EA003255B1 - Комбинация производных тетрагидропиридинов и ингибиторов ацетилхолинэстеразы для лечения старческой деменции по типу альцгеймера - Google Patents

Комбинация производных тетрагидропиридинов и ингибиторов ацетилхолинэстеразы для лечения старческой деменции по типу альцгеймера Download PDF

Info

Publication number: EA003255B1
Authority: EA; Eurasian Patent Office
Prior art keywords: tetrahydropyridine; trifluoromethylphenyl; ethyl; biphenylyl; alkyl
Prior art date: 1997-11-14

Application number

EA200000412A

Other languages

English (en)

Russian (ru)

Other versions

EA200000412A1 (ru

Inventor

Жан-Пьер Маффран

Филипп Субрие

Жан-Поль Терранова

Original Assignee

Санофи-Синтелябо

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.)

1997-11-14

Filing date

1998-11-09

Publication date

2003-02-27

1997-11-14 Priority claimed from FR9714324A external-priority patent/FR2771006B1/fr

1997-11-14 Priority claimed from FR9714322A external-priority patent/FR2771007B1/fr

1998-11-09 Application filed by Санофи-Синтелябо filed Critical Санофи-Синтелябо

2000-12-25 Publication of EA200000412A1 publication Critical patent/EA200000412A1/ru

