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US 12,760,060 B2Granted
Androgen receptor modulators
AssigneeTrustees of Dartmouth College
InventorGlenn C. Micalizio
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to polycyclic (e.g., tetracyclic) androgen receptor (AR) modulators, synthetic methods for preparing such AR modulators, and methods of using such AR modulators to treat an androgen-dependent condition, such as prostate cancer or BPH. Exemplary compounds have quaternary centers at C10 and C13 and a fused cyclic ring comprising C14 and C15.
Claims18
A compound or pharmaceutically acceptable salt thereof, wherein the compound has a structure corresponding to Formula (VII-A) or Formula (VII-D):
- wherein
- n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;
- each RA is independently selected from the group consisting of hydrogen, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, halogen, —ORAX, —SRAY, —S(O)2NRZ1RZ2, —S(O)2RZ1, —S(O)RZ1, —NRZ1RZ2, —N(RZ1)C(O)RZ2, —N(RZ1)S(O)2RZ2, C6-10-aryl, and 5- to 10-membered heteroaryl,
- wherein RAX is hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, —C(O)—C6-10-aryl, —C(O)-heteroaryl, —C(O)—O—C1-10-alkyl, —C(O)—O—C6-10-aryl, —C(O)—O-heteroaryl, —C(O)—NRZ1RZ2, —S(O)2NRZ1RZ2, —S(O)2RZ1, C6-10-aryl, or 5- to 10-membered heteroaryl,
- wherein RAY is hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, —C(O)—C6-10-aryl, —C(O)-heteroaryl, C6-10-aryl, or 5- to 10-membered heteroaryl,
- wherein each of RZ1 and RZ2 are independently hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —(CH2)m—C6-10-aryl, —(CH2)m-5- to 10-membered heteroaryl, hydroxy, or C1-6-alkoxy:
- R3 is oxo or —OR3X, wherein R3X is hydrogen or C1-6-alkyl;
- R10 is selected from the group consisting of C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —(CH2)m—C6-10-aryl, and —(CH2)m-5- to 10-membered heteroaryl;
- R13 is selected from the group consisting of C1-C14-alkyl, C1-C14-haloalkyl, C2-C14-alkenyl, C2-C14-haloalkenyl, C2-C14-alkynyl, C2-C14-haloalkynyl, each of which is optionally interrupted by one or more of —O—, —NRZ—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NRZ—, —NRZC(O)—, —S(O)y—, —S(O)yNRZ—, —NRZS(O)y—, —C(S)NRZ—, —NRZC(S)—, —(CH2)m—C6-10-aryl, and —(CH2)m-5- to 10-membered heteroaryl;
- R16 is —ORD and RD is selected from the group consisting of hydrogen, C1-10-alkyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, and —C(O)—C1-10-haloalkyl;
- and
- each - - - independently represents a single bond or a double bond;
- m is an integer selected from the group consisting of 0, 1, 2, and 3;
- wherein any C6-10-aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more halogen, hydroxy, C1-6-alkyl, C1-6-haloalkyl, or C1-6-alkoxy.
11 more elements
A compound or pharmaceutically acceptable salt thereof, wherein the compound has a structure corresponding to:
A compound or pharmaceutically acceptable salt thereof, wherein the compound has a structure corresponding to Formula (VII-A):
- wherein
- n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;
- each RA is independently selected from the group consisting of hydrogen, C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, halogen, —ORAX, —SRAY, —S(O)2NRZ1RZ2, —S(O)2RZ1, —S(O)RZ1, —NRZ1RZ2, —N(RZ1)C(O)RZ2, —N(RZ1)S(O)2RZ2, C6-10-aryl, and 5- to 10-membered heteroaryl,
- wherein RAX is hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, —C(O)—C6-10-aryl, —C(O)-heteroaryl, —C(O)—O—C1-10-alkyl, —C(O)—O—C6-10-aryl, —C(O)—O-heteroaryl, —C(O)—NRZ1RZ2, —S(O)2NRZ1RZ2, —S(O)2RZ1, C6-10-aryl, or 5- to 10-membered heteroaryl,
- wherein RAY is hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, —C(O)—C6-10-aryl, —C(O)-heteroaryl, C6-10-aryl, or 5- to 10-membered heteroaryl,
- wherein each of RZ1 and RZ2 are independently hydrogen, C1-6-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —(CH2)m—C6-10-aryl, —(CH2)m-5- to 10-membered heteroaryl, hydroxy, or C1-6-alkoxy;
- R3 is oxygen or —OR3X, wherein R3X is hydrogen or C1-6-alkyl;
- R10 is selected from the group consisting of C1-10-alkyl, C2-10-alkenyl, C2-10-alkynyl, C1-10-haloalkyl, —(CH2)m—C6-10-aryl, and —(CH2)m-5- to 10-membered heteroaryl;
- R13 is selected from the group consisting of C1-C14-alkyl, C1-C14-haloalkyl, C2-C14-alkenyl, C2-C14-haloalkenyl, C2-C14-alkynyl, C2-C14-haloalkynyl, each of which is optionally interrupted by one or more of —O—, —NRZ—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NRZ—, —NR2C(O)—, —S(O)y—, —S(O)yNRZ—, —NRZS(O)y—, —C(S)NRZ—, —NR2C(S)—, —(CH2)m—C6-10-aryl, and —(CH2)m-5- to 10-membered heteroaryl;
- R16 is —ORD and RD is selected from the group consisting of hydrogen, C1-10-alkyl, C1-10-haloalkyl, —C(O)—C1-10-alkyl, and —C(O)—C1-10-haloalkyl;
- and
- each independently represents a single bond or a double bond;
- m is an integer selected from the group consisting of 0, 1, 2, and 3;
- wherein any C6-10-aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more halogen, hydroxy, C1-6-alkyl, C1-6-haloalkyl, or C1-6-alkoxy.
11 more elements
Dependencies are inferred from the claim text.