Claims
- 1. A compound of the formula:
- 2. A compound according to claim 1 wherein
R1 is aryl, heteroaryl, heterocyclyl, aryl-(C1-C6)alkyl-, heteroaryl-(C1-C6)alkyl-, or heterocyclyl-(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, —OH, —SH, —C≡N, —NO2, —NR105R′105, —CO2R, —N(R)COR′, or —N(R)SO2R′, —C(═O)—(C1-C4) alkyl, —SO2-amino, —SO2-mono or dialkylamino, —C(═O)-amino, —C(═O)-mono or dialkylamino, —SO2—(C1-C4) alkyl, or
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, —C1-C6 alkyl and mono- or dialkylamino, or C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —CAN, —CF3, —C1-C3 alkoxy, amino, mono- or dialkylamino and —C1-C3 alkyl, or C2-C10 alkenyl or C2-C10alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, —OH, —SH, —C≡N, —CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo.
- 3. A compound according to claim 2 wherein
RN is —C (═O)—(CRR′)0-6R100; R100 represents aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, —CH[(CH2)0-2—O—R150]—(CH2)0-2-aryl, —CH [(CH2)0-2—O—R150]—(CH2)0-2-heterocyclyl or —CH[(CH2)0-2—O—R150]-(CH2)0-2-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
—OR, —NO2, C1-C6 alkyl, halogen, —C═N, —OCF3, —CF3, —(CH2)0-4—O—P(═O)(OR)(OR′), —(CH2)0-4—CO—NR105R′105, —(CH2)0-4—O—(CH2)0-4—CONR102R102′, —(CH2)0-4—CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), —(CH2)0-4—CO—(C2-C12 alkynyl), —(CH2)0-4—CO—(CH2)0-4 (C3-C7 cycloalkyl), —(CH2)0-4—R110, —(CH2)0-4—R120, —(CH2)0-4—R130, —(CH2)0-4—CO—R110, —(CH2)0-4—CO—R120, —(CH2)0-4—CO—R130, —(CH2)0-4—CO—R140, —(CH2)0-4—CO—O—R150, —(CH2)0-4—SO2—NR105R′105, —(CH2)0-4—SO—(C1-C8 alkyl), —(CH2)0-4—SO2—(C1-C12 alkyl), —(CH2)0-4—SO2—(CH2)0-4—(C3-C7 cycloalkyl), —(CH2)0-4—N(R150)—CO—O—R150, —(CH2)0-4—N(R150)—CO—N(R150)2, —(CH2)0-4—N(R150) —CS—N(R150)2, —(CH2)0-4—N(R150) —CO—R105, —(CH2)0-4—NR105R′105, —(CH2)0-4—R140, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(O—R110)2, —(CH2)0-4—O—CO—N(R150)2, —(CH2)0-4—O—CS—N(R150)2, —(CH2)0-4—O—(R150), —(CH2)0-4—O—R150′—COOH, —(CH2)0-4—S—(R150), —(CH2)0-4—N(R150)—SO2—R105, —(CH2)0-4—C3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-C10)alkynyl, or R100 is C1-C10 alkyl optionally substituted with 1, 2, or 3 R115 groups, or R100 is —(C1-C6 alkyl)-O—C1-C6 alkyl) or —(C1-C6 alkyl)-S—(C1-C6 alkyl), each of which is optionally substituted with 1, 2, or 3 R115 groups, or R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 R115 groups.
- 4. A compound according to claim 3 wherein
RN is —C(═O)—R100; and R100 represents aryl, or heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
—OR, —NO2, C1-C6 alkyl, halogen, —C≡N, —OCF3, —CF3, (CH2)0-4—O—P(═O)(OR)(OR′), —(CH2)0-4—CO—NR105R′105, —(CH2)0-4—O—(CH2)0-4—CONR102R102′, —(CH2)0-4—CO—(C1-C12 alkyl), —(CH2)0-4—CO—(C2-C12 alkenyl), (CH2)0-4—CO—(C2-C12 alkynyl), —(CH2)0-4—CO—(CH2)0-4(C3-C7 cycloalkyl), —(CH2)0-4—R110, —(CH2)0-4—R120, —(CH2)0-4—R130, —(CH2)0-4—CO—R110, —(CH2)0-4—CO—R120, —(CH2)0-4—CO—R130, —(CH2)0-4—CO—R140, —(CH2)0-4—CO—O—R150, —(CH2)0-4—SO2—NR105R′105, —(CH2)0-4SO—(C1-C8 alkyl), —(CH2)0-4—SO2—(C1-C12 alkyl), —(CH2)0-4—SO2—(CH2)0-4—(C3-C7 cycloalkyl), —(CH2)0-4—N(R150) —CO—O—R150, —(CH2)0-4—N(R150) —CO—N(R150)2, —(CH2)0-4—N(R150)—CS—N(R150)2, —(CH2)0-4—N(R150) —CO—R105, —(CH2)0-4—NR105R′105, —(CH2)0-4—R140, —(CH2)0-4—O—CO—(C1-C6 alkyl), —(CH2)0-4—O—P(O)—(O—R110)2, —(CH2)0-4—O—CO—N(R150)2, —(CH2)0-4—O—CS—N(R150)2, —(CH2)0-4—O—(R150), —(CH2)0-4—O—R150′—COOH, —(CH2)0-4—S—(R150), —(CH2)0-4—N(R150) —SO2—R105, —(CH2)0-4-C3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-C10)alkynyl.