2003-02-27 Publication of EA003255B1 publication Critical patent/EA003255B1/ru

Links

208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 18
206010039966 Senile dementia Diseases 0.000 title claims abstract description 14
VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 title 1
102000012440 Acetylcholinesterase Human genes 0.000 title 1
108010022752 Acetylcholinesterase Proteins 0.000 title 1
229940022698 acetylcholinesterase Drugs 0.000 title 1
230000002401 inhibitory effect Effects 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 48
239000000203 mixture Substances 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 35
ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims abstract description 30
-1 phenoxy, phenylamino Chemical group 0.000 claims abstract description 30
239000004480 active ingredient Substances 0.000 claims abstract description 25
229910052736 halogen Inorganic materials 0.000 claims abstract description 25
150000002367 halogens Chemical group 0.000 claims abstract description 21
125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 20
125000000217 alkyl group Chemical group 0.000 claims abstract description 20
239000000544 cholinesterase inhibitor Substances 0.000 claims abstract description 19
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
239000001257 hydrogen Substances 0.000 claims abstract description 18
229960003530 donepezil Drugs 0.000 claims abstract description 15
238000011282 treatment Methods 0.000 claims abstract description 15
WJJYZXPHLSLMGE-UHFFFAOYSA-N xaliproden Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C4C=CC=CC4=CC=3)CC=2)=C1 WJJYZXPHLSLMGE-UHFFFAOYSA-N 0.000 claims abstract description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims abstract description 12
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 12
150000002431 hydrogen Chemical group 0.000 claims abstract description 12
229960001685 tacrine Drugs 0.000 claims abstract description 8
YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical group C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims abstract description 8
CNEWKIDCGDXBDE-UHFFFAOYSA-N 1-[2-(4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC=CC=3)CC=2)=C1 CNEWKIDCGDXBDE-UHFFFAOYSA-N 0.000 claims abstract description 7
238000002360 preparation method Methods 0.000 claims abstract description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000006529 (C3-C6) alkyl group Chemical group 0.000 claims abstract description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
125000004442 acylamino group Chemical group 0.000 claims abstract description 6
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 6
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 6
125000005111 carboxyalkoxy group Chemical group 0.000 claims abstract description 6
125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 6
125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 6
125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 6
125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 6
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims abstract description 6
239000003814 drug Substances 0.000 claims abstract description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 6
ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 6
125000005504 styryl group Chemical group 0.000 claims abstract description 6
229940079593 drug Drugs 0.000 claims abstract description 5
CLAAWCXSVHYZOF-UHFFFAOYSA-N 1-[2-(2-chloro-4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C(=CC(=CC=3)C=3C=CC=CC=3)Cl)CC=2)=C1 CLAAWCXSVHYZOF-UHFFFAOYSA-N 0.000 claims abstract description 3
DRUFLWBKCQQARQ-UHFFFAOYSA-N 1-[2-(2-methoxy-5-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound COC1=CC=C(C=2C=CC=CC=2)C=C1CCN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 DRUFLWBKCQQARQ-UHFFFAOYSA-N 0.000 claims abstract description 3
PYPATGSHJOYCQF-UHFFFAOYSA-N 1-[2-(3-chloro-4-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=CC=CC=3)CC=2)=C1 PYPATGSHJOYCQF-UHFFFAOYSA-N 0.000 claims abstract description 3
IYEVNGCQLBOKSD-UHFFFAOYSA-N 1-[2-(3-fluoro-4-phenylphenyl)propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C=1C=C(C=2C=CC=CC=2)C(F)=CC=1C(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 IYEVNGCQLBOKSD-UHFFFAOYSA-N 0.000 claims abstract description 3
QQYINFSTLSPFDL-UHFFFAOYSA-N 1-[2-(3-phenylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(C=CC=3)C=3C=CC=CC=3)CC=2)=C1 QQYINFSTLSPFDL-UHFFFAOYSA-N 0.000 claims abstract description 3
RMTTZCBMBRCQRV-UHFFFAOYSA-N 1-[2-(4-benzylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(CC=4C=CC=CC=4)=CC=3)CC=2)=C1 RMTTZCBMBRCQRV-UHFFFAOYSA-N 0.000 claims abstract description 3
WCLDJGHFRWOPJG-UHFFFAOYSA-N 1-[2-(4-butoxyphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(OCCCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 WCLDJGHFRWOPJG-UHFFFAOYSA-N 0.000 claims abstract description 3
RWPHWFAGKMQMNQ-UHFFFAOYSA-N 1-[2-(4-butylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(CCCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 RWPHWFAGKMQMNQ-UHFFFAOYSA-N 0.000 claims abstract description 3
VALBFTWRAPRFAG-UHFFFAOYSA-N 1-[2-(4-cyclohexylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C3CCCCC3)CC=2)=C1 VALBFTWRAPRFAG-UHFFFAOYSA-N 0.000 claims abstract description 3
ABBQYZDVGHQSMF-UHFFFAOYSA-N 1-[2-(4-phenoxyphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(OC=4C=CC=CC=4)=CC=3)CC=2)=C1 ABBQYZDVGHQSMF-UHFFFAOYSA-N 0.000 claims abstract description 3
AKTLNRAASMIFMW-UHFFFAOYSA-N 1-[2-[3,4-bis(2-methylpropyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=C(CC(C)C)C(CC(C)C)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 AKTLNRAASMIFMW-UHFFFAOYSA-N 0.000 claims abstract description 3
SNFRDRZUPBHGJT-UHFFFAOYSA-N 1-[2-[3-chloro-4-(3-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C(Cl)C(=CC=3)C=3C=C(Cl)C=CC=3)CC=2)=C1 SNFRDRZUPBHGJT-UHFFFAOYSA-N 0.000 claims abstract description 3
CDLNSVYOVRTZMA-UHFFFAOYSA-N 1-[2-[4-(2,4-dichlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC(Cl)=CC=3)Cl)CC=2)=C1 CDLNSVYOVRTZMA-UHFFFAOYSA-N 0.000 claims abstract description 3
PXDPEQSARDZRSU-UHFFFAOYSA-N 1-[2-[4-(2-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC=CC=3)Cl)CC=2)=C1 PXDPEQSARDZRSU-UHFFFAOYSA-N 0.000 claims abstract description 3
WSPBZUSIEIUXCY-UHFFFAOYSA-N 1-[2-[4-(3,5-dichlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(Cl)C=C(Cl)C=3)CC=2)=C1 WSPBZUSIEIUXCY-UHFFFAOYSA-N 0.000 claims abstract description 3
