Inhibitors of melanocyte tyrosinase as topical skin lighteners
AssigneeMediQuest Therapeutics, Inc.
InventorsThomas P. Dooley, Ernest V. Curto
Life of this patent
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Abstract
Methods and formulations are provided to reduce pigmentation in skin, using an array of compounds selected from benzimidazoles, phenylthioureas, phenyltiols, phenylamines, bi- and multicyclic phenols, thiopheneamines, and benzothiamides. The compounds preferably inhibit pigment systhesis in melanocytes through the tyrosinase pathway. The methods can be used for lightening skin, and for treating uneven skin complexions which result from hyperpigmentation-related medical conditions such as melasma, age spots, freckles, ochronosis, and lentigo. The compounds can be used medically or cosmetically.
Claims21
1) A method of reducing pigmentation of skin for cosmetic effects in a mammal comprising administering to the mammal an effective amount of a compound defined by structure (I), or a pharmaceutically acceptable salt or ester thereof:
- wherein:
- R1 is H;
- R2 is selenium;
- R″ is C or CH;
- when R′ is C, R′ is C(R8)2 or NR3, and forms a bond with R″;
- when R″ is CH, R′ is CH3 or NH2;
- R4, R5, R6, and R7 are independently CR8, or N;
- R3 is (i) substituted or unsubstituted alkyl, alkenyl, aryl, or heterocycle, (ii) —C1-5 alkoxy, (iii) —OH, (iv) hydrogen, (v) C(O)—C1-3 alkyl, or (vi) —(CH2)1-5SC(O)NR9R10;
- R8 is (i) hydrogen, (ii) halogen, (iii) NO2, (iv) —CN, (v) —OR10, (vi) —NHSO2—C1-3alkyl, (vii) —NHCO—C1-5 alkyl, (viii) oxime, (ix) hydrazine, (x) —NR9R10, (xi) HSO2, (xii) HSO3, (xiii) thio-C1-5 alkyl, (xiv) C1-5 acyloxy, (xv) H2PO3, (xvi) thiol, (xvii) —COOR9, (xiii) C1-5 alkynyl, or (xix) —C1-5 alkyl, —C1-5 alkenyl, aryl, heteroaryl, or heterocycle, optionally substituted with one or more of —OH, —SH, C(O)H, COOR9, C1-5 acyloxy, halogen, NR9R10, C1-5 thioether, or C1-5 alkoxy;
- R9 is hydrogen or C1-3 alkyl;
- and
- R10 is hydrogen, or C1-5 alkyl optionally substituted with —OH.
11) A method of inhibiting tyrosinase comprising administering an effective amount of a compound defined by structure (I), or a pharmaceutically acceptable salt or ester thereof:
- wherein:
- R1 is H;
- R2 is selenium;
- R″ is C or CH;
- when R′ is C, R′ is C(R8)2 or NR3, and forms a bond with R″;
- when R″ is CH, R′ is CH3 or NH2;
- R4, R5, R6, and R7 are independently CR8, or N;
- R3 is (i) substituted or unsubstituted alkyl, alkenyl, aryl, or heterocycle, (ii) —C1-5 alkoxy, (iii) —OH, (iv) hydrogen, (v) C(O)—C1-3 alkyl, or (vi) —(CH2)1-5SC(O)NR9R10;
- R8 is (i) hydrogen, (ii) halogen, (iii) NO2, (iv) —CN, (v) —OR10, (vi) —NHSO2—C1-3alkyl, (vii) —NHCO—C1-5 alkyl, (viii) oxime, (ix) hydrazine, (x) —NR9R10, (xi) HSO2, (xii) HSO3, (xiii) thio-C1-5 alkyl, (xiv) C1-5 acyloxy, (xv) H2PO3, (xvi) thiol, (xvii) —COOR9, (xiii) C1-5 alkynyl, or (xix) —C1-5 alkyl, —C1-5 alkenyl, aryl, heteroaryl, or heterocycle, optionally substituted with one or more of —OH, —SH, C(O)H, COOR9, C1-5 acyloxy, halogen, NR9R10, C1-5 thioether, or C1-5 alkoxy;
- R9 is hydrogen or C1-3 alkyl;
- and
- R10 is hydrogen, or C1-5 alkyl optionally substituted with —OH.
Dependencies are inferred from the claim text.