US2010028839A1PendingUtilityA1
Methods and systems for evaluating memory agents
Est. expiryJul 18, 2028(~2 yrs left)· nominal 20-yr term from priority
H04N 23/80H04N 23/60H04N 23/951G09G 2320/0693G09G 3/006
57
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Claims
Abstract
The present invention provides methods and systems for identifying, evaluating, and testing various compounds as memory agents and regimens as training protocols related to memory enhancement and/or impairment. Such methods and systems may test any compounds or protocols, including the memory agents and training protocols described herein. The methods can comprise combining training protocols with the general administration of memory agents. In some embodiments, the present invention may involve identifying, selecting, testing, evaluating or assessing a compound as a drug candidate for a memory agent, for example, as one effective for enhancing or impairing memory.
Claims
exact text as granted — not AI-modified1 . A method comprising the steps of:
assessing the effectiveness of a memory agent administered to a subject, wherein said assessing comprises presenting to said subject sets of stimuli; and evaluating said subject's response to said stimuli.
2 . The method of claim 1 , wherein said stimuli affect a CREB pathway.
3 . The method of claim 2 , wherein said stimuli affect the subject's long term memory.
4 . The method of claim 1 , wherein said assessing further comprises selecting a performance criterion and evaluating the number of days of training required for the subject to reach the performance criterion.
5 . The method of claim 1 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
6 . The method of claim 5 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
7 . The method of claim 6 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
8 . The method of claim 1 wherein said subject is an animal.
9 . The method of claim 8 wherein said animal is a mammal.
10 . The method of claim 9 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
11 . The method of claim 10 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
12 . The method of claim 11 wherein said primate is a human.
13 . The method of claim 1 wherein said subject is a plurality of subjects.
14 . The method of claim 13 wherein said plurality of subjects comprises a control group and an experimental group.
15 . The method of claim 14 wherein said assessing comprises comparing said control group to said experimental group.
16 . The method of claim 1 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
17 . The method of claim 1 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
18 . A method comprising the steps of assessing the effectiveness of a memory agent administered to a subject, wherein said assessing comprises selecting a performance criterion, training the subject by presenting the subject with sets of stimuli, evaluating the subject's response to the stimuli to determine whether the subject has reached the performance criterion, and determining the number of days of training required to reach the performance criterion.
19 . The method of claim 18 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
20 . The method of claim 19 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
21 . The method of claim 20 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
22 . The method of claim 18 wherein said stimuli affect a CREB pathway.
23 . The method of claim 18 wherein said stimuli affect the subject's long term memory.
24 . The method of claim 18 wherein the performance criterion is a percentage representing the quality of the subject's response to the stimuli.
25 . The method of claim 18 , wherein the performance criteria represents the subject's acquisition of long term memory.
26 . The method of claim 18 wherein said subject is an animal.
27 . The method of claim 26 wherein said animal is a mammal.
28 . The method of claim 27 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
29 . The method of claim 28 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
30 . The method of claim 29 wherein said primate is a human.
31 . The method of claim 18 wherein said subject is a plurality of subjects.
32 . The method of claim 31 wherein said plurality of subjects comprises a control group and an experimental group.
33 . The method of claim 32 wherein said assessing comprises comparing said control group to said experimental group.
34 . The method of claim 18 , wherein said, memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
35 . The method of claim 18 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
36 . A method comprising the steps of assessing the effectiveness of a memory agent administered to a subject, wherein said assessing comprises selecting a performance criterion, training the subject by presenting the subject with sets of stimuli, evaluating the subject's response to said stimuli to determine whether the subject has reached the performance criterion, repeating said presenting and evaluating until the subject reaches the performance criterion, and determining the number of days of training required for the subject to reach the performance criterion.
37 . The method of claim 36 , wherein said stimuli affect a CREB pathway.
38 . The method of claim 36 , wherein said stimuli affect the subject's long term memory.
39 . The method of claim 36 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
40 . The method of claim 39 wherein each of said plurality of pairs of stimuli comprises a element that has an identifiable association with the other element of said pair.
41 . The method of claim 40 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
42 . The method of claim 36 wherein said subject is an animal.
43 . The method of claim 42 wherein said animal is a mammal.
44 . The method of claim 43 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
45 . The method of claim 44 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
46 . The method of claim 45 wherein said primate is a human.
47 . The method of claim 36 wherein said subject is a plurality of subjects.
48 . The method of claim 47 wherein said plurality of subjects comprises a control group and an experimental group.
