US 12,187,742 B2
Dual ATM and DNA-PK inhibitors for use in anti-tumor therapy
Jianmin Fu, Beijing (CN); Yaode Wang, Beijing (CN); Yue Sun, Beijing (CN); Guosheng Wu, Beijing (CN); Aijun Lu, Beijing (CN); Shuang Zhang, Beijing (CN); Robert Goodnow, Concord, MA (US); Tona Gilmer, Rougemont, NC (US); Michael Kastan, Chapel Hill, NC (US); and David Kirsch, Durham, NC (US)
Assigned to XRAD Therapeutics, Inc., Orlando, FL (US)
Filed by XRAD Therapeutics, Inc., New York, NY (US)
Filed on Oct. 19, 2020, as Appl. No. 17/074,425.
Application 17/074,425 is a continuation of application No. PCT/CN2019/083104, filed on Apr. 17, 2019.
Claims priority of provisional application 62/665,296, filed on May 1, 2018.
Claims priority of application No. 201810359447.6 (CN), filed on Apr. 20, 2018.
Prior Publication US 2022/0315606 A1, Oct. 6, 2022
Int. Cl. C07D 519/00 (2006.01); C07D 471/04 (2006.01); C07D 491/20 (2006.01)
CPC C07D 519/00 (2013.01) [C07D 471/04 (2013.01); C07D 491/20 (2013.01)] 25 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, enantiomer, tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt thereof;
wherein
m is 0, 1, 2, 3, or 4;
n is 1, 2, 3, or 4;
p and q are each independently 0, 1, 2, or 3;

OG Complex Work Unit Chemistry
is a fused cyclyl, a fused heterocyclyl, a fused aryl or a fused heteroaryl;

OG Complex Work Unit Chemistry
is a mono-cyclic or bi-cyclic ring, a mono-heterocyclic or bi-heterocyclic ring, an aryl or heteroaryl;
Y is —(C(R1a)H—, —C(O)—, —O—, —N(R5)—, —S(O)r— (where r is 0, 1 or 2), —S(O)t(NR5)— (where t is 1 or 2), —P(O)(R3)—O—, —O—P(O)(R3)—, P(O)(R3)—N(R5)—, —N(R5)—P(O)(R3)—, —CHF—, —CF2—, —OC(O)—, —C(O)O—, —C(O)N(R5)— or —N(R5)C(O)—,
M is O, S, or NR5;
U is hydrogen or alkyl;
V, W, and X are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted haloalkyl, optionally substituted haloalkenyl, optionally substituted haloalkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —R6—CN, —R6—NO2, —R6—OR5, —R6—N(R4)R5, —O—R6—N(R4)R5, —N═C(R4)R5, —S(O)rR4, —OS(O)2CF3, —R6—C(O)R4, —C(S)R4, —R6—C(O)OR4, —C(S)OR4, —R6—C(O)N(R4)R5, —C(S)N(R4)R5, —N(R5)C(O)R4, —N(R5)C(S)R4, —N(R5)C(O)OR4, —N(R5)C(S)OR4, —N(R5)C(O)N(R4)R5, —N(R5)C(S)N(R4)R5, —N(R5)S(O)tR4, —N(R5)S(O)tN(R4)R5, —R6—S(O)tN(R4)R5, —O—P(O)(R4)R5, —O—P(O)R4O(R4), —O—P(O)R4N(R4)R5, —N(R5)—P(O)(R4)R5, —N(R5)—P(O)R4O(R4), —N(R5)—P(O)R4N(R4)R5, —N(R5)—P(O)O(R4)N(R4)R5, —N(R5)—P(O)N(R4)R5N(R4)R5, —N(R5)C(═NR5)R4, —N(R5)C(═NR5)N(R4)R5, and —N(R5)C(═N—CN)N(R4)R5, wherein each r is independently 0, 1, or 2 and each t is independently 1 or 2;
or two adjacent V, or W, or X together with the carbon ring atoms to which they are directly attached, form a fused ring selected from optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl;
Z is C(R1a) or N;
R1a is a hydrogen, optionally substituted alkyl, halo, CN, NO2, or —OR5;
R3 is an optionally substituted alkyl, —OR5, or —N(R4)R5;
each R4 and R5 is independently selected from group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted haloalkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl;
or when R4 and R5 are each attached to the same nitrogen atom, R4 and R5, together with the nitrogen atom to which they are attached, form a optionally substituted heterocyclyl or optionally substituted heteroaryl; and
each R6 is a direct bond or a linear or branched optionally substituted alkylene chain, a linear or branched optionally substituted alkenylene chain, a linear or branched optionally substituted alkynylene chain, or optionally substituted heterocyclylene.