초록 ▼

A method for treating skin disorders in warm-blooded animals, said method comprising administering to said warm-blooded animals an effective amount of an appropriately substituted benzimidazole or benzotriazole which suppresses the metabolism of retinoids. Compositions comprising said compounds and

A method for treating skin disorders in warm-blooded animals, said method comprising administering to said warm-blooded animals an effective amount of an appropriately substituted benzimidazole or benzotriazole which suppresses the metabolism of retinoids. Compositions comprising said compounds and an effective amount of a retinoid.

대표청구항 ▼

A method of treating subjects suffering from disorders which are characterized by an increased proliferation and/or abnormal differentiation of normal, preneoplastic or neoplastic epithelial cells by the systemic or topical administration to said subjects of an effective amount of a compound of form

A method of treating subjects suffering from disorders which are characterized by an increased proliferation and/or abnormal differentiation of normal, preneoplastic or neoplastic epithelial cells by the systemic or topical administration to said subjects of an effective amount of a compound of formula [Figure] (I) or [Figure] (II) a pharmaceutically acceptable acid addition salt thereof or a stereochemically isomeric form thereof, wherein R, R1, R2, －A1〓A2－A3〓A4－and A in formula (I) have the following meaning －A1〓A2－A3〓A4－is a bivalent radical having the formula －CH〓N－CH〓CH－(x); －CH〓N－CH〓N－(y); or －CH〓N－N〓CH－(z); R is hydrogen or C1-6alkyl; R1 is hydrogen; C1-10alkyl; C3-7cycloalkyl; Ar1 or Ar1－C1-6alkyl; R2 is hydrogen; C3-7cycloalkyl; Ar1; C1-10alkyl; C1-6alkyl substituted with Ar1 or C3-7cycloalkyl; hydroxy; C1-10alkyloxy; C1-6alkyloxy substituted with Ar1 or C3-7cycloalkyl; C3-6alkenyloxy optionally substituted with Ar2; C3-6alkynloxy optionally substituted with Ar2; or Ar1-oxy; A is a bivalent radical having the formula [Figure] wherein the carbon atom in the bivalent radical (a) and (b) is connected to －NR2; said R3 being hydrogen; halo; C1-4alkyl substituted with up to 4 halo atoms; C3-7cycloalkyl; Ar1; quinolinyl; indolinyl; C1-10alkyl; C1-6alkyl substituted with Ar1, C3-7cycloalkyl, quinolinyl, indolinyl or hydroxy; C1-10alkyloxy; C1-6alkyloxy substituted with Ar1 or C3-7cycloalkyl; C2-6alkenyl optionally substituted with Ar1; Ar2-oxy; C1-6alkyloxycarbonyl; carboxyl; C1-6alkylcarbonyl; Ar1-carbonyl or Ar1－(CHOH)－; said X being O or S; said R4 being hydrogen, C1-6alkyl or Ar2－C1-6alkyl; wherein Ar1 is phenyl, substituted phenyl, pyridinyl, aminopyridinyl, imidazolyl, thienyl, halothienyl, furanyl, halofuranyl or thiazolyl; and Ar2 is phenyl or substituted phenyl; said substituted phenyl in Ar1 and Ar2 being phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, hydroxy, trifluoromethyl, C1-6alkyl, C1-6alkyloxy, cyano, amino, mono- and di(C1-6alkyl)amino, nitro, carboxyl, formyl and C1-6alkyloxycarbonyl; and wherein R, R5, R6, R7 and －A1〓A2－A3〓A4－in formula (II) have the following meaning －A1〓A2－A3〓A4－is a bivalent radical having the formula －CH〓N－CH〓CH－(x); －CH〓N－CH〓N－(y); or －CH〓N－N〓CH－(z); R is hydrogen or C1-6alkyl; R5 is hydrogen; C1-10alkyl; C3-7cycloalkyl; Ar3; Ar4－C1-6alkyl; C2-6alkenyl or C2-6alkynyl; R6 is hydrogen; C1-10alkyl optionally substituted with Ar3, C3-7cycloalkyl, hydroxy or C1-6alkyloxy; Ar3; C2-6alkenyl; C2-6alkynyl; C3-7cycloalkyl; bicyclo[2.2.1]heptan-2-yl; 2,3-dihydro-1-indenyl; 1,2,3,4-tetrahydronaphthalenyl; or a radical of formula OR7, R7 is hydrogen; C2-6alkenyl optionally substituted with Ar4; C2-6alkynyl; pyrimidinyl, di(Ar4)methyl; 1-C1-4alkyl-4-piperidinyl; or C1-10alkyl optionally substituted with halo, hydroxy, C1-6alkyloxy, amino, mono-and di(C1-6alkyl)-amino, trifluoromethyl, carboxyl, C1-6alkyloxycarbonyl, Ar3, Ar4－O－, Ar4－S－, C3-7cycloalkyl, 2,3-dihydro-1,4-benzodioxinyl, 1-benzimidazolyl, C1-4alkyl substituted 1-benzimidazolyl, (1,1′-biphenyl)-4-yl or with 2,3-dihydro-2-oxo-1-benzimidazolyl; R8 is hydrogen, nitro, amino, mono- and di(C1-6alkyl)amino, halo, C1-6alkyl, hydroxy or C1-6alkyloxy; wherein Ar3 is phenyl, substituted phenyl, naphthalenyl, pyridinyl, aminopyridinyl, imidazolyl, triazolyl, thienyl, halothienyl, furanyl, C1-6alkylfuranyl, halofuranyl or thiazolyl; Ar4 is phenyl, substituted phenyl or pyridinyl, said substituted phenyl in Ar3 and Ar4 being phenyl substituted with up to 3 substituents each independently selected from halo, hydroxy, hydroxymethyl, trifluoromethyl, C1-6alkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, formyl, (hydroxyimino)methyl, cyano, amino, mono-and di(C1-6alkyl)amino and nitro.