Cosmetic use of 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamides and related compounds
View Patent ↗Cosmetic compositions comprising 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamides and methods of using such compositions to impart anti-aging benefits to the skin are disclosed. The 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamides are believed to have modulatory activity against one or more biochemical pathways implicated in skin aging.
1. A method for providing a benefit to human skin comprising topically applying to the skin of an individual in need thereof an effective amount of 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide or cosmetically acceptable salt thereof in a cosmetically acceptable vehicle comprising a water-in-oil or oil-in-water emulsion, wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide has the structure of formula I:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are independently hydrogen or a group —R 9 -R 10 ;
R 9 represents, independently at each occurrence, a bond; an aliphatic C 1 -C 20 hydrocarbon radical; a C 1 -C 20 aromatic hydrocarbon radical; or a C 1 -C 20 heteroaryl radical;
R 10 is selected independently at each occurrence from hydrogen; —F; —Cl; —Br; —I; —OH; —OR; —NH 2 ; —NHR; —N(R) 2 ; —N(R) 3 + ; —N(R)—OH; —N(→O)(R) 2 ; —O—N(R) 2 ; —N(R)—O—R; —N(R)—N(R) 2 ; —C═N—R; —N═C(R) 2 ; —C═N—N(R) 2 ; —C(═NR)—N(R) 2 ; —SH; —SR; —CN; —NC; —CHO; —CO 2 H; —CO 2 − ; —CO 2 R; —(C═O)—S—R; —O—(C═O)—H; —O—(C═O)—R; —S—(C═O)—R; —(C═O)—NH 2 ; —(C═O)—N(R) 2 ; —(C═O)—NHNH 2 ; —O—(C═O)—NHNH 2 ; —(C═S)—NH 2 ; —(C═S)—N(R) 2 ; —N(R)—CHO; —N(R)—(C═O)—R; —(C═NR)—O—R; —O—(C═NR)—R; —SCN; —NCS; —NSO; —SSR; —N(R)—C(═O)—N(R) 2 ; —N(R)—C(═S)—N(R) 2 ; —SO 2 —R; —O—S(═O) 2 —R; —S(═O) 2 —OR; —N(R)—SO 2 —R; —SO 2 —N(R) 2 ; —O—SO 3 − ; —O—S(═O) 2 —OR; —O—S(═O)—OR; —O—S(═O)—R; —S(═O)—OR; —S(═O)—R; —NO; —NO 2 ; —NO 3 ; —O—NO; —O—NO 2 ; —N 3 ; —N 2 —R; —N(C 2 H 4 ); —Si(—R) 3 ; —CF 3 ; —O—CF 3 ; —(C═O)—R; —PR 2 ; —O—P(═O)(OR) 2 ; —P(═O)(OR) 2 ; ═O; ═S; ═NR; an aliphatic C 1 -C 20 hydrocarbon radical; a C 1 -C 20 aromatic hydrocarbon radical; or a C 1 -C 20 heteroaryl radical;
where R is independently at each occurrence hydrogen or a saturated, partially saturated, or aromatic C 1 -C 20 hydrocarbon radical or halogenated derivative thereof;
and where any two adjacent groups R 1 , R 2 , R 3 , R 4 , and R 5 may, together with the phenyl ring to which they are attached, form a five-membered or six-membered aliphatic or aromatic ring, optionally substituted with one or more groups R 10 and optionally including one or more heteroatoms selected from O, N, or S in the ring.
2. The method according to claim 1 ,
where R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , and R 8 are independently hydrogen, an alkyl of from 1 to 6 carbons, or an alkoxy of from 1 to 6 carbons; and
where R 6 is (C═O)—R, where R is hydrogen or a substituted or unsubstituted branched, straight chain or cyclic C 1 -C 20 alkyl, alkenyl, aryl, heteroaryl, alkyl-aryl, aryl-alkyl, alkyl-heteroaryl, heteroaryl-alkyl, heteroaryl-aryl, bicyclic alkyl, aryl, or heteroaryl radical.
3. The method according to claim 1 ,
where R 1 , R 2 , R 3 , R 4 , R 5 , R7, and R 8 are independently hydrogen, an alkyl of from 1 to 6 carbons, or an alkoxy of from 1 to 6 carbons; and
where R 6 is —SO 2 —R, where R is hydrogen or a substituted or unsubstituted branched, straight chain or cyclic C 1 -C 20 alkyl, alkenyl, aryl, heteroaryl, alkyl-aryl, aryl-alkyl, alkyl-heteroaryl, heteroaryl-alkyl, heteroaryl-aryl, bicyclic alkyl, aryl, or heteroaryl radical.
