Collagen stimulators and their use in the treatment of skin

1. A method for reducing one or more dermatological signs of aging comprising topically applying to an area of the skin in need thereof a composition according to Formula I(a):

wherein,

Q represents a 3-6 membered heterocyclic ring, wherein L 1 and L 2 are independently selected from a bond or a group ε 1 -(L 3 ) l -ε 2 , where “l” is an integer from 0 to 4; where L 3 is selected from —CH 2 —, —CHR*—, —C(R*) 2 —, —CH—, —CR*—, or a bond; and ε 1 and ε 2 are independently selected from —N—, —NH—, —NR N —, —O—, —S—, —(C═O)—, or a bond; Y is selected from —CH—, —CR*—, —CHR*—, —C(R*) 2 —, —N—, —O—, —S—, —NR N —, or a bond (i.e. absent);

Z 1 represents a bond, —CH 2 —, or —(C═O)—;

Z 2 represents a bond, —O—, NH—, —NR N —, —CH 2 —, —CHR*—, —C(R*) 2 —, —(CH 2 ) p —, —(CH 2 ) p —NH, or —(CH 2 ) p —NR N —, where p is an integer from 1-6;

X 1 represents —CH 2 —, —CHR*—, —C(R*) 2 —, —NH—, —NR N —, —O—, or —S—;

X 2 and X 3 represents nitrogen, —CH—, or —CR*—;

R 1 -R 5 are independently selected, at each occurrence, from a group R; wherein R is selected 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; —(C═O)—R*; —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 ; —PR* 2 ; —O—P(═O)(OR*) 2 ; —P(═O)(OR*) 2 ; perfluoroalkyl; an aliphatic C 1 -C 12 hydrocarbon radical; a C 1 -C 12 aromatic hydrocarbon radical; or a C 1 -C 12 heteroaryl radical; where R* is independently at each occurrence hydrogen or a straight chained, branched, or cyclic C 1 -C 20 hydrocarbon radical, which may be saturated, partially saturated, or aromatic, each of which may be optionally substituted with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;

R N is hydrogen or a saturated, partially saturated, or aromatic C 1 -C 20 hydrocarbon radical, optionally substituted with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;

and cosmetically acceptable salts thereof;

for a time sufficient to improve the aesthetic appearance of said human skin.

2. The method according to claim 1 , wherein said one or more dermatological signs of aging is selected from the group consisting of:

(a) treatment, reduction, and/or prevention of fine lines or wrinkles;

(b) reduction of skin pore size;

(c) improvement in skin thickness, plumpness, and/or tautness;

(d) improvement in skin smoothness, 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 aging and/or menopause;

(n) improvement in skin moisturization;

(o) increase in skin elasticity and/or resiliency;

(p) treatment, reduction, and/or prevention of skin sagging;

(q) improvement in skin firmness; and

(r) reduction of pigment spots and/or mottled skin; and

(s) improvement of optical properties of skin by light diffraction or reflection.

3. A method for improving one or more dermatological signs of aging comprising topically applying to an area of skin in need thereof a composition according to claim 1 , for a time sufficient to improve said one or more dermatological signs of aging.

4. The method according to claim 3 , wherein said one or more dermatological signs of aging comprises wrinkles and/or fine lines on the skin, and wherein said method comprises topically applying the composition to affected skin of an individual in need thereof, at least once daily for a period of at least four weeks.

5. The method according to claim 3 , wherein said one or more dermatological signs of aging comprises wrinkles and/or fine lines on the skin, and wherein said method comprises topically applying the composition to affected skin of an individual in need thereof, at least once daily for a period of at least eight weeks.

6. A method for improving the one or more dermatological signs of aging comprising topically applying to an area of skin in need thereof a topical composition comprising a cosmetically acceptable vehicle and an effective amount of a compound having the structure of Formula I(b):

and cosmetically acceptable salts thereof, for a time sufficient to improve said one or more dermatological signs of aging.

