Claims
- 1. A compound having the structure: in which:R1 is oxygen or sulfur; R2 and R3 are independently selected from the group consisting of —CR═and —CX═; M is ═CR4—, wherein R4 and R8 are independently R or together form a moiety which links M to the ring vertex 2′ to form a ring, the moiety which links being selected from the group consisting of a single bond, —CRR’—, —CR═CR’—, —C(O)—, —O—, —S(O)y—, —NR—, and —N═; R5 is —(CRR′)n—, ; R6 is —O—; and R7 is selected from the group consisting of—CRR′—, —C(O)—, —CXX’— and —CRX—; whereinX and X′ are independently selected from —Br, —Cl, —F, —CN, —NO2, —OR, —SR, —NRR′,—C(O)R, —CO2R, or —CONRR′, wherein two groups R or R′ on an individual group X, or on two adjacent groups X, may together form a ring; and R and R′ are independently selected from (i) hydrogen, (ii) C1-C6 branched or unbranched alkyl or C3 to C6 cycloalkyl groups, which may be unsubstituted or substituted with one or more functionalities selected from halogen, nitro, alkoxy, hydroxy, alkylthio, amino, keto, aldehyde, carboxylic acid, carboxylic ester, or carboxylic amide, and wherein when R and R’ are alkyl groups, said alkyl groups may together form a ring, and (iii) aryl groups, which may be unsubstituted or substituted with one or more functionalities selected from halogen, nitro, alkoxy, hydroxy, aryloxy, alkylthio, amino, keto, aldehyde, carboxylic acid, carboxylic ester, or carboxylic amide; p is 0 or 1; and n is one and y is 0, 1 or 2.
- 2. A compound in accordance with claim 1 in which R and R′ are independently selected from (i) hydrogen and (ii) C1-C6 branched or unbranched alkyl or C3 to C6 cylcoalkyl groups, which may be unsubstituted or substituted with one or more functionalities selected from halogen, nitro, alkoxy, hydroxy, alkylthio, amino, keto, aldehyde, carboxylic acid, carboxylic ester, or carboxylic amide, and wherein when R and R’ are alkyl groups, said alkyl groups may together form a ring.
- 3. A compound in accordance with claim 1 in which R2 and R3 are —CR═ and M is ═CR4—.
- 4. A compound in accordance with claim 3 in which p is 0, R1 is oxygen, and R4 and R8 are hydrogen.
- 5. A compound in accordance with claim 4 in which R5 and R7 are —(CRR′)n—.
- 6. A compound in accordance with claim 5 in which R and R′ are hydrogen, said compound being 4-(benzofurazan-5-ylcarbonyl)morpholine.
- 7. A compound in accordance with claim 1 wherein R4 and R8 together form a moiety which links M to the ring vertex 2′ form a ring, the moiety which links being a single bond, —CRR′—, —CR═CR′—, —C(O)—, —O—, —S—, —NR—, or —N═.
- 8. A compound in accordance with claim 7 in which R2 and R3 are —CR═.
- 9. A pharmaceutical composition comprising an effective amount of the compound according to claim 1 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 10. A pharmaceutical composition comprising an effective amount of the compound according to claim 2 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 11. A pharmaceutical composition comprising an effective amount of the compound according to claim 3 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 12. A pharmaceutical composition comprising an effective amount of the compound according to claim 4 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 13. A pharmaceutical composition comprising an effective amount of the compound according to claim 5 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 14. A pharmaceutical composition comprising an effective amount of the compound according to claim 7 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 15. A pharmaceutical composition comprising an effective amount of the compound according to claim 8 in combination with a pharmaceutically acceptable carrier, additive or excipient.
- 16. A method of enhancing AMPA receptor function in a mammalian subject in need thereof comprising administering to said subject an effective amount of a compound according to claim 1.
- 17. The method according to claim 16, wherein said enhancing is effective to alleviate impairment of memory, or other cognitive functions caused by a hypoglutamatergic condition or by deficiency in the number or strength of excitatory synapses or in the number of AMPA receptors.
- 18. The method according to claim 16, wherein said enhancing is effective to treat schizophrenia, or schizophreniform behavior resulting from a cortical/striatal imbalance caused by a hypoglutamatergic condition or by deficiency in the number or strength of excitatory synapses or in the number of AMPA receptors.
- 19. The method according to claim 16, wherein said enhancing is effective to facilitate learning of behaviors dependent on AMPA receptor functioning.
- 20. The method according to claim 16, wherein in said compound R and R′ are independently selected from (i) hydro and (ii) C1-C6 branched or unbranched alkyl groups which may be unsubstituted or substituted with one or more functionalities selected from halogen, nitro, alkoxy, hydroxy, alkylthio, amino keto, aldehyde, carboxylic acid, carboxylic ester, or carboxylic amide, and wherein R and R′ are alkyl group, said alkyl groups may together form a ring.
- 21. The method according to claim 17, wherein said compound is 4-benzofurazan-5-ylcarbonyl)morpholine.
RELATED APPLICATION
This application is a §371 of international application no. PCT/US98/02713, which is a continuation-in-part application of U.S. application Ser. No. 08/800,108, filed Feb. 13, 1997, now U.S. Pat. No. 6,110,935.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US98/02713 |
|
WO |
00 |
10/4/1999 |
10/4/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/35950 |
8/20/1998 |
WO |
A |
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3981864 |
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Sep 1976 |
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5112824 |
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May 1992 |
|
Foreign Referenced Citations (5)
Number |
Date |
Country |
0 431 943 A2 |
Jun 1991 |
EP |
0709384A |
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EP |
WO 9402475 |
Feb 1994 |
WO |
9402475 |
Feb 1994 |
WO |
WO 9736907A |
Oct 1997 |
WO |
Non-Patent Literature Citations (3)
Entry |
Bauer et al., (J.Med.Chem.Chem. 1976, vol. 19, No. 11, pp. 1315-1324). |
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(Neuroscience. 1997, pp. 465 and 480) Edited by Dale Purves. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08/800108 |
Feb 1997 |
US |
Child |
09/355139 |
|
US |