.delta. ligands and nsaids
EP2657219B1 (en)	2007-09-28	2014-12-10	Daiichi Sankyo Company, Limited	Intermediate for producing bicyclic y-amino acid derivative
JP5557292B2 (ja)	2009-03-26	2014-07-23	第一三共株式会社	二環性γ−アミノ酸誘導体の製造方法
EP2719676B1 (en)	2011-06-08	2017-12-13	Daiichi Sankyo Company, Limited	Method for producing bicyclic compound via iminium salt
WO2012169475A1 (ja)	2011-06-08	2012-12-13	第一三共株式会社	クライゼン転位反応による二環性化合物の製造方法
IN2014MN01046A (2)	2011-12-15	2015-05-01	Daiichi Sankyo Companyltd
EP2837689B1 (en)	2012-04-10	2017-02-15	Daiichi Sankyo Company, Limited	Optical resolution method for bicyclic compound using enzyme
US9066853B2 (en)	2013-01-15	2015-06-30	Warsaw Orthopedic, Inc.	Clonidine compounds in a biodegradable fiber
TWI635071B (zh)	2013-07-08	2018-09-11	第一三共股份有限公司	光學活性二環γ－胺基酸衍生物及其製造方法
WO2018166855A1 (en)	2017-03-16	2018-09-20	Basf Se	Heterobicyclic substituted dihydroisoxazoles
CN113045410A (zh) *	2021-03-29	2021-06-29	华东理工大学	一种双环降二萜类化合物及其合成基因及制备方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3641129A (en)	1969-06-17	1972-02-08	Merck & Co Inc	Antifibrinolytic compounds
DE2460891C2 (de)	1974-12-21	1982-09-23	Gödecke AG, 1000 Berlin	1-Aminomethyl-1-cycloalkanessigsäuren und deren Ester, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
US4087544A (en) *	1974-12-21	1978-05-02	Warner-Lambert Company	Treatment of cranial dysfunctions using novel cyclic amino acids
HUP0004310A3 (en)	1997-10-27	2001-11-28	Warner Lambert Co	Cyclic amino acids, and derivatives thereof and pharmaceutical compositions comprising the said compounds as active agents

2000
- 2000-10-05 HN HN2000000224A patent/HN2000000224A/es unknown
- 2000-10-06 SV SV2000000188A patent/SV2001000188A/es not_active Application Discontinuation
- 2000-10-17 GE GE4783A patent/GEP20043297B/en unknown
- 2000-10-17 DZ DZ003197A patent/DZ3197A1/xx active
- 2000-10-17 TR TR2002/01094T patent/TR200201094T2/xx unknown
- 2000-10-17 SI SI200030670T patent/SI1226110T1/xx unknown
- 2000-10-17 HR HRP20040709 patent/HRP20040709A2/xx not_active Application Discontinuation
- 2000-10-17 JP JP2001531783A patent/JP3632191B2/ja not_active Expired - Fee Related
- 2000-10-17 EA EA200200293A patent/EA005206B1/ru unknown
- 2000-10-17 AP AP2004003186A patent/AP2004003186A0/xx unknown
- 2000-10-17 AU AU10920/01A patent/AU778871B2/en not_active Ceased
- 2000-10-17 CZ CZ20021310A patent/CZ295960B6/cs not_active IP Right Cessation
- 2000-10-17 HU HU0203325A patent/HUP0203325A3/hu unknown
- 2000-10-17 KR KR1020027005036A patent/KR100593349B1/ko not_active Expired - Fee Related
- 2000-10-17 NZ NZ517961A patent/NZ517961A/xx unknown
- 2000-10-17 UA UA2002032434A patent/UA72931C2/uk unknown
- 2000-10-17 KR KR1020067002249A patent/KR100566462B1/ko not_active Expired - Fee Related
- 2000-10-17 CA CA2386297A patent/CA2386297C/en not_active Expired - Fee Related
- 2000-10-17 SK SK523-2002A patent/SK5232002A3/sk unknown
- 2000-10-17 EE EEP200200211A patent/EE200200211A/xx unknown
- 2000-10-17 HK HK03101868.4A patent/HK1049826B/zh not_active IP Right Cessation
- 2000-10-17 WO PCT/US2000/028687 patent/WO2001028978A1/en not_active Ceased
- 2000-10-17 IL IL14914300A patent/IL149143A0/xx not_active IP Right Cessation
