AMINOQUINOLINE COMPOUNDS HAVING ANTICANCER ACTIVITY

1 . A method for treating a neoplastic disease in a mammalian subject, comprising administering to the subject an effective amount of a compound represented by Formula IA1a or a pharmaceutically acceptable salt thereof

wherein n is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

p is 0 or 1, provided that if p is 1 then n must not be 0 or 1;

q is 0 or 1;

one of R 1 and R 2 is hydrogen and the other is selected from the group consisting of hydrogen, halo, methyl, and perfluoromethyl;

R 4 is hydrogen or halo; and

R 5 is selected from the group consisting of hydrogen; halo; unbranched or branched alkyl having from 1 to 6 carbon atoms unsubstituted or substituted by phenyl or phenoxy; alkoxy having from 1 to 10 carbon atoms unsubstituted or substituted by phenyl or phenoxy, provided that when substituted by phenoxy the alkoxy must have more than one carbon atom; phenyl; phenoxy; C(O)OR 6 ; C(O)NHR 6 ; or NHC(O)R 6 , wherein R 6 is alkyl having from 1 to 6 carbon atoms.

2 . The method of claim 1 wherein R 1 is hydrogen and R 2 is hydrogen.

3 . The method of claim 2 , wherein p is 1 and R 4 is hydrogen.

4 . The method of claim 3 , wherein R 5 is hydrogen.

5 . The method of claim 4 , selected from the group consisting of:

N-[8-(Benzyloxy)octyl]quinolin-4-amine,

N-(6-Phenoxyhexyl)quinolin-4-amine,

N-(8-Phenoxyoctyl)quinolin-4-amine.

6 . The method of claim 3 , wherein q is 0, and R 5 is alkoxy having from 1 to 6 carbon atoms unsubstituted or substituted by phenyl.

7 . The method of claim 6 , wherein R 5 is in the ortho position.

8 . The method of claim 7 , wherein the compound is selected from the group consisting of:

N-{2-[2-(Hexyloxy)phenoxy]ethyl}quinolin-4-amine,

N-{3-[2-(Hexyloxy)phenoxy]propyl}quinolin-4-amine,

N-{4-[2-(Hexyloxy)phenoxy]butyl}quinolin-4-amine,

N-[3-(2-Ethoxyphenoxy)propyl]quinolin-4-amine,

N-[3-(2-Methoxyphenoxy)propyl]quinolin-4-amine,

N-{3-[2-(Benyloxy)phenoxy]propyl}quinolin-4-amine.

9 . The method of claim 6 , wherein R 5 is in the meta position.

10 . The method of claim 9 , wherein the compound is selected from the group consisting of:

N-[8-(3-Methoxyphenoxy)octyl]quinolin-4-amine,

N-{4-[3-(Hexyloxy)phenoxy]butyl}quinolin-4-amine,

N-{3-[3-(Hexyloxy)phenoxy]propyl}quinolin-4-amine,

N-{12-[3-(Hexyloxy)phenoxy]ethyl}quinolin-4-amine.

11 . The method of claim 6 , wherein R 5 is in the para position.

12 . The method of claim 11 , wherein the compound is selected from the group consisting of:

N-[8-(4-Methoxyphenoxy)octyl]quinolin-4-amine,

N-[6-(4-Methoxyphenoxy)hexyl]quinolin-4-amine,

N-{2-[4-(Hexyloxy)phenoxy]ethyl}quinolin-4-amine,

N-{3-[4-(Hexyloxy)phenoxy]propyl}quinolin-4-amine,

N-{4-[4-(Hexyloxy)phenoxy]butyl}quinolin-4-amine.

13 . The method of claim 3 , wherein R 5 is unbranched or branched alkyl having from 1 to 6 carbon atoms.

14 . The method of claim 13 , wherein the compound is selected from the group consisting of:

N-[8-(m-Tolyloxy)octyl]quinolin-4-amine,

N-[8-(p-Tolyloxy)octyl]quinolin-4-amine,

N-[8-(o-Tolyloxy)octyl]quinolin-4-amine,

N-[8-(4-tert-Butylphenoxy)octyl]quinolin-4-amine.

