CA2371827C - Amide compounds for the potentiation of cholinergic activity - Google Patents
Amide compounds for the potentiation of cholinergic activity Download PDFInfo
- Publication number
- CA2371827C CA2371827C CA002371827A CA2371827A CA2371827C CA 2371827 C CA2371827 C CA 2371827C CA 002371827 A CA002371827 A CA 002371827A CA 2371827 A CA2371827 A CA 2371827A CA 2371827 C CA2371827 C CA 2371827C
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- Prior art keywords
- salt
- compound
- mixture
- dementia
- substituted
- Prior art date
- Legal status (The legal status 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 status listed.)
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- -1 Amide compounds Chemical class 0.000 title claims abstract description 41
- 230000001713 cholinergic effect Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 150000003839 salts Chemical class 0.000 claims abstract description 76
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
- 229910052736 halogen Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical group 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 125000005569 butenylene group Chemical group 0.000 claims abstract description 5
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 206010012289 Dementia Diseases 0.000 claims description 22
- 208000000044 Amnesia Diseases 0.000 claims description 9
- 208000031091 Amnestic disease Diseases 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 230000006986 amnesia Effects 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- MKGPZKDTSVIAGL-MRXNPFEDSA-N 4-fluoro-n-[(2r)-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N[C@H]1CC2=CC=CC=C2CC1 MKGPZKDTSVIAGL-MRXNPFEDSA-N 0.000 claims description 2
- BOFMSBVSYVESTM-UHFFFAOYSA-N n-(2,3-dihydro-1h-inden-2-yl)-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC1CC2=CC=CC=C2C1 BOFMSBVSYVESTM-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 abstract description 13
- 125000000217 alkyl group Chemical group 0.000 abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 abstract description 7
- 125000004104 aryloxy group Chemical group 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 49
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000001704 evaporation Methods 0.000 description 20
- 230000008020 evaporation Effects 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 125000004450 alkenylene group Chemical group 0.000 description 4
- 125000001769 aryl amino group Chemical group 0.000 description 4
- 230000002490 cerebral effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- PCOYCFJCVTWMFV-UHFFFAOYSA-N tert-butyl n-(4-methylcyclohex-3-en-1-yl)carbamate Chemical compound CC1=CCC(NC(=O)OC(C)(C)C)CC1 PCOYCFJCVTWMFV-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- IVSFUQXCASICCK-UHFFFAOYSA-N 4-methylcyclohex-3-en-1-amine;hydrochloride Chemical compound Cl.CC1=CCC(N)CC1 IVSFUQXCASICCK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 230000018052 penile erection Effects 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011369 resultant mixture Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- DSVGFKBFFICWLZ-UHFFFAOYSA-N 1-fluoro-4-isocyanatobenzene Chemical compound FC1=CC=C(N=C=O)C=C1 DSVGFKBFFICWLZ-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 2
