Application of 5-HT6 receptor antagonists for the alleviation of cognitive deficits of down syndrome
AssigneeUniversity of Utah Research Foundation
InventorsJulie Ruth Korenberg, Karen Sue Wilcox, Peter Jeffrey West, Raymond Pierre Kesner
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Abstract
Methods for treating Down syndrome and improving cognitive function of a patient with an intellectual disability are disclosed. 5-hydroxytryptamine sub-receptor six (5-HT6) receptor antagonists are provided for improving the cognition of a Down syndrome patient.
Claims20
A method of improving cognitive function in a subject with Down syndrome, comprising administering to the subject a 5-HT6 receptor antagonist in an amount sufficient for a therapeutic effect by binding to a 5-HT6 receptor, wherein the subject has chronic cognitive impairment caused by a genetic anomaly, wherein the 5-HT6 receptor antagonist is an effective amount of a compound having a structure according to Formula I:
- wherein, for compounds having a structure according to Formula I:
- RA is selected from —H, —NH2, —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, —N(aryl)(alkyl), —NH-heterocycle, or —NH-heterocycloalkyl, where, in the case of —N(alkyl)2 or —N(aryl)2, the alkyl groups or the aryl groups can be identical or different;
- RB is selected from —H, —NH2, —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, —N(aryl)(alkyl), —NH-heterocycle, or —NH-heterocycloalkyl, where, in the case of —N(alkyl)2 or —N(aryl)2, the alkyl groups or the aryl groups can be identical or different;
- RC is selected from —H, —OH, —O(alkyl), —O(aryl), -halogen, -alkyl, or haloalkyl;
- RD is selected from —H, -alkyl, -halogen, -haloalkyl, or -aryl;
- RE is selected from —H, -halogen, —OH, —O(alkyl), —NH2, —NH(alkyl), or —N(alkyl)2, where, in the case of —N(alkyl)2, the alkyl groups can be identical alkyl chains or can be of different length alkyl chains;
- RF is —H, —NH2, —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, —N(aryl)(alkyl), —NH-heterocycle, or —NH-heterocycloalkyl, where, in the case of a dialkyl or diaryl nitrogen the alkyl groups or the aryl groups can be identical or different;
- X and Y are independently —N— or —C(H)—;
- and
- Z is selected from —CH2—, —CHX—, —CX2—, —CH(alkyl)-, —CH(aryl)-, —C(aryl)(alkyl)-, —C(alkyl)2-, —C(aryl)2-, —O—, —S—, —S(═O)—, or —S(═O)2—, where X is a halogen and where, in the case of —C(alkyl)2- or —C(aryl)2-, the alkyl groups or aryl groups can be identical or different;
- and pharmaceutically acceptable hydrates, solvates, tautomers, salts, and complexes thereof.
A method of improving cognitive function in a subject with Down syndrome, comprising administering to the subject a 5-HT6 receptor antagonist in an amount sufficient for a therapeutic effect by binding to a 5-HT6 receptor, wherein:
- (i) the 5-HT6 receptor antagonist is a small molecule 5-HT6 receptor antagonist;
- (ii) the small molecule 5-HT6 receptor antagonist has a molecular weight of less than 800 Daltons;
- and
- (iii) the subject has chronic cognitive impairment caused by a genetic anomaly,
- wherein the 5-HT6 antagonist is an effective amount of compound 7, having the chemical formula:
- or pharmaceutically acceptable hydrates, solvates, tautomers, salts, and complexes thereof.
A method of improving cognitive function in a subject with Down syndrome, comprising administering to the subject a 5-HT6 receptor antagonist in an amount sufficient for a therapeutic effect by binding to a 5-HT6 receptor, wherein the subject has chronic cognitive impairment caused by a genetic anomaly, wherein the 5-HT6 receptor antagonist is an effective amount of a compound having a structure according to Formula II:
- wherein, for compounds having a structure according to Formula II:
- RZ is selected from —H, —OH, —O(alkyl), —O(aryl)-O—S-phenyl, —O—S(═O) -phenyl, —O—S(═O)2-phenyl, —O—S-alkyl, —O—S(═O)-alkyl, —O—S(═O)2-alkyl, —O—S-haloalkyl, —O—S(═O)-haloalkyl, —O—S(═O)2-haloalkyl, —O—S-2,6-dihalophenyl, —O—S(═O)-2,6-dihalophenyl, or —OS(═O)2-2,6-dihalophenyl;
- RY is selected from —H, -halogen, —NH2, —NH(alkyl), —N(alkyl)2, —NH(aryl), —N(aryl)2, —N(aryl)(alkyl), —NH-heterocycle, or —NH-heterocycloalkyl, where, in the case of —N(alkyl)2 or —N(aryl)2, the alkyl groups or the aryl groups can independently be identical or different;
- RW is selected from —H, —OH, —O(alkyl), —O(aryl), -halogen, -alkyl, or haloalkyl;
- RV is selected from —H, -2-ethyl-NH(alkyl), -2-ethyl-N(alkyl)2, -2-ethyl-NH(aryl), -2-ethyl-NH(arylalkyl), -2-ethyl-NH(benzyl), -2-ethyl-NH(alkoxybenzyl), -2-ethyl-NH(haloalkoxybenzyl), -2-ethyl-NH(m-haloalkoxybenzyl), -2-ethyl-N(aryl)2, -2-ethyl-N(alkyl)(aryl), -3-propyl-NH(alkyl), -3-propyl-N(alkyl)2, -3-propyl-NH(aryl), -3-propyl-N(aryl)2, -3-propyl-N(aryl)(alkyl), —NH-heterocycle, or —NH-heterocycloalkyl, where, in the case of a dialkyl or diaryl nitrogen, the alkyl groups or the aryl groups can be identical or different;
- Z′ is selected from —H, —CH2—, —CHX—, —CX2—, —CH(alkyl)-, —CH(aryl)-, —C(aryl)(alkyl)-, —C(alkyl)2-, —C(aryl)2-, —O—, —S—, —S(═O)—, or —S(═O)2—, where X is a halogen and where, in the case of —C(alkyl)2- or —C(aryl)2-, the alkyl groups or the aryl groups can be identical or different;
- and
- RX is optionally present, and if present is selected from —H, —OH, —O(alkyl), —O(aryl), -halogen, -alkyl, -haloalkyl, or -aryl;
- and pharmaceutically acceptable hydrates, solvates, tautomers, salts, and complexes thereof.
Dependencies are inferred from the claim text.