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US5336689A
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Tri- and tetra-substituted guanidines and their use as excitatory amino acid antagonists
Assignee: Oregon State Board of Higher Education
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Filing: 1993-08-11
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Granted: 1994-08-09
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Expires: 2013-08-11
Abstract
Abstract Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders.
Inventors
- 👤 Eckard Weber
- 👤 John F. W. Keana
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 05:16
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/13; A61K31/155; C; C07; C07C; C07C279/00; C07C279/18; C07D; C07D311/00; C07D311/02; C07D311/04; C07D311/06; C07D311/08; C07D311/18
Claims Analysis
Total Claims: 55
Claim 1
Independent Claim
293 words
A method for treating a disease of the nervous system in which the pathophysiology of the disorder involves excessive excitation of nerve cells by agonists of NMDA-receptors, comprising the administration to a mammal exhibiting symptoms of such disorders or is susceptible to such disorders an effective amount of a N,N,N'-trisubstituted guanidine having the formula: ##STR4## wherein R R' and R" are a C 1 -C 8 alkyl group, a C 2 -C 8 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted by one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano. C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 --C 8 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl; and wherein said guanidine exhibits high binding to the PCP receptor in mammalian nerve cells.
Claim 2
Independent Claim
293 words
A method for treating a disease of the nervous system in which the pathophysiology of the disorder involves excessive excitation of nerve cells by agonists of NMDA-receptors, comprising the administration to a mammal exhibiting symptoms of such disorders or is susceptible to such disorders an effective amount of a N,N,N'-trisubstituted guanidine having the formula: ##STR4## wherein R R' and R" are a C 1 -C 8 alkyl group, a C 2 -C 8 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted by one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano. C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 --C 8 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl; and wherein said guanidine exhibits high binding to the PCP receptor in mammalian nerve cells.
Claim 3
Dependent Claim
32 words
The method according to claim 1, wherein siad N,N,N'-trisubstituted guanidine is N,N'-di-(1-naphthyl)-N-methylguanidine, N,N'-di-(m-ethylphenyl)-N-methylguanidine,N-(o-isopropylphenyl-N'-methyl-N'-(1-naphthyl)guanidine, N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-ethylguanidine, N,N'-di-(1-naphthyl)-N-ethylguanidine, N-methyl-N'-(m-ethylphenyl)-N-(1-naphthyl)-guanidine, N,N'-di-(1-naphthyl)-N-phenylguanidine, N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-methylguanidine, N-(8-coumarinyl)-N'-(3-ethylphenyl)-N-ethylguanidine, N-(1-naphthyl)-N'-(3-methylphenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-azidophenyl)-N'-methylguanidine, N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine, or N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; or a physiologically acceptable salt thereof.
Claim 4
Dependent Claim
16 words
The method of claim 1 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, or a physiologically acceptable salt thereof.
Claim 5
Dependent Claim
11 words
The method of claim 1 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine hydrochloride.
Claim 6
Dependent Claim
10 words
The method of claim 1 where the guanidine is N-(m-trifluoromethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine.
Claim 7
Dependent Claim
15 words
The method of claim 1 where the guanidine is a physiologically acceptable salt of N-(m-trifluoromethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine.
Claim 8
Dependent Claim
24 words
The method according to claim 1, wherein said disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sslerosis, Down's Syndrome or Korsakoff's disease.
Claim 9
Dependent Claim
33 words
The method according to claim 7, wherein the N,N,N'-trisubstituted guanidine is N,N'-di-(1-naphthyl)-N-methyl-guanidine, N,N'-di-(m-ethylphenyl)-N-methylguanidine, N-(o-isopropylphenyl)-N'-methyl-N'-(1-naphthyl)guanidine, N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-ethylguanidine, N,N'-di-(1-naphthyl)-N-ethylguanidine, N-methyl-N'-(m-ethylphenyl)-N-(1-naphthyl)-guanidine, N,N'-di-(1-naphthyl)-N-phenylguanidine, N-(8-coumarinyl)-N' -(3-ethylphenyl)-N'-methylguanidine, N-(8-coumarinyl)-N'-(3-ethylphenyl)-N-ethylguanidine,N-(1-naphthyl)-N'-(3-methylphenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-azidophenyl)-N'-methylguanidine, N-(7-fluoro-1-napthyl)-N'-(3-ethylphenyl)-N'-methylguanidine, or N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; or a physiologically acceptable salt thereof.