PUPRBDYGCRMPKP-UHFFFAOYSA-N 1-[2-[4-(3-chloro-4-fluorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=C(Cl)C(F)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 PUPRBDYGCRMPKP-UHFFFAOYSA-N 0.000 claims abstract description 3
ZDSKKYNVKVTUBT-UHFFFAOYSA-N 1-[2-[4-(3-chlorophenyl)phenyl]-2-methylpropyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C=1C=C(C=2C=C(Cl)C=CC=2)C=CC=1C(C)(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 ZDSKKYNVKVTUBT-UHFFFAOYSA-N 0.000 claims abstract description 3
XNACPFPQUNDICM-UHFFFAOYSA-N 1-[2-[4-(3-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(Cl)C=CC=3)CC=2)=C1 XNACPFPQUNDICM-UHFFFAOYSA-N 0.000 claims abstract description 3
WAFSHDHWRRPPSQ-UHFFFAOYSA-N 1-[2-[4-(4-chlorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC(Cl)=CC=3)CC=2)=C1 WAFSHDHWRRPPSQ-UHFFFAOYSA-N 0.000 claims abstract description 3
CPNHRQSEIFVLQO-UHFFFAOYSA-N 1-[2-[4-(4-fluorophenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(F)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 CPNHRQSEIFVLQO-UHFFFAOYSA-N 0.000 claims abstract description 3
KRZBYJLACJFLEQ-UHFFFAOYSA-N 1-[2-[4-(4-methoxyphenyl)phenyl]ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(OC)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 KRZBYJLACJFLEQ-UHFFFAOYSA-N 0.000 claims abstract description 3
VZTXRLKHUFPMRC-UHFFFAOYSA-N 1-[2-methyl-2-(4-phenylphenyl)propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(C)(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 VZTXRLKHUFPMRC-UHFFFAOYSA-N 0.000 claims abstract description 3
XQHBVCWPLIENDJ-UHFFFAOYSA-N 2-chloro-6-[1-[2-(4-cyclohexylphenyl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound ClC1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C3CCCCC3)CC=2)=N1 XQHBVCWPLIENDJ-UHFFFAOYSA-N 0.000 claims abstract description 3
WALYRZRLDDOTJG-UHFFFAOYSA-N 2-chloro-6-[1-[2-(4-phenylphenyl)ethyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound ClC1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=CC=CC=3)CC=2)=N1 WALYRZRLDDOTJG-UHFFFAOYSA-N 0.000 claims abstract description 3
GKZWPTSMKCVFMZ-UHFFFAOYSA-N 2-chloro-6-[1-[2-[4-(2-methylpropyl)phenyl]propyl]-3,6-dihydro-2h-pyridin-4-yl]pyridine Chemical compound C1=CC(CC(C)C)=CC=C1C(C)CN1CC=C(C=2N=C(Cl)C=CC=2)CC1 GKZWPTSMKCVFMZ-UHFFFAOYSA-N 0.000 claims abstract description 3
NVJCKHLCZVJYHR-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-[2-(4-phenylphenyl)ethyl]-3,6-dihydro-2h-pyridine Chemical compound C1=CC(F)=CC=C1C(CC1)=CCN1CCC1=CC=C(C=2C=CC=CC=2)C=C1 NVJCKHLCZVJYHR-UHFFFAOYSA-N 0.000 claims abstract description 3
ZWLXREOJYZDTTE-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1-[2-[4-[2-(trifluoromethyl)phenyl]phenyl]ethyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C(=CC=CC=3)C(F)(F)F)CC=2)=C1 ZWLXREOJYZDTTE-UHFFFAOYSA-N 0.000 claims abstract description 3
JJZHILQQKTVDMU-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1-[2-[4-[3-(trifluoromethyl)phenyl]phenyl]ethyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=CC(=CC=3)C=3C=C(C=CC=3)C(F)(F)F)CC=2)=C1 JJZHILQQKTVDMU-UHFFFAOYSA-N 0.000 claims abstract description 3
RRTUHDMSMMCWNI-UHFFFAOYSA-N 4-[4-[2-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]ethyl]phenyl]phenol Chemical compound C1=CC(O)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 RRTUHDMSMMCWNI-UHFFFAOYSA-N 0.000 claims abstract description 3
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical group CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims abstract description 3
229960003980 galantamine Drugs 0.000 claims abstract description 3
ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims abstract description 3
229960004136 rivastigmine Drugs 0.000 claims abstract description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 16
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract 4
GAPOASFZXBWUGS-UHFFFAOYSA-N 2,2,2-trifluoro-1-(3-trimethylsilylphenyl)ethanone Chemical compound C[Si](C)(C)C1=CC=CC(C(=O)C(F)(F)F)=C1 GAPOASFZXBWUGS-UHFFFAOYSA-N 0.000 claims abstract 2
229960001952 metrifonate Drugs 0.000 claims abstract 2
NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 claims abstract 2
229950004402 zifrosilone Drugs 0.000 claims abstract 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
LKGFRTZVCPEBMJ-UHFFFAOYSA-N ethyl 5-[4-[4-[2-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]ethyl]phenyl]phenoxy]pentanoate Chemical compound C1=CC(OCCCCC(=O)OCC)=CC=C1C(C=C1)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 LKGFRTZVCPEBMJ-UHFFFAOYSA-N 0.000 claims description 2
UZUNKXVWQYZGAZ-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound FC(F)(F)C1=CC=CC(N2CC=CCC2)=C1 UZUNKXVWQYZGAZ-UHFFFAOYSA-N 0.000 claims 1
QRXBOJSFBITNAZ-UHFFFAOYSA-N 1-[2-(3,4-dipropylphenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1=C(CCC)C(CCC)=CC=C1CCN1CC=C(C=2C=C(C=CC=2)C(F)(F)F)CC1 QRXBOJSFBITNAZ-UHFFFAOYSA-N 0.000 abstract description 2
RRGMXBQMCUKRLH-CTNGQTDRSA-N [(3ar,8bs)-3,4,8b-trimethyl-2,3a-dihydro-1h-pyrrolo[2,3-b]indol-7-yl] n-heptylcarbamate Chemical compound C12=CC(OC(=O)NCCCCCCC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C RRGMXBQMCUKRLH-CTNGQTDRSA-N 0.000 abstract description 2
229950010753 eptastigmine Drugs 0.000 abstract description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 6
125000005843 halogen group Chemical group 0.000 abstract 4
HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 abstract 1
HLVVITIHAZBPKB-UHFFFAOYSA-N 9-amino-1,2,3,4-tetrahydroacridin-1-ol Chemical compound C1=CC=C2C(N)=C(C(O)CCC3)C3=NC2=C1 HLVVITIHAZBPKB-UHFFFAOYSA-N 0.000 abstract 1
LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 abstract 1
BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 abstract 1
IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 abstract 1
229950001843 velnacrine Drugs 0.000 abstract 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
201000010099 disease Diseases 0.000 description 9
230000000694 effects Effects 0.000 description 6
238000002636 symptomatic treatment Methods 0.000 description 6
241000700159 Rattus Species 0.000 description 5
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
229960004373 acetylcholine Drugs 0.000 description 3
239000013256 coordination polymer Substances 0.000 description 3
230000015654 memory Effects 0.000 description 3
238000000034 method Methods 0.000 description 3
230000000508 neurotrophic effect Effects 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
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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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/28—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