- GJIKAJOLWXMKEG-UHFFFAOYSA-N 4-methylcyclohex-3-en-1-amine Chemical compound CC1=CCC(N)CC1 GJIKAJOLWXMKEG-UHFFFAOYSA-N 0.000 description 2
- OYOQOLNBTPTFEM-UHFFFAOYSA-N 4-methylcyclohex-3-ene-1-carboxylic acid Chemical compound CC1=CCC(C(O)=O)CC1 OYOQOLNBTPTFEM-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- 206010003805 Autism Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 201000009906 Meningitis Diseases 0.000 description 2
- 206010068871 Myotonic dystrophy Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010036018 Pollakiuria Diseases 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- 208000037132 Subdural Chronic Hematoma Diseases 0.000 description 2
- 208000002667 Subdural Hematoma Diseases 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
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- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 201000003631 narcolepsy Diseases 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 201000003077 normal pressure hydrocephalus Diseases 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- ASYPRKQJWDKLCV-UHFFFAOYSA-N phenyl n-pyridin-4-ylcarbamate Chemical compound C=1C=CC=CC=1OC(=O)NC1=CC=NC=C1 ASYPRKQJWDKLCV-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 208000018726 traumatic encephalopathy Diseases 0.000 description 2
- FJQOAYUXVCSSQR-HNCPQSOCSA-N (2r)-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC=C2C[C@H](N)CCC2=C1 FJQOAYUXVCSSQR-HNCPQSOCSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- FJQOAYUXVCSSQR-PPHPATTJSA-N (2s)-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=CC=C2C[C@@H](N)CCC2=C1 FJQOAYUXVCSSQR-PPHPATTJSA-N 0.000 description 1
- IQZBVVPYTDHTIP-UHFFFAOYSA-N (4-fluorophenyl)urea Chemical compound NC(=O)NC1=CC=C(F)C=C1 IQZBVVPYTDHTIP-UHFFFAOYSA-N 0.000 description 1
- VGRXAHXMIDCTNV-UHFFFAOYSA-N (6-chlorobenzotriazol-1-yl) 4-chlorobenzenesulfonate Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)ON1C2=CC(Cl)=CC=C2N=N1 VGRXAHXMIDCTNV-UHFFFAOYSA-N 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- LCGFVWKNXLRFIF-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=CC=C2CC(N)CCC2=C1 LCGFVWKNXLRFIF-UHFFFAOYSA-N 0.000 description 1
- JGEJOHKJHBRJEX-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-(4-methylcyclohex-3-en-1-yl)urea Chemical compound C1CC(C)=CCC1NC(=O)NC1=CC=C(F)C=C1 JGEJOHKJHBRJEX-UHFFFAOYSA-N 0.000 description 1
- FRGMCDALMCFVNE-UHFFFAOYSA-N 1-(4-methylcyclohex-3-en-1-yl)-3-pyridin-4-ylurea;hydrochloride Chemical compound Cl.C1CC(C)=CCC1NC(=O)NC1=CC=NC=C1 FRGMCDALMCFVNE-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 description 1
- WPQFHUORSWAEOP-UHFFFAOYSA-N 2-azido-3,4-diphenyl-1h-phosphole Chemical compound [N-]=[N+]=NC=1PC=C(C=2C=CC=CC=2)C=1C1=CC=CC=C1 WPQFHUORSWAEOP-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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- 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 1
- MKGPZKDTSVIAGL-UHFFFAOYSA-N 4-fluoro-n-(1,2,3,4-tetrahydronaphthalen-2-yl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC1CC2=CC=CC=C2CC1 MKGPZKDTSVIAGL-UHFFFAOYSA-N 0.000 description 1
