Pharmaceutical compositions and Methods of treatment or prevention of diseases or conditions inhibiting inflammatory Skin Disorders and diseases, Disorders or conditions associated with the decrease of Collagen

摘要

Compositions and methods for preventing, treating, or inhibiting inflammatory skin diseases, disorders, or conditions, and diseases, disorders, or conditions associated with collagen decrease using one or more estrogenic agents. Claim 1: A method of preventing, treating, or inhibiting an inflammatory skin disease, disorder, or condition, or a disease, disorder, or condition associated with collagen depletion, comprising providing a mammal that is requires, a therapeutically effective amount of at least one compound of formula (1),In the case that Q1 and Q2 are independent h, hexosa residue or s (o) t-oh, which has never been modified or modified, is the residual sugar selected from s (o) t-oh, provided that Q1 and Q2 are not the same as H; t is 0, 1 or 2; R1 is alquenilo c2-7; the rest of alquenilo can choose to replace - CN, halogeno, C1-6 with hydroxy group, -Cor5, co2r5, co2r5, NO2, conr5r6, nr5r5o-n (R5) cor6, R2 and R2A are respectively hydrogen, hydroxy, halide, C1-6 tar, alcox C1-4, alqueilo c2-7, c12-7, trifluoropropyl compound C1-6, or oxyfluoride C1-6; in both cases, the residue can be replaced by hydroxy, alquenio, Nile or carbon chloride.C1-6 trifluoroalkyl, C1-6 trifluoroalkoxy, -COR5, -CO2R5, -NO2, -CONR5R6, -NR5R6, or -N (R5) COR6; R3 and R3a are each independently hydrogen, C1-6alkyl, C2-7alkenyl, C2-7alkynyl, halogen, C1-4alkoxy, C1-6 trifluoroalkyl, or C1-6 trifluoroalkoxy; wherein the alkyl, alkenyl, or alkynyl moieties are optionally substituted with hydroxyl, -CN, halogen, trifluoroalkyl C1-6, trifluoroalkoxy C1-6, -COR5, -CO2R5, -NO2, -CONR5R6, -NR5R6 or -N (R5 ) COR6; R5 and R6 are each independently hydrogen, C1-6 alkyl, or C6-10 aryl; X is O, S, or NR7; R7 is hydrogen, C1-6 alkyl, C6-10 aryl, -COR5, -CO2R5 or -SO2R5; a pharmaceutically acceptable salt thereof;Or glucose, sulfate or glucose sulfate derivative. The third requirement: a method of preventing, treating or inhibiting a disease, skin disease or inflammation, or a disease, disease or disease related to cholesterol reduction, including: providing to mammals in need, 1. Effective amount of one or more estrogen preparations in the treatment, at least one or more of which is selected from glucose derivative, sulfate derivative or glucose derivative sulfate, the content of which is: 2 - (5-hydroxi-1, 3-benzoxazol-2-il) ben-1, 4-diol;, 2 - (2 - (2) - phenyl-1-phenyl-1-1-phenyl 2 - (3-fluoro-4-hydroxyphenyl) - 1, 3-benzoxazol-6-ol; 2 - (3-tri-ethyl-butyl-4-hydroxyphenyl) - 1, Benzene, 3-benzene, 6 -, 1-1, 3-benzene 1-1-1, 3-1, 3-benzene 1, 3 xazol-2-il) Benzene-1, 3-diol; 4 - (6-hydroxi-1, 3-benzoxazol-2-il) bensen-1, 3-diol;- 1-1-1-1-1-1-1-1-1-1-1-1-azol-5-ol; 7-bromo-2 - (2-fluoro-4-hydroxyphenyl) - 1,3-benzoxazol-5-ol; 7-bromo-2 - (2) Phenyl phenyl phenyl phenyl 5-hydroxy; 2 - (4-hydroxyphenyl) - 7-propyl-1,3-benzoxazol-5-hydroxy; 7-butyl-2 - (4-hydroxyphenyl) - 1, 3-benzodiazepine-5-ol;Keywords phenyl toluene toluene toluene toluene methyl; 71. A; 7-ethyl-2 - (2-ethyl-4-hydroxyphenyl) - 1,3-benzoxazol-5-ol; Benzo-methoxyoxy-1 -, 1 -, 1-phenyl-1,3-benzoxazol-5-ol; 2 - (4-hydroxyphenyl) - 7-isopropylphenyl-1, 3-benzodiazepine-5-ol;- phenyl-phenyl-2 - (2) - 1 - (2-1-2-ii-1,3-benzoxazol-5-ol; 2 - (4-hydroxyphenyl) - 7 - (1,3-thiazol-2-1) - 1,3-benzoxazol-5-ol; 1; 7-phenyl 1-phenyl-phenylmethyl-benzyl-benzo they are acceptable. Requirement 5: method of requirement 4,At least one or more of the estrogen preparations is: (a) formula compound (2),wherein R8 is C2-7 alkenyl; wherein the alkenyl moiety is optionally substituted with hydroxyl, -CN, halogen, C1-6 trifluoroalkyl, C1-6 trifluoroalkoxy, -COR12, -CO2R12, -NO2, CONR12R13, NR12R13 