US 12,421,239 B2
5H-pyrrolo[3,2-d]pyrimidine-2,4-diamino compounds and antibody conjugates thereof
Andreas Maderna, South San Francisco, CA (US); Adam A. Galan, South San Francisco, CA (US); and Krishna Bajjuri, South San Francisco, CA (US)
Assigned to SUTRO BIOPHARMA, INC., South San Francisco, CA (US)
Appl. No. 17/617,573
Filed by SUTRO BIOPHARMA, INC., South San Francisco, CA (US)
PCT Filed Jun. 10, 2020, PCT No. PCT/US2020/037024
§ 371(c)(1), (2) Date Dec. 8, 2021,
PCT Pub. No. WO2020/252043, PCT Pub. Date Dec. 17, 2020.
Claims priority of provisional application 62/859,638, filed on Jun. 10, 2019.
Prior Publication US 2022/0242871 A1, Aug. 4, 2022
Int. Cl. C07D 487/04 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 47/6803 (2017.08); A61K 47/6849 (2017.08); A61P 35/00 (2018.01)] 59 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, solvate or N-oxide thereof;
wherein
R1a, R1b, R2a, and R2b are independently, at each occurrence, selected from hydrogen, and C1-6alkyl;
ring A is cycloalkyl, heterocycloalkyl, monocyclic aryl, monocyclic heteroaryl, fused bicyclic aryl, or fused bicyclic heteroaryl, where heterocycloalkyl and each heteroaryl comprise 1, 2, 3 or 4 heteroatoms independently selected from N, S, and O;
ring B is a 4-membered N-linked heterocycloalkyl, which is substituted with 1-2 R3; wherein the heterocycloalkyl includes 1 or 2 heteroatoms independently selected from N, S, and O;
and wherein R3 is, independently, at each occurrence, —N(R3a)2, —OR3b, —C(R3c)2NH2, C1-6alkyl, heterocycloalkyl, heteroaryl, or partially saturated heteroaryl, or two R3 attached to the same carbon, together with the carbon atom to which they are attached, form a spiro-heterocycloalkyl; wherein heterocycloalkyl, spiro-heterocycloalkyl, heteroaryl, and partially saturated heteroaryl in R3 include 1, 2, 3 or 4 heteroatoms independently selected from N, S, and O, and are optionally substituted with 1-2 C1-3alkyl; or
ring B is a 5-6 membered N-linked heterocycloalkyl, which is substituted with 1-3 R3, or a 5-6 membered N-linked heteroaryl, which is substituted with 1-3 R3; wherein the heterocycloalkyl includes 1 or 2 heteroatoms independently selected from N, S, and O; and wherein R3 is, independently, at each occurrence, —N(R3a)2, —OR3b, —C(R3c)2NH2 heterocycloalkyl, heteroaryl, or partially saturated heteroaryl, or two R3 attached to the same carbon, together with the carbon atom to which they are attached, form a spiro-heterocycloalkyl; wherein heterocycloalkyl, spiro-heterocycloalkyl, heteroaryl, and partially saturated heteroaryl in R3 include 1, 2, 3 or 4 heteroatoms independently selected from N, S, and O, and are optionally substituted with 1-2 C1-3alkyl;
or
ring B is a 7-10 membered N-linked heterocycloalkyl, which is substituted with 1-3 R3, or a 5-10 membered N-linked heteroaryl which is substituted with 1-3 R3; wherein R3 is, independently, at each occurrence, —N(R3a)2, —OR3b, —C(R3c)2NH2, C1-6alkyl, heterocycloalkyl, heteroaryl, or partially saturated heteroaryl, or two R3 attached to the same carbon, together with the carbon atom to which they are attached, form a spiro-heterocycloalkyl; wherein heterocycloalkyl, spiro-heterocycloalkyl, heteroaryl, and partially saturated heteroaryl in R3 include 1, 2, 3 or 4 heteroatoms independently selected from N, S, and O, and are optionally substituted with 1-2 C1-3alkyl;
or
ring B is unsubstituted 2,5-diazabicyclo[2.2.2]octanyl or 3,9-diazabicyclo[3.3.2]decanyl;
R3a is independently, at each occurrence, selected from hydrogen, C1-6alkyl, —C(═O)—CH2NH2, and cycloalkyl;
R3b is independently, at each occurrence, selected from hydrogen,

OG Complex Work Unit Chemistry
 where q1 is 1, 2, or 3, and —CH2-aryl-CH2NH2;
R3c is independently, at each occurrence, selected from hydrogen, and C1-6alkyl, or two R3c, together with the carbon atom to which they are attached, form a cycloalkyl;
R4 is C1-6alkyl; and
R5 is C3-6cycloalkyl, or C1-6alkyl, each of which is optionally substituted with 1, 2, or 3 R5a groups independently selected from halo, hydroxy, alkoxy, amino, C1-6alkylamino, C1-6 dialkylamino, C3-6cycloalkyl, aryl, and heteroaryl, wherein heteroaryl includes 1, 2, 3 or 4 heteroatoms independently selected from N, S, and O, and wherein any of the R5a C3-6cycloalkyl, aryl, and heteroaryl groups are optionally further substituted with 1, 2, or 3 groups independently selected from halo, hydroxy, alkyl, and haloalkyl.