4. The method according to claim 2 , where R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , and R 8 represent hydrogen, methyl ethyl, methoxy, or ethoxy, and where R is a C 1 -C 8 alkyl or aryl.
5. The method according to claim 3 , where R 1 , R 2 , R 3 , R 4 , R 5 , R 7 and R 8 represent hydrogen, methyl, ethyl, methoxy, or ethoxy, and where R is a C 1 -C 8 alkyl or aryl.
6. The method according to claim 5 , where R 1 , R 2 , R 4 , R 5 , R 7 , and R 8 represent hydrogen.
7. The method according to claim 4 , where R 1 , R 2 , R 4 , R 5 , R 7 , and R 8 represent hydrogen.
8. The method according to claim 7 , where R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, toluyl, or benzyl.
9. The method according to claim 8 , where R is phenyl.
10. The method according to claim 6 , where R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, toluyl, or benzyl.
11. The method according to claim 10 , where R is a methyl, ethyl, or propyl.
12. The method according to claim 2 , wherein said skin benefit is selected from the group consisting of:
(a) treatment and/or reduction of fine lines or wrinkles,
(b) reduction of skin pore size,
(c) improvement in skin thickness, plumpness, and/or tautness;
(d) improvement in skin suppleness and/or softness;
(e) improvement in skin tone, radiance, and/or clarity;
(f) improvement in procollagen and/or collagen production;
(g) improvement in maintenance and remodeling of elastin;
(h) improvement in skin texture and/or promotion of retexturization;
(i) improvement in skin barrier repair and/or function;
(j) improvement in appearance of skin contours;
(k) restoration of skin luster and/or brightness;
(l) replenishment of essential nutrients and/or constituents in the skin;
(m) improvement of skin appearance decreased by menopause;
(n) improvement in skin moisturization;
(o) increase in skin elasticity and/or resiliency; or
(p) treatment and/or reduction of skin sagging.
13. The method according to claim 12 , wherein said skin benefit is the treatment and/or reduction of fine lines or wrinkles.
14. The method according to claim 12 , wherein said skin benefit is the treatment and/or reduction of skin sagging.
15. A method for treating wrinkles and/or fine lines comprising topically applying to said wrinkle and/or fine line on the skin of an individual in need thereof an effective amount of a 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide or a cosmetically acceptable salt thereof in a cosmetically acceptable vehicle for a time sufficient to reduce the severity of said wrinkles of fine lines wherein said vehicle comprises a water-in-oil or oil-in-water emulsion and wherein said 1-aroyl-N-(2-oxo-2-piperdinyl)-2-piperazine carboxamide has the structure of formula I:
where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are independently hydrogen or a group —R 9 —R 10 ;
R 9 represents, independently at each occurrence, a bond; and aliphatic C 1 -C 20 hydrocarbon radical; a C 1 -C 20 hydrocarbon radical; a C 1 -C 20 aromatic hydrocarbon radical; or a C 1 -C 20 heteroaryl radical;
R 10 is selected independently at each occurrence from hydrogen; —F; —Cl; —Br; —I; —OH; —OR; —NH 2 ; NHR; —N(R) 2 ; —N(R) 3 + ; —N(R)—OH; —N(→O)(R) 2 ; —O—N(R) 2 ; —N(R)—O—R; —N(R)—N(R) 2 ; —C═N—R; —N═C(R) 2 ; —C═N—N(R) 2 ; —C(═NR)—N(R) 2 ; —SH; —SR; —CN; —NC; —CHO; —CO 2 H; —CO 2 − ; —CO 2 R; —(C═O)—S—R; —O—(C═O)—H; —O—(C═O)—R; —S—(C═O)—R; —(C═O)—NH 2 ; —(C═O)—N(R) 2 ; —(C═O)—NHNH 2 ; —O—(C═O)—NHNH 2 ; —(C═S)—NH 2 ; —(C═S) —N(R) 2 ; —N(R)—CHO; —N(R)—(C═O)—R; —(C═NR)—O—R; —O—(C═NR)—R; —SCN; —NCS; —NSO; —SSR; —N(R)—C(═O)—N(R) 2 ; —N(R)—C(═S)—N(R) 2 ; —SO 2 —R; —O—S(═O) 2 —R; —S(═O) 2 —OR; —N(R)—SO 2 —R; —SO 2 —N(R) 2 ; —O—SO 3 − ; —O—S(═O) 2 —OR; —O—S(═O)—OR; —O—S(═O)—R; —S(═O)—OR; —S(═O)—R; —NO; —NO 2 ; NO 3 ; —O—NO; —O—NO 2 ; —N 3 ; —N 2 —R; —N(C 2 H 4 ); —Si(—R) 3 ; —CF 3 ; —O—CF 3 ; —(C═O)—R; —PR 2 ; —O—P(═O)(OR) 2 ; —P(═O)(OR) 2 ; ═O; ═S; ═NR; an aliphatic C 1 -C 20 hydrocarbon radical; a C 1 -C 20 aromatic hydrocarbon radical; or a C 1 C 20 heteroaryl radical;
where R is independently at each occurrence hydrogen or a saturated, partially saturate, or aromatic C 1 -C 20 hydrocarbon radical or halogenated derivative thereof;
and where any two adjacent groups R 1 , R 2 , R 3 , R 4 , and R 5 may, together with the phenyl ring to which they are attached, form a five-membered or six-membered aliphatic or aromatic ring, optionally substituted with one or more groups R 10 and optionally including one or more heteroatoms selected from O, N, or S in the ring.
