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US 10,208,087 B2Granted
Peptides
AssigneeHoffmann-La Roche Inc.
InventorsPer-Ola Freskgard, Eric A. Kitas
Life of this patent
Estimating the term…
Abstract
The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
Claims6
A dual-site BACE1 inhibitor, selected from the group consisting of:
- (SEQ ID NO:
- 34)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 36)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoleic)-NH2,
- (SEQ ID NO:
- 38)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Oleic)-NH2,
- (SEQ ID NO:
- 40)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Elaidic)-NH2,
- (SEQ ID NO:
- 42)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Vaccenic)-NH2,
- (SEQ ID NO:
- 44)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Erucic)-NH2,
- (SEQ ID NO:
- 46)
- Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Myristoleic)-NH2,
- (SEQ ID NO:
- 35)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 37)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoleic)-NH2,
- (SEQ ID NO:
- 39)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Oleic)-NH2,
- (SEQ ID NO:
- 41)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Elaidic)-NH2,
- (SEQ ID NO:
- 43)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Vaccenic)-NH2,
- (SEQ ID NO:
- 45)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Erucic)-NH2,
- (SEQ ID NO:
- 47)
- Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Myristoleic)-NH2,
- (SEQ ID NOS:
- 33 and 53)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-(PEG)3-Glu-Val-Asn-
- MetSta-Val-Ala-Glu-DPhe-Lys(Palm)-NH2,
- (SEQ ID NOs:
- 32 and 53)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-(PEG)4-Glu-Val-Asn-
- MetSta-Val-Ala-Glu-DPhe-Lys(Palm)-NH2,
- (SEQ ID NO:
- 2)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Ala-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 11)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DAla-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 27)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DLys-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 18)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DPro-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 3)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Ala-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 21)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DAla-DLys-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 12)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DAla-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 17)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 28)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 19)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DPro-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 4)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Ala-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 13)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DAla-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 29)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DLys-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 20)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DPro-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 1)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 22)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 30)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Gly-Gly-Glu-
- Val-Asn-MetSta-Val-Ala-Glu-DPhe-Lys(Palm)-NH2,
- (SEQ ID NO:
- 31)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Gly-Gly-Gly-
- Glu-Val-Asn-MetSta-Val-Ala-Glu-DPhe-Lys(Palm)-
- NH2,
- (SEQ ID NO:
- 26)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Lys-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 7)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Nle-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 16)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Pro-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 10)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Ser-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 23)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Lys-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 6)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Nle-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 24)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Orn-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 15)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Pro-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 9)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Ser-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 25)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Lys-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH2,
- (SEQ ID NO:
- 5)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Nle-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- (SEQ ID NO:
- 14)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Pro-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- and
- (SEQ ID NO:
- 8)
- Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Ser-Gly-Gly-Glu-Val-
- Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH2,
- or a pharmaceutically acceptable salt thereof.
188 more elements
Dependencies are inferred from the claim text.