Estrogen receptor modulators

Patent metadata

Field	Value
Publication number	US-10400006-B2
Application number	US-201515531245-A
Country	US
Kind code	B2
Filing date	Nov 20, 2015
Priority date	Nov 26, 2014
Publication date	Sep 3, 2019
Grant date	Sep 3, 2019

Abstract

Described herein, inter alia, are compositions and methods for treating or preventing hyperproliferative disorders, including cancer.

First claim

What is claimed is:

1. A compound having the formula:

wherein
R 1 is independently a hydrogen, halogen, —NR 2 R 3 , —CX a 3 , —CN, —SO 2 Cl, —SO n1 R 10 , —SO v1 NR 2 R 3 , —NHNR 2 R 3 , —ONR 2 R 3 , —NHC═(O)NHNR 2 R 3 , —NHC═(O)NR 2 R 3 , —N(O) m1 , —C(O)R 9 , —C(O)—OR 9 , —C(O)NR 2 R 3 , —OR 10 , —NR 2 SO 2 R 10 , —NR 2 C═(O)R 9 , —NR 2 C(O)—OR 9 , —NR 2 OR 9 , —OCX a 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
L is independently a bond, —NR 4 —, —NR 4 C(O)—, —C(O)NR 4 —, —O—, —S—, —C(O)—, —S(O)—, —S(O) 2 —, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene; or a substituted or unsubstituted spirocyclic linker;
R 2 is independently a hydrogen, halogen, —CX b 3 , —CN, —SO 2 Cl, —SO n2 R 14 , —SO v2 NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 , —NHC═(O)NR 11 R 12 , —N(O) m2 , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , —NR 11 SO 2 R 14 , —NR 11 C═(O)R 13 , —NR 11 C(O)—OR 13 , —NR 11 OR 13 , —OCX b 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 3 is independently a hydrogen, halogen, —CX c 3 , —CN, —SO 2 Cl, —SO n3 R 18 , —SO v3 NR 15 R 16 , —NHNH 2 , —ONR 15 R 16 , —NHC═(O)NHNH 2 , —NHC═(O)NR 15 R 16 , —N(O) m3 , —NR 15 R 16 , —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , R 18 , —NR 15 SO 2 R 18 , —NR 15 C═(O)R 17 , —NR 15 C(O)—OR 17 , —NR 15 OR 17 , —OCX c 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 2 and R 3 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 4 is independently a hydrogen, halogen, —CX d 3 , —CN, —SO 2 Cl, —SO n4 R 22 , —SO v4 NR 19 R 20 , —NHNH 2 , —ONR 19 R 20 , —NHC═(O)NHNH 2 , —NHC═(O)NR 19 R 20 , —N(O) m4 , —NR 19 R 20 , —C(O)R 21 , —C(O)—OR 21 , —C(O)NR 19 R 20 , —OR 22 , —NR 19 SO 2 R 22 , —NR 19 C═(O)R 21 , —NR 19 C(O)—OR 21 , —NR 19 OR 21 , —OCX d 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , and R 22 are independently hydrogen, halogen, —CX 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 Cl, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 3 , —OCHX 2 , —CF 3 , —OCF 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 11 and R 12 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 15 and R 16 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; R 19 and R 20 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
n is an integer from 0 to 5;
m1, m2, m3, m4, v1, v2, v3, and v4 are independently 1 or 2;
n1, n2, n3, and n4 are independently an integer from 0 to 4;
X, X a , X b , X c and X d are independently —Cl, —Br, —I, or −F.

2. The compound of claim 1 , having the formula:

wherein
R 5 is independently a hydrogen, halogen, —CX e 3 , —CN, —SO 2 Cl, —SO n5 R 26 , —SO v5 NR 23 R 24 , —NHNH 2 , —ONR 23 R 24 , —NHC═(O)NHNH 2 , —NHC═(O)NR 23 R 24 , —N(O) m5 , —NR 23 R 24 , —C(O)R 25 , —C(O)—OR 25 , —C(O)NR 23 R 24 , —OR 26 , —NR 23 SO 2 R 26 , —NR 23 C═(O)R 25 , —NR 23 C(O)—OR 25 , —NR 23 OR 25 , —OCX e 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 23 , R 24 , R 25 , and R 26 are independently hydrogen, halogen, —CX 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 Cl, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 3 , —OCHX 2 , —CF 3 , —OCF 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 23 and R 24 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
m5 and v5 are independently 1 or 2;
n5 is independently an integer from 0 to 4;
X e is independently —Cl, —Br, —I, or −F.

3. The compound of claim 1 , having the formula:

4. The compound of claim 1 , having the formula:

5. The compound of claim 1 , having the formula:

wherein
R 5 is independently a hydrogen, halogen, —CX e 3 , —CN, —SO 2 Cl, —SO n5 R 26 , —SO v5 NR 23 R 24 , —NHNH 2 , —ONR 23 R 24 , —NHC═(O)NHNH 2 , —NHC═(O)NR 23 R 24 , —N(O) m5 , —NR 23 R 24 , —C(O)R 25 , —C(O)—OR 25 , —C(O)NR 23 R 24 , —OR 26 , —NR 23 SO 2 R 26 , —NR 23 C═(O)R 25 , —NR 23 C(O)OR 25 , —NR 23 OR 25 , —OCX e 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 23 , R 24 , R 25 , and R 26 are independently hydrogen, halogen, —CX 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 2 Cl, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O) NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)—OH, —NHOH, —OCX 3 , —OCHX 2 , —CF 3 , —OCF 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 23 and R 24 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstitu

Assignees

• Univ California

Inventors

• Pietras Richard J
• Jung Michael E
• Marquez-Garban Diana C
• Deng Gang

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P5/32

  Antioestrogens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P15/08

  for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis · CPC title

• A61P13/08

  of the prostate · CPC title