Heterobifunctional compounds and methods of treating disease
The invention provides heterobifunctional compounds, pharmaceutical compositions, and their use treating disease, such as cancer.
1 . A compound represented by Formula It or Iv, or a pharmaceutically acceptable salt thereof:
wherein
L is one of the following:
(i)-(7-11 membered spirocyclic or fused bicyclic saturated heterocyclic ring containing 1, 2, or 3 heteroatoms independently selected from nitrogen and oxygen)-O-***, wherein *** is the point of attachment to the phenylene group in said formula;
(ii) a 7-11 membered spirocyclic or fused bicyclic saturated heterocyclic ring containing 1, 2, or 3 heteroatoms independently selected from nitrogen and oxygen; or
(iii)-(7-11 membered spirocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms selected from nitrogen)-(C 2-4 alkynylene)-***, wherein *** is the point of attachment to the phenylene group in said formula; and
t is 0 or 1.
2 . The compound of claim 1 , wherein the compound is a compound of Formula It.
3 . The compound of claim 2 , wherein tis 0 .
4 . The compound of claim 3 , wherein L is a -(7-11 membered spirocyclic or fused bicyclic saturated heterocyclic ring containing 1, 2, or 3 heteroatoms independently selected from nitrogen and oxygen)-O-***, wherein * is the point of attachment to the phenylene group in said formula.
5 . The compound of claim 3 , wherein L is -(7-11 membered spirocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms selected from nitrogen)-(C 2-4 alkynylene)-***, wherein *** is the point of attachment to the phenylene group in said formula.
6 . The compound of claim 1 , wherein the compound is represented by Formula Iab or a pharmaceutically acceptable salt thereof:
7 . The compound of claim 1 , wherein the compound is represented by Formula Iac or a pharmaceutically acceptable salt thereof:
8 . The compound of claim 1 , wherein the compound is
9 . A compound represented by:
or a pharmaceutically acceptable salt thereof.
10 . The compound of claim 9 , wherein the compound is
11 . A compound selected from the following or a pharmaceutically acceptable salt thereof:
12 . The compound of claim 11 , wherein the compound is
13 . The compound of claim 11 , wherein the compound is
14 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
15 . A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier.
16 . A pharmaceutical composition comprising a compound of claim 10 and a pharmaceutically acceptable carrier.
17 . A pharmaceutical composition comprising a compound of claim 13 and a pharmaceutically acceptable carrier.
18 . A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat the cancer, wherein the cancer is prostate cancer or breast cancer.
19 . The method of claim 18 , wherein the compound is a compound of claim 10 .
20 . A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 13 to treat the cancer, wherein the cancer is prostate cancer, or breast cancer.
21 . A method of treating prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat the prostate cancer.
22 . A method of treating prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 10 to treat the prostate cancer.
23 . The method of claim 22 , wherein the patient is a human.
24 . A method of treating prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 13 to treat the prostate cancer.
25 . A method of treating castrate resistant metastatic prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 to treat the castrate resistant metastatic prostate cancer.
26 . A method of treating castrate resistant metastatic prostate cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 10 to treat the castrate resistant metastatic prostate cancer.
27 . The method of claim 26 , wherein the patient is a human.
28 . A method of causing death of a cancer cell, comprising contacting a cancer cell with an effective amount of a compound of claim 1 to cause death of the cancer cell, wherein the cancer cell is selected from a prostate cancer, or breast cancer cell.
29 . A method of causing death of a prostate cancer cell, comprising contacting a prostate cancer cell with an effective amount of a compound of claim 1 to cause death of the prostate cancer cell.
30 . A method of causing death of a prostate cancer cell, comprising contacting a prostate cancer cell with an effective amount of a compound of claim 10 to cause death of the prostate cancer cell.