N- or C- terminally modified small peptides
View Patent ↗N- or C-terminally modified small peptides having antiarrhythmic properties are disclosed, and in particular small peptides that possess improved pharmacokinetic properties such as having a reduced tendency to inhibit the activity of isozyme 3A4 of cytochrome P 450 oxidase. The invention further relates to uses of said compounds in the preparation of a medicament, and to pharmaceutical compositions comprising said compounds.
1. A compound selected from the group consisting of:
N-(7-hydroxycoumarin-4-acetyl)-Asn-Gly-NH 2 (Compound 1),
N-(9-fluorenylmethyloxycarbonyl)-Asn-Gly-NH 2 (Compound 4),
N-(acridin-9-carbonyl)-Asn-Gly-NH 2 (Compound 5),
N-(pyrenyl-1-carbonyl)-Asn-Tyr-NH 2 (Compound 6),
H-Gly-Asn-NH(4-methyl-coumarin-7-yl) (Compound 9),
H-Gly-Asn-NH(4-nitrophenyl) (Compound 10),
Ac-Gly-Asn-NH(4-nitrophenyl) (Compound II),
H-Gly-Asn-NH(pyrenylmethyl) (Compound 12),
Ac-Gly-Asn-NH(pyrenylmethyl) (Compound 13),
Ac-Gly-Asn-NH(quinolin-6-yl) (Compound 14), and
N-(7-hydroxycoumarin-4-acetyl)-D-Asn-Gly-OH (Compound 15), or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein said compound is N-(7-hydroxycoumarin-4-acetyl)-Asn-Gly-NH 2 (Compound I), or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein said compound is N-(9-fluorenylmethyloxycarbonyl)-Asn-Gly-NH 2 (Compound 4), or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein said compound is N-(acridin-9-carbonyl)-Asn-Gly-NH 2 (Compound 5), or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein said compound is N-(pyrenyl-1-carbonyl)-Asn-Tyr-NH 2 (Compound 6), or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein said compound is H-Gly-Asn-NH(4-methyl-coumarin-7-yl) (Compound 9), or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein said compound is H-Gly-Asn-NH(4-nitrophenyl) (Compound 10), or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein said compound is Ac-Gly-Asn-NH(4-nitrophenyl) (Compound 11), or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein said compound is H-Gly-Asn-NH(pyrenylmethyl) (Compound 12), or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , wherein said compound is Ac-Gly-Asn-NH(pyrenylmethyl) (Compound 13), or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , wherein said compound is Ac-Gly-Asn-NH(quinolin-6-yl) (Compound 14), or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein said compound is N-(7-hydroxycoumarin-4-acetyl)-D-Asn-Gly-OH (Compound 15), or a pharmaceutically acceptable salt thereof.