Claim 10
Dependent Claim
16 words
The method of claim 7 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, or a physiologically acceptable salt thereof.
Claim 11
Dependent Claim
11 words
The method of claim 7 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine hydrochloride.
Claim 12
Dependent Claim
16 words
The method according to claim 1, wherein the mammal is a human being suffering from epilepsy.
Claim 13
Dependent Claim
34 words
The method according to claim 11, wherein the said N,N,N'-trisubstituted guanidine is N,N'-di-(1-naphthyl)-N-methylguanidine, N,N'-di-(m-ethylphenyl)-N-methylguanidine,N-(o-isopropylphenyl)-N'-methyl-N'-(1-naphthyl)guanidine, N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-ethylguanidine, N,N'-di-(1-naphthyl)-N-ethylguanidine, N-methyl-N'-(m-ethylphenyl)-N-(1naphthyl)-guanidine, N,N'-di-(1-naphthyl)-N-phenylguanidine, N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-methylguanidine, N-(8-coumarinyl)-N'-(3-ethylphenyl)-N-ethylguanidine, N-(1naphthyl)-N'-(3-methylphenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-methylguanidine, N-(1-naphthyl)-N'-(3-azidophenyl)-N' -methylguanidine, N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine, or N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; or a physiologically acceptable salt thereof.
Claim 14
Independent Claim
290 words
A method for treating a disease of the nervous system in which the pathophysiology of the disorder involves excessive excitation of nerve cells by agonists of NMDA receptors, comprising the administration to a mammal exhibiting symptoms of such disorders or is susceptible to such disorders an effective amount of a N,N,N',N'-tetrasubstituted guanidine of the formula: ##STR5## wherein R, R', R" and R"' are independently a C 1 -C 8 alkyl group, a C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted with one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted with one or more substituents, alkaryl group, alkaryl group substituted with one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted with one or more substituents, heteroaryl group, or a heteroaryl group substituted with one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl; and wherein said guanidine exhibits high binding to the receptor.
Claim 15
Independent Claim
290 words
A method for treating a disease of the nervous system in which the pathophysiology of the disorder involves excessive excitation of nerve cells by agonists of NMDA receptors, comprising the administration to a mammal exhibiting symptoms of such disorders or is susceptible to such disorders an effective amount of a N,N,N',N'-tetrasubstituted guanidine of the formula: ##STR5## wherein R, R', R" and R"' are independently a C 1 -C 8 alkyl group, a C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted with one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted with one or more substituents, alkaryl group, alkaryl group substituted with one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted with one or more substituents, heteroaryl group, or a heteroaryl group substituted with one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl; and wherein said guanidine exhibits high binding to the receptor.
Claim 16
Dependent Claim
16 words
The method of claim 13, wherein said N,N,N',N'-tetrasubstituted guanidine is N-methyl-N'-phenyl-N,N'-di-(1-naphthyl)guanidine, N-methyl-N'-ethyl-N,N'-(1-naphthyl)-guanidine, N,N'-di(1-naphthyl)-N,N'-dimethylguanidine, N-(1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine, or N-(1-naphthyl)-N'-(3-ethylphenyl)-N-ethyl-N'-methylguanidine.
Claim 17
Dependent Claim
24 words
The method according to claim 13, wherein said disease is Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome, or Korsakoff's disease.
Claim 18
Dependent Claim
16 words
The method of claim 15, wherein said N,N,N',N'-tetrasubstituted guanidine is N-methyl-N'-phenyl-N,N'-di-(1-naphthyl)guanidine, N-methyl-N'-ethyl-N,N'-di-(1-naphthyl)-guanidine, N,N'-di(1-naphthyl)-N,N'-dimethylguanidine, N-(1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine, or N-(1-naphthyl)-N'-(3-ethylphenyl)-N-ethyl-N'-methylguanidine.
Claim 19
Dependent Claim
16 words
The method according to claim 13, wherein the mammal is a human being suffering from epilepsy.