16. The method according to claim 9 , wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide has the structure:
or a cosmetically acceptable salt thereof.
17. The method according to claim 11 , wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide has the structure:
or a cosmetically acceptable salt thereof.
18. The method according to claim 1 , where R 1 , R 2 , R 3 , R 4 , and R 5 are independently hydrogen; —Cl; —OH; —OR; —CHO; —CO 2 H; —NH 2 ; —NHR, —N(R) 2 ; a substituted or unsubstituted alkyl of from 1 to 6 carbons, the substituents of the alkyl being selected from the group —Cl, —OH, —OR, —CHO, —CO 2 H, —NH 2 , —NHR, or —N(R) 2 ; or a substituted or unsubstituted alkoxy of from 1 to 6 carbons, the substituents of the alkoxy being selected from the group consisting of —Cl, —OH, —OR, —CHO, —CO 2 H, —NH 2 , —NHR, or —N(R) 2 ; R independently in each instance being an alkyl of from 1 to 6 carbons, —CHO or —CO 2 H,
where R 7 and R 8 are independently hydrogen or a substituted or unsubstituted alkyl of from 1 to 6 carbons, the substituents of the alkyl being selected from the group —Cl, —OH, —OR, —CHO, —CO 2 H, —NH 2 , —NHR or —N(R) 2 , R independently in each instance being an alkyl of from 1 to 6 carbons, —CHO or —CO 2 H, and
where R 6 , is (C═O)—R or —SO 2 —R, where R is hydrogen or a substituted or unsubstituted branched, straight chain or cyclic C 1 -C 20 alkyl, alkenyl, aryl, heteroaryl, alkyl-aryl, aryl-alkyl, alkyl-heteroaryl, heteroaryl-alkyl, heteroaryl-aryl, bicyclic alkyl, aryl, or heteroaryl radical.
19. The method according to claim 18 , where R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , and R 8 represent hydrogen, methyl, ethyl, methoxy, or ethoxy, and where R 6 is (C═O)—R or —SO 2 —R, where R is a C 1 -C 8 alkyl or aryl.
20. The method according to claim 19 , where R 1 , R 2 , R 4 , R 5 , R 7 , and R 8 represent hydrogen, R 3 is OCH 3 , and R is C 6 H 5 when R 6 is (C═O)—R and R is CH 3 when R 6 is —SO 2 —R.
21. The method according to claim 16 , wherein said skin benefit is selected from the group consisting of:
(a) treatment and/or reduction of fine lines or wrinkles,
(b) reduction of skin pore size,
(c) improvement in skin thickness, plumpness, and/or tautness;
(d) improvement in skin suppleness and/or softness;
(e) improvement in skin tone, radiance, and/or clarity;
(f) improvement in procollagen and/or collagen production;
(g) improvement in maintenance and remodeling of elastin;
(h) improvement in skin texture and/or promotion of retexturization;
(i) improvement in skin barrier repair and/or function;
(j) improvement in appearance of skin contours;
(k) restoration of skin luster and/or brightness;
(l) replenishment of essential nutrients and/or constituents in the skin;
(m) improvement of skin appearance decreased by menopause;
(n) improvement in skin moisturization;
(o) increase in skin elasticity and/or resiliency; or
(p) treatment and/or reduction of skin sagging.
22. The method according to claim 21 , wherein said skin benefit is the treatment and/or reduction of fine lines or wrinkles.