Search

CN-121971305-A - Composition of compound containing fluorene or fluorenone skeleton

CN121971305ACN 121971305 ACN121971305 ACN 121971305ACN-121971305-A

Abstract

The invention relates to a composition of a compound containing fluorene or fluorenone skeleton, in particular to a composition which comprises a compound shown as a formula II or pharmaceutically acceptable salt thereof, wherein the compound provided by the invention can be used as a tyrosinase inhibitor, has excellent whitening, antioxidant and ultraviolet absorption effects, has better water solubility and lower cytotoxicity compared with the traditional resorcinol structure, and provides a thought for designing and screening future whitening effect compounds.

Inventors

  • YU JIE
  • YU HAINING
  • LIU ZHONGWANG
  • YANG HUIPING

Assignees

  • 上海中翊日化有限公司
  • 上海上美化妆品股份有限公司

Dates

Publication Date
20260505
Application Date
20260326

Claims (10)

  1. 1. A composition is characterized by comprising a compound shown as a formula II or pharmaceutically acceptable salt thereof, wherein the composition is a cosmetic composition, a skin care composition or a pharmaceutical composition; ; Wherein R 3 and R 4 are independently hydroxy or C 1-3 alkyl; A is CR 1 R 2 or CO; R 1 and R 2 are independently H or C 1-10 alkyl; x is 0,1, 2, 3, 4 or 5; y is 0,1, 2, 3, 4 or 5.
  2. 2. The composition of claim 1, which satisfies one or more of the following conditions: (1) 0,1 or 2R 3 are hydroxy; (2) 0,1 or 2R 4 are hydroxy; (3) R 3 and R 4 together have 1 or 2 hydroxyl groups; (4) R 3 and R 4 are independently hydroxy or methyl; (5) R 1 and R 2 are independently H or C 1-10 straight-chain alkyl or C 1-10 mono-branched alkyl.
  3. 3. The composition of claim 1, wherein R 1 and R 2 are independently C 1-3 alkyl.
  4. 4. The composition of claim 1, which satisfies one or more of the following conditions: (1) 0 or 1R 3 is hydroxy; (2) 0 or 1R 4 is hydroxy; (3) R 3 and R 4 are hydroxyl; (4) x is 0 or 1; (5) y is 0 or 1; (6) R 1 and R 2 are independently H.
  5. 5. The composition of claim 1, wherein the compound of formula II is 、 、 、 、 、 、 、 Or (b) 。
  6. 6. The composition of claim 1, wherein when the composition is a cosmetic composition or a skin care composition, the compound of formula II or a pharmaceutically acceptable salt thereof acts as one or more of (1) a whitening effect, (2) an antioxidant effect, and (3) an ultraviolet absorbing effect.
  7. 7. The composition of claim 1, which satisfies one or more of the following conditions: (1) In the composition, the compound shown as the formula II or pharmaceutically acceptable salt thereof plays a role in preventing skin melanin deposition or pigmentation; (2) In the composition, when the composition is a cosmetic composition or a skin care composition, the compound shown as the formula II or the pharmaceutically acceptable salt thereof is the only whitening active ingredient; (3) In the composition, when the composition is a cosmetic composition or a skin care composition, the compound shown as the formula II or the pharmaceutically acceptable salt thereof is the sole antioxidant active ingredient; (4) In the composition, when the composition is a cosmetic composition or a skin care composition, the compound shown as the formula II or the pharmaceutically acceptable salt thereof is the sole ultraviolet absorption active ingredient; (5) In the composition, the weight of the compound shown as the formula II or the pharmaceutically acceptable salt thereof accounts for 0.000005% -20% of the total weight of the composition; (6) The pharmaceutical composition also comprises pharmaceutically acceptable auxiliary materials; (7) The pharmaceutical composition is selected from one or more of cream, gel, patch, spray, ointment, plaster, emulsion, liniment, paste or cataplasm; (8) The cosmetic composition is selected from one or more of astringent, foundation, concealer, BB cream, eye shadow, lipstick, mascara, eyebrow tracing, eyelid or makeup remover; (9) The skin care product composition is selected from one or more of skin softening water, skin refreshing water, emulsion, massage cream, nutrition cream, moisturizing cream, hand cream, essence, facial mask, soap, facial cleanser, skin lotion, shampoo or bath lotion; (10) The cosmetic composition further comprises a cosmetically acceptable adjuvant; (11) The skin care product composition also comprises auxiliary materials which are acceptable in skin care product science.
  8. 8. The application of the compound shown in the formula II in preparing the composition is characterized in that, The composition is a cosmetic composition, a skin care composition or a pharmaceutical composition, and the compound shown in the formula II is defined in any one of claims 1-5.
  9. 9. The use according to claim 8, wherein the cosmetic or skin care composition has one or more of (1) whitening, (2) antioxidant and (3) uv absorption.
  10. 10. Use according to claim 8, characterized in that it fulfils one or more of the following conditions: (1) The cosmetic or skin care composition acts to prevent skin melanin deposition or pigmentation; (2) In the cosmetic composition or the skin care composition, the compound shown in the formula II or the pharmaceutically acceptable salt thereof is the only whitening active ingredient; (3) In the cosmetic composition or the skin care composition, the compound shown as the formula II or the pharmaceutically acceptable salt thereof is the only antioxidant active ingredient; (4) In the cosmetic composition or the skin care composition, the compound shown as the formula II or the pharmaceutically acceptable salt thereof is the only ultraviolet absorption active ingredient; (5) In the composition, the weight of the compound shown as the formula II or the pharmaceutically acceptable salt thereof accounts for 0.000005% -20% of the total weight of the medicine, the cosmetic or the skin care product; (6) The pharmaceutical composition is selected from one or more of cream, gel, patch, spray, ointment, plaster, emulsion, liniment, paste or cataplasm; (7) The cosmetic composition is selected from one or more of astringent, foundation, concealer, BB cream, eye shadow, lipstick, mascara, eyebrow tracing, eyelid or makeup remover; (8) The skin care product composition is selected from one or more of skin softening water, skin refreshing water, emulsion, massage cream, nutrition cream, moisturizing cream, hand cream, essence, facial mask, soap, facial cleanser, skin lotion, shampoo or bath lotion; (9) The pharmaceutical composition also comprises pharmaceutically acceptable auxiliary materials; (10) The cosmetic composition further comprises a cosmetically acceptable adjuvant; (11) The skin care product composition also comprises auxiliary materials which are acceptable in skin care product science.