Claim 20
Dependent Claim
22 words
The method of claim 17, wherein said N,N,N',N'tetrasubstituted guanidine is N-methyl-N'-phenyl-N,N'-di-(1-naphthyl)guanidine, N-methyl-N'-ethyl-N,N'-di-(1-naphthyl)-guanidine, N,N'-di(1-naphthyl)-N,N'-dimethylguanidine, N-(1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine, or N-(1-naphthyl)-N'-(3-ethylphenyl)-N-ethyl-N'-methylguanidine; or a physiologically acceptable salt thereof.
Claim 21
Dependent Claim
15 words
The method of claim 11 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, or a physiologically acceptable thereof.
Claim 22
Dependent Claim
11 words
The method of claim 11 wherein the guanidine is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine hydrochloride.
Claim 23
Dependent Claim
113 words
The method of claim of claim 1 wherein R and R" are independently a cycloalkyl, cycloalkyl substituted by one or more substituents, cycloalkenyl, cycloalkenyl substituted by one or more substituents, carbocyclic aryl, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted by one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; and R' is a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, an alkaryl group or a substituted alkaryl group.
Claim 24
Dependent Claim
38 words
The method of claim of claim 1 wherein R and R" are independently a carbocyclic aryl group or a carbocyclic aryl group substituted by one or more substituents and R' is a C 1 -C 8 alkyl group.
Claim 25
Dependent Claim
33 words
The method of claim 22 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl and anthracyl.
Claim 26
Dependent Claim
30 words
The method of claim 22 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.
Claim 27
Dependent Claim
12 words
The method of claim 24 wherein R' is methyl, ethyl or propyl.
Claim 28
Dependent Claim
9 words
The method of claim 24 wherein R' is methyl.
Claim 29
Dependent Claim
107 words
The method of claim 1 wherein the guanidine is N,N'-di-(1-naphthyl)-N-methylguanidine; N,N'-di-(1-naphthyl)-N-ethylguanidine; N,N'-di-(m-ehthylphenyl)-N-methylguanidine; N-(o-isopropylphenyl)-N'-methyl-N'-(1-naphthyl)-guanidine; N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine; N-ethyl-N,N'-di-(m-ethylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N,N'-di-(m-ethylphenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-isopropyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-methyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N-ethylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N'-methylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(2-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(5-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(8-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(6-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2,4-difluoro-3-ethylphenyl-N'-methylguanidine; N-(1-naphthyl)-N'-(2,6-difluoro-3-ethylphenyl-N'-methylguanidine; N-(1-naphthyl)-N'-(2,4,6-trifluoro-3-ethylphenyl-N'-methylguanidine; N-(2,4-difluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4-difluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4,5-trifluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4,8-trifluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(2,6-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(2,4-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(7-fluoro-1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(6-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-ethylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(8-coumarinyl)-N'-(3-nitrophenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N,N'-di(8-coumarinyl)-N-methylguanidine; N,N'-di(8-coumarinyl)-N-ethylguanidine; N-(2-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(4-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(5-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(7-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4-difluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4,5-trifluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4,8-trifluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(5-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-ethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N-methylguanidine; N-(1-naphthyl)-N'-(3-trifluoromethylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-trifluoromethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-trifluoromethylphenyl)-N'-ethylguanidine; or N-(8-coumarinyl)-N'-(3-trifluoromethylphenyl)-N'-ethylguanidine; or a physiologically acceptable salt thereof.
Claim 30
Dependent Claim
115 words
The method of claim of claim 13 wherein R and R" are independently a cycloalkyl, cycloalkyl substituted by one or more substituents, cycloalkenyl, cycloalkenyl substituted by one or more substituents, carbocyclic aryl, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted by one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; and R' and R"' is a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, an alkaryl group or a substituted alkaryl group.
Claim 31
Dependent Claim
68 words
The method of claim of claim 13 wherein R and R" are independently cycloalkyl groups, substituted cycloalkyl groups, cycloalkenyl groups, cycloalkenyl groups substituted with one or more substituents, carbocyclic aryl groups, carbocyclic aryl groups substituted with one or more substituents, alkaryl groups, substituted alkaryl groups, heterocyclic groups, substituted heterocyclic groups, heteroaryl groups or substituted heteroaryl groups; and R' and R"' are independently C 1 -C 8 alkyl groups.
