US 11,866,433 B2
Diarylthiohydantoin compound as androgen receptor antagonist
Chunli Shen, Jiangsu (CN); Chengde Wu, Jiangsu (CN); Shenglin Chen, Jiangsu (CN); Shuhui Chen, Jiangsu (CN); Xiquan Zhang, Jiangsu (CN); and Xin Tian, Jiangsu (CN)
Assigned to CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Jiangsu (CN)
Filed by CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD., Jiangsu (CN)
Filed on Oct. 15, 2021, as Appl. No. 17/503,141.
Application 17/503,141 is a continuation of application No. 16/637,236, granted, now 11,332,465, previously published as PCT/CN2018/099161, filed on Aug. 7, 2018.
Claims priority of application No. 201710667860.4 (CN), filed on Aug. 7, 2017; and application No. 201810333652.5 (CN), filed on Apr. 13, 2018.
Prior Publication US 2023/0035184 A1, Feb. 2, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 401/14 (2006.01); C07D 403/10 (2006.01); C07D 405/14 (2006.01); C07D 413/10 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 401/14 (2013.01); C07D 403/10 (2013.01); C07D 405/14 (2013.01); C07D 413/10 (2013.01)] 20 Claims
 
1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein,
T is selected from the group consisting of CH and N;
R1 is selected from the group consisting of hydrogen, halogen, C1-12 alkyl, and halogen-substituted C1-12 alkyl;
the ring A is selected from the group consisting of

OG Complex Work Unit Chemistry
R2 and R3 are each independently selected from C1-12 alkyl, or R2 and R3 are connected to each other to form a 3- to 6-membered cycloalkyl together;
X1, X2, X3, and X4 are each independently selected from the group consisting of CH and N, and at least one of them is N;
n is 0, 1, 2, or 3;
each R4 is independently selected from C1-12 alkyl;
the ring B is

OG Complex Work Unit Chemistry
R5 is selected from the group consisting of hydrogen, C1-12 alkyl, C1-12 alkoxy, and halogen;
R6 is selected from C1-12 alkylaminocarbonyl;
one of X5, X6, and X7 is N(—Ra), and the others are CH or N;
Ra is selected from 5-membered heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted by halogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, C1-4 alkoxy, hydroxyl, or amino;
X8, X9, X10, and X11 are each independently selected from the group consisting of CH, C(═O), N, and NH, and three of X8, X9, X10, and X11 are C(═O), N, and NH, respectively;
Rb is selected from C1-12 alkyl, wherein the C1-12 alkyl is optionally substituted by halogen;
Y8, Y9, Y10, and Y11 are each independently selected from the group consisting of CH and N, and at least two of Y8, Y9, Y10, and Y11 are N;
m is 0, 1, or 2;
each R7 is independently selected from the group consisting of halogen, C1-12 alkyl, hydroxyl, C1-12 alkoxy, amino, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, and C1-12 alkylamino, wherein the C1-12 alkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, or C1-12 alkylamino is optionally substituted by halogen, and wherein the hydroxyl is substituted by: —C1-12 alkyl-OH, —C1-12 alkyl-(3- to 10-membered heterocycloalkyl), —C1-12 alkyl-S(═O)2Rc, —C1-12 alkyl-NRdRe, —C1-12 alkyl-C(═O)NRfRg, —C1-12 alkyl-(3- to 10-membered cycloalkyl) optionally substituted by halogen or hydroxyl, or 3- to 10-membered heterocycloalkyl optionally substituted by halogen or hydroxyl;
Z8, Z9, Z10, and Z11 are each independently selected from the group consisting of CH, C(═O), and N;
j is 0, 1, or 2;
each R9 is independently selected from the group consisting of halogen, C1-12 alkyl, C1-12 alkoxy, and hydroxyl, wherein the C1-12 alkyl is optionally substituted by halogen or C1-12 alkoxy, and wherein the hydroxyl is optionally substituted by: —C1-12 alkyl-O—C1-12 alkyl, —C1-12 alkyl-OH, or —C1-12 alkyl-C(═O)NRfRg;
Rc, Rd, Re, Rf, and Rg are each independently selected from the group consisting of hydrogen, C1-12 alkyl, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl, C1-12 alkoxy, hydroxyl, and amino;
two of X12, X13, X14, X15, and X16 are NH and C(═O), respectively, and the others are CH2, O, or S;
q is 0, 1, 2, 3, or 4; and
each R8 is independently selected from the group consisting of halogen, C1-12 alkyl, hydroxyl, amino, 3- to 10-membered cycloalkyl, C1-12 alkoxy, 3- to 10-membered heterocycloalkyl, and C1-12 alkylamino;
provided that: when the ring A is selected from

OG Complex Work Unit Chemistry
the ring B is not

OG Complex Work Unit Chemistry
and when R7 is selected from C1-12 alkoxy, R7 substitutes the hydrogen on Y9, Y10, or Y11.