US 12,459,945 B2
Use of caseinolytic protease P function as a biomarker of drug response to imipridone-like agents
Edwin Iwanowicz, Cary, NC (US)
Assigned to Madera Therapeutics, LLC, Cary, NC (US)
Filed by Madera Therapeutics, LLC, Cary, NC (US)
Filed on Aug. 27, 2021, as Appl. No. 17/459,960.
Application 17/459,960 is a continuation in part of application No. PCT/US2020/019944, filed on Feb. 26, 2020.
Claims priority of provisional application 62/975,088, filed on Feb. 11, 2020.
Claims priority of provisional application 62/931,043, filed on Nov. 5, 2019.
Claims priority of provisional application 62/901,142, filed on Sep. 16, 2019.
Claims priority of provisional application 62/885,055, filed on Aug. 9, 2019.
Claims priority of provisional application 62/871,694, filed on Jul. 8, 2019.
Claims priority of provisional application 62/840,254, filed on Apr. 29, 2019.
Claims priority of provisional application 62/825,667, filed on Mar. 28, 2019.
Claims priority of provisional application 62/819,204, filed on Mar. 15, 2019.
Claims priority of provisional application 62/811,432, filed on Feb. 27, 2019.
Prior Publication US 2022/0089596 A1, Mar. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/14 (2006.01); A61P 35/00 (2006.01); C07D 471/04 (2006.01)
CPC C07D 471/14 (2013.01) [A61P 35/00 (2018.01); C07D 471/04 (2013.01)] 9 Claims
 
1. A compound of the general Formula I:
Z1-Q   Formula I
or a pharmaceutically acceptable salt thereof, wherein:
Z1 is:

OG Complex Work Unit Chemistry
Z2 is:

OG Complex Work Unit Chemistry
Q is

OG Complex Work Unit Chemistry
Ar1 and Ar2 are independently selected from aryl, heteroaryl, thiophenyl and phenyl;
Ar1 may be optionally substituted with from 1 to 3 J groups;
Ar2 is substituted with from 1 to 3 JJ groups;
J is independently selected from halogen, —CN, (C1-C6) optionally substituted alkyl, (C3-C9) optionally substituted cycloalkyl, (C3-C9)cycloalkyl (C1-C6)alkyl, (C1-C6)haloalkyl, —CF3, —NH2, —NO2, —SH, —SR15, —OH, (C1-C6) optionally substituted alkoxy, —NR17R18, substituted (C3-C9)cycloalkyl (C1-C6)alkyl, (C3-C9)cycloalkyl (C2-C6)alkynyl, (C4-C8)cycloalkenyl, (C4-C8)cycloalkenyl (C1-C6)alkyl, aryl, heteroaryl, heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —C(O)OH, —C(O)OR15, —OC(O)OR15, (C2-C6)alkynyl, (C2-C8)alkenyl, (C1-C6)haloalkyoxy, —S(O)2OR15, —SO2NR17R18, —S(O)2R15, —NR15S(O)2R16, —C(O)NR17R18, —C(O)R15, and —NR15C(O)R16;
JJ is independently selected from halogen, —CN, (C1-C6)haloalkyl, (C1-C6) optionally substituted alkyl, —CF3, —NH2, —NO2, —SH, —SR15, —OH, (C1-C6) optionally substituted alkoxy, —NR17R18, heteroaryl, —C(O)OH, —C(O)OR15, —OC(O)OR15, (C2-C6)alkynyl, (C2-C8)alkenyl, (C1-C6)haloalkyoxy, —S(O)2OR15, —SO2NR17R18, —S(O)2R15, —NR15S(O)2R16, —C(O)NR17R18, —C(O)R15, and —NR15C(O)R16;
R1, R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen, halogen, —OH and (C1-C3) optionally substituted alkyl;
R5 and R6 may be taken together to form ═O;
R7 and R8 may be taken together to form ═O;
R14 is independently selected from hydrogen, halogen, (C1-C6) optionally substituted alkyl, (C3-C6)cycloalkyl, (C1-C6)haloalkyl, (C2-C6) optionally substituted alkenyl, (C2-C6) optionally substituted alkynyl, —CN, —S(O)2R15, —NR17R18, —S(O)2R15, —C(NH)NH2, —C(O)R15, and —C(O)OR15;
R15, R16, R17, and R18 are independently selected from hydrogen and (C1-C6) optionally substituted alkyl;
R17 and R18 together with nitrogen to which they are attached may form a ring of 3 to 6 atoms; and
W4 is independently selected from the group consisting of ═C (R14)- and nitrogen.