US2015272962A1PendingUtilityA1
Methods for treating or preventing cancer and neurodegenerative diseases
Assignee: SLOAN KETTERING INST CANCERPriority: Dec 22, 2008Filed: Jun 10, 2015Published: Oct 1, 2015
Est. expiryDec 22, 2028(~2.4 yrs left)· nominal 20-yr term from priority
A61P 35/02A61P 43/00A61P 35/00A61P 25/28A61P 25/16A61P 25/00A61P 21/00A61K 31/5513A61K 31/381C07D 333/34C07D 409/12
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Claims
Abstract
Provided are methods of treating or preventing a neurodegenerative disease comprising administering to a subject having a neurodegenerative disease an effective amount of a compound of Formula I: where X, R 1 , R 2 , subscript m, subscript n and subscript v are as defined herein.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method for treating or preventing cancer, comprising administering to a subject in need of treatment or prevention of the cancer an effective amount of a compound of Formula I
or a pharmaceutically acceptable salt thereof, wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 2 is
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
Z 1 is NH, O, or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
n is 1;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
2 . The method of claim 1 , wherein the compound of Formula I has the following Formula Ia
wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
Z 1 is NH, O, or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
3 . The method of claim 2 , wherein the compound of Formula Ia has the following Formula Iaa
wherein:
X is halo;
each R 1 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 3 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
4 . The method of any one of claims 1 to 3 , wherein each R 1 is H.
5 . The method of any one of claims 1 to 4 , wherein q is 0.
6 . The method of any one of claims 1 to 5 , wherein v is 1 and X is in the 5-position of the thiopheno group.
7 . The method of any one of claims 1 to 6 , wherein p is 1 and R 3 is in the 4-position of the phenyl group.
8 . The method of claim 3 , wherein the compound of Formula Iaa has the structure:
or a pharmaceutically acceptable salt thereof.
9 . The method of claim 3 , wherein the compound of Formula Iaa has the structure:
or a pharmaceutically acceptable salt thereof.
10 . A method for treating or preventing cancer, comprising administering to a subject in need of treatment or prevention of the cancer an effective amount of a compound of Formula II
or a pharmaceutically acceptable salt thereof, wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 4 is
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 5 is H, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 1 is NH, O, or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)- or —(C 2 -C 6 alkenylene)-;
m is 3;
n is 1;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
11 . The method of claim 10 , wherein the compound of Formula II has the following Formula IIa
wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 5 is H, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 1 is NH, O or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)- or —(C 2 -C 6 alkenylene)-;
m is 3;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
12 . The method of claim 11 , wherein the compound of Formula IIa has the following Formula IIaa
wherein:
X is halo;
each R 1 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 3 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 2 is —(C 1 -C 6 alkylene)- or —(C 2 -C 6 alkenylene)-;
R 5 is H, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
m is 3;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
13 . The method of any one of claims 10 to 12 , wherein each R 1 is H.
14 . The method of any one of claims 10 to 13 , wherein R 5 is H or methyl.
15 . The method of any one of claims 10 to 14 , wherein R 5 is methyl.
16 . The method of any one of claims 10 to 15 , wherein q is 0.
17 . The method of any one of claims 10 to 16 , wherein v is 1 and X is in the 5-position of the thiopheno group.
18 . The method of claim 12 , wherein the compound of Formula IIaa has the structure:
or a pharmaceutically acceptable salt thereof.
19 . The method of claim 12 , wherein the compound of Formula IIaa has the structure:
or a pharmaceutically acceptable salt thereof.
20 . A method for treating or preventing a neurodegenerative disease, comprising administering to a subject in need of treatment or prevention of the neurodegenerative disease an effective amount of a compound of Formula I
or a pharmaceutically acceptable salt thereof, wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 2 is
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
Z 1 is NH, O, or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
n is 1;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
21 . The method of claim 20 , wherein the compound of Formula I has the following Formula Ia
wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
Z 1 is NH, O, or CH 2 ;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
22 . The method of claim 21 , wherein the compound of Formula Ia has the following Formula Iaa
wherein:
X is halo;
each R 1 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 3 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 2 is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, or —(O—(C 2 -C 6 alkylene))-;
m is 3;
p is an integer from 1 to 5;
q is 0 or 1; and
v is an integer from 1 to 3.
23 . The method of any one of claims 20 to 22 , wherein each R 1 is H.
24 . The method of any one of claims 20 to 23 , wherein q is 0.
25 . The method of any one of claims 20 to 24 , wherein v is 1 and X is in the 5-position of the thiopheno group.
26 . The method of any one of claims 20 to 25 , wherein p is 1 and R 3 is in the 4-position of the phenyl group.
27 . The method of claim 22 , wherein the compound of Formula Iaa has the structure:
or a pharmaceutically acceptable salt thereof.
28 . The method of claim 22 , wherein the compound of Formula Iaa has the structure:
or a pharmaceutically acceptable salt thereof.
29 . The method of any one of claims 20 to 28 , wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, ALS, or MS.
30 . The method of any one of claims 20 to 29 , wherein the neurodegenerative disease is Alzheimer's disease.
31 . A method for treating or preventing a neurodegenerative disease, comprising administering to a subject in need of treatment or prevention of the neurodegenerative disease an effective amount of a compound of Formula II
or a pharmaceutically acceptable salt thereof, wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 4 is
R 5 is H, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 1 is NH, O, or CH 2 ;
Z 2 alkylene)- or —(C 2 -C 6 alkenylene)-;
m is 3;
n is 1;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
32 . The method of claim 31 , wherein the compound of Formula II has the following Formula IIa
wherein:
X is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 1 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
each R 3 is independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or cyano;
R 5 is H, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 1 is NH, O or CH 2 ;
Z 2 alkylene)- or —(C 2 -C 6 alkenylene)-;
m is 3;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
33 . The method of claim 32 , wherein the compound of Formula IIa has the following Formula IIaa
wherein:
X is halo;
each R 1 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
each R 3 is independently H, halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;
Z 2 is —(C 1 -C 6 alkylene)- or —(C 2 -C 6 alkenylene)-;
m is 3;
p is 5;
t is 4;
q is 0 or 1; and
v is an integer from 1 to 3.
34 . The method of any one of claims 31 to 33 , wherein each R 1 is H.
35 . The method of any one of claims 31 to 34 , wherein R 5 is H or methyl.
36 . The method of any one of claims 31 to 35 , wherein R 5 is methyl.
37 . The method of any one of claims 31 to 36 , wherein q is 0.
38 . The method of any one of claims 31 to 37 , wherein v is 1 and X is in the 5-position of the thiopheno group.
39 . The method of claim 33 , wherein the compound of Formula IIaa has the structure:
or a pharmaceutically acceptable salt thereof.
40 . The method of claim 33 , wherein the compound of Formula IIaa has the structure:
or a pharmaceutically acceptable salt thereof.
41 . The method of any one of claims 31 to 40 , wherein the neurodegenerative disease is Alzheimer's disease, Parkinson's disease, ALS, or MS.
42 . The method of any one of claims 31 to 41 , wherein the neurodegenerative disease is Alzheimer's disease.Join the waitlist — get patent alerts
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