Landscapes

Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Biomedical Technology (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

EA200000412A 1997-11-14 1998-11-09 Комбинация производных тетрагидропиридинов и ингибиторов ацетилхолинэстеразы для лечения старческой деменции по типу альцгеймера EA003255B1 (ru)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9714324A FR2771006B1 (fr)	1997-11-14	1997-11-14	Association de principes actifs pour le traitement de la demence senile du type alzheimer
FR9714322A FR2771007B1 (fr)	1997-11-14	1997-11-14	Association de principes actifs pour le traitement de la demence senile du type alzheimer
PCT/FR1998/002384 WO1999025363A1 (fr)	1997-11-14	1998-11-09	Association de principes actifs, notamment de tetrahydropyridines et d'agents inhibiteurs de l'acetylcholinesterase, pour le traitement de la demence senile du type alzheimer

Publications (2)

Publication Number	Publication Date
EA200000412A1 EA200000412A1 (ru)	2000-12-25
EA003255B1 true EA003255B1 (ru)	2003-02-27

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Application Number	Title	Priority Date	Filing Date
EA200000412A EA003255B1 (ru)	1997-11-14	1998-11-09	Комбинация производных тетрагидропиридинов и ингибиторов ацетилхолинэстеразы для лечения старческой деменции по типу альцгеймера

Country Status (27)

Country	Link
EP (1)	EP1030671A1 (is)
JP (1)	JP2001523642A (is)
KR (1)	KR100599350B1 (is)
CN (1)	CN1243540C (is)
AU (1)	AU743228B2 (is)
BG (1)	BG64819B1 (is)
BR (1)	BR9814035A (is)
CA (1)	CA2309966A1 (is)
CO (1)	CO4980891A1 (is)
DZ (1)	DZ2649A1 (is)
EA (1)	EA003255B1 (is)
EE (1)	EE04235B1 (is)
HU (1)	HUP0100098A3 (is)
ID (1)	ID24933A (is)
IL (2)	IL136122A0 (is)
IS (1)	IS5482A (is)
MY (1)	MY120461A (is)
NO (1)	NO20002450L (is)
NZ (1)	NZ504420A (is)
OA (1)	OA11464A (is)
PL (1)	PL194597B1 (is)
SA (1)	SA98190747B1 (is)
SK (1)	SK286040B6 (is)
TR (1)	TR200001262T2 (is)
TW (1)	TW585766B (is)
UY (1)	UY25247A1 (is)
WO (1)	WO1999025363A1 (is)