Description

Composition of compound containing fluorene or fluorenone skeleton Technical Field The present invention relates to a composition of a compound containing a fluorene or fluorenone skeleton. Background Skin color is determined primarily by how many melanocytes are in the epidermis and how fast melanin is synthesized (Melanogenesis). The melanin is formed through a series of complex physiological and biochemical processes, and the whitening and freckle removing product developed at present mainly achieves the whitening effect by inhibiting tyrosinase so as to inhibit melanin production. Are currently used as skin whitening substances, such as hydroquinone, hexadecene-1, 16-dicarboxylic acid, kojic acid and its derivatives, nicotinamide, arbutin, ascorbic acid and its derivatives, flavonoids, ellagic acid and its derivatives, tranexamic acid and its various resorcinol derivatives, 4-n-butylresorcinol, 4-n-hexylresorcinol and 4- (1-phenethyl) benzene-1, 3-diol. Wherein, the long-time use of hydroquinone can cause irreversible change of skin pigment system, generate cytotoxicity to melanocyte, and cause permanent decolorization of skin, and the addition of hydroquinone in skin care products is forbidden in China, and can only be used in the form of prescription. Kojic acid has sensitization and cytomutation defects, nicotinamide and analogues thereof have teratogenicity and intolerance defects of partial crowds, and arbutin has high concentration dependence. While resorcinol derivatives disclosed in the prior art can be well embedded into a tyrosinase double-copper active pocket to play a role in enzyme inhibition, and main representative small molecules comprise 377 (phenethyl resorcinol), more peptide amine, glabridin and the like, the resorcinol derivatives still have certain problems of insufficient human tyrosinase inhibition activity or unstable physicochemical properties, skin irritation, unfriendly sensitive muscles and the like, and cannot meet the requirements of patients with pigmentation. Tyrosinase, which is a key target in multiple fields, can participate in skin melanin generation and also in nerve melanin generation, catalyzes the oxidation of dopa to dopaquinone, mediates the synthesis of nerve melanin, and oxidative stress caused by overexpression is directly related to the neurodegenerative disease processes such as Parkinson disease, huntington disease and the like. In the fields of agriculture and food, the shelf life is obviously prolonged by inhibiting the browning reaction of fruits and vegetables (blocking the oxidative polymerization of phenols), and meanwhile, the green biological pesticide can be developed by targeting the blackening path of the pest epidermis, and in the field of cosmetology, the effects of whitening, lightening spots, resisting photoaging and the like are realized by inhibiting the generation of melanin. The characteristic of 'one-target multi-treatment' is derived from broad spectrum (monophenol/diphenol/catechol) and cross-species conservation of tyrosinase substrates, and currently research is focused on dual-function molecular design (such as integrated antioxidant and inhibitory activity) and nano delivery system development so as to cooperatively promote industrialized application thereof in the fields of disease intervention, agricultural product fresh-keeping, environment-friendly pesticides, efficacy skin care products and the like. Disclosure of Invention The invention aims to overcome the defects that resorcinol brings skin irritation and potential health risk in the prior art, and provides a small molecular skeleton structure with fluorene or fluorenone skeleton, the compound provided by the invention can be used as tyrosinase inhibitor, the resorcinol-modified resorcinol compound has the advantages of excellent whitening, antioxidant and ultraviolet absorption effects, better water solubility and lower cytotoxicity compared with the traditional resorcinol structure, and provides a thought for future design and screening of whitening efficacy compounds. The invention solves the technical problems by the following technical scheme: the invention also provides a composition, which comprises a compound shown as a formula II or pharmaceutically acceptable salt thereof, wherein the composition is a cosmetic composition, a skin care composition or a pharmaceutical composition; ; Wherein R 3 and R 4 are independently hydroxy or C 1-3 alkyl; A is CR 1R2 or CO; R 1 and R 2 are independently H or C 1-10 alkyl; x is 0,1, 2, 3, 4 or 5; y is 0,1, 2, 3, 4 or 5. In some embodiments, 0, 1, or 2R 3 are hydroxy groups, e.g., 0 or 1R 3 are hydroxy groups. In some embodiments, 0, 1, or 2R 4 are hydroxy groups, e.g., 0 or 1R 4 are hydroxy groups. In some embodiments, R 3 and R 4 together have 1 or 2 hydroxyl groups. In some embodiments, R 3 and R 4 are independently hydroxy or methyl, e.g., hydroxy. In some embodiments, x is 0 or 1. In some embodiments, y is 0 or 1. In some