- JPZRGJYQFFHGMR-UHFFFAOYSA-N 4-fluoro-n-(4-methylcyclohex-3-en-1-yl)benzamide Chemical compound C1CC(C)=CCC1NC(=O)C1=CC=C(F)C=C1 JPZRGJYQFFHGMR-UHFFFAOYSA-N 0.000 description 1
- UDWVJVXXKPFREM-UHFFFAOYSA-N 4-fluoro-n-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)benzamide Chemical compound C1CC2=CC(OC)=CC=C2CC1NC(=O)C1=CC=C(F)C=C1 UDWVJVXXKPFREM-UHFFFAOYSA-N 0.000 description 1
- YWZSQXHBYZIAGY-UHFFFAOYSA-N 4-fluoro-n-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)benzamide Chemical compound C1C2=CC(OC)=CC=C2CCC1NC(=O)C1=CC=C(F)C=C1 YWZSQXHBYZIAGY-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 1
- NZZITUYJLJVUTI-UHFFFAOYSA-N 4-methylcyclohex-3-ene-1-carbonyl chloride Chemical compound CC1=CCC(C(Cl)=O)CC1 NZZITUYJLJVUTI-UHFFFAOYSA-N 0.000 description 1
- TZCYLJGNWDVJRA-UHFFFAOYSA-N 6-chloro-1-hydroxybenzotriazole Chemical compound C1=C(Cl)C=C2N(O)N=NC2=C1 TZCYLJGNWDVJRA-UHFFFAOYSA-N 0.000 description 1
- WASIYUSITZITPW-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C(N)CCC2=CC(OC)=CC=C21 WASIYUSITZITPW-UHFFFAOYSA-N 0.000 description 1
- ZNWNWWLWFCCREO-UHFFFAOYSA-N 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1CC(N)CC2=CC(OC)=CC=C21 ZNWNWWLWFCCREO-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical class OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- PTKRIJQZPBQGGV-UHFFFAOYSA-N N-(4-fluorophenyl)-3,4-dihydro-1H-isoquinoline-2-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1CC2=CC=CC=C2CC1 PTKRIJQZPBQGGV-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- XNPOFXIBHOVFFH-UHFFFAOYSA-N N-cyclohexyl-N'-(2-(4-morpholinyl)ethyl)carbodiimide Chemical compound C1CCCCC1N=C=NCCN1CCOCC1 XNPOFXIBHOVFFH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920005439 Perspex® Polymers 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940125682 antidementia agent Drugs 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- BNTRVUUJBGBGLZ-UHFFFAOYSA-N hydron;pyridine-4-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=NC=C1 BNTRVUUJBGBGLZ-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- XNBKKRFABABBPM-UHFFFAOYSA-N n,n-diphenylcarbamoyl chloride Chemical compound C=1C=CC=CC=1N(C(=O)Cl)C1=CC=CC=C1 XNBKKRFABABBPM-UHFFFAOYSA-N 0.000 description 1
- KTMVLAUGJXPCRK-UHFFFAOYSA-N n-(1,2,3,4-tetrahydronaphthalen-2-yl)pyridine-4-carboxamide Chemical compound C1CC2=CC=CC=C2CC1NC(=O)C1=CC=NC=C1 KTMVLAUGJXPCRK-UHFFFAOYSA-N 0.000 description 1
- RBQOQDIAHULFRC-UHFFFAOYSA-N n-(4-fluorophenyl)-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)N1CC=CCC1 RBQOQDIAHULFRC-UHFFFAOYSA-N 0.000 description 1
- YMUJFSGCXFTYLB-UHFFFAOYSA-N n-(4-methylcyclohex-3-en-1-yl)pyridine-4-carboxamide Chemical compound C1CC(C)=CCC1NC(=O)C1=CC=NC=C1 YMUJFSGCXFTYLB-UHFFFAOYSA-N 0.000 description 1
- BADKRQPGXLYDGH-UHFFFAOYSA-N n-benzhydryl-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC(C=1C=CC=CC=1)C1=CC=CC=C1 BADKRQPGXLYDGH-UHFFFAOYSA-N 0.000 description 1
- QQMLJLZQRCNQCQ-UHFFFAOYSA-N n-pyridin-4-yl-3,6-dihydro-2h-pyridine-1-carboxamide;hydrochloride Chemical compound Cl.C1CC=CCN1C(=O)NC1=CC=NC=C1 QQMLJLZQRCNQCQ-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- IYPZRUYMFDWKSS-UHFFFAOYSA-N piperazin-1-amine Chemical class NN1CCNCC1 IYPZRUYMFDWKSS-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- 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
