Substituted benzene compounds
The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
1. A compound of Formula VI or VII:
or a pharmaceutically acceptable salt thereof;
wherein
n 5 is 0, 1, or 2;
n 6 is 1 or 2;
R 501 is C(H) or N;
R 502 , R 503 , R 504 and R 505 are, independently for each occurrence, C 1-4 alkyl;
R 506 is cyclohexyl substituted by N(C 1-4 alkyl) 2 or piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups;
when R 501 is C(H), R 507 is morpholine; piperidine; diazepane; pyrrolidine; azetidine; O-C 1-6 alkyl; or O-heterocycle, wherein the heterocycle is a 4-7 membered heterocycle containing an oxygen or nitrogen, or both, and wherein the nitrogen can optionally be substituted with C 1-3 alkyl; wherein the piperidine, diazepane, pyrrolidine or azetidine groups can be optionally further substituted with OH, C 1-6 alkyl, or O-C 1-3 alkyl;
or when R 501 is C(H), R 507 can be piperazine optionally further substituted with C 1-6 alkyl, provided that R 506 is piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups;
when R 501 is N, R 507 is morpholine; piperidine; piperazine; diazepane; pyrrolidine; azetidine; O—C 1-6 alkyl; or O-heterocycle, wherein the heterocycle is a 4-7 membered heterocycle containing an oxygen or nitrogen, or both, and wherein the nitrogen can optionally be substituted with C 1-3 alkyl; wherein the piperidine, piperazine, diazepane, pyrrolidine or azetidine groups can be optionally further substituted with OH, C 1-6 alkyl, or O-C 1-3 alkyl;
R 602 , R 603 , R 604 and R 605 are, independently for each occurrence, C 1-4 alkyl;
R 606 is cyclohexyl substituted by N(C 1-4 alkyl) 2 or piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups; and
R 607 is morpholine, piperidine, piperazine, pyrrolidine, diazepane, azetidine or O-C 1-6 alkyl, wherein the piperidine, diazepane or azetidine groups can be optionally further substituted with OH or C 1-6 alkyl.
2. The compound of claim 1 , wherein the compound is of Formula (VI), wherein (i) R 501 is C(H), and R 507 is piperidine; diazepane; pyrrolidine; azetidine; O-C 1-6 alkyl; or O-heterocycle, wherein the heterocycle is a 4-7 membered heterocycle containing an oxygen or nitrogen, or both, and wherein the nitrogen can optionally be substituted with C 1-3 alkyl; wherein the piperidine, diazepane, pyrrolidine or azetidine groups can be optionally further substituted with OH, C 1-6 alkyl, or O-C 1-3 alkyl; or (ii) R 501 is C(H) and R 507 is piperidine, diazepane, pyrroloidine, azetidine or O-C 1-6 alkyl, wherein the piperidine, diazepane, pyrrolidine or azetidine groups can be optionally further substituted with OH or C 1-6 alkyl; or (iii) R 501 is C(H), R 507 is piperazine optionally substituted with C 1-6 alkyl, and R 506 is piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups; or (iv) R 501 is N, and R 507 is morpholine, piperidine, piperazine, diazepane, pyrrolidine, azetidine or O-C 1-6 alkyl, wherein the piperidine, piperazine, diazepane, pyrrolidine or azetidine groups can be optionally further substituted with OH or C 1-6 alkyl.
3. The compound of claim 1 , wherein the compound is of Formula (VI), wherein (i) R 502 is methyl or isopropyl, and R 503 is methyl; or (ii) R 504 is methyl; or (iii) R 505 is ethyl; or (iv) R 506 is
4. The compound of claim 1 , wherein the compound is of Formula (VI), wherein (i) when R 501 is C(H), R 507 is piperidine or diazepane, which are substituted with OH or C 1-6 alkyl, or when R 501 is N, R 507 is piperidine, piperazine, or diazepane, which are optionally further substituted with OH or C 1-6 alkyl; or (ii) when R 501 is C(H), R 507 is piperidine substituted with C 1-6 alkyl, or when R 501 is N, R 507 is piperidine substituted with OH or piperazine substituted with C 1-6 alkyl; or (iii) when R 501 is N, R 507 is unsubstituted piperazine; or (iv) when R 501 is C(H) or N, R 507 is O-C 1-6 alkyl or O-heterocycle, and n 5 is 1; or (v) when R 501 is C(H), R 507 is unsubstituted piperazine and R 506 is piperidine substituted by 1, 2, or 3 C 1-4 alkyl groups; or (vi) ns is 0 or 1.
5. The compound of claim 1 , being of Formula VII:
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 5 , wherein (i) R 602 is methyl or isopropyl and R 603 is methyl; or (ii) R 604 is methyl and R 605 is ethyl; or (iii) R 607 is piperidine or diazepane, each of which is substituted with OH or C 1-6 alkyl; or (iv) R 607 is piperidine substituted with OH; or (v) R 606 is
or (vii) n 6 is 2.
7. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
8. A method of treating lymphoma, the method comprising administering to a subject a compound of claim 1 or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL), non-Hodgkin's lymphoma (NHL), or follicular lymphoma.
10. The method of claim 9 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL).
11. The method of claim 9 , wherein the lymphoma is non-Hodgkin's lymphoma (NHL).
12. The method of claim 9 , wherein the lymphoma is follicular lymphoma.