7. The method according to claim 6 , wherein said one or more dermatological signs of aging is selected from the group consisting of:

(a) treatment, reduction, and/or prevention of fine lines or wrinkles;

(b) reduction of skin pore size;

(c) improvement in skin thickness, plumpness, and/or tautness;

(d) improvement in skin smoothness, 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 aging and/or menopause;

(n) improvement in skin moisturization;

(o) increase in skin elasticity and/or resiliency;

(p) treatment, reduction, and/or prevention of skin sagging;

(q) improvement in skin firmness; and

(r) reduction of pigment spots and/or mottled skin; and

(s) improvement of optical properties of skin by light diffraction or reflection.

8. The method according to claim 7 , wherein said one or more dermatological signs of aging comprises wrinkles and/or fine lines on the skin, and wherein said method comprises topically applying the composition to affected skin of an individual in need thereof, at least once daily for a period of at least four weeks.

9. The method according to claim 8 , wherein said composition is topically applied to affected skin of an individual in need thereof at least once daily for a period of at least eight weeks.

10. The method according to claim 6 , wherein said composition further comprises a retinoid.

11. The method according to claim 6 , wherein said composition further comprises an alpha-hydroxy or beta-hydorxy acid.

12. The method according to claim 11 , wherein said alpha-hydroxy acid is glycolic acid.

13. The method according to claim 11 , wherein said beta-hydroxy acid is salicylic acid.

14. A method for enhancing the production of collagen in human skin comprising topically applying to an area of the skin in need thereof a topical composition comprising a cosmetically acceptable vehicle, and an effective amount of a compound having the structure of Formula I(b):

and cosmetically acceptable salts thereof.

15. The method according to claim 12 , wherein said composition further comprises a retinoid.

16. The method according to claim 14 , wherein said composition further comprises an alpha-hydroxy or beta-hydorxy acid.

17. The method according to claim 16 , wherein said alpha-hydroxy acid is glycolic acid.

18. The method according to claim 16 , wherein said beta-hydroxy acid is salicylic acid.

19. A method for enhancing the production of collagen in human skin comprising topically applying to an area of the skin in need thereof a topical composition comprising a cosmetically acceptable vehicle, and an effective amount of a compound having the structure of Formula I(a):

wherein,

Q represents a 3-6 membered heterocyclic ring, wherein L 1 and L 2 are independently selected from a bond or a group ε 1 -(L 3 ) l -ε 2 , where “l” is an integer from 0 to 4; where L 3 is selected from —CH 2 —, —CHR*—, —C(R*) 2 —, —CH—, —CR*—, or a bond; and ε 1 and ε 2 are independently selected from —N—, —NH—, —NR N —, —O—, —S—, —(C═O)—, or a bond; Y is selected from —CH—, —CR*—, —CHR*—, —C(R*) 2 —, —N—, —O—, —S—, —NR N —, or a bond (i.e. absent);

Z 1 represents a bond, —CH 2 —, or —(C═O)—;

Z 2 represents a bond, —O—, NH—, —NR N —, —CH 2 —, —CHR*—, —C(R*) 2 —, —(CH 2 ) p —, —(CH 2 ) p —NH, or —(CH 2 ) p —NR N —, where p is an integer from 1-6;

X 1 represents —CH 2 —, —CHR*—, —C(R*) 2 —, —NH—, —NR N —, —O—, or —S—;

X 2 and X 3 represents nitrogen, —CH—, or —CR*—;

R 1 -R 5 are independently selected, at each occurrence, from a group R; wherein R is selected 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; —(C═O)—R*; —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 ; —PR* 2 ; —O—P(═O)(OR*) 2 ; —P(═O)(OR*) 2 ; perfluoroalkyl; an aliphatic C 1 -C 12 hydrocarbon radical; a C 1 -C 12 aromatic hydrocarbon radical; or a C 1 -C 12 heteroaryl radical; where R* is independently at each occurrence hydrogen or a straight chained, branched, or cyclic C 1 -C 20 hydrocarbon radical, which may be saturated, partially saturated, or aromatic, each of which may be optionally substituted with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;

R N is hydrogen or a saturated, partially saturated, or aromatic C 1 -C 20 hydrocarbon radical, optionally substituted with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;

and cosmetically acceptable salts thereof.