- 2000-10-17 AT AT04027485T patent/ATE358116T1/de not_active IP Right Cessation
- 2000-10-17 US US10/130,023 patent/US6689906B1/en not_active Expired - Fee Related
- 2000-10-17 TR TR2005/00221T patent/TR200500221T2/xx unknown
- 2000-10-17 CN CNB008145644A patent/CN1165518C/zh not_active Expired - Fee Related
- 2000-10-17 YU YU73004A patent/YU73004A/sh unknown
- 2000-10-17 DE DE60034157T patent/DE60034157T2/de not_active Expired - Lifetime
- 2000-10-17 MX MXPA02003229A patent/MXPA02003229A/es active IP Right Grant
- 2000-10-17 EP EP04027485A patent/EP1506955B1/en not_active Expired - Lifetime
- 2000-10-17 PL PL00354607A patent/PL354607A1/xx not_active Application Discontinuation
- 2000-10-17 ES ES00972226T patent/ES2237464T3/es not_active Expired - Lifetime
- 2000-10-17 BR BRPI0014972-1A patent/BR0014972B1/pt not_active IP Right Cessation
- 2000-10-17 AT AT00972226T patent/ATE293590T1/de not_active IP Right Cessation
- 2000-10-17 YU YU29302A patent/YU29302A/sh unknown
- 2000-10-17 AP APAP/P/2002/002517A patent/AP2002002517A0/en unknown
- 2000-10-17 DE DE60019628T patent/DE60019628T2/de not_active Expired - Lifetime
- 2000-10-17 OA OA1200200117A patent/OA12070A/en unknown
- 2000-10-17 EP EP00972226A patent/EP1226110B1/en not_active Expired - Lifetime
- 2000-10-17 HR HR20020428A patent/HRP20020428B1/xx not_active IP Right Cessation
- 2000-10-17 PT PT00972226T patent/PT1226110E/pt unknown
- 2000-10-17 ES ES04027485T patent/ES2282785T3/es not_active Expired - Lifetime
- 2000-10-17 IL IL16406000A patent/IL164060A0/xx unknown
- 2000-10-18 MY MYPI20004896A patent/MY127678A/en unknown
- 2000-10-18 PA PA20008505201A patent/PA8505201A1/es unknown
- 2000-10-19 GT GT200000183AK patent/GT200000183AA/es unknown
- 2000-10-19 CO CO00079741A patent/CO5280060A1/es not_active Application Discontinuation
- 2000-10-19 DO DO2000000083A patent/DOP2000000083A/es unknown
- 2000-10-19 PE PE2000001116A patent/PE20010740A1/es not_active Application Discontinuation
- 2000-10-19 AR ARP000105497A patent/AR026087A1/es unknown
- 2000-10-19 GT GT200000183A patent/GT200000183A/es unknown
- 2000-10-20 TW TW089122115A patent/TWI225855B/zh not_active IP Right Cessation
- 2000-10-20 TW TW093125953A patent/TW200505824A/zh unknown
2002
- 2002-03-28 ZA ZA200202543A patent/ZA200202543B/xx unknown
- 2002-04-15 IL IL149143A patent/IL149143A/en unknown
- 2002-04-16 CU CU78A patent/CU23112A3/es unknown
- 2002-04-16 NO NO20021780A patent/NO20021780D0/no not_active Application Discontinuation
- 2002-04-17 IS IS6348A patent/IS6348A/is unknown
- 2002-04-18 CR CR6620A patent/CR6620A/es not_active Application Discontinuation
- 2002-05-10 MA MA26634A patent/MA26842A1/fr unknown
- 2002-05-20 BG BG108860A patent/BG108860A/en unknown
- 2002-05-20 BG BG106719A patent/BG106719A/bg unknown
2004
- 2004-01-21 US US10/762,026 patent/US6835751B2/en not_active Expired - Fee Related
- 2004-07-28 EC EC2004005393A patent/ECSP045393A/es unknown
- 2004-08-17 AR ARP040102937A patent/AR045456A2/es unknown
- 2004-09-01 NO NO20043663A patent/NO20043663L/no not_active Application Discontinuation
- 2004-09-14 JP JP2004266488A patent/JP3744928B2/ja not_active Expired - Fee Related
- 2004-10-08 IS IS7497A patent/IS7497A/is unknown
2005
- 2005-03-23 AU AU2005201268A patent/AU2005201268A1/en not_active Abandoned