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPP8912A AUPP891299A0 (en) | 1999-02-26 | 1999-02-26 | New 6-membered cyclic compounds |
| AUPP8912 | 1999-02-26 | ||
| PCT/JP2000/000601 WO2000051970A1 (en) | 1999-02-26 | 2000-02-03 | Amide compounds for the potentiation of cholinergic activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2371827A1 CA2371827A1 (en) | 2000-09-08 |
| CA2371827C true CA2371827C (en) | 2008-06-10 |
Family
ID=3813111
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002371827A Expired - Fee Related CA2371827C (en) | 1999-02-26 | 2000-02-03 | Amide compounds for the potentiation of cholinergic activity |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1159258B1 (enExample) |
| JP (1) | JP4089159B2 (enExample) |
| KR (1) | KR100620406B1 (enExample) |
| CN (1) | CN1170814C (enExample) |
| AR (1) | AR029618A1 (enExample) |
| AT (1) | ATE282022T1 (enExample) |
| AU (2) | AUPP891299A0 (enExample) |
| BR (1) | BR0010225A (enExample) |
| CA (1) | CA2371827C (enExample) |
| DE (1) | DE60015732T2 (enExample) |
| DK (1) | DK1159258T3 (enExample) |
| ES (1) | ES2226775T3 (enExample) |
| HK (1) | HK1044934B (enExample) |
| HU (1) | HUP0200116A3 (enExample) |
| PT (1) | PT1159258E (enExample) |
| RU (1) | RU2211215C2 (enExample) |
| TR (1) | TR200102494T2 (enExample) |
| TW (1) | TWI225856B (enExample) |
| WO (1) | WO2000051970A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2351347A1 (en) | 1998-11-23 | 2000-06-02 | Bonnie Davis | Dosage formulations for acetylcholinesterase inhibitors |
| CN100370990C (zh) | 1998-12-24 | 2008-02-27 | 詹森药业有限公司 | 控释加兰他敏组合物 |
| MY136316A (en) | 2001-02-13 | 2008-09-30 | Sanofi Aventis Deutschland | Acylated 6,7,8,9-tetrahydro-5h-benzocycloheptenyl amines and their use as pharmaceutical. |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| PE20020856A1 (es) | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
| TWI241190B (en) | 2001-02-13 | 2005-10-11 | Aventis Pharma Gmbh | 4-Fluoro-N-indan-2-yl benzamide and its use as pharmaceutical |
| US6984647B2 (en) * | 2002-05-17 | 2006-01-10 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid VR1 receptor |
| JP5036310B2 (ja) | 2003-08-06 | 2012-09-26 | セノミックス インコーポレイテッド | 新規な風味、風味改質剤、味覚剤、味覚向上剤、旨味および甘味味覚剤、および／またはそれらの向上剤および使用 |
| EP3398452B1 (en) | 2006-04-21 | 2024-10-02 | Firmenich Incorporated | Comestible compositions comprising high potency savory flavorants |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| UY32442A (es) | 2009-02-13 | 2010-09-30 | Sanofi Aventis | Nuevos indanos sustituidos, procesos para su preparacion y uso de los mismos como un medicamento |
| JP2025066196A (ja) * | 2022-03-14 | 2025-04-23 | 国立大学法人東北大学 | 認知機能改善剤 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR8287M (enExample) * | 1968-12-31 | 1970-11-09 | ||
| US4797419A (en) * | 1986-11-03 | 1989-01-10 | Warner-Lambert Company | Method of treating the symptoms of senile cognitive decline employing di- or trisubstituted urea cholinergic agents |
| EP0306375A1 (fr) * | 1987-08-07 | 1989-03-08 | Synthelabo | Dérivés de[(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 isoquinoléine, leur préparation et leur application en thérapeutique |
