Compounds useful in the treatment and/or care of the skin, hair, nails, and/or mucous membranes
Compounds of general formula (I): R1-Wm-Xn-AA1-AA2-AA3-AA4-AA5-AA6-Yp-Zq-R2 (I) their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts, cosmetic and/or pharmaceutical compositions which contain them and their use in medicine, and in processes of treatment and/or care of the skin, hair and/or mucous membranes, in particular in the aging and photoaging of the skin.
1. A compound of general formula (I):
R 1 -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -R 2 (I)(SEQ ID NO.33),
its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:
AA 1 is selected from the group consisting of Gln, Glu, Asp and Asn;
AA 2 is selected from the group consisting of Glu, Gln and Asp;
AA 3 is selected from the group consisting of Met, Ile and Leu;
AA 4 is selected from the group consisting of Arg, Lys and Orn;
AA 5 is selected from the group consisting of Met, Leu, Ile and Val;
AA 6 is selected from the group consisting of Gln, Asn and Glu;
R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;
R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 and —SR 3 , wherein R 3 and R 4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and
R 1 and R 2 are not α-amino acids,
with the proviso that the compound is not Ac-Asn-Glu-Met-Arg-Met-Gln-OH (Ac-[SEQ ID NO.30]-OH), Ac-Gln-Glu-Met-Arg-Leu-Gln-OH (Ac-[SEQ ID NO.31]-OH), or Palm-Gln-Glu-Met-Arg-Met-Asn-OH (Palm-[SEQ ID NO.32]-OH).
2. A compound according to claim 1 , wherein:
(i) AA 1 is Gln, AA 2 is Glu, AA 3 is Met, AA 4 is Arg, AA 5 is Met, and AA 6 is Gln, or
(ii) AA 1 is Gln, AA 2 is Glu, AA 3 is Met, AA 4 is Arg, AA 5 is Met and AA 6 is Gln, and 1 to 3 of AA 1 , AA 2 , AA 3 , AA 4 , AA 5 and AA 6 are replaced providing that:
when AA 1 is replaced, it is replaced by an amino acid selected from the group consisting of Glu, Asp and Asn;
when AA 2 is replaced, it is replaced by an amino acid selected from the group consisting of Gln and Asp;
when AA 3 is replaced, it is replaced by an amino acid selected from the group consisting of Ile and Leu;
when AA 4 is replaced, it is replaced by an amino acid selected from the group consisting of Lys and Orn;
when AA 5 is replaced, it is replaced by an amino acid selected from the group consisting of Leu, Ile and Val; and
when AA 6 is replaced, it is replaced by an amino acid selected from the group consisting of Asn and Glu.
3. A compound according to claim 2 , wherein three of AA 1 , AA 2 , AA 3 , AA 4 , AA 5 and AA 6 are replaced.
4. A compound according to claim 3 , wherein AA 1 , AA 3 and AA 5 are replaced or AA 2 , AA 4 and AA 6 are replaced.
5. A compound according to claim 2 , wherein two of AA 1 , AA 2 , AA 3 , AA 4 , AA 5 and AA 6 are replaced.
6. A compound according to claim 5 , wherein AA 2 and AA 6 are replaced, AA 4 and AA 5 are replaced, AA 1 and AA 2 are replaced, or AA 1 and AA 3 are replaced.
7. A compound according to claim 2 , wherein one of AA 1 , AA 2 , AA 3 , AA 4 , AA 5 and AA 6 is replaced.
8. A compound of general formula:
R 1 —W m —X n -Gln-Glu-Met-Arg-Met-Gln-Y p —Z q —R 2 (R 1 -[SEQ ID NO.34]—R 2 ),
its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:
m, n, p and q are each independently 0 or 1;
R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;
R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 and —SR 3 , wherein R 3 and R 4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and
R 1 and R 2 are not α-amino acids.
9. A compound according to claim 1 , wherein R 1 is selected from H, acetyl, myristoyl and palmitoyl and R 2 is selected from —OH, —NH 2 and —NHR 3 , wherein R 3 is a C 6 to C 18 alkyl group.
10. A cosmetic or pharmaceutical composition which comprises at least one compound of general formula (I), its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, according to claim 1 and at least one cosmetically or pharmaceutically acceptable excipient or adjuvant.
11. A composition according to claim 10 , wherein said compound of general formula (I), its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, is incorporated into a cosmetically or pharmaceutically acceptable delivery system or sustained release system selected from the group consisting of liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, milliparticles, microparticles, nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactant-phospholipid mixed micelles, millispheres, microspheres, nanospheres, lipospheres, millicapsules, microcapsules, nanocapsules, microemulsions and nanoemulsions or is absorbed onto a solid organic polymer or solid mineral support selected from the group consisting of talc, bentonite, silica, starch and maltodextrin.
