DIGLYCIDIC ETHER DERIVATIVE THERAPEUTICS AND METHODS FOR THEIR USE
This invention provides compound having a structure of Formula I or Formula II. Uses of such compounds for treatment of various indications, including prostrate cancer as well as methods of treatment involving such compounds are also provided.
1 .- 89 . (canceled)
90 . A compound having a structure of Formula II
wherein
each J and J′ is independently H;
each L and L′ is independently O;
each Q and Q′ is O;
each Z and Z′ is independently CH, CF, CCl, CBr, or CI;
R 1 and R 2 are each independently H, or a branched or unbranched, substituted or unsubstituted C 1 -C 10 alkyl;
X is CH 2 O (isopropyl), CH 2 OC 2 H 4 OC 4 H 9 , CH 2 I, CH 2 Br, or CH 2 F;
X′ is H, CH 3 , CH 2 F, CH 2 Cl, CH 2 F, CH 2 OJ′″, or CH 2 OG;
J′″ is independently H;
G is a branched or unbranched, non-aromatic cyclic, substituted or unsubstituted, saturated C 1 -C 10 alkyl;
wherein the optional substituent is selected from the group consisting of: oxo, COOH, R, OH, OR, F, Cl, Br, or I, wherein R is an unsubstituted C 1 -C 10 alkyl; and
wherein X′ is no —CH 2 O(CH 2 ) 2 CH 3 , or —CH 2 O(CH 2 ) 3 CH 3 ; and
wherein X is not —CH 2 O(CH 2 ) 2 —O—(CH 2 ) 3 CH 3 when X′ is CH 2 OH.
91 . The compound of claim 90 , wherein each L and L′, when present, is O.
92 . The compound of claim 90 , wherein each Z and Z′ is CH.
93 . The compound of claim 90 , wherein each R 1 and R 2 is CH 3 .
94 . The compound of claim 90 , wherein X is CH 2 F, or CH 2 O (isopropyl).
95 . The compound of claim 90 , wherein X′ is CH 2 F, CH 2 Cl or CH 2 OG.
96 . The compound of claim 90 , wherein X′ is CH 2 F, CH 2 Cl, CH 2 OCH 3 or CH 2 O (isopropyl).
97 . The compound of claim 90 , wherein X′ is CH 2 OH.
98 . A pharmaceutical composition comprising a compound according to claim 90 and a pharmaceutically acceptable excipient.
99 . A method for modulating androgen receptor (AR) activity for treatment of at least one indication selected from the group consisting of: prostate cancer, breast cancer, ovarian cancer, endometrial cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty, and age-related macular degeneration;
wherein, the method comprises administering to a subject in need thereof, a compound according to claim 90 .
100 . The method of claim 99 , wherein the modulating AR activity is transactivation of the AR N-terminal domain (NTD).
101 . The method of claim 99 , wherein the indication is prostate cancer.
102 . The method of claim 101 , wherein the prostate cancer is castration-resistant prostate cancer.
103 . A method for modulating androgen receptor (AR) activity for treatment of at least one indication selected from the group consisting of: prostate cancer, breast cancer, ovarian cancer, endometrial cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty, and age-related macular degeneration;
wherein, the method comprises administering to a subject in need thereof, a compound having a structure of Formula II′:
wherein
each L and L′ is O;
X is CH 2 F, CH 2 I, CF 2 Br, CH 2 OH, CH 2 OCH 3 , or CH 2 O (isopropyl), or CH 2 OC 2 H 4 OC 4 H 9 ;
X′ is CH 2 Cl, CH 2 F, CH 2 I, CH 2 Br, CH 2 OCH 3 , CH 2 O (isopropyl), or CH 2 OC 2 H 4 OC 4 H 9 ;
each Q and Q′ is O;
each Z and Z′ is independently CH, CF, CCl, CBr, or CI;
R 1 and R 2 are each independently H, or a branched or unbranched, substituted or unsubstituted C 1 -C 10 alkyl;
J and J′ are each independently H; and
wherein the optional substituent is selected from the group consisting of: oxo, COOH, R, OH, OR, F, Cl, Br, or I, wherein R is an unsubstituted C 1 -C 10 alkyl.
104 . The method of claim 103 , wherein X is CH 2 OH.
105 . The method of claim 103 , wherein X is CH 2 F, CH 2 I, CH 2 Br, or CH 2 OCH 3 .
106 . The method of claim 103 , wherein X′ is CH 2 Cl.
107 . The method of claim 103 , wherein X′ is CH 2 Cl, CH 2 F, CH 2 I, CH 2 Br, or CH 2 OCH 3 .
108 . The method of claim 103 , wherein Z and Z′ is CH.
109 . The method of claim 103 , wherein R 1 and R 2 is CH 3 .
110 . The method of claim 103 , wherein the modulating AR activity is transactivation of the AR N-terminal domain (NTD).
111 . The method of claim 103 , wherein the indication is prostate cancer.
112 . The method of claim 111 , wherein the prostate cancer is castration-resistant prostate cancer.