US 11,723,908 B2
Quinazoline derivatives as antitumor agents
Ding Zhou, Shanghai (CN); and Ziqiang Cheng, Shanghai (CN)
Assigned to SUZHOU ZANRONG PHARMA LIMITED, Suzhou (CN)
Appl. No. 17/51,176
Filed by SUZHOU ZANRONG PHARMA LIMITED, Suzhou (CN)
PCT Filed Sep. 17, 2019, PCT No. PCT/CN2019/106233
§ 371(c)(1), (2) Date Oct. 28, 2020,
PCT Pub. No. WO2020/057511, PCT Pub. Date Mar. 26, 2020.
Claims priority of application No. PCT/CN2018/106098 (WO), filed on Sep. 18, 2018; and application No. PCT/CN2019/091078 (WO), filed on Jun. 13, 2019.
Prior Publication US 2021/0386742 A1, Dec. 16, 2021
Int. Cl. A61K 31/519 (2006.01); A61P 35/00 (2006.01); A61K 31/5377 (2006.01); A61K 31/7068 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01); A61K 39/395 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 31/5377 (2013.01); A61K 31/7068 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07D 487/04 (2013.01); C07D 519/00 (2013.01)] 36 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
G is C(R5) or N;
A is CH or N;
B is CH or N;
X1, X2, X3, X4, X5, X6, and X7 are each independently CH or N, with the provision that X6 is N and X7 is CH, or Xe is CH and X7 is N;
E is O, NH, or S;
L is selected from the group consisting of O, S and N(R6);
R1 is each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, N(R7)(R8), and O(R9), wherein said cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, carboxy, carbamoyl, acyl, alkyl, alkenyl, alkynyl, and haloalkyl;
R2 is selected from the group consisting of alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, wherein said alkyl, cycloalkyl, and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, cyano, nitro, hydroxyl, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, haloalkyl, saturated or partially unsaturated cycloalkyl, and N(R10)(R11);
R6 is hydrogen or alkyl; or
when L is N(R6), R2 and R5 together with the nitrogen atom to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O and S, wherein said 3 to 10 membered heterocyclyl ring is optionally substituted with one or more groups independently selected from the group consisting of halogen, cyano, nitro, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, haloalkyl, saturated and partially unsaturated cycloalkyl, and N(R10)(R11);
R3 and R4 are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl and alkoxyl;
R5 is selected from the group consisting of hydrogen, halogen and cyano;
R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, acyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, alkylamino, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl optionally substituted by alkyl, aryl, and heteroaryl; or
R7 and R8 together with the atom to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR12, wherein said heterocyclyl ring is optionally substituted with one or more groups independently selected from the group consisting of oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, haloalkyl, haloalkoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
R9 is selected from the group consisting of alkyl, alkenyl, alkynyl, acyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, wherein said alkyl, alkenyl, alkynyl, acyl, cycloalkyl, heterocyclyl are optionally substituted by one or more groups independently selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, alkoxyl, acyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, haloalkyl, haloalkoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, and heteroaryl; or
R10 and R11 together with the atom to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR12, wherein said heterocyclyl ring is optionally substituted with one or more groups independently selected from the group consisting of oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, haloalkyl, haloalkoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
R12 is selected from the group consisting of hydrogen, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
n is 0, 1 or 2.