US 12,012,467 B2
Small molecule DCN1 inhibitors and therapeutic methods using the same
Shaomeng Wang, Superior Township, MI (US); Haibin Zhou, Ann Arbor, MI (US); Jianfeng Lu, Ann Arbor, MI (US); Liu Liu, Ann Arbor, MI (US); Yi Sun, Superior Township, MI (US); and Denzil Bernard, Ann Arbor, MI (US)
Assigned to REGENTS OF THE UNIVERSITY OF MICHIGAN, Ann Arbor, MI (US)
Appl. No. 16/496,974
Filed by THE REGENTS OF THE UNIVERSITY OF MICHIGAN, Ann Arbor, MI (US)
PCT Filed Mar. 28, 2018, PCT No. PCT/US2018/024708
§ 371(c)(1), (2) Date Sep. 24, 2019,
PCT Pub. No. WO2018/183411, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/477,498, filed on Mar. 28, 2017.
Prior Publication US 2020/0109167 A1, Apr. 9, 2020
Int. Cl. A61K 31/426 (2006.01); A61K 31/427 (2006.01); A61K 31/428 (2006.01); A61K 31/454 (2006.01); A61K 31/5377 (2006.01); A61K 38/05 (2006.01); A61K 38/06 (2006.01); A61K 38/07 (2006.01); A61K 45/06 (2006.01); C07D 277/30 (2006.01); C07D 277/64 (2006.01); C07D 417/12 (2006.01); C07K 5/02 (2006.01); C07K 5/062 (2006.01); C07K 5/078 (2006.01); C07K 5/097 (2006.01); C07K 5/113 (2006.01); C07K 5/117 (2006.01); C07K 7/02 (2006.01)
CPC C07K 5/1021 (2013.01) [A61K 31/426 (2013.01); A61K 31/427 (2013.01); A61K 31/428 (2013.01); A61K 31/454 (2013.01); A61K 31/5377 (2013.01); A61K 38/05 (2013.01); A61K 38/06 (2013.01); A61K 38/07 (2013.01); A61K 45/06 (2013.01); C07D 277/30 (2013.01); C07D 277/64 (2013.01); C07D 417/12 (2013.01); C07K 5/02 (2013.01); C07K 5/021 (2013.01); C07K 5/06026 (2013.01); C07K 5/06139 (2013.01); C07K 5/0821 (2013.01); C07K 5/1024 (2013.01); C07K 7/02 (2013.01)] 7 Claims
 
1. A compound having a structural formula

OG Complex Work Unit Chemistry
wherein;
Ar1 is selected from the group consisting of

OG Complex Work Unit Chemistry
 optionally substituted with up to four R2 substituents;
R1 is selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkylmethylene, NHMe, N(Me)2, NHEt, NH-cyclopropyl, OMe, OEt, O-cyclopropyl;
R2 are independently selected from the group consisting of halo, CN, N3, CF3, NO2, H, C1-6 alkyl, substituted C1-6 alkyl, C2-6 alkenyl, substituted C2-6 alkenyl, C2-6 alkynyl, substituted C2-6 alkynyl, C3-6 cycloalkyl, substituted C3-6 cycloalkyl, C4-6 cycloalkenyl substituted C4-6 cycloalkenyl, phenyl, substituted phenyl, monocyclic heteroaryl, substituted monocyclic heteroaryl, OR5, NR3R4, COOR5, CONR3R4;
R3 and R4, independently, are selected from the group consisting of hydrogen, C1-6 alkyl, allyl, C3-6 cycloalkyl, C4-6 heterocyclyl, aryl, heteroaryl, C1-6 alkyl-C3-6 cycloalkyl, C1-6 alkyl-C4-6 cycloalkenyl, C1-6 alkyl-C4-6 heterocyclyl, C1-6 alkaryl, C1-6 alkyl-heteroaryl, C1-6 acyl, C3-6 cycloalkylcarbonyl, C4-6 heterocyclylcarbonyl, aroyl, heteroaroyl, or are taken together with the nitrogen atom to which they are attached to form a ring of four to seven members, optionally including any chemically stable combination of one to three O, C═O, NR5 and S;
R5 is selected from the group consisting of hydrogen, C1-6 alkyl, allyl, propargyl, C3-6 cycloalkyl, C1-6 alkyl-C4-6 cycloalkenyl, C4-6 heterocyclyl, aryl, heteroaryl, C1-6 alkyl-C3-6 cycloalkyl, C1-6 alkyl-C4-6 heterocyclyl, C1-6 alkaryl, C1-6 alkyl-heteroaryl, C1-6 acyl, C3-6 cycloalkylcarbonyl, C4-6 heterocyclylcarbonyl, aroyl, heteroaroyl, each optionally substituted with up to three substituents independently selected from halo, hydroxy, oxo, thio, thiono, amino, cyano, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylamino, C1-6 dialkylamino, C4-6 heterocyclo, aryl, and heteroaryl;
R6 and R7, independently, are hydrogen or C1-6 alkyl, or R6 and R7 are taken together to form ═O, ═S, or R6 and R7 are taken together with the carbon atom to which they are attached to form a three to six membered ring, optionally including any chemically stable combination of one to three of O, C═O, S(O)x or NR5;
R13 is C1-6 alkyl, C3-6 cycloalkyl, C4-6 cycloalkenyl, C4-6 heterocyclo, C1-6 alkyl-C3-6 cycloalkyl, C1-6 alkyl-C4-6 cycloalkenyl, C4-6 heterocyclo, C1-6 alkyl-C4-6 heterocyclo, aryl, C1-6 alkylaryl, heteroaryl, C1-6 alkyl-heteroaryl, C2-4 alkenylaryl, C2-4 alkenylheteroaryl, with these groups optionally substituted with up to five substituents independently selected from the group consisting of C1-6 alkyl, halo, hydroxy, oxo, thio, thiono, cyano, hydroxymethyl, aminomethyl, C1-6 alkoxy, C1-6 alkylamino, C1-6 dialkylamino, C1-6 alkylS(O)x, C1-6 aminoacyl, C1-6 alkylaminosulfonyl, sulfonamido, C4-6 heterocyclo(carbonyl), aryl, aroyl, heteroaryl, and heteroaroyl;
x is 0, 1, or 2;
or a pharmaceutically acceptable salt, hydrate, or solvate thereof.