12. A composition according to claim 10 , wherein said composition is in a formulation selected from the group consisting of creams, multiple emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, sera, soaps, shampoos, conditioners, serums, polysaccharide films, ointments, mousses, pomades, powders, bars, pencils, sprays, aerosols, capsules, gelatin capsules, soft capsules, hard capsules, tablets, sugar coated tablets, pills, powders, granules, chewing gum, solutions, suspensions, emulsions, syrups, elixirs, jellies and gelatins.
13. A compound of general formula (I):
R 1 —W m —X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p —Z q —R 2 (I),
its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:
W, X, Y and Z are each independently an amino acid;
m, n, p and q are each independently 0 or 1;
R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;
R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 and —SR 3 , wherein R 3 and R 4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and
R 1 and R 2 are not α-amino acids,
wherein:
AA 1 is Gln, AA 2 is Glu, AA 3 is Met, AA 4 is Arg, AA 5 is Met, and AA 6 is Gln (SEQ ID NO.1), or when
AA 1 is Gln, AA 2 is Glu, AA 3 is Leu, AA 4 is Arg, AA 5 is Met, and AA 6 is Gln (SEQ ID NO.11).
14. A compound of general formula (I):
R 1 —W m —X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p —Z q —R 2 (I),
its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:
W, X, Y and Z are each independently an amino acid;
m, n, p and q are each independently 0 or 1;
R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;
R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 and —SR 3 , wherein R 3 and R 4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and
R 1 and R 2 are not α-amino acids, and
wherein W m —X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p —Z q is selected from:
SEQ ID NO. 1
Gln-Glu-Met-Arg-Met-Gln,
SEQ ID NO. 2
Asp-Glu-Met-Arg-Met-Gln,
SEQ ID NO. 3
Glu-Glu-Met-Arg-Met-Gln,
SEQ ID NO. 4
Gln-Gln-Met-Arg-Met-Gln,
SEQ ID NO. 5
Gln-Glu-Met-Lys-Met-Gln,
SEQ ID NO. 6
Gln-Glu-Met-Orn-Met-Gln,
SEQ ID NO. 7
Gln-Glu-Met-Arg-Met-Glu,
SEQ ID NO. 8
Gln-Glu-Met-Arg-Met-Asn,
SEQ ID NO. 10
Gln-Asp-Met-Arg-Met-Gln,
SEQ ID NO. 11
Gln-Glu-Leu-Arg-Met-Gln,
SEQ ID NO. 12
Gln-Glu-Ile-Arg-Met-Gln,
SEQ ID NO. 13
Gln-Glu-Met-Arg-Ile-Gln,
SEQ ID NO. 14
Gln-Glu-Met-Arg-Leu-Gln,
SEQ ID NO. 15
Glu-Glu-Ile-Arg-Met-Gln,
SEQ ID NO. 16
Asp-Gln-Met-Arg-Met-Gln,
SEQ ID NO. 17
Glu-Gln-Met-Arg-Met-Gln,
SEQ ID NO. 18
Gln-Glu-Met-Lys-Leu-Gln,
SEQ ID NO. 19
Gln-Asp-Met-Arg-Met-Asn,
SEQ ID NO. 20
Asn-Glu-Ile-Arg-Val-Gln,
SEQ ID NO. 21
Gln-Asp-Met-Lys-Met-Asn,
SEQ ID NO. 22
Pro-Gln-Glu-Met-Arg-Met-Gln,
SEQ ID NO. 23
Gln-Glu-Met-Arg-Met-Gln-Val-Tyr,
and
SEQ ID NO. 24
Ser-Gln-Glu-Met-Arg-Met-Gln-Thr.