| IL90279A (en) * | 1988-05-24 | 1995-03-30 | American Home Prod | Piperazinyl carboxamide derivatives, their preparation and pharmaceutical com¦ositions containing them |
| GB8917687D0 (en) * | 1989-08-02 | 1989-09-20 | Fujisawa Pharmaceutical Co | Aminopiperazine derivatives,processes for preparation thereof and pharmaceutical composition comprising the same |
| RU2024507C1 (ru) * | 1991-11-18 | 1994-12-15 | Евгений Яковлевич Левитин | 5-хлор-2-пиридиламид-4-нитро-n-(карбоксиметил)антраниловой кислоты, проявляющий противовоспалительную активность |
| JPH06107544A (ja) * | 1992-09-29 | 1994-04-19 | Taisho Pharmaceut Co Ltd | コリン作動性神経不全の改善・治療薬 |
| JPH06298732A (ja) * | 1993-02-16 | 1994-10-25 | Taisho Pharmaceut Co Ltd | インドール誘導体 |
-
1999
- 1999-02-26 AU AUPP8912A patent/AUPP891299A0/en not_active Abandoned
-
2000
- 2000-02-03 TR TR2001/02494T patent/TR200102494T2/xx unknown
- 2000-02-03 AT AT00902080T patent/ATE282022T1/de not_active IP Right Cessation
- 2000-02-03 CA CA002371827A patent/CA2371827C/en not_active Expired - Fee Related
- 2000-02-03 HU HU0200116A patent/HUP0200116A3/hu unknown
- 2000-02-03 RU RU2001126120/04A patent/RU2211215C2/ru not_active IP Right Cessation
- 2000-02-03 DK DK00902080T patent/DK1159258T3/da active
- 2000-02-03 ES ES00902080T patent/ES2226775T3/es not_active Expired - Lifetime
- 2000-02-03 AU AU23257/00A patent/AU766655B2/en not_active Ceased
- 2000-02-03 EP EP00902080A patent/EP1159258B1/en not_active Expired - Lifetime
- 2000-02-03 KR KR1020017010325A patent/KR100620406B1/ko not_active Expired - Fee Related
- 2000-02-03 JP JP2000602198A patent/JP4089159B2/ja not_active Expired - Fee Related
- 2000-02-03 DE DE60015732T patent/DE60015732T2/de not_active Expired - Lifetime
- 2000-02-03 HK HK02106646.3A patent/HK1044934B/zh not_active IP Right Cessation
- 2000-02-03 WO PCT/JP2000/000601 patent/WO2000051970A1/en not_active Ceased
- 2000-02-03 CN CNB008043035A patent/CN1170814C/zh not_active Expired - Fee Related
- 2000-02-03 PT PT00902080T patent/PT1159258E/pt unknown
- 2000-02-03 BR BR0010225-3A patent/BR0010225A/pt not_active Application Discontinuation
- 2000-02-14 TW TW089102410A patent/TWI225856B/zh not_active IP Right Cessation
- 2000-02-24 AR ARP000100793A patent/AR029618A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1044934B (zh) | 2005-06-03 |
| TWI225856B (en) | 2005-01-01 |
| AU766655B2 (en) | 2003-10-23 |
| DE60015732T2 (de) | 2005-03-31 |
| JP2002538132A (ja) | 2002-11-12 |
| RU2211215C2 (ru) | 2003-08-27 |
| WO2000051970A1 (en) | 2000-09-08 |
| AU2325700A (en) | 2000-09-21 |
| ES2226775T3 (es) | 2005-04-01 |
| PT1159258E (pt) | 2005-02-28 |
| TR200102494T2 (tr) | 2002-01-21 |
| CN1170814C (zh) | 2004-10-13 |
| EP1159258A1 (en) | 2001-12-05 |
| JP4089159B2 (ja) | 2008-05-28 |
| HK1044934A1 (en) | 2002-11-08 |
| HUP0200116A3 (en) | 2002-11-28 |
| DK1159258T3 (da) | 2005-02-14 |
| EP1159258B1 (en) | 2004-11-10 |
| DE60015732D1 (de) | 2004-12-16 |
| AUPP891299A0 (en) | 1999-03-25 |
| ATE282022T1 (de) | 2004-11-15 |
| KR20010102140A (ko) | 2001-11-15 |
| BR0010225A (pt) | 2002-01-22 |
| AR029618A1 (es) | 2003-07-10 |
| CN1341095A (zh) | 2002-03-20 |
| CA2371827A1 (en) | 2000-09-08 |
| KR100620406B1 (ko) | 2006-09-13 |
| HUP0200116A2 (hu) | 2002-05-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150203 |