US 9,434,764 B2Granted

Skin care compositions and methods comprising selective agonists of melanocortin 1 receptor

AssigneeUniversity of Cincinnati

InventorsZalfa A. Abdel-Malek, Leonid Koikov, James J. Knittel

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Abstract

Short tri- and tetrapeptides according to the following Formula I Ar(CH2)mX1—X2—CO—X3—X4—X5-(Trp)n-NX6R are potent, selective agonists of melanocortin 1 receptor (MC1R). Provided herein are skin care compositions including Formula I peptide agonists of MC1R and methods of regulating a skin condition of a mammal that include applying to a treatment surface of the body a safe and effective amount of a skin care composition including a Formula I peptide. The peptides, skin care compositions, and skin care methods described herein are useful in regulating a skin condition of a mammal associated with exposure ultraviolet (UV) radiation, including sunburn, UV sensitivity, photoaging, and skin pigmentation, particularly in the absence of sun exposure.

Claims20

Dependent claims

A peptide agonist of melanocortin 1 receptor (MC1R) selective for MC1R versus melanocortin 3 receptor (MC3R), melanocortin 4 receptor (MC4R), and melanocortin 5 receptor (MC5R) according to the following formula:

Ar(CH2)mX1—X2—CO—X3—X4—X5-(Trp)n-NX6R Formula I
or a dermatologically-acceptable salt, solvate, or enantiomer thereof, wherein:
Ar is selected from the group consisting of unsubstituted or substituted phenyl and 5- or 6-membered heteroaryl;
m is 0, 1, 2, or 3;
X1 is absent or X1 is selected from the group consisting of O, NR′, S, Se, and CR′R″ wherein R′ is selected from the group consisting of H, linear or branched C1-C4 alkyl, OH, and linear or branched C1-C4 O-alkyl and R″ is selected from the group consisting of H and linear or branched C1-C4 alkyl;
or wherein CR′R″ is a C3-C6 cycloalkyl;
X2 is absent or X2 is selected from the group consisting of 1,2-phenylene, 1,3-phenylene, 1,4-phenylene, and CQ′Q″ wherein Q′ and Q″ are each independently selected from the group consisting of H and linear or branched C1-C4 alkyl;
X3 is selected from the group consisting of unsubstituted or substituted L-histidine (His), 3-(2-pyridyl)-L-alanine (2-PAL), 3-(3-pyridyl)-L-alanine (3-PAL), 3-(4-pyridyl)-L-alanine (4-PAL), 3-(2-thienyl)-L-alanine (2-Thi), 3-(3-thienyl)-L-alanine (3-Thi), 3-(2-furyl)-L-alanine (2-FurAla), 3-(3-furyl)-L-alanine (3 FurAla), L-homoserine (HoSer), O-methyl-L-homoserine (HoSer(Me)), and L-allylglycine;
X4 is selected from the group consisting of unsubstituted or substituted L-alpha-MePhe, 3-(2-thienyl)-D-alanine (D-2-Thi), 3-(3-thienyl)-D-alanine (D-3-Thi), 3-(2-furyl)-D-alanine (D-2-FurAla), 3-(3-furyl)-D-alanine (D-3-FurAla), and substituted D-phenylalanine (D-Phe);
X5 is selected from the group consisting of unsubstituted or substituted L-arginine (Arg) and L-citrulline;
n is 0 or 1;
X6 is selected from the group consisting of H, linear or branched C1-C4 alkyl, and C3-C4 cycloalkyl;
and
R is selected from the group consisting of H, linear or branched C1-C12 alkyl, linear or branched C1-C12 arylalkyl, and C3-C5 cycloalkyl;
or wherein X6 and R together form a C3-C5 heterocycloalkyl.