15. A compound of general formula (I):
R 1 —W m —X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p —Z q —R 2 (I),
its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, wherein:
W, X, Y and Z are each independently an amino acid;
m, n, p and q are each independently 0 or 1;
R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroarylalkyl;
R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 and —SR 3 , wherein R 3 and R 4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, substituted or unsubstituted non-cyclic aliphatic group, substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and
R 1 and R 2 are not α-amino acids, and
wherein W m —X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p —Z q is selected from:
Ac-Gln-Glu-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 1]-OH),
H-Gln-Glu-Met-Arg-Met-Gln-OH
(H-[SEQ ID NO. 1]-OH),
Palm-Gln-Glu-Met-Arg-Met-Gln-OH
(Palm-[SEQ ID NO. 1]-OH),
Ac-Gln-Glu-Met-Arg-Met-Gln-NH 2
(Ac-[SEQ ID NO. 1]-NH 2 ),
Ac-Gln-Glu-Met-Arg-Met-Gln-NHC 6 H 13
(Ac-[SEQ ID NO. 1]-NHC 6 H 13 ),
Myr-Gln-Glu-Met-Arg-Met-Gln-NH 2
(Myr-[SEQ ID NO. 1]-NH 2 ),
Ac-Asp-Glu-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 2]-OH),
Ac-Glu-Glu-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 3]-OH),
Ac-Gln-Gln-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 4]-OH),
Ac-Gln-Glu-Met-Lys-Met-Gln-OH
(Ac-[SEQ ID NO. 5]-OH),
Ac-Gln-Glu-Met-Orn-Met-Gln-OH
(Ac-[SEQ ID NO. 6]-OH),
Ac-Gln-Glu-Met-Arg-Met-Glu-OH
(Ac-[SEQ ID NO. 7]-OH),
Ac-Gln-Glu-Met-Arg-Met-Asn-OH
(Ac-[SEQ ID NO. 8]-OH),
Myr-Glu-Glu-Met-Arg-Met-Gln-OH
(Myr-[SEQ ID NO. 3]-OH),
Ac-Gln-Asp-Met-Arg-Met-Gln-NHC 6 H 13
(Ac-[SEQ ID NO. 10]-NHC 6 H 13 ),
Palm-Gln-Glu-Leu-Arg-Met-Gln-OH
(Palm-[SEQ ID NO. 11]-OH),
H-Gln-Glu-Ile-Arg-Met-Gln-NH 2
(H-[SEQ ID NO. 12]-NH 2 ),
H-Gln-Glu-Met-Arg-Ile-Gln-NH 2
(H-[SEQ ID NO. 13]-NH 2 ),
H-Gln-Glu-Met-Arg-Leu-Gln-NH 2
(H-[SEQ ID NO. 14]-NH 2 ),
Ac-Glu-Glu-Ile-Arg-Met-Gln-NHC 16 H 33
(Ac-[SEQ ID NO. 15]-NHC 16 H 33 ),
Ac-Asp-Gln-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 16]-OH),
Ac-Glu-Gln-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 17]-OH),
Ac-Gln-Glu-Met-Lys-Leu-Gln-OH
(Ac-[SEQ ID NO. 18]-OH),
H-Gln-Asp-Met-Arg-Met-Asn-NH 2
(H-[SEQ ID NO. 19]-NH 2 ),
Ac-Asn-Glu-Ile-Arg-Val-Gln-OH
(Ac-[SEQ ID NO. 20]-OH),
Ac-Gln-Asp-Met-Lys-Met-Asn-OH
(Ac-[SEQ ID NO. 21]-OH),
Ac-Pro-Gln-Glu-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 22]-OH),
Ac-Gln-Glu-Met-Arg-Met-Gln-Tyr-OH
(Ac-[SEQ ID NO. 26]-OH),
Ac-Gln-Glu-Met-Arg-Met-Gln-Thr-NH 2
(Ac-[SEQ ID NO. 27]-NH 2 ),
Ac-Pro-Val-Gln-Glu-Met-Arg-Met-Gln-OH
(Ac-[SEQ ID NO. 28]-OH),
Ac-Gln-Glu-Met-Arg-Met-Gln-Val-Tyr-OH
(Ac-[SEQ ID NO. 29]-OH), and
Ac-Ser-Gln-Glu-Met-Arg-Met-Gln-Thr-NH 2
(Ac-[SEQ ID NO. 24]-NH 2 ).
16. A method for cosmetic, non-therapeutic treatment and/or non-therapeutic care of the skin, hair, and/or nails which comprises administering to the skin, hair, and/or nails of a subject a cosmetically effective quantity of a compound according claim 1 .
17. A method for alleviation of symptoms of skin aging which comprises administering to the skin of a subject a cosmetically effective quantity of a compound according to claim 1 .
18. A method for alleviation of symptoms of skin aging which comprises administering to the skin of a subject a cosmetically effective quantity of a compound according to claim 8 .
19. A method for alleviation of symptoms of skin aging which comprises administering to the skin of a subject a cosmetically effective quantity of a compound according to claim 13 .
20. A method for alleviation of symptoms of skin aging which comprises administering to the skin of a subject a cosmetically effective quantity of a compound according to claim 14 .
21. A method for alleviation of symptoms of skin aging which comprises administering to the skin of a subject a cosmetically effective quantity of a compound according to claim 15 .