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JP4675103B2 (ja) *	2002-06-14	2011-04-20	富山化学工業株式会社	脳機能を改善する医薬組成物および脳機能を改善するための方法
CA2494585A1 (en) *	2002-08-07	2004-02-19	Novartis Ag	Methods for the treatment of dementia based on apo e genotype
CN1520818A (zh) *	2003-02-09	2004-08-18	山东绿叶天然药物研究开发有限公司	治疗老年性痴呆的胆碱酯酶抑制剂药物组合物
CA2592605C (en)	2004-12-27	2010-12-07	Eisai R&D Management Co., Ltd.	Method for stabilizing anti-dementia drug
CN106163516B (zh)	2014-01-31	2019-05-28	考格尼申治疗股份有限公司	异吲哚啉组合物和治疗神经变性疾病的方法
CN110869011B (zh)	2017-05-15	2024-01-05	考格尼申治疗股份有限公司	用于治疗神经退行性疾病的组合物
KR102224918B1 (ko)	2018-03-20	2021-03-09	(주)인벤티지랩	도네페질 및 메만틴을 포함하는 인지 장애 관련 질병의 예방 또는 치료용 약학적 복합 조성물 및 이의 제조 방법
WO2019182319A1 (ko) *	2018-03-20	2019-09-26	(주)인벤티지랩	인지 장애 관련 질병의 예방 또는 치료용 약학적 조성물의 제조 방법 및 이의 제조 방법으로 제조된 인지 장애 관련 질병의 예방 또는 치료용 약학적 조성물
CN109265391B (zh) *	2018-11-13	2021-11-19	枣庄学院	联苯多取代1,2,5,6-四氢吡啶化合物及其合成方法与应用

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FR2662355B1 (fr) *	1990-05-22	1994-11-10	Sanofi Sa	Utilisation de la 1-[2-(2-naphtyl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine pour la preparation de medicaments destines au traitement de troubles cerebraux et neuronaux.
US5453428A (en) *	1991-02-14	1995-09-26	The Mount Sinai School Of Medicine Of The City Of New York	Method and composition for the treatment of apathy-amotivation syndrome
JPH11511732A (ja) *	1995-03-06	1999-10-12	インターニューロンファーマシューティカルズ，インコーポレーテッド	シチコリンを用いる梗塞容積の低減
FR2736053B1 (fr) *	1995-06-28	1997-09-19	Sanofi Sa	Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines

1998
- 1998-10-26 CO CO98062479A patent/CO4980891A1/es unknown
- 1998-10-28 TW TW087117874A patent/TW585766B/zh not_active IP Right Cessation
- 1998-11-09 CA CA002309966A patent/CA2309966A1/en not_active Abandoned
- 1998-11-09 KR KR1020007005231A patent/KR100599350B1/ko not_active Expired - Fee Related
- 1998-11-09 PL PL98340500A patent/PL194597B1/pl not_active IP Right Cessation
- 1998-11-09 TR TR2000/01262T patent/TR200001262T2/xx unknown
- 1998-11-09 IL IL13612298A patent/IL136122A0/xx not_active IP Right Cessation
- 1998-11-09 HU HU0100098A patent/HUP0100098A3/hu unknown
- 1998-11-09 WO PCT/FR1998/002384 patent/WO1999025363A1/fr not_active Ceased
- 1998-11-09 EP EP98954538A patent/EP1030671A1/fr not_active Withdrawn
- 1998-11-09 SK SK711-2000A patent/SK286040B6/sk unknown
- 1998-11-09 CN CNB988130947A patent/CN1243540C/zh not_active Expired - Fee Related
- 1998-11-09 AU AU11609/99A patent/AU743228B2/en not_active Ceased
- 1998-11-09 JP JP2000520796A patent/JP2001523642A/ja not_active Withdrawn
- 1998-11-09 BR BR9814035-3A patent/BR9814035A/pt not_active Application Discontinuation
- 1998-11-09 EE EEP200000290A patent/EE04235B1/xx not_active IP Right Cessation
- 1998-11-09 ID IDW20000860A patent/ID24933A/id unknown
- 1998-11-09 EA EA200000412A patent/EA003255B1/ru not_active IP Right Cessation
- 1998-11-09 NZ NZ504420A patent/NZ504420A/en unknown
- 1998-11-11 DZ DZ980259A patent/DZ2649A1/xx active
- 1998-11-12 UY UY25247A patent/UY25247A1/es not_active IP Right Cessation
- 1998-11-14 SA SA98190747A patent/SA98190747B1/ar unknown
- 1998-11-14 MY MYPI98005180A patent/MY120461A/en unknown
2000
- 2000-05-09 IS IS5482A patent/IS5482A/is unknown
- 2000-05-11 BG BG104428A patent/BG64819B1/bg unknown
- 2000-05-11 NO NO20002450A patent/NO20002450L/no unknown
- 2000-05-12 OA OA1200000141A patent/OA11464A/en unknown
- 2000-05-14 IL IL136122A patent/IL136122A/en unknown