12 more elements

Ph(CH2)3CO-His-(D-Phe)-Arg-Trp-NHEt;
Ph(CH2)3CO-His-(D-1-Nal)-Arg-Trp-NHEt;
Ph(CH2)3CO-His-(D-2-Nal)-Arg-Trp-NHEt;
Ph(CH2)3CO-His-(D-4-Bip)-Arg-Trp-NHEt;
Ph(CH2)3CO-His-(D-4-tBuPhe)-Arg-Trp-NHEt;
4-FC6H4CH2CO-His-(D-Phe)-Arg-Trp-NHEt;
4-FC6H4CH2CO-His-(D-1-Nal)-Arg-Trp-NHEt;
4-FC6H4CH2CO-His-(D-2-Nal)-Arg-Trp-NHEt;
4-FC6H4CH2CO-His-(D-4-Bip)-Arg-Trp-NHEt;
4-FC6H4CH2CO-His-(D-4-tBuPhe)-Arg-Trp-NHEt;
Ph(CH2)3CO-His-(D-Phe)-Arg-Trp-NHMe;
4-FC6H4CH2CO-His-(D-Phe)-Arg-Trp-NHMe;
Ph(CH2)3CO-His-(D-1-Nal)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-2-Nal)-Arg-Trp-NH2;
4-BrC6H4CH2CO-His-(D-Phe)-Arg-Trp-NH2;
4-FC6H4CH2CO-His-(D-4-FPhe)-Arg-Trp-NH2;
4-BrC6H4CH2CO-His-(D-4-FPhe)-Arg-Trp-NH2;
4-CF3C6H4CH2CO-His-(D-4-FPhe)-Arg-Trp-NH2;
3,4-O(CH2)2C6H4CH2CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(D)-C6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(L)-C6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(D,L)-C6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(D,L)-C6H4CH(OMe)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(D)-4-ClC6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(L)-4-ClC6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
(D,L)-4-ClC6H4CH(OH)CO-His-(D-4-FPhe)-Arg-Trp-NH2;
C6F5CH2CO-His-(D-4-FPhe)-Arg-Trp-NH2;
4-C6H5C6H4CO-His-(D-4-FPhe)-Arg-Trp-NH2;
4-C6H5OC6H4CO-His-(D-4-FPhe)-Arg-Trp-NH2;
3-C6H5OC6H4CO-His-(D-4-FPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-4-FPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-4-ClPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-4-BrPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-4-IPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-2-Thi)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-4-NO2Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-3-NO2Phe)-Arg-Trp-NH2;
4-IC6H4CH2CO-His-(D-Phe)-Arg-Trp-NH2;
4-IC6H4CH2CO-His-(D-4-IPhe)-Arg-Trp-NH2;
Ph(CH2)3CO-(4-PAL)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-(2-Thi)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-(3-Thi)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-(2-FurAla)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO—(HoSer)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO—(HoSer(Me))-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-(AllGly)-(D-Phe)-Arg-Trp-NH2;
Ph(CH2)3CO-His-(D-1-Nal)-Arg-NH2;
Ph(CH2)3CO-His-(D-2-Nal)-Arg-NH2;
Ph(CH2)3CO-His-(D-4-Bip)-Arg-NH2;
Ph(CH2)3CO-His-(D-4-tBuPhe)-Arg-NH2;
4-BrC6H4CH2CO-His-(D-4-FPhe)-Arg-NH2;
4-HOC6H4CH2CO-His-(D-4-FPhe)-Arg-NH2;
3,4-O(CH2)2C6H4CH2CO-His-(D-4-FPhe)-Arg-NH2;
Ph(CH2)3CO-His-(D-1-Nal)-Arg-NHMe;
Ph(CH2)3CO-His-(D-2-Nal)-Arg-NHMe;
Ph(CH2)3CO-His-(D-4-Bip)-Arg-NHMe;
Ph(CH2)3CO-His-(D-4-tBuPhe)-Arg-NHMe;
Ph(CH2)3CO-His-(D-1-Nal)-Arg-NHEt;
Ph(CH2)3CO-His-(D-2-Nal)-Arg-NHEt;
Ph(CH2)3CO-His-(D-4-Bip)-Arg-NHEt;
Ph(CH2)3CO-His-(D-4-tBuPhe)-Arg-NHEt;
4-FC6H4CH2CO-His-(D-Phe)-Arg-NHEt;
4-FC6H4CH2CO-His-(D-4-FPhe)-Arg-NHEt;
4-FC6H4CH2CO-His-(D-1-Nal)-Arg-NHEt;
4-FC6H4CH2CO-His-(D-2-Nal)-Arg-NHEt;
4-FC6H4CH2CO-His-(D-4-Bip)-Arg-NHEt;
and
4-FC6H4CH2CO-His-(D-4-tBuPhe)-Arg-NHEt.

65 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/646,407Filed 20 Nov 2013 · us provisional application
Priority: 21 Nov 2012
Published: US 2015/0299251 A122 Oct 2015
Granted: 6 Sep 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07K 5/1024
Tetrapeptides: with the first amino acid being heterocyclic
A61K 8/06
Dispersions; Emulsions: emulsions
A61K 8/64
Containing organic compounds: proteins; Peptides; Derivatives or degradation products thereof
A61K 9/0014
Galenical forms characterised by the site of application: skin, i.e. galenical aspects of topical compositions

Family

Application61/729,018Us provisional application · filed 21 Nov 2012
US 2015/0299251 A1Pre-grant publication · published 22 Oct 2015
US 9,434,764 B2This patent

From the US filing history. Foreign family members aren’t listed.

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