(bis)urea and (bis)thiourea compounds as epigenic modulators of lysine-specific demethylase 1 and methods of treating disorders
View Patent ↗The invention provides for novel (bis)urea and (bis)thiourea compounds which are inhibitors of lysine-specific demethylase 1 (LSD1). Such compounds may be used to treat disorders, including cancer.
1. A compound of formula II-a, II-b, II-c, or II-d
and salts, solvates and hydrates thereof, wherein,
each R is independently H, —C 1 -C 8 alkyl, —C 6 -C 20 aralkyl, or —C 3 -C 12 aryl; each of which is optionally substituted;
each R′ is independently H, —C 1 -C 8 alkyl, —C 6 -C 20 aralkyl, or —C 3 -C 12 aryl; each of which is optionally substituted;
each of R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently selected from H, alkyl, aralkyl, haloalkyl, aryl, heteroaryl, and heteroaralkyl, each of which is optionally substituted;
each of R 7 , R 8 , and R 9 are independently selected from H, —C 1 -C 8 alkyl, —C 2-8 alkenyl or —C 2 -C 8 alkynyl, each containing 0, 1, 2, or 3 heteroatoms independently selected from O, S, and N; —C 3 -C 12 cycloalkyl, —C 3 -C 12 heterocycloalkyl, —C 6 -C 20 aralkyl, —C 3 -C 12 aryl, —C 3 -C 12 heteroaryl, OR A , SR A , and NR A R A ; each of which is optionally substituted;
each R A is independently selected from H, alkyl, aralkyl, aryl, or heteroaryl, each of which is optionally substituted; and
n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
2. The compound of claim 1 , wherein each R is independently H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, phenyl, benzyl, ethyl phenyl, propyl phenyl, or naphthyl, each of which is optionally substituted.
3. The compound of claim 1 , wherein each R is independently H, methyl, ethyl, propyl, phenyl, benzyl, 3,3-diphenylpropyl, 2,2-diphenylethyl, or diphenylmethyl.
4. The compound of claim 1 , wherein each R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are H.
5. The compound of claim 1 , wherein each R 7 , R 8 , and R 9 are H.
6. The compound of claim 1 , wherein each n is independently 1, 2, 3, 4, 5, or 6.
7. A kit comprising an effective amount of a compound of claim 1 in unit dosage form, together with instructions for administering the compound to a subject suffering from or susceptible to a LSD1-related disease.
8. A compound selected from the group consisting of: