US 11,667,621 B2
Antiestrogen compounds
Abhishek Sharma, Edison, NJ (US); Sarat Chandarlapaty, New York, NY (US); Lucia Wang, Jersey City, NJ (US); Shengjia Lin, Secaucus, NJ (US); Weiyi Toy, New York, NY (US); and John Katzenellenbogen, Urbana, IL (US)
Assigned to STEVENS INSTITUTE OF TECHNOLOGY, Hoboken, NJ (US); THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS, Urbana, IL (US); and MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US)
Appl. No. 17/251,771
Filed by STEVENS INSTITUTE OF TECHNOLOGY, Hoboken, NJ (US); MEMORIAL SLOAN-KETTERING CANCER CENTER, New York, NY (US); and THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS, Urbana, IL (US)
PCT Filed Jun. 11, 2019, PCT No. PCT/US2019/036526
§ 371(c)(1), (2) Date Dec. 11, 2020,
PCT Pub. No. WO2019/241231, PCT Pub. Date Dec. 19, 2019.
Claims priority of provisional application 62/683,383, filed on Jun. 11, 2018.
Prior Publication US 2021/0130320 A1, May 6, 2021
Int. Cl. C07D 401/04 (2006.01); C07C 233/20 (2006.01); C07C 233/21 (2006.01); C07D 209/12 (2006.01); C07D 333/64 (2006.01); C07D 409/14 (2006.01)
CPC C07D 401/04 (2013.01) [C07C 233/20 (2013.01); C07C 233/21 (2013.01); C07D 209/12 (2013.01); C07D 333/64 (2013.01); C07D 409/14 (2013.01)] 24 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
wherein:
TL is chosen from:

OG Complex Work Unit Chemistry
L is selected from divalent (C3-C7)hydrocarbyl, (C2-C10)oxaalkyl, and (C2-C10)azaalkyl;
DG is selected from:

OG Complex Work Unit Chemistry
R20 and R21 are independently a (C1-C12)hydrocarbyl, or, taken together along with the carbon to which they are attached, R20 and R21 optionally combine to form a (C3-C12)carbocyclyl;
substructure

OG Complex Work Unit Chemistry
 as drawn above, represents either

OG Complex Work Unit Chemistry
wherein:
J is selected from: S, O, and NR17, and, G is C when

OG Complex Work Unit Chemistry
 and
J is C—R16 and G is N
when

OG Complex Work Unit Chemistry
Y is —O— or —CH2—;

OG Complex Work Unit Chemistry
represents either a single or a double bond connecting a carbon atom to G′;
G′ is CH or N when

OG Complex Work Unit Chemistry
 is a single bond, or, G′ is C when

OG Complex Work Unit Chemistry
 is a double bond;
R1 is selected from H and (C1-C3)alkyl;
R2 is

OG Complex Work Unit Chemistry
 or optionally substituted (C1-C15)hydrocarbyl, wherein the optional substituents for (C1-C15)hydrocarbyl are selected from halo and (C1-C3)perfluoroalkyl;
R5 and R6 are selected from H and (C1-C3)alkyl;
R7 is selected from any of the sidechains present in naturally-occurring α-amino acids;
R8 is H or (C1-C3)alkyl;
R9 is chosen from H, (C1-C3)alkyl, or —C(═O)—O—(C1-C6)alkyl;
R13 and R14 are selected from H and (C1-C3)alkyl;
R15 is

OG Complex Work Unit Chemistry
 and
R16 and R17 are selected from: H and (C1-C6)alkyl;
with the proviso that the compound is not:

OG Complex Work Unit Chemistry
 
24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound according to claim 1.