Claim 32
Dependent Claim
33 words
The method of claim 29 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl and anthracyl.
Claim 33
Dependent Claim
30 words
The method of claim 29 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.
Claim 34
Dependent Claim
15 words
The method of claim 31 wherein R' and R"' are independently methyl, ethyl or propyl.
Claim 35
Dependent Claim
12 words
The method of claim 31 wherein R' and R"' are each methyl.
Claim 36
Dependent Claim
113 words
The method of claim 13 wherein the guanidine is N,N'-diethyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diethyl-N,N'-di-(1-naphthyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N,N'-diethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N,N'-dimethyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-ethyl-N'-isopropyl-N,N'-di-(m-ethylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-isopropylguanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N,N'-diisopropyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-idanyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-idenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N,N'-diisopropyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(o-iosopropylphenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N,N'-di-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-isopropy-phenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-isopropylguanidine; N-methyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N,N'-di-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-methylguanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N,N'-di(1-naphthyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine; N,N'-di(8-coumarinyl)-N,N'-dimethylguanidine; N,N'-di(8-coumarinyl)-N-methyl-N'-ethylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-nitrophenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-azidophenyl)-N,N'-dimethylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylphenylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-methylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N,N'-diethylguanidine; N-(8-coumarinyl)-N'-(3-nitrophenyl)-N,N'-diethylguanidine; N-(8-coumarinyl)-N'-(3-azidophenyl)-N,N'-diethylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-diethylphenylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N,N'-diethylguanidine; or N-(8-coumarinyl)-N-(3-methylphenyl)-N,N'-diethylguanidine; or a physiologically acceptable salt thereof.
Claim 37
Independent Claim
268 words
A method of treating a disease selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome, Korsakoff's disease or epilepsy, comprising administering to a mammal suffering from said disease an effective amount of a compound of the formula: ##STR6## wherein R, R' and R" are independently a C 1 -C 8 alkyl group, a C 2 -C 6 alkenyl group, a C 2 -C 6 alkynyl group, a cycloalkyl group, cycloalkyl group substituted by one or more substituents, a cycloalkenyl group, cycloalkenyl group substituted by one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl groups, or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 6 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl.
Claim 38
Independent Claim
268 words
A method of treating a disease selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome, Korsakoff's disease or epilepsy, comprising administering to a mammal suffering from said disease an effective amount of a compound of the formula: ##STR6## wherein R, R' and R" are independently a C 1 -C 8 alkyl group, a C 2 -C 6 alkenyl group, a C 2 -C 6 alkynyl group, a cycloalkyl group, cycloalkyl group substituted by one or more substituents, a cycloalkenyl group, cycloalkenyl group substituted by one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl groups, or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 6 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 6 N-alkylcarbamoyl, C 2 -C 15 N,N-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl.
Claim 39
Dependent Claim
110 words
The method of claim 35 wherein R and R" are independently a cycloalkyl, cycloalkyl substituted by one or more substituents, cycloalkenyl, cycloalkenyl substituted by one or more substituents, carbocyclic aryl, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted by one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; R' is a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, an alkaryl group or a substituted alkaryl group.
Claim 40
Dependent Claim
36 words
The method of claim 35 wherein R and R" are independently a carbocyclic aryl group or a carbocyclic aryl group substituted by one or more substituents and R' is a C 1 -C 8 alkyl group.
Claim 41
Dependent Claim
33 words
The method of claim 37 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl and anthracyl.
Claim 42
Dependent Claim
30 words
The method of claim 37 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.
Claim 43
Dependent Claim
12 words
The method of claim 39 wherein R' is methyl, ethyl or propyl.
Claim 44
Dependent Claim
9 words
The method of claim 39 wherein R' is methyl.
