Claims
- 1. A method for treating dementia in a subject comprising administering to the subject a therapeutically effective amount of a compound of the formula: ##STR12## or a pharmaceutically acceptable salt thereof; wherein
- n is 0 or 1;
- R.sub.1 and R.sub.2 are each independently hydrogen, substituted or unsubstituted C.sub.1 -C.sub.4 alkyl, halogen, nitro, --NH--R.sub.11, --C(O)--R.sub.11 or --C(O)--NR.sub.9 R.sub.10, wherein
- R.sub.11 is hydrogen, substituted or unsubstituted C.sub.1 C.sub.4 alkyl, hydroxy, substituted or unsubstituted C.sub.1 -C.sub.4 alkoxy, and
- R.sub.9 and R.sub.10 are each independently hydrogen, C.sub.1 -C.sub.12 alkyl, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, or indanyl;
- R.sub.3 is hydrogen, substituted or unsubstituted C.sub.1 -C.sub.4 alkyl, hydroxy, substituted or unsubstituted C.sub.1 -C.sub.4 alkoxy;
- R.sub.4 is hydrogen, substituted or unsubstituted C.sub.1 -C.sub.12 alkyl, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, or --C(O)--R.sub.6,
- wherein R.sub.6 is hydrogen, C.sub.1 -C.sub.12 alkly, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl;
- R.sub.5 is hydrogen, C.sub.1 -C.sub.12 alkyl, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, or A--NR.sub.9 R.sub.10, --Y--C(O)--R.sub.7 or --Y--(SO2)NR.sub.9 R.sub.10,
- wherein A is substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, and
- R.sub.9 and R.sub.10 are each independently hydrogen, substituted C.sub.1 -C.sub.12 alkyl, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, or indanyl;
- Y is substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl, and
- R.sub.7 is hydrogen, hydroxy, substituted or unsubstituted C.sub.6 -C.sub.12 aryl, substituted or unsubstituted C.sub.7 -C.sub.12 aralkyl.
- 2. The method according to claim 1, wherein a compound selected from the group consisting of: N-(4-aminobutanoyl)-1-aminoindan,(R)-N-formyl-1-aminoindan, (S)-N-formyl-1-aminoindan, (R)-N-acetyl-1-aminoindan, (S)-N-acetyl-1-aminoindan, N-acetyl-7-methyl-1-aminoindan, N-acetyl-6-fluoro-1-aminoindan, (R)-N-acetyl-6-fluoro-1-aminoindan, N-acetyl-6-methoxy-1-aminoindan, (R)-N-acetyl-4,5-dimethoxy-1-aminoindan, N-(2-acetamido)-1-aminoindan, (R)-N-(2-acetamido)-1-aminoindan, (S)-N-(2-acetamido)-1-aminoindan, N-(2-acetamido)-6-fluoro-1-aminoindan, N-(3-cyanopropyl)-1-aminoindan, N-(2-N-Boc-aminoacetyl)-1-aminoindan, N-(2-aminoacetyl)-1-aminoindan, N-benzoyl-1-aminoindan, N-(2-n-propylpentanoyl)-1-aminoindan, N-(2-propionamido)-1-aminoindan, N-butyryl-1-aminoindan, N-(2-phenylacetyl)-1-aminoindan, N-(m-anisoyl)-1-aminoindan, N-(4'-fluorobenzoyl)-1-aminoindan, N-(p-4-toluoyl)-1-aminoindan, (S)-(1-indanyl)-glycine, N,N-di-(2-acetamido)-1-aminoindan, N-(1-indanyl)aminoacetonitrile, 6-cyano-N-acetyl-1-aminoindan, 6-carboxamido-N-acetyl-1-aminoindan, 6-ethoxycarbonyl-N-acetyl-1aminoindan, 2-(1-indanamino)-N-isopropylethanesulfonamide, 2-(1-indanamino)-N-(1-indanyl) ethanesulfonamide, (R,R)-2-(1-indanamino)-N-(1-indanyl) ethanesulfonamide, N-(4-di-n-propylsulfamoyl) benzoyl-1-aminoindan, N-N'-bis-(1-indanyl) adipamide, N-N'-bis-(R)-(1-indanyl) adipamide, N-N'-bis-(R)-(1-indanyl) succinamide, (trans)-2-methyl-N-acetyl-1-aminoindan, (cis)-2-methyl-N-acetyl-1-aminoindan, N-methyl-N-acetyl-1-aminoindan, (R)-N-methyl-N-acetyl-1-aminoindan, and salts thereof.
- 3. The method according to claim wherein the dementia is senile dementia.
- 4. The method according to claim 1, wherein the dementia is dementia of the Alzheimer's type.
- 5. The method according to claim 1, wherein the dementia is dementia of the Parkinson's type.
- 6. The method according to claim 1, wherein the subject is a human subject.
- 7. The method according to claim 1, wherein the administering comprises administering orally, rectally, transdermally, or parenterally.
- 8. The method according to claim 1, wherein the therapeutically effective amount is from about 1 milligram to about 1000 milligrams.
