US 11,851,433 B2
Compounds, compositions and methods
Giorgio Bonanomi, Verona (IT); Anthony A. Estrada, South San Franscisco, CA (US); Jianwen A. Feng, South San Francisco, CA (US); Brian Fox, South San Francisco, CA (US); Cinzia Maria Francini, Verona (IT); Cheng Hu, South San Francisco, CA (US); Colin Philip Leslie, Verona (IT); Maksim Osipov, South San Franscisco, CA (US); Anantha Sudhakar, South San Francisco, CA (US); Zachary K. Sweeney, South San Francisco, CA (US); and Javier De Vicente Fidalgo, South San Francisco, CA (US)
Assigned to Denali Therapeutics Inc., South San Francisco, CA (US)
Filed by Denali Therapeutics Inc., South San Francisco, CA (US)
Filed on Oct. 5, 2021, as Appl. No. 17/494,336.
Application 17/494,336 is a division of application No. 16/683,970, filed on Nov. 14, 2019, granted, now 11,174,262.
Application 16/683,970 is a continuation of application No. PCT/US2018/033269, filed on May 17, 2018.
Claims priority of provisional application 62/507,682, filed on May 17, 2017.
Prior Publication US 2022/0024938 A1, Jan. 27, 2022
Int. Cl. C07D 267/08 (2006.01); A61K 31/553 (2006.01); A61P 25/00 (2006.01); A61P 25/16 (2006.01); A61P 25/28 (2006.01); C07D 487/04 (2006.01); C07D 498/04 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 498/04 (2013.01)] 17 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, deuterated analog, stereoisomer, mixture of stereoisomers, tautomer, or prodrug thereof, wherein:
X is CR4, wherein R4 is H or optionally substituted alkyl;
Cy is optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
Y1 and Y3 are independently CR5R6;
Y2 is O;
R1 is cyano, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, —SR8, —SOR8, —SO2R8, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
or R1 and Y3 together form an optionally substituted heterocyclyl;
R2 is cyano, hydrogen, halo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; or R1 and R2 together form an optionally substituted cycloalkyl or optionally substituted heterocyclyl;
each R3 is independently halo, cyano, or optionally substituted alkyl; or two R3 together form an optionally substituted cycloalkyl or an optionally substituted heterocyclyl;
R5 and R6 are independently cyano, halo, hydrogen, hydroxyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, —SH, —SR8, —SOR8, —SO2R8, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; or R5 and R6 together with the carbon atom to which they are both attached form an optionally substituted cycloalkyl, optionally substituted heterocyclyl, or oxo; or any two R5 groups attached to adjacent carbon atoms together form an optionally substituted cycloalkyl or optionally substituted heterocyclyl;
R7 is hydrogen or optionally substituted alkyl;
R8 is optionally substituted alkyl; and
n is 0, 1, 2, 3, 4, or 5.