Claim 45
Dependent Claim
107 words
The method of claim 35 wherein the guanidine is N,N'-di-(1-naphthyl)-N-methylguanidine; N,N'-di-(1-naphthyl)-N-ethylguanidine; N,N'-di-(m-ethylphenyl)-N-methylguanidine; N-(o-isopropylphenyl)-N'-methyl-N'-(1-naphthyl)-guanidine; N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)-guanidine; N-ethyl-N,N'-di-(m-ethylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-ethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N,N'-di-(m-ethylphenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-isopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-isopropyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-isopropyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N-methyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-methyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N-ethylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N'-methylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(2-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(5-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(8-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(6-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2,4-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2,6-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2,4,6-trifluoro-3-ethylphenyl)-N'-methylguanidine; N-(2,4-difluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4-difluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4,5-trifluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(2,4,8-trifluoro-1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(2,6-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(2,4-difluoro-3-ethylphenyl)-N'-methylguanidine; N-(7-fluoro-1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(4-fluoro-1-naphthyl)-N'-(6-fluoro-3-ethylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N'-ethylguanidine; N-(1-naphthyl)-N'-(8-coumarinyl)-N-ethylguanidine; N-(8-coumarinyl)-N'-(3-nitrophenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(4-fluoro-3-ethylphenyl)-N'-methylguanidine; N,N'-di(8-coumarinyl)-N-methylguanidine; N,N'-di(8-coumarinyl)-N-ethylguanidine; N-(2-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(4-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(5-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(7-fluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4-difluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4,5-trifluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(2,4,8-trifluoronaphthyl)-N'-(3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(2-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(5-fluoro-3-methylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N'-ethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N-methylguanidine; N-(1-naphthyl)-N'-(3-trifluoromethylphenyl)-N'-methylguanidine; N-(8-coumarinyl)-N'-(3-trifluoromethylphenyl)-N'-methylguanidine; N-(1-naphthyl)-N'-(3-trifluoromethylphenyl)-N'-ethylguanidine; or N-(8-coumarinyl)-N'-(3-trifluoromethylphenyl)-N'-ethylguanidine; or a physiologically acceptable salt thereof.
Claim 46
Dependent Claim
16 words
The method of claim 35 wherein the compound is N-(m-ethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, or a physiologically acceptable salt thereof.
Claim 47
Dependent Claim
16 words
The method of claim 35 wherein the compound is N-(m-trifluoromethylphenyl)-N-methyl-N'-(1-naphthyl)guanidine, or a physiologically acceptable salt thereof.
Claim 48
Independent Claim
271 words
A method of treating or preventing a disease selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome, Korsakoff's disease or epilepsy, comprising administering to a mammal suffering from or susceptible to said disease an effective amount of a compound of the formula: ##STR7## wherein R, R', R" and R"' are independently a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted by one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 8 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N'-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl.
Claim 49
Independent Claim
271 words
A method of treating or preventing a disease selected from Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome, Korsakoff's disease or epilepsy, comprising administering to a mammal suffering from or susceptible to said disease an effective amount of a compound of the formula: ##STR7## wherein R, R', R" and R"' are independently a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, cycloalkyl group, cycloalkyl group substituted by one or more substituents, cycloalkenyl group, cycloalkenyl group substituted with one or more substituents, carbocyclic aryl group, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted with one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group or a heteroaryl group substituted by one or more substituents; or a physiologically acceptable salt thereof; wherein said substituent is chloro, fluoro, bromo, iodo, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, cyano, C 3 -C 15 dialkylaminoalkyl, carboxy, carboxamido, C 1 -C 8 alkylthio, allyl, aralkyl, alkaryl, C 3 -C 8 cycloalkyl, aroyl, aralkoxy, C 2 -C 8 acyl, aryl, heteroaryl, an aryl fused to a benzene ring, a heteroaryl fused to a benzene ring, C 3 -C 6 heterocycloalkyl, a C 3 -C 6 heterocycloalkyl ring fused to a benzene ring, C 1 -C 8 alkylsulfonyl, arylthio, amino, C 1 -C 8 alkylamino, C 2 -C 15 dialkylamino, hydroxy, hydroxyalkyl, carbamoyl, C 1 -C 8 N-alkylcarbamoyl, C 2 -C 15 N,N'-dialkylcarbamoyl, nitro, azido or C 2 -C 15 dialkylsulfamoyl.
