Aryl-aniline and heteroaryl-aniline compounds for treatment of birthmarks

A method of treating a birthmark, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of formula (I), (II), (III), (IV), and (V):

• or a N-oxide, stereoisomer, mixture of stereoisomers, and/or a pharmaceutically acceptable salt thereof,
• wherein:
• X1 is —CR13b or N;
• X2 is C1-C6 alkyl;
• X3 is S or O;
• subscript n is an integer from 0 to 2;
• bond “a” is a single or double bond;
• R1 is —OR4, —NR5R5a, —N(OR5b)R5a, or a N-linked heterocycloalkyl which is unsubstituted or substituted with one or two R6′;
• R2 is halo, C1-C6 alkyl, —S—C1-C6 alkyl, C3-C8 cycloalkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
• R2a is halo or C1-C6 alkyl;
• R4, R5, and R5b are each independently hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6 alkyl, amino-C1-C6 alkyl, C1-C6 alkylamino-C1-C6 alkyl, di-(C1-C6 alkyl)amino-C1-C6 alkyl, heterocycloalkyl, heterocycloalkyl-C1-C6 alkyl, or R7—C(O)—C1-C6 alkyl, wherein each of the C3-C8 cycloalkyl and heterocycloalkyl groups is unsubstituted or substituted with one to six R6;
• R5a is hydrogen or C1-C6 alkyl;
• each R6 is independently halo, hydroxy, oxo, C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, C1-C6-hydroxyalkyl, C1-C6 haloalkyl, amino, C1-C6 alkylamino, di-(C1-C6 alkyl)amino, amino-C1-C6 alkyl, C1-C6 alkylamino-C1-C6 alkyl, or di-(C1-C6 alkyl)amino-C1-C6 alkyl;
• R7 is hydroxy, C1-C6 alkoxy, amino, C1-C6 alkylamino, di-(C1-C6 alkyl)amino, hydroxyamino, or N—C1-C6 alkyl hydroxyamino;
• R13, R13a, and R13b are each independently hydrogen, halo, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
• R23, R23a, and R23b are each independently hydrogen, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, or C3-C8 cycloalkoxy;
• R33, R33a, and R33b are each independently hydrogen, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, or C3-C8 cycloalkoxy;
• R43 is cyano, —C(O)NR48R48a, or —C(O)R46;
• R43a is hydrogen, halo, C1-C6 alkyl;
• or
• R43 and R43a together form —CH2CH2C(O)— or —CH2CH2CH2C(O)—, each of which is unsubstituted or substituted with one or two R49;
• R46 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl or heterocycloalkyl;
• R48 and R48a are independently hydrogen or C1-C6 alkyl;
• and
• each R49 is independently C1-C6 alkyl, C3-C8 cycloalkyl, or C3-C8 cycloalkyl-C1-C6 alkyl;
• R51 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6 alkyl, amino-C1-C6 alkyl, C1-C6 alkylamino-C1-C6 alkyl, di-(C1-C6 alkyl)amino-C1-C6 alkyl, heterocycloalkyl, heterocycloalkyl-C1-C6 alkyl, R7—C(O)—C1-C6 alkyl, orOR54, wherein each of the C3-C8 cycloalkyl and heterocycloalkyl groups is unsubstituted or substituted with one to six R6;
• each R53 is independently halo or C1-C6 alkyl;
• R53a and R53b are each independently hydrogen, halo, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
• and
• R54 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkyl-C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C6 alkyl, amino-C1-C6 alkyl, C1-C6 alkylamino-C1-C6 alkyl, di-(C1-C6 alkyl)amino-C1-C6 alkyl, heterocycloalkyl, heterocycloalkyl-C1-C6 alkyl, or R7—C(O)—C1-C6 alkyl, wherein each of the C3-C8 cycloalkyl and heterocycloalkyl groups is unsubstituted or substituted with one to six R6.