Also Published As

Publication number	Publication date
KR100593349B1 (ko)	2006-06-26
YU73004A (sh)	2005-11-28
ECSP045393A (es)	2004-10-23
ZA200202543B (en)	2003-09-23
MY127678A (en)	2006-12-29
ES2282785T3 (es)	2007-10-16
IS6348A (is)	2002-04-17
CA2386297A1 (en)	2001-04-26
CN1382118A (zh)	2002-11-27
NO20043663L (no)	2002-04-16
JP2003512348A (ja)	2003-04-02
CZ295960B6 (cs)	2005-12-14
DE60019628D1 (de)	2005-05-25
SI1226110T1 (en)	2005-08-31
KR20060013701A (ko)	2006-02-13
JP3744928B2 (ja)	2006-02-15
TR200500221T2 (tr)	2005-03-21
IL164060A0 (en)	2005-12-18
EA200200293A1 (ru)	2002-10-31
US6689906B1 (en)	2004-02-10
OA12070A (en)	2003-11-10
BG108860A (en)	2006-03-31
HUP0203325A2 (hu)	2003-02-28
CN1165518C (zh)	2004-09-08
ATE293590T1 (de)	2005-05-15
PA8505201A1 (es)	2002-08-29
AU778871B2 (en)	2004-12-23
CA2386297C (en)	2010-02-09
HK1049826B (zh)	2005-02-25
HK1049826A1 (en)	2003-05-30
MA26842A1 (fr)	2004-12-20
AP2004003186A0 (en)	2004-12-31
JP3632191B2 (ja)	2005-03-23
EP1506955A1 (en)	2005-02-16
DE60019628T2 (de)	2006-01-19
KR20020040900A (ko)	2002-05-30
HN2000000224A (es)	2001-04-11
HRP20020428A2 (en)	2005-02-28
DE60034157T2 (de)	2007-12-13
EP1506955B1 (en)	2007-03-28
NO20021780L (no)	2002-04-16
DE60034157D1 (de)	2007-05-10
NO20021780D0 (no)	2002-04-16
CU23112A3 (es)	2006-02-27
EP1226110B1 (en)	2005-04-20
TR200201094T2 (tr)	2002-09-23
CR6620A (es)	2004-02-02
AU2005201268A1 (en)	2005-04-21
UA72931C2 (uk)	2005-05-16
BR0014972B1 (pt)	2011-09-06
SK5232002A3 (en)	2003-07-01
MXPA02003229A (es)	2002-09-30
DZ3197A1 (fr)	2001-04-26
AR026087A1 (es)	2002-12-26
EE200200211A (et)	2003-06-16
ES2237464T3 (es)	2005-08-01
IL149143A (en)	2007-02-11
HUP0203325A3 (en)	2003-12-29
BG106719A (bg)	2003-02-28
US20040152779A1 (en)	2004-08-05
PL354607A1 (en)	2004-01-26
JP2005036009A (ja)	2005-02-10
NZ517961A (en)	2002-12-20
IS7497A (is)	2004-10-08
PE20010740A1 (es)	2001-07-27
IL149143A0 (en)	2002-11-10
GEP20043297B (en)	2004-01-12
GT200000183A (es)	2000-10-19
KR100566462B1 (ko)	2006-03-31
WO2001028978A1 (en)	2001-04-26
AU1092001A (en)	2001-04-30
ATE358116T1 (de)	2007-04-15
BR0014972A (pt)	2002-07-16
AP2002002517A0 (en)	2002-06-30
SV2001000188A (es)	2001-09-07
YU29302A (sh)	2005-06-10
AR045456A2 (es)	2005-10-26
US6835751B2 (en)	2004-12-28
TWI225855B (en)	2005-01-01
PT1226110E (pt)	2005-07-29
HRP20040709A2 (en)	2004-12-31
DOP2000000083A (es)	2002-03-30
CO5280060A1 (es)	2003-05-30
EP1226110A1 (en)	2002-07-31
TW200505824A (en)	2005-02-16
HRP20020428B1 (en)	2006-02-28
CZ20021310A3 (cs)	2003-05-14
GT200000183AA (es)	2005-06-17

Publication	Publication Date	Title
EA005206B1 (ru)	2004-12-30	Бициклические аминокислоты в качестве фармацевтических агентов
JP4263717B2 (ja)	2009-05-13	医薬として有用な環状アミノ酸およびその誘導体
CZ286398A3 (cs)	1999-03-17	Nové substituované cyklické aminokyseliny jako farmaceutická činidla
JP2002516312A (ja)	2002-06-04	カルシウムチャンネルのα２δサブユニットに対する親和性を有する立体配座的に制約されたアミノ酸化合物
EA001214B1 (ru)	2000-12-25	Новые мостиковые циклические аминокислоты как фармацевтически применимые вещества
JP2002524551A (ja)	2002-08-06	分枝鎖アルキルピロリジン−３−カルボン酸
EA004398B1 (ru)	2004-04-29	Одно- и двузамещенные 3-пропил-гамма-аминомасляные кислоты
MXPA01001044A (en)	2001-11-21	Branched alkyl pyrrolidine-3-carboxylic acids