US 11,667,643 B2
RIP1K inhibitors
Somasekhar Bhamidipati, Foster City, CA (US); Simon Shaw, Oakland, CA (US); Ihab Darwish, San Carlos, CA (US); Jiaxin Yu, San Carlos, CA (US); Rao Kolluri, Foster City, CA (US); Vanessa Taylor, San Francisco, CA (US); Esteban Masuda, Menlo Park, CA (US); and Mark Irving, San Francisco, CA (US)
Assigned to Rigel Pharmaceuticals, Inc., South San Francisco, CA (US)
Filed by Rigel Pharmaceuticals, Inc., South San Francisco, CA (US)
Filed on Jun. 25, 2021, as Appl. No. 17/358,698.
Claims priority of provisional application 63/047,194, filed on Jul. 1, 2020.
Prior Publication US 2022/0009936 A1, Jan. 13, 2022
Int. Cl. A61P 9/00 (2006.01); A61P 25/00 (2006.01); A61P 29/00 (2006.01); A61P 37/00 (2006.01); A61K 31/55 (2006.01); A61K 31/551 (2006.01); A61K 31/553 (2006.01); A61K 31/554 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 498/04 (2006.01); C07D 498/14 (2006.01); C07D 498/22 (2006.01); C07D 513/04 (2006.01); C07D 513/14 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 471/04 (2013.01); C07D 498/04 (2013.01); C07D 498/22 (2013.01); C07D 513/14 (2013.01); C07D 519/00 (2013.01)] 19 Claims
 
1. A compound according to the formula

OG Complex Work Unit Chemistry
wherein
X is selected from CH2, O, S, S(O), S(O)2 and NRa;
Ra is for each occurrence selected from hydrogen, C1-6 alkyl and C1-6 acyl;
Y1, Y2 and Y3 are independently selected from the group consisting of N, N(Ra), O, C(Rb)1-2 and C═O;
Rb is selected from hydrogen, C1-6 alkyl and halo;
Z is C(Rc) or NRc;
Rc is a C1-4 unsaturated carbon chain optionally substituted with one or more R1 groups, optionally interrupted by 1 or 2 heteroatoms selected from O, N and S;
Rz is N, CH or C(R1) and together with ZRc and the carbon to which they are bound form a 5- or 6-membered heteroaryl or 6-membered aryl ring substituted with m R1 groups;
R1 is a linker-R6 group, wherein the linker is a bond, (C1-C4) alkanyl, (C2-C4) alkenyl or (C2-C4) alkynyl, optionally substituted by one or more Rb and R6 is Re, —C(Rf)3, or —C(Rf)═C(Rf)2;
R2 is Ra;
ring B is 5-10-membered heteroaryl;
R3 is, for each occurrence, independently selected from Rb and ORa;
L is O, NRa or alkylene;
W is 5-10 membered aryl or heteroaryl optionally substituted by p R4;
R4 is for each occurrence selected from Rb and ORa;
Rd is for each occurrence independently selected from hydrogen, C1-6 alkyl, aralkyl, C5-10 aryl or heteroaryl, or two Rd together with a nitrogen to which they are both attached form a C3-10heterocyclic group optionally substituted by one or more Re;
Re is independently for each occurrence halo, —ORd, —SRd, —S(O)2Rd, —NRdRd, —Si(Ra)3, —C(O)OH, —C(O)ORa, or —C(O)NRdRd;
Rf is independently for each occurrence Ra, Rb, or Re, or two Rf groups together with the carbon atom bound thereto provide a C3-6 cycloalkyl group or a C3-10heterocyclic group each optionally substituted with one or more Re;
m is 1, 2, 3, or 4;
n is 0, 1 or 2; and
p is 0, 1, 2, 3, 4, or 5.