49 . The method of claim 48 wherein said assessing comprises comparing said control group to said experimental group.
50 . The method of claim 36 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
51 . The method of claim 36 wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
52 . A method comprising selecting a memory agent as a drug candidate, wherein said selecting comprises the steps of assessing said memory agent by administering said memory agent to a subject; and presenting to said subject sets of stimuli and evaluating said subject's response to said stimuli.
53 . The method of claim 52 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
54 . The method of claim 53 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
55 . The method of claim 54 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
56 . The method of claim 52 wherein said stimuli affect a CREB pathway.
57 . The method of claim 52 wherein said stimuli affect the subject's long term memory.
58 . The method of claim 52 , wherein said assessing further comprises selecting a performance criterion, and said evaluating comprises determining the quantity of stimuli required for the subject to reach the performance criterion.
59 . The method of claim 58 , wherein the performance criterion is a percentage representing the quality of the subject's response to the stimuli.
60 . The method of 59 , wherein the performance criteria represents the subject's acquisition of long term memory.
61 . The method of claim 52 wherein said subject is an animal.
62 . The method of claim 61 wherein said animal is a mammal.
63 . The method of claim 62 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
64 . The method of claim 63 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
65 . The method of claim 64 wherein said primate is a human.
66 . The method of claim 52 wherein said subject is a plurality of subjects.
67 . The method of claim 66 wherein said plurality of subjects comprises a control group and an experimental group.
68 . The method of claim 67 wherein said assessing comprises comparing said control group to said experimental group.
69 . The method of claim 52 , wherein said, memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
70 . The method of claim 52 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
71 . A method comprising:
testing a memory agent as a long term memory enhancer, wherein said testing comprises the steps of: administering said memory agent to a subject; presenting to said subject sets of stimuli; and evaluating said subject's response to said stimuli.
72 . The method of claim 71 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
73 . The method of claim 72 wherein each of said plurality of pairs of stimuli comprises a element that has an identifiable association with the other element of said pair.
74 . The method of claim 73 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
75 . The method of claim 71 wherein the second subject is an animal.
76 . The method of claim 75 , wherein the animal is a mammal.
77 . The method of claim 76 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
78 . The method of claim 77 , wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
79 . The method of claim 78 wherein said primate is a human.
80 . The method of claim 71 wherein said subject is a plurality of subjects.
81 . The method of claim 80 wherein said plurality of subjects comprises a control group and an experimental group.
82 . The method of claim 81 wherein said assessing comprises comparing said control group to said experimental group.
83 . The method of claim 71 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
84 . The method of claim 71 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
85 . A system comprising: sets of stimuli, wherein said sets of stimuli are configured to permit evaluation of a subject's response to said sets of stimuli and thereby assess the effectiveness of a memory agent administered to said subject.
86 . The system of claim 85 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
87 . The system of claim 86 wherein each of said plurality of pairs of stimuli comprises a positive element or a negative element.
88 . The system of claim 86 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
89 . The system of claim 88 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
90 . The system of claim 85 wherein said subject is an animal.
91 . The system of claim 90 wherein said animal is a mammal.
92 . The system of claim 91 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
93 . The method of claim 92 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
94 . The method of claim 93 wherein said primate is a human.
95 . The system of claim 85 wherein said subject is a plurality of subjects.
96 . The system of claim 95 wherein said plurality of subjects comprises a control group and an experimental group.
97 . The system of claim 96 wherein said assessing comprises comparing said control group to said experimental group.
98 . The system of claim 85 , wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group; wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl; wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN; wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl; wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 or aryl; wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl; wherein B is aryl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolizinyl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, isoindolyl, benzo[b]furan-4-yl, benzo[b]furan-5-yl, benzo[b]furan-6-yl, benzo[b]furan-7-yl, benzo[b]thiophen-4-yl, benzo[b]thiophen-5-yl, benzo[b]thiophen-6-yl, benzo[b]thiophen-7-yl, indazolyl, benzimidazolyl, benzo[b]thiazolyl, purinyl, imidazo[2,1-b]thiazolyl, quinolinyl, isoquinolinyl, quinazolinyl, 2,1,3-benzothiazolyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzoxazolyl, benzisoxazolyl, cinnolinyl, quinoxalinyl, 1,8-napthyridinyl, pteridinyl, or phthalimidyl; provided however, that the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy; wherein n is an integer from 1 to 4 inclusive; wherein aryl is phenyl or napthyl, including phenyl and napthyl substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —OR 4 , SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m CH 3 ; or a pharmaceutically acceptable salt thereof.
