	US 12,227,512 B2
	Benzimidazoles and methods of using same
Darrell Davis, Salt Lake City, UT (US); and Shuanghu Liu, Salt Lake City, UT (US)
Assigned to University of Utah Research Foundation, Salt Lake City, UT (US)
Filed by University of Utah Research Foundation, Salt Lake City, UT (US)
Filed on Nov. 10, 2023, as Appl. No. 18/388,765.
Application 18/388,765 is a division of application No. 17/732,447, filed on Apr. 28, 2022, abandoned.
Application 17/732,447 is a continuation of application No. 17/023,323, filed on Sep. 16, 2020, granted, now 11,339,173, issued on May 24, 2022.
Claims priority of provisional application 63/013,473, filed on Apr. 21, 2020.
Claims priority of provisional application 62/901,678, filed on Sep. 17, 2019.
Prior Publication US 2024/0116944 A1, Apr. 11, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 491/147 (2006.01); C07D 235/30 (2006.01); C07D 487/04 (2006.01); C07D 491/048 (2006.01); C07D 491/052 (2006.01); C07D 495/14 (2006.01)

CPC C07D 491/147 (2013.01) [C07D 235/30 (2013.01); C07D 487/04 (2013.01); C07D 491/048 (2013.01); C07D 491/052 (2013.01); C07D 495/14 (2013.01)]

12 Claims

1. A method for treating a disorder of uncontrolled cellular proliferation in a subject, the method comprising administering to the subject an effective amount of a compound having a structure represented by a formula selected from:

wherein

is a single or a double covalent bond;

wherein n is 0 or 1;

wherein Z, when present, is selected from N and CR¹⁰;

wherein R¹⁰, when present, is selected from hydrogen and halogen;

wherein R¹is selected from —(C1-C4 alkyl)OR¹¹, —(C1-C4 alkyl)NR^12aR^12b, —CO₂R¹³, and —C(O)NR^14aR^14b;

wherein each of R¹¹, R^12a, and R^12b, when present, is independently selected from hydrogen, C1-C4 alkyl, —C(═NH)NH₂, —CO₂(C1-C4 alkyl), —(C1-C4 alkyl)OR²⁰, —(C1-C4 alkyl)NR^21aR^21b, —(C1-C4 alkyl)Ar¹, and Ar¹;

wherein Ar¹, when present, is selected from aryl and heteroaryl and substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH₂, —OH, —NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;

wherein each of R¹³, R^14a, and R^14b, when present, is independently selected from hydrogen and C1-C4 alkyl;

wherein R², when present, is selected from C1-C4 alkyl and —(C1-C4 alkyl)NR^15aR^15b;

wherein each of R^15aand R^15b, when present, is independently selected from hydrogen and C1-C4 alkyl;

wherein R³is selected from hydrogen and C1-C4 alkyl;

or wherein each of R², when present, and R³together comprise a 5- to 6-membered heterocycle substituted with a group selected from C1-C4 alkyl and —(C1-C4 alkyl)NR^16aR^16b

wherein each of R^16aand R^16b, when present, is independently selected from hydrogen and C1-C4 alkyl; and

wherein Ar²is a heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH₂, —OH, —NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino,

or a pharmaceutically acceptable salt thereof,

wherein treating is one or more selected from active treatment, causal treatment, palliative treatment, and supportive treatment.