Cytoprotective compounds, pharmaceutical and cosmetic formulations, and methods

Abstract

Cytoprotective compounds, many of which are phenolic derivatives characterized by a substituted phenol having certain conjugated bonds, are useful in the treatment of certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. They are also useful in the manufacture of pharmaceutical and cosmetic formulations for the treatment of such conditions.

1 - 110 . (canceled)  
     
     
         111 . A compound selected from the group consisting of: 
 4-{2-[4-(5-Hydroxy-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol;    5-{4-[2-(3,4-Bis-methoxymethoxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one;    4-{2-[4-(5-Hydroxy-1-phenyl-1H-pyrazol-3-yl)-phenyl]-vinyl}-benzene-1,2-diol;    5-{4-[2-(3,4-Dihydroxy-phenyl)-vinyl]-phenyl}-2-phenyl-2,4-dihydro-pyrazol-3-one;    3-{4-[2-(3,4-Dihydroxy-phenyl)-vinyl]-phenyl}-4H-isoxazol-5-one;    2-{4-[2-(3,4-Dimethoxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one;    5-Methyl-2-(4-styryl-phenyl)-2,4-dihydro-pyrazol-3-one;    2-{4-[2-(3,4-Dihydroxy-phenyl)-vinyl]-phenyl}-5-methyl-2,4-dihydro-pyrazol-3-one;    including single stereoisomers, mixtures of stereoisomers, and pharmaceutically acceptable salts thereof.    
     
     
         112 . The compound of  claim 111 , wherein the single stereoisomer is a cis-stereoisomer.  
     
     
         113 . The compound of  claim 111 , wherein the single stereoisomer is a trans-stereoisomer.  
     
     
         114 . A skin care composition comprising a therapeutically effective amount of one or more compounds of  claim 111 , further optionally comprising a pharmaceutically or cosmetically acceptable carrier or excipient.  
     
     
         115 . The skin care composition of  claim 114 , formulated for topical administration to the skin of a mammalian subject.  
     
     
         116 . The skin care composition of  claim 115 , wherein said composition is included in a topical cosmetic formulation.  
     
     
         117 . The skin care composition of  claim 115 , wherein said composition is included in a topical pharmaceutical formulation.  
     
     
         118 . The skin care composition of  claim 114 , formulated for transdermal administration to a mammalian subject.  
     
     
         119 . The skin care composition of  claim 115 , formulated for oral administration to a mammalian subject.  
     
     
         120 . A method of regulating skin condition wherein the skin condition is characterized by oxidative stress, the method comprising administering to a subject suffering from such a skin condition a composition of  claim 114 .  
     
     
         121 . The method of  claim 120 , wherein the skin condition is selected from the group consisting of dermatitis, contact dermatitis, acne, pimples, blackheads, oiliness, facial shine, foundation breakthrough, excessive sebum production, visible and/or tactile discontinuities, psoriasis, and combinations thereof.  
     
     
         122 . The method of  claim 121 , wherein the skin condition is acne, pimples, blackheads, oiliness, facial shine, foundation breakthrough, and excessive sebum production.  
     
     
         123 . The method of  claim 122 , wherein the skin condition is acne.  
     
     
         124 . A method of regulating and/or preventing signs of skin aging comprising administering to a subject a composition of  claim 114 .  
     
     
         125 . The method of  claim 120 , wherein the signs of the skin condition are selected from the group consisting of the development of textural discontinuities, wrinkles, fine superficial wrinkles, coarse deep wrinkles, skin lines, facial frown lines, expression lines, rhytides, dermatoheliosis, photodamage, premature skin aging, crevices, bumps, pits, large pores, “orange-peel” skin appearance, dryness, scaliness, flakiness, blemishes, acne, pimples, breakouts, excess skin oil problems, over production of sebum, oiliness, facial shine, foundation breakthrough, abnormal desquamation, abnormal epidermal differentiation, abnormal skin turnover, keratoses, hyperkeratinization; inadequate skin moisturization, environmental dryness, loss of skin elasticity, elastosis, sagging, puffiness in the eye area and jowls, loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, non-melanin skin discoloration, undereye circles, blotching, rosacea, sallowness, discoloration caused by telangiectasia or spider vessels, melanin-related hyperpigmented skin regions, age spots, liver spots, brown spots, freckles, post-inflammatory hyperpigmentation, inflammation due to acne lesion, in-grown hair, insect/spider bite or sting, scratch, cut, wound, and/or abrasion, atrophy, collagen breakdown and structural alterations or abnormalities, changes in the stratum corneum, dermis, epidermis, the skin vascular system such as telangiectasia or spider vessels; tissue responses to insult from itch or pruritus; and alterations to underlying tissues such as subcutaneous fat, cellulite, muscles, trabeculae, and septae, and combinations thereof.  
     
     
         126 . The method of  claim 124 , wherein the signs of skin aging are selected from the group consisting of the development of textural discontinuities, wrinkles, fine superficial wrinkles, coarse deep wrinkles, skin lines, facial frown lines, expression lines, rhytides, dermatoheliosis, photodamage, premature skin aging, crevices, bumps, pits, large pores, “orange-peel” skin appearance, dryness, scaliness, flakiness, blemishes, acne, pimples, breakouts, excess skin oil problems, over production of sebum, oiliness, facial shine, foundation breakthrough, abnormal desquamation, abnormal epidermal differentiation, abnormal skin turnover, keratoses, hyperkeratinization; inadequate skin moisturization, environmental dryness, loss of skin elasticity, elastosis, sagging, puffiness in the eye area and jowls, loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, non-melanin skin discoloration, undereye circles, blotching, rosacea, sallowness, discoloration caused by telangiectasia or spider vessels, melanin-related hyperpigmented skin regions, age spots, liver spots, brown spots, freckles, post-inflammatory hyperpigmentation, inflammation due to acne lesion, in-grown hair, insect/spider bite or sting, scratch, cut, wound, and/or abrasion, atrophy, collagen breakdown and structural alterations or abnormalities, changes in the stratum corneum, dermis, epidermis, the skin vascular system such as telangiectasia or spider vessels; tissue responses to insult from itch or pruritus; and alterations to underlying tissues such as subcutaneous fat, cellulite, muscles, trabeculae, and septae, and combinations thereof.  
     
     
         127 . A method of regulating and/or preventing signs of skin damage due to extrinsic factors comprising administering to a subject a composition of  claim 114 .  
     
     
         128 . The method as in  claim 126 , wherein the extrinsic factors are selected from exposure to UV radiation, smoke, ozone, pollutants, stress and/or fatigue, sunlight, wearing diapers and combinations thereof.  
     
     
         129 . The method as in  claim 127 , wherein exposure to the extrinsic factors lead to diaper rash, erythema, UV radiation damage, sunburn, photoaging, contact dermatitis, and combinations thereof.  
     
     
         130 . The method as in  claim 128 , wherein the exposure leads to erythema.  
     
     
         131 . The method as in  claim 128 , wherein the exposure leads to diaper rash.  
     
     
         132 . A product comprising instructions directing a user to apply a skin care composition comprising a skin care composition of  claim 114 .  
     
     
         133 . A method of promoting a product by directing a user to apply a skin care composition comprising a skin care composition of  claim 114 .  
     
     
         134 . Use of a composition comprising a skin care composition of  claim 114  in the manufacture of a cosmetic for treating a mammalian subject of a dermatologic condition.