99 . The system of claim 85 wherein said memory agent is one or more selected from the group consisting of a compound having the structure:
wherein Me is methyl, cPent is cyclopentyl and the 3 and 5 carbons are in the S configuration.
100 . A method comprising the steps of:
assessing the effectiveness of a training protocol administered to a subject, wherein said assessing comprises presenting to said subject sets of stimuli and evaluating said subject's response to said stimuli.
101 . A method comprising:
testing a training protocol as a long term memory enhancer, wherein said testing comprises the steps of: administering a training protocol to a subject; and presenting to said subject sets of stimuli and evaluating said subject's response to said stimuli.
102 . A system comprising: sets of stimuli, wherein said sets of stimuli are configured to permit evaluation of a subject's response to said sets of stimuli and thereby assess the effectiveness of a training protocol administered to said subject.
103 . The system of claim 102 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
104 . The system of claim 103 wherein each of said plurality of pairs of stimuli comprises a positive element or a negative element.
105 . The system of claim 103 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
106 . The system of claim 105 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
107 . A method comprising the steps of:
assessing the effectiveness of a memory impairer administered to a subject, wherein said assessing comprises presenting to said subject sets of stimuli and evaluating said subject's response to said stimuli.
108 . The method of claim 107 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
109 . The method of claim 108 wherein each of said plurality of pairs of stimuli comprises a positive element or a negative element.
110 . The method of claim 108 wherein each of said plurality of pairs of stimuli comprises a element that has an identifiable association with the other element of said pair.
111 . The method of claim 110 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
112 . The method of claim 107 wherein said subject is an animal.
113 . The method of claim 112 wherein the animal is a mammal
114 . The method of claim 113 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
115 . The method of claim 114 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
116 . The method of claim 115 wherein said primate is a human.
117 . The method of claim 107 wherein said subject is a plurality of subjects.
118 . The method of claim 117 wherein said plurality of subjects comprises a control group and an experimental group.
119 . The method of claim 118 wherein said assessing comprises comparing said control group to said experimental group.
120 . A method comprising:
selecting a memory impairer as a drug candidate, wherein said selecting comprises the steps of: assessing said memory impairer by administering said memory impairer to a subject; and presenting to said subject sets of stimuli and evaluating said subject's response to said stimuli.
121 . The method of claim 120 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
122 . The method of claim 121 wherein each of said plurality of pairs of stimuli comprises a positive element or a negative element.
123 . The method of claim 121 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
124 . The method of claim 123 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
125 . The method of claim 120 wherein the subject is an animal.
126 . The method of claim 125 , wherein said animal is a mammal.
127 . The method of claim 126 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
128 . The method of claim 127 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
129 . The method of claim 128 wherein said primate is a human.
130 . The method of claim 120 wherein said subject is a plurality of subjects.
131 . The method of claim 130 wherein said plurality of subjects comprises a control group and an experimental group.
132 . The method of claim 131 wherein said assessing comprises comparing said control group to said experimental group.
133 . A system comprising: sets of stimuli, wherein said sets of stimuli are configured to permit evaluation of a subject's response to said sets of stimuli and thereby assess the effectiveness of a memory impairer administered to said subject.
134 . The system of claim 133 wherein said sets of stimuli comprise a plurality of pairs of stimuli.
135 . The system of claim 134 wherein each of said plurality of pairs of stimuli comprises a positive element or a negative element.
136 . The system of claim 134 wherein each of said plurality of pairs of stimuli comprises an element that has an identifiable association with the other element of said pair.
137 . The system of claim 136 wherein said identifiable association is selected from the group consisting of a face—name association and a word—word association.
138 . The system of claim 133 wherein the subject is an animal.
139 . The system of claim 138 , wherein said animal is a mammal.
140 . The system of claim 139 wherein said mammal is selected from the group consisting of a primate, a mouse and a rat.
141 . The system of claim 140 wherein said primate is selected from the group consisting of a human, a monkey, a lemur, a macaque and an ape.
142 . The system of claim 141 wherein said primate is a human.
143 . The system of claim 133 wherein said subject is a plurality of subjects.
144 . The system of claim 143 wherein said plurality of subjects comprises a control group and an experimental group.
145 . The system of claim 144 wherein said assessing comprises comparing said control group to said experimental group.Cited by (0)
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