JP2014210799A5

JP2014210799A5 -

Info

Publication number: JP2014210799A5
Application number: JP2014139114A
Authority: JP
Filing date: 2014-07-04
Publication date: 2015-01-22
Anticipated expiration: 2028-12-15

Claims

Formula R ¹ -XZR ²
{Where,
R ¹ is H, C _1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;
R ² is OH or NH ₂ ;
X is the following formula (I):
His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Arg-Arg-Ala-Lys-Asp-Phe-Ile-Glu-Trp- Leu-Leu-Ser-Ala (SEQ ID NO: 4)
Or, if different from formula (I), the following:
The residue at position 2 is selected from: D-Ser, Aib ;
The residue at position 16 is: Ser;
The residue at position 20 is: Gln;
The residue at position 24 is selected from: Gln, Arg ; and the residue at position 28 is: Arg;
A peptide that differs from formula (I) by a maximum of 4 of these; and Z is absent or is 4 , 5 , 6 or 7 consecutive lysine residues . Or a pharmaceutically acceptable salt thereof.

When different from the formula (I), the X is
The residue at position 2 is selected from: D-Ser, Aib;
The residue at position 16 is: Ser ; and the residue at position 20 is: Gln ;
2. A compound according to claim 1 which differs from formula (I) by a maximum of three of

The compound according to any one of claims 1 to 2, wherein the residues at positions 16 and 20 and / or positions 20 and 24 can form a salt bridge.

Wherein X is the following set of residues:
20-Lys, 24-Glu;
20-Lys, 23-Ile, 24-Glu;
16-Glu, 20-Lys, 24-Glu;
16-Glu, 20-Lys;
16-Glu, 20-Lys, 29-Ala;
16-Glu, 20-Lys, 23-Ile, 24-Glu;
16-Glu, 20-Lys, 23-Ile, 24-Glu, 29-Ala;
16-Glu, 20-Lys, 24-Glu, 29-Ala;
20-Lys, 23-Ile, 24-Glu, 29-Ala;
27-Leu, 28-Ser, 29-Ala;
29-Ala;
16-Ser;
20-Gln ;
24-Gln;
16-Ser, 20-Gln ;
24-Arg; or 28-Arg,
4. A compound according to any one of claims 1 to 3 comprising one or more of the above.

Said X is the following sequence:
HSQGTFTSDYSKYLDSRRAKDFIEWLLSA (SEQ ID NO: 13);
HSQGTFTSDYSKYLDERRAQDFIEWLLSA (SEQ ID NO: 5) ;
HSQGTFTSDYSKYLDERRAKDFIQWLLSA (SEQ ID NO: 7);
HSQGTFTSDYSKYLDSRRAQDFIEWLLSA (SEQ ID NO: 8) ;
HSQGTFTSDYSKYLDERRAKDFIRWLLSA (SEQ ID NO: 11);
HSQGTFTSDYSKYLDERRAKDFIEWLLRA (SEQ ID NO: 12) ;
HSQGTFTSDYSKYLDERRAKDFIEWLLSA (SEQ ID NO: 17),
The compound of claim 1 having

The compound according to claim 1, wherein R ¹ is H.

The compound according to any one of claims 1 to 6, wherein R ² is NH ₂ .

8. A compound according to any one of claims 1 to 7, wherein Z is absent.

9. A compound according to any one of claims 1 to 8, wherein one or more of the amino acid side chains in such a compound, for example peptide X, are linked to a lipophilic substituent or polymer moiety. Said compound.

The nucleic acid which codes the compound of any one of Claims 1-8.

An expression vector comprising the nucleic acid according to claim 10.

A host cell comprising the nucleic acid according to claim 10 or the expression vector according to claim 11.

A pharmaceutical composition comprising the compound, nucleic acid, expression vector or host cell of any one of claims 1 to 9 in a mixture with a pharmaceutically acceptable carrier.

Overweight or obesity to prevent weight gain or promote weight loss, or include morbid obesity, obesity-related inflammation, obesity-related gallbladder disease and obesity-induced sleep apnea For the treatment of physical conditions caused by or related to them, or insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertension, atherogenic dyslipidemia, atherosclerosis, arteriosclerosis, Use of a compound, nucleic acid, expression vector or host cell according to any one of claims 1 to 9 in the preparation of a medicament for the treatment of coronary heart disease or stroke.

Prevents weight gain, promotes weight loss, or is caused by morbid obesity, obesity-related inflammation, obesity-related gallbladder disease and obesity-induced sleep apnea or obesity For treatment of or related physical conditions, or insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertension, atherogenic dyslipidemia, atherosclerosis, arteriosclerosis, coronary 10. A pharmaceutical composition comprising a compound according to any one of claims 1-9 in a method for the treatment of heart disease or stroke.