Claim 50
Dependent Claim
114 words
The method of claim of claim 45 wherein R and R" are independently a cycloalkyl, cycloalkyl substituted by one or more substituents, cycloalkenyl, cycloalkenyl substituted by one or more substituents, carbocyclic aryl, carbocyclic aryl group substituted by one or more substituents, alkaryl group, alkaryl group substituted by one or more substituents, aralkyl group, aralkyl group substituted by one or more substituents, heterocyclic group, heterocyclic group substituted by one or more substituents, heteroaryl group, or a heteroaryl group substituted by one or more substituents; and R' and R"'is a C 1 -C 8 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, an alkaryl group or a substituted alkaryl group.
Claim 51
Dependent Claim
67 words
The method of claim of claim 45 wherein R and R" are independently cycloalkyl groups, substituted cycloalkyl groups, cycloalkenyl groups, cycloalkenyl groups substituted with one or more substituents, carbocyclic aryl groups, carbocyclic aryl groups substituted with one or more substituents, alkaryl groups, substituted alkaryl groups, heterocyclic groups, substituted heterocyclic groups, heteroaryl groups or substituted heteroaryl groups; and R' and R"'are independently C 1 -C 8 alkyl groups.
Claim 52
Dependent Claim
33 words
The method of claim 47 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, biphenyl, phenanthryl and anthracyl.
Claim 53
Dependent Claim
30 words
The method of claim 47 wherein said carbocyclic aryl group or carbocyclic aryl substituted by one or more substituents is selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.
Claim 54
Dependent Claim
15 words
The method of claim 50 wherein R' and R"' are independently methyl, ethyl or propyl.
Claim 55
Dependent Claim
113 words
The method of claim 45 wherein the guanidine is N,N'-diethyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diethyl-N,N'-di-(1-naphthyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N,N'-diethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N,N'-dimethyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-dimethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N-ethyl-N'-isopropyl-N,N'-di-(m-ethylphenyl)guanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-isopropylguanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N,N'-diisopropyl-N,N'-di-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indanyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(4-indenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(1-naphthyl)guanidine; N,N'-diisopropyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)guanidine; N,N'-diisopropyl-N-(4-indanyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(4-indenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine; N,N'-diisopropyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)guanidine; N-methyl-N,N'-di-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-isopropylguanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-isopropylquanidine; N-methyl-N-(m-ethylphenyl)-N'-(o-isopropyl-phenyl)-N'-isopropylquanidine; N-methyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-isopropylquanidine; N-methyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-isopropylquanidine; N-methyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-isopropylquanidine; N-methyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-isopropylquanidine; N-methyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-methyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)-N'-isopropylguanidine; N-ethyl-N,N'-di-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indanyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(4-indenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-iodophenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(o-isopropylphenyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(1-naphthyl)-N'-methylguanidine; N-ethyl-N-(m-ethylphenyl)-N'-(m-methylphenyl)-N'-methylguanidine; N-ethyl-N-(4-indanyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(4-indenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(o-iodophenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(o-isopropylphenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(1-naphthyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N-ethyl-N-(m-methylphenyl)-N'-(m-ethylphenyl)-N'-methylguanidine; N,N'-di(1-naphthyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine; N,N'-di(8-coumarinyl)-N,N'-dimethylguanidine; N,N'-di(8-coumarinyl)-N-methyl-N'-ethylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-nitrophenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N'-(3-azidophenyl)-N,N'-dimethylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylphenylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N,N'-dimethylguanidine; N-(8-coumarinyl)-N-(3-methylphenyl)-N,N'-dimethylguanidine; N-(1-naphthyl)-N'-(3-nitrophenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(3-azidophenyl)-N,N'-diethylguanidine; N-(8-coumarinyl)-N-(3-nitrophenyl)-N,N'-diethylguanidine; N-(8-coumarinyl)-N-(3-azidophenyl)-N,N'-diethylguanidine; N-(7-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-diethylphenylguanidine; N-(4-fluoro-1-naphthyl)-N'-(3-ethylphenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(4-fluoro-3-ethylphenyl)-N,N'-diethylguanidine; N-(1-naphthyl)-N'-(3-methylphenyl)-N,N'-diethylguanidine; or N-(8-coumarinyl)-N-(3-methylphenyl)-N,N'-diethylguanidine; or a physiologically acceptable salt thereof.
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