15 . The method of claim 3 , wherein R 5 is fluoro.

16 . The method of claim 15 , wherein the compound is selected from the group consisting of:

N-[8-(4-Fluorophenoxy)octyl]quinolin-4-amine,

N-[8-(3-Fluorophenoxy)octyl]quinolin-4-amine,

N-[8-(2-Fluorophenoxy)octyl]quinolin-4-amine.

17 . The method of claim 2 , wherein p is 0.

18 . The method of claim 17 wherein q is 0.

19 . The method of claim 18 , wherein n is 0

20 . The method of claim 19 , wherein the compound is selected from the group consisting of:

N-(Biphenyl-4-yl)quinolin-4-amine,

N-(4-Hexylphenyl)quinolin-4-amine,

Hexyl 4-(quinolin-4-ylamino)benzoate,

N-(4-Phenoxyphenyl)quinolin-4-amine,

N-(3-Phenoxyphenyl)quinolin-4-amine,

N-(2-Phenoxyphenyl)quinolin-4-amine,

N-[4-(Quinolin-4-ylamino)phenyl]hexanamide,

N-[3-(Quinolin-4-ylamino)phenyl]hexanamide,

N-Hexyl-4-(quinolin-4-ylamino)benzamide,

N-Hexyl-3-(quinolin-4-ylamino)benzamide.

21 . The method of claim 19 , wherein R 5 is alkoxy having from 1 to 10 carbon atoms unsubstituted or substituted by phenyl.

22 . The method of claim 21 , wherein the compound is selected from the group consisting of:

N-(4-Methoxyphenyl)quinolin-4-amine,

N-[4-(Benzyloxy)phenyl]quinolin-4-amine,

N-(4-Butoxyphenyl)quinolin-4-amine,

N-[4-(Hexyloxy)phenyl]quinolin-4-amine,

N-[3-(Benzyloxy)phenyl]quinolin-4-amine,

N-[3-(Hexyloxy)phenyl]quinolin-4-amine,

N-[2-(Benzyloxy)phenyl]quinolin-4-amine,

N-[2-(Hexyloxy)phenyl]quinolin-4-amine,

N-[2-Fluoro-4-(hexyloxy)phenyl]quinolin-4-amine.

23 . The method of claim 18 , wherein n is 1 or 2.

24 . The method of claim 23 , wherein the compound is selected from the group consisting of:

N-Benzylquinolin-4-amine,

N-Phenethylquinolin-4-amine.

25 . The method of claim 17 , wherein q is 1.

26 . The method of claim 25 , wherein R 5 is alkoxy having from 1 to 10 carbon atoms.

27 . The method of claim 26 , wherein the compound is selected from the group consisting of:

N-[4-(Hexyloxy)benzyl]quinolin-4-amine,

N-[3-(Hexyloxy)benzyl]quinolin-4-amine,

N-[2-(Hexyloxy)benzyl]quinolin-4-amine,

N-[3-Fluoro-4-(hexyloxy)benzyl]quinolin-4-amine,

N-[4-(Decyloxy)benzyl]quinolin-4-amine,

N-[3-(Decyloxy)benzyl]quinolin-4-amine.

28 . The method of claim 25 , wherein R 5 is phenoxy, or alkoxy having from 1 to 10 carbon atoms substituted by phenyl.

29 . The method of claim 28 , wherein the compound is selected from the group consisting of:

N-(3-Phenoxybenzyl)quinolin-4-amine,

N-[3-(Benzyloxy)benzyl]quinolin-4-amine,

N-(3-Phenethoxybenzyl)quinolin-4-amine.

30 . The method of claim 1 , wherein the neoplastic disease is a hematologic cancer.

31 . The method of claim 1 wherein the neoplastic disease is a solid tumor.

32 . The method of claim 1 wherein the compound is administered topically to the subject.

33 . The method of claim 1 wherein the compound or composition is administered systemically to the subject.

34 . The method of claim 33 , wherein the compound is administered orally, rectally, parenterally, or nasally.