- 9. The method according to claim 1, wherein the therapeutically effective amount is from about 10 milligrams to about 100 milligrams.
- 10. The method according to claim 1, wherein the pharmaceutically acceptable salt is a hydrochloride salt, a mesylate salt, an ethylsulfonate salt, or a sulfate salt.
- 11. The method according to claim 1, wherein n is 1.
- 12. The method according to claim 1, wherein n is 2.
- 13. The method according to claim 1, wherein R.sub.1 and .sub.2 R are each independently hydrogen, fluoro, or methyl.
- 14. The method according to claim 1, wherein R.sub.4 and R.sub.5 are each independently hydrogen, or substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 15. The method according to claim 1, wherein R.sub.4 is C.sub.1 -C.sub.12 alkyl substituted with a lipophilic group, C.sub.6 -C.sub.12 aryl substituted with a lipophilic group, or C.sub.7 -C.sub.12 aralkyl substituted with a lipophilic group.
- 16. The method according to claim 15, wherein the lipophilic group is selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, adamantyl, quinuclindyl, and substituted derivatives thereof.
- 17. The method according to claim 1, wherein R.sub.5 is C.sub.1 -C.sub.12 alkyl substituted with a lipophilic group, C.sub.6 -C.sub.12 aryl substituted with a lipophilic group, or C.sub.7 -C.sub.12 aralkyl substituted with a lipophilic group.
- 18. The method according to claim 17, wherein the lipophilic group is selected from the group consisting of piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, adamantyl, quinuclindyl, and substituted derivatives thereof.
- 19. The method of claim 1, wherein A is substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 20. The method of claim 1, wherein Y is substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 21. The method of claim 1, wherein R.sub.7 is substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 22. The method according to claim 1, wherein R.sub.4 is --C(O)--R.sub.6, wherein R.sub.6 is alkyl or ANR.sub.9 R.sub.10,
- wherein A is alkyl, and R.sub.9 and R.sub.10 are each independently hydrogen, or substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 23. The method according to claim 1, wherein R.sub.5 is --C(O)--R.sub.6, wherein R.sub.6 is alkyl or ANR.sub.9 R.sub.10,
- wherein A is alkyl, and R.sub.9 and R.sub.10 are each independently hydrogen, or substituted or unsubstituted C.sub.1 -C.sub.12 alkyl.
- 24. The method according to claim 1 wherein R.sub.4 is --Y--C(O)--R.sub.7, wherein Y is substituted or unsubstituted C.sub.1 -C.sub.12 alkyl and R.sub.7 is NR.sub.9 R.sub.10.
- 25. The method according to claim 1 wherein R.sub.5 is --Y--C(O)--R.sub.7, wherein Y is substituted or unsubstituted C.sub.1 -C.sub.12 alkyl and R.sub.7 is NR.sub.9 R.sub.10.
- 26. The method according to claim 1 wherein R.sub.3 and NR.sub.4 R.sub.5 are in a cis spatial configuration.
- 27. The method according to claim 1 wherein R.sub.3 and NR.sub.4 R.sub.5 are in a trans spatial configuration.
- 28. The method according to claim 1 wherein the compound is an R enantiomer.
- 29. The method according to claim 1 wherein the compound is an S enantiomer.
Parent Case Info
This is a continuation of application Ser. No. 08/477,163, filed Jun. 7, 1995, abandoned, which is a divisional of U.S. Ser. No. 08/372,064, filed Jan. 12, 1995, now abandoned, which is a continuation-in-part of U.S. application Ser. Nos. 08/179,539 and 08/179,607, both filed Jan. 10, 1994, both now abandoned, the contents of which are hereby incorporated by reference.
Throughout this application, various references are referred to. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains.
US Referenced Citations (31)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0436492A2 |
Oct 1991 |
EPX |
Non-Patent Literature Citations (6)
Entry |
Oshiro, Y., et al., "Novel Cerebroprotective Agents with Central Nervous System Stimulating Activity. 1. Synthesis and Pharmacology of 1-Amino-7-hydroxyindan Derivatives" J. Medicinal Chem. (1991) 34(7): 2004-2013. |
J. Pharm. Exp. Ther., 180:523-530, 1975. |
Horn et al, "Steric Requirements for Catecholamine Up-take by Rat Brain Synapsomes Studies with Rigid Analogs of Amphetamine", J. Pharm. Exp. Ther., vol. 180, pp. 523-530, 1972. |
Martin et al (I), "Potential anti-Parkinson drugs designed by receptor mapping", CA78:119099 from J.Med.Chem., vol. 16,No. 2, pp. 147-150, 1973. |
Martin et al (II), "Discriminant Analysis of the Relationship Between Physical Properties and Inhibition of MAO by Aminotetralins and Aminoindans", J. Mod. Chem., vol. 17, No. 4, pp. 409-413, 1974. |
Merck Manual, 15th Edition, pp. 1030-1033, 1987. |
Related Publications (1)
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179607 |
Jan 1994 |
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Divisions (1)
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372064 |
Jan 1995 |
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Continuations (1)
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477163 |
Jun 1995 |
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Continuation in Parts (1)
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179539 |
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