Peptides

Patent metadata

Field	Value
Publication number	US-10208087-B2
Application number	US-201515528204-A
Country	US
Kind code	B2
Filing date	Nov 25, 2015
Priority date	Nov 28, 2014
Publication date	Feb 19, 2019
Grant date	Feb 19, 2019

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.

First claim

The invention claimed is:

1. 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)-NH 2 ,

(SEQ ID NO: 36)

Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoleic)-NH 2 ,

(SEQ ID NO: 38)

Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Oleic)-NH 2 ,

(SEQ ID NO: 40)

Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Elaidic)-NH 2 ,

(SEQ ID NO: 42)

Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Vaccenic)-NH 2 ,

(SEQ ID NO: 44)

Tyr-Pro-Lys-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Erucic)-NH 2 ,

(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)-NH 2 ,

(SEQ ID NO: 37)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Palmitoleic)-NH 2 ,

(SEQ ID NO: 39)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Oleic)-NH 2 ,

(SEQ ID NO: 41)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Elaidic)-NH 2 ,

(SEQ ID NO: 43)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Vaccenic)-NH 2 ,

(SEQ ID NO: 45)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Erucic)-NH 2 ,

(SEQ ID NO: 47)

Tyr-Pro-Tyr-Phe-Ile-Pro-DLys-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Myristoleic)-NH 2 ,

(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)-NH 2 ,

(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)-NH 2 ,

(SEQ ID NO: 2)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Ala-Gly-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 11)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DAla-Gly-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 27)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DLys-Gly-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH 2 ,

(SEQ ID NO: 18)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-DPro-Gly-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 3)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Ala-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 21)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DAla-DLys-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 12)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DAla-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 17)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 28)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DLys-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH 2 ,

(SEQ ID NO: 19)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-DPro-Gly-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 4)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-Ala-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 13)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DAla-Glu-Val-

Asn-Sta-Val-Ala-Glu-Phe-Lys(Palmityl)-NH 2 ,

(SEQ ID NO: 29)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DLys-Glu-Val-

Asn-Sta-Val-Ala-Glu-DPro-Lys(Palm)-NH 2 ,

(SEQ ID NO: 20)

Tyr-Pro-Tyr-Phe-Ile-Pro-Leu-Gly-Gly-DPro-Glu-Val-

Assignees

• Hoffmann La Roche

Inventors

• Freskgard Per-Ola
• Kitas Eric A

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title