NOVEL DERIVATIVES OF N-HYDROXY-N'-PHENYLUREE AND N-HYDROXY-N'-PHENYLTHIOUREE AND THEIR USE AS INHIBITORS OF MELANIN SYNTHESIS

摘要

N-Hydroxy-N'-phenyl thiourea derivatives (I) are new. N-Hydroxy-N'-phenyl thiourea derivatives of formula (I) are new. X : O or S; R1H, cation, 1-6C alkyl, optionally substituted aryl or SiQ1Q2Q3; Q1-Q31-6C alkyl or phenyl; R2H, 1-12C alkyl (optionally substituted by OH, NH2, COOH, NO2, OQ4, C(O)Q4 or NQ5Q6), -C(O)Q7, 4-6 membered heterocycle (containing C, N, S and O) or 6-12C aryl or aralkyl (substituted by OH, NH2, COOH, NO2, OQ4, C(O)Q4 or NQ5Q6); Q71-12C alkyl, phenyl, 6-12C aralkyl, OW1 or -NW2W3; W11-6C alkyl or phenyl; W2, W3H or W1; Q4phenyl, 1-12C alkyl or 6-12C aralkyl; Q5, Q6H or Q4; R3H, 1-4C alkyl or 6-12C aralkyl; R4-R8CQ8; Q8H, 1-6C haloalkyl, 1-12C alkyl, halo, NO2, CN, NHC(O), NHOH, OW4, C(O) W4, C(O)OW4, SW4, OSO2W4, C(S)W4, NHC(O)W4, NHC(S)W4, NW5W6 or (CO)NW5W6; and W4-W-6 : H, phenyl, 1-12C alkyl, 6-12C aralkyl or 1-6C haloalkyl. Provided that R6 and R7 are boned by a 4C alkyl chain (optionally saturated) to form a bicyclic derivative (optionally substituted by Q8). Provided that one or two group of R4-R8 is N. Independent claims are also included for: (1) the preparations of (I); and (2) a composition (A) comprising (I). [Image] ACTIVITY : Dermatological; Cytostatic; Nootropic. MECHANISM OF ACTION : Melanine synthase inhibitor. The ability of (I) to inhibit melanine synthesis was tested. The results showed that N-hydroxy-N'-(4-nitrophenyl)urea exhibited 86% exhibition of melanine synthesis.