or N (R12) COR13; R9 and R9a are each independently hydrogen, hydroxyl, halogen, C1-6 alkyl, C1-4 alkoxy, C2-7 alkenyl, C2-7 alkynyl, C1-6 trifluoroalkyl, or C1-6 trifluoroalkoxy; wherein the alkyl, alkenyl, or alkynyl moieties are optionally substituted with hydroxyl, -CN, halogen, trifluoroalkylC1-6, trifluoroalkoxyC1-6, -COR12, -CO2R12, -NO2, -CONR12R13, -NR12R13 or -N (R12 ) COR13; R10, R10a and R11 are each, independently, hydrogen, C1-6 alkyl,Alquenilo c2-7, c12-7, halogeno, alcoxi C1-4, trifluoalcoquilo C1-6, or trifluoalcoxy C1-6; in these places, the hydroxyl group (CN, halogeno, trifluoalcoquilo C1-6, trifluoalcoxic C1-6, cor12, co2r12, NO2, conr12, nr1223-nr12o-r12 (R13) and R13 (R13) can be used as alternatives. Independent hydrogen, C1-6 asphalt, arilo C6-10; O, s, or nr14; R14 hydrogen, C1-6 asphalt, arilo C6-10, cor12, co2r12 or so2r12, or acceptable sa (b) a formula compound (3),wherein R15, R16, R17, and R18 are each, independently, selected from hydrogen, hydroxyl, C1-6 alkyl, C1-6 alkoxy, or halogen; R19, R20, R21, R22, R23, and R24 are each, independently, hydrogen, hydroxyl, C1-6 alkyl, C2-7 alkenyl, C2-7 alkynyl, halogen, C1-6 alkoxy, -CN, -CHO , phenyl, or a 5- or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from O, N, or S; wherein the alkyl or alkenyl moieties of R19, R20, R21, R22, R23, or R24 may be optionally substituted with hydroxyl, -CN, halogen, trifluoroalkyl, trifluoroalkoxy, -NO2, or phenyl; wherein the phenyl moiety of R19, R20, R21, R22, R23,or R24 may optionally be mono, di, or trisubstituted with C1-6 alkyl, C2-7 alkenyl, halogen, hydroxyl, C1-6 alkoxy, -CN, -NO2, amino, C1-6 alkylamino, C1-6 dialkylamino per group alkyl, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, C 2-7 alkoxycarbonyl, C 2-7 alkylcarbonyl, or benzoyl; with the proviso that at least one of R15, R16, R17, R18, R21, R22, R23, or R24 is hydroxyl, or a pharmaceutically acceptable salt thereof; c) a compound of formula (4),Among them, "P" and "P" are hydrogen, C1-6 hydrocarbon or c2-7 respectively; Z is hydrogen or halogen; R25 is hydrogen, C1-6 hydrocarbon, halogenated CN, o-cho; R26 is alcox C1-6, or cyanoquilo containing 1-6 carbon atoms in other hydrocarbon groups; or a salt acceptable on drugs; (d) a coordination compound (5),wherein A and A 'are each independently OH, H, or OU; each U is independently selected from the group consisting of C1-6 alkyl, alkenyl, benzyl, C2-7 acyl, aroyl, alkoxycarbonyl, sulfonyl and phosphoryl; R27 and R28 are independently selected from the group consisting of H, halogen, C1-6alkyl, perhaloC1-6alkyl, -CF3, C2-7alkenyl, and C1-6alkoxy; R29, R30, R31 and R32 are each independently selected from the group consisting of H, halogen, -CF3, perhaloC1-6alkyl, C1-6alkyl, C2-7alkenyl, C2-7alkyl, C3-7cycloalkyl, C1alkoxy -6, -CN, -CHO, C2-7 acyl, phenyl, aryl and heteroaryl; wherein each alkyl or alkenyl moiety of R29, R30,R31 and R32 can be replaced as an alternative by up to three independently selected halogenated products: oh-cn, C1-6 trifluoropropyl compound, C1-6 trifluoropoxy compound, NO2 and phenyl, among which up to three independently selected R33 groups can be selected to replace the phenyl; in each of these alternatives, R29 and R30 mixture, R31 and R32 can be selectively replaced by up to three alternatives selected from halogenated CN CHO, acilo, C1-6, trial quilsililo and phenyl, of which up to three independently selected R33 alternatives can be selected to replace such phenyl;Each R33 is selected separately from halide, C1-6 tar, c2-7 halodiol, alcoxi C1-6, - CN, - CHO, - N O 2, amino, C1-6 lease, C1-6 lease, endosulfan and C1-6 asphalt, and a category with n of 0, 1, 2 or 3; provided that a and a'n o are 0; if n is 0, R29 is non halogen; and at least 1, R30 is R30. R31 is halogenated C1-6 tar, alquenilo c2-7 tar, c2-7 cyclopentanediol c3-7