- 5. A compound according to claim 4 wherein R2 and R3 are each hydrogen.
- 6. A compound according to claim 5 wherein Rp is hydrogen.
- 7. A compound according to claim 1 wherein
RC is hydrogen, —(CR245R250)0-4-aryl, —(CR245R250)0-4-heteroaryl, —(CR245R250)0-4-heterocyclyl,
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, R110, R120, R130, —OC═ONR235R240, —S (═O)0-2 (C1-C6 alkyl), —SH, and —S(═O)2NR235R240, —(CH2)0-3-(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, —CO2H, and —CO2—(C1-C4 alkyl), or C2-C10alkenyl or C2-C10alkynyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R210 groups.
- 8. A compound according to claim 7 wherein RC is hydrogen.
- 9. A compound according to claim 1 selected from the group consisting of:
1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-ethylbenzyl)amino]-D-erythro-pentitol, 5-amino-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol, 5-amino-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-L-threopentitol, 5-(cyclohexylamino)-1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-D-erythro-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(3-ethylbenzyl)amino]-L-threo-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(2-ethylbenzyl)amino]-D-erythro-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(4-ethylbenzyl)amino]-L-threo-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-({3-[(dipropylamino)carbonyl]-5-methylbenzoyl}amino)-5-[(4-ethylbenzyl)amino]-D-erythro-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-[(3-[(dipropylamino)carbonyl]-5-{[(2-hydroxyethyl)amino]sulfonyl}benzoyl)amino]-5-[(3-ethylbenzyl)amino]-L-threo-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-{[3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoyl]amino}-5-[(3-ethylbenzyl)amino]-L-threo-pentitol, 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-[(3-[(dipropylamino)carbonyl]-5-{[(2-hydroxyethyl)amino]sulfonyl}benzoyl)amino]-5-[(2-ethylbenzyl)amino]-D-erythro-pentitol, and 1,2,4,5-tetradeoxy-1-(3,5-difluorophenyl)-2-[(3-[(dipropylamino)carbonyl]-5-{[(2-hydroxyethyl)amino]sulfonyl}benzoyl)amino]-5-[(3-ethylbenzyl)amino]-D-erythro-pentitol.
- 10. A method for the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with -progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease compriseing administration of a therapeutically effective amount of a compound or salt according to claim 1, to a patient in need thereof.
- 11. A method of treatment as in claim 10, wherein the patient is a human.
- 12. A method of treatment according to claim 10, wherein the disease is dementia.
- 13. The use of a compound or salt according to claim 1 for the manufacture of a medicament.
- 14. The use of a compound or salt according to claim 1 for the manufacture of a medicament for use in the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease.
- 15. A compound of the formula 5:
- 16. A compound of the formula 4:
- 17. A method for the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease compriseing administration of a therapeutically effective amount of a compound or salt according to claim 1, to a patient in need thereof.
- 18. A method of treatment as in claim 17, wherein the patient is a human.
- 19. A method of treatment according to claim 17, wherein the disease is dementia.
- 20. The use of a compound or salt according to claim 1 for the manufacture of a medicament.
- 21. The use of a compound or salt according to claim 1 for the manufacture of a medicament for use in the treatment or prevention of Alzheimer's disease, mild cognitive impairment Down's syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, or diffuse Lewy body type of Alzheimer's disease.
- 22. A method according to claim 17, where the method is for treating Alzheimer's disease.
- 23. A method of preparing a compound of claim 1.
- 24. A pharmaceutical composition comprising a compound according to claim 1.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional Application Serial No. 60/327,149, filed Oct. 4, 2001, and U.S. Provisional Application Serial No. 60/334,058, filed Nov. 28, 2001, the disclosure of both which are incorporated herein by reference in their entirety.
Provisional Applications (2)
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Number |
Date |
Country |
|
60327149 |
Oct 2001 |
US |
|
60334058 |
Nov 2001 |
US |