Granted Patent B2

US 8,168,640 · App. 13/164,915 · Granted May 1, 2012

Abstract

Claims (43)

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 a 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide compound or diastereomer or a cosmetically acceptable salt thereof in a cosmetically acceptable vehicle.

2. The method according to claim 1 wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide compound 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 hydro'carbon 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 ; —N(C 2 H 4 ); —Si(—R) 3 ; —CF 3 ; —OCF 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 0, N, or S in the ring.

3. The method according to claim 2 , where R 1 , R 2 , R 4 , and R 5 represent hydrogen.

4. The method according to claim 2 , where R 3 represents a group —OR.

5. The method according to claim 4 , where R 3 represents —OCH 3 .

6. The method according to claim 2 , where R 7 and R 8 represent hydrogen.

7. The method according to claim 2 , where R 6 is a group —(C═O)—R, where R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, toluoyl, and benzyl.

8. The method according to claim 7 , where R 6 is a group —(C═O)—(C 6 H 5 ).

9. The method according to claim 2 , where R 6 is a group —SO 2 —R, where R is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, phenyl, toluoyl, and benzyl.

10. The method according to claim 9 , where R 6 is a group —SO 2 —CH 3 .

11. The method according to claim 1 , wherein said skin benefit is selected from the group consisting of:

(a) treatment and/or reduction, of fine lines or wrinkles, and/or reduction of severity of existing fine lines or wrinkles and/or inhibition of formation of new 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; and

(p) treatment and/or reduction of skin sagging.

12. The method according to claim 11 , wherein said skin benefit is the treatment and/or reduction of fine lines or wrinkles and/or reduction of severity of existing fine lines or wrinkles and/or inhibition of formation of new fine lines or wrinkles.

13. The method according to claim 11 , wherein said skin benefit is the treatment and/or reduction of skin sagging.

14. The method according to claim 1 , wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide compound has the structure:

or a diastereomer or a cosmetically acceptable salt thereof.

15. The method according to claim 1 , wherein said 1-aroyl-N-(2-oxo-3-piperidinyl)-2-piperazine carboxamide compound has the structure:

or a diastereomer or a cosmetically acceptable salt thereof.

16. 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 compound or a diastereomer or a cosmetically acceptable salt thereof in a cosmetically acceptable vehicle for a time sufficient to reduce the severity of said wrinkles or fine lines.

17. The method according to claim 2 , wherein an (R,R) diastereomer comprises at least 95% by weight of the total weight of said compound having the structure of formula I.

18. The method according to claim 2 , wherein an (R,S) diastereomer comprises at least 95% by weight of the total weight of said compound having the structure of formula I.

19. The method according to claim 2 , wherein an (S,R) diastereomer comprises at least 95% by weight of the total weight of said compound having the structure of formula I.

20. The method according to claim 2 , wherein an (S,S) diastereomer comprises at least 95% by weight of the total weight of said compound having the structure of formula I.

Assignments (9)