Patent FR-2869224-A1 (FR)
Title: Stimulating growth and/or inhibiting loss of keratin fibers, e.g. human hair or eyelashes, using new or known oxy-acetamide derivatives having 15-hydroxyprostaglandin dehydrogenase type 1 inhibiting action
Inventor: ROZOT ROGER
IPC: C07D215/26
Filed: 2004-04-22
Abstract: Use of new and known N-substituted or N,N-disubstituted 2-(alkoxy, carbocyclyloxy or heterocyclyloxy)-acetamide (I) for inducing and/or stimulating the growth of keratin fibers, inhibiting their loss and/or increasing their density or for inhibiting 15-hydroxy-prostaglandin dehydrogenase (15-PGDH-1) type 1 is claimed. Use of oxyacetamide derivative(s) of formula R3OCH2C(O)NR1R2 (I) or their salts and/or solvates is claimed: (1) as agent for inducing and/or stimulating the growth of (preferably human) keratin fibers, inhibiting their loss and/or increasing their density or for inhibiting (preferably human) 15-hydroxyprostaglandin dehydrogenase (15-PGDH-1) type 1; (2) in cosmetic care and/or make-up compositions for keratin fibers, inhibiting their loss and/or increasing their density; or (3) for the production of care or treatment compositions for keratin fibers, inducing and/or stimulating their growth, inhibiting their loss and/or increasing their density or for treating disorders associated with 15-PGDH type 1. R1, R2 = H, 1-20C alkyl or mono- or bicyclic heterocycle (all optionally substituted (os)) or carbocycle C(=NR)R', C(=NR)NR'R'', C(O)R, C(S)R, C(O)OR, C(O)NRR', SO2R or SO2NRR', provided that R1 and R2 are not both H; R3 = 1-20C alkyl or mono- or bicyclic heterocycle (all os); and R, R', R'' = H or 1-20C alkyl or mono- or bicyclic heterocycle (all os). Full definitions are given in the Definitions: Full Definitions section. Independent claims are also included for: (A) cosmetic care or make-up compositions for keratin fibers comprising a suitable medium containing (I) or its salt and/or solvate; (B) a cosmetic treatment process for human keratin fibers (and/or the skin in the region of the fibers) to improve the condition and/or appearance of the fibers, involving application of a composition containing (I) (or its salt and/or solvate), optionally followed by rinsing; and (C) New compounds (I) and their salts and solvates where: (I) R1 = H; R2 = 2-(R7)-6-(R8)-phenyl; R3 = 8-quinolyl; (II) R1 = H; R2 = phenyl substituted by X and Y; R3 = Z; (III) R1 = H; R2 = A; R3 = benzyl; and (IV) R1 = H; R2 = trimethylsilylmethyl. R7, R8 = H, F, Cl, CF3, CN, OQ4, SQ4, NQ4Q'4 (but not NH2), OC(O)Q4, C(O)Q4, C(S)Q4, C(O)OQ4, SO2Q4, SiQ4Q'4Q''4, OCF3; 1-20C alkyl (os by OR5) or 4-7 membered ring C11> (optionally containing heteroatom(s) to form a heterocycle Hy11 and/or optionally fused with a 4-7 membered ring C12>, where rings C11> and C12> are os by O or S); Z = 4-pyrrolophenyl, 4-pyrazolophenyl, 9-oxofluoren-2-yl, 2-methylbenzothiazol-5-yl, 4-acetyl-2-methoxyphenyl, dibenzofuran-3-yl or 4-acetylphenyl; X, Y = H or A2; or X+Y = fused 4-7 (preferably 5 or 6) membered ring C13> (optionally containing N, O and/or S heteroatom(s), os by group(s) A2 and optionally fused with another ring C14>); provided that (i) if Z = dibenzofuran-3-yl, then X and Y are other than 2-20C alkoxy (os by phenyl), Me or CH2OR5; C11> is not substituted by A3; and X and Y do not together form C13>; and (ii) if Z = 4-acetylphenyl, then X and Y are not both H; X and Y are other than Cl, Br, I, CF3, CN, COOH, SO2R4, Me or CH2OR5; OR4 may only be OH, OCH2Ph or 3-20C alkoxy (os by Ph); and C13> may only be 5-membered rings (optionally containing 1 or 2 O heteroatoms and optionally fused with another ring C14>); A = 5-methyl-furan-2-ylmethyl, tetrahydrofuran-2-ylmethyl or cyclopentyl. ACTIVITY : Antialopecia. MECHANISM OF ACTION : 15-Hydroxyprostaglandin dehydrogenase (15-PGDH-1) type 1 inhibitor. N-Benzyl-2-cyclohexyloxy-acetamide (Ia) at a concentration of 50 mu M inhibited 15-PGDH type-1 by 63% and prostaglandin F synthase (PGFS) by 24%.