Also Published As

Publication number	Publication date
DZ2649A1 (fr)	2004-12-28
KR20010032099A (ko)	2001-04-16
AU743228B2 (en)	2002-01-24
SA98190747B1 (ar)	2006-11-04
IS5482A (is)	2000-05-09
CA2309966A1 (en)	1999-05-27
TW585766B (en)	2004-05-01
ID24933A (id)	2000-08-31
BG64819B1 (bg)	2006-05-31
IL136122A (en)	2006-07-05
SK286040B6 (sk)	2008-01-07
HUP0100098A2 (hu)	2001-07-30
EA200000412A1 (ru)	2000-12-25
TR200001262T2 (tr)	2001-01-22
BG104428A (en)	2001-08-31
SK7112000A3 (en)	2000-10-09
HUP0100098A3 (en)	2001-12-28
KR100599350B1 (ko)	2006-07-12
PL340500A1 (en)	2001-02-12
NO20002450L (no)	2000-07-14
AU1160999A (en)	1999-06-07
CN1285742A (zh)	2001-02-28
OA11464A (en)	2003-11-18
IL136122A0 (en)	2001-05-20
EP1030671A1 (fr)	2000-08-30
NZ504420A (en)	2003-08-29
PL194597B1 (pl)	2007-06-29
MY120461A (en)	2005-10-31
NO20002450D0 (no)	2000-05-11
EE04235B1 (et)	2004-02-16
EE200000290A (et)	2001-06-15
WO1999025363A1 (fr)	1999-05-27
CO4980891A1 (es)	2000-11-27
JP2001523642A (ja)	2001-11-27
CN1243540C (zh)	2006-03-01
UY25247A1 (es)	2001-05-31
BR9814035A (pt)	2000-09-26

Publication	Publication Date	Title
AU743609B2 (en)	2002-01-31	Use of cholinesterase inhibitors to treat disorders of attention
US20030144255A1 (en)	2003-07-31	Compositions for prevention and treatment of dementia
DE60122928T2 (de)	2007-09-06	Therapeutische zusammensetzung von amlodipin und benazepril / benazeprilat
NZ547152A (en)	2009-12-24	Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an acetylcholinesterase inhibitor
AU2003271103B2 (en)	2008-02-28	Solid preparation
CA2690110A1 (en)	2009-01-22	Ampa receptor antagonists for neuropathic pain
EA003255B1 (ru)	2003-02-27	Комбинация производных тетрагидропиридинов и ингибиторов ацетилхолинэстеразы для лечения старческой деменции по типу альцгеймера
JPS5910585A (ja)	1984-01-20	スピロスクシンイミド誘導体のアルツハイマ−型痴「ほう」の治療における使用
US20050148614A1 (en)	2005-07-07	Combination of active ingredients for the treatment of senile dementia of the Alzheimer type
US20060217395A1 (en)	2006-09-28	Combinations of paroxetine and 4- (s) - (4-acetyl-piperazin-1-yl) -2- (r)- (4-fluoro-2-methyl- phenyl -piperidine-1-carboxylic acid [1- (r) (3,5-bis-trifluoromethyl-phenyl) -ethyl] methylamide for treatment of depression and / or anxiety
CA2188227C (en)	2000-08-08	Combination antiemetic therapy using nk-1 receptor antagonists
MXPA00004600A (en)	2001-05-07	Combination of active principles, in particular of tetrahydropyridins and acetylcholinesterase inhibiting agents, for treating senile dementia such as alzheimer dementia
WO2014055047A1 (en)	2014-04-10	Combination of idebenone and donezepil
JPH0576925B2 (is)	1993-10-25
US5326781A (en)	1994-07-05	Medicaments
FR2771006A1 (fr)	1999-05-21	Association de principes actifs pour le traitement de la demence senile du type alzheimer
HK1080385B (en)	2014-03-28	Solid preparation
FR2771007A1 (fr)	1999-05-21	Association de principes actifs pour le traitement de la demence senile du type alzheimer
CA2768356A1 (en)	2011-01-20	Compositions comprising a cholinesterase inhibitor for treating cognitive disorders

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