US 12,410,170 B2
2,3,5-trisubstituted pyrazolo[1,5-A]pyrimidine compounds
Joel Worley Beatty, San Mateo, CA (US); Samuel Lawrie Drew, Millbrae, CA (US); Jeremy Thomas Andre Fournier, Fremont, CA (US); Jenna Leigh Jeffrey, Oakland, CA (US); Kenneth Victor Lawson, San Francisco, CA (US); Manmohan Reddy Leleti, Dublin, CA (US); Artur Karenovich Mailyan, Hayward, CA (US); Guillaume Mata, Berkeley, CA (US); Dillon Harding Miles, Berkeley, CA (US); Jay Patrick Powers, Pacifica, CA (US); Ehesan Ui Sharif, Menlo Park, CA (US); Rhiannon Thomas-Tran, San Jose, CA (US); and Xuelei Yan, Foster City, CA (US)
Assigned to Arcus Biosciences, Inc., Hayward, CA (US)
Appl. No. 17/615,550
Filed by Arcus Biosciences, Inc., Hayward, CA (US)
PCT Filed Jun. 3, 2020, PCT No. PCT/US2020/035920
§ 371(c)(1), (2) Date Nov. 30, 2021,
PCT Pub. No. WO2020/247496, PCT Pub. Date Dec. 10, 2020.
Claims priority of provisional application 62/857,148, filed on Jun. 4, 2019.
Prior Publication US 2023/0024302 A1, Jan. 26, 2023
Int. Cl. C07D 487/04 (2006.01); A61K 45/06 (2006.01); A61N 5/06 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 45/06 (2013.01); A61N 5/06 (2013.01); A61N 2005/0636 (2013.01)] 13 Claims
 
1. A compound represented by Formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein,
X is C(R2) or N;
R1a and R1b are each a member independently selected from the group consisting of H, C1-6 alkyl, C3-6 alkenyl, C3-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, —Y1, —X1—C(O)2Ra, —X1—ORa, —X1—NRaRb, —X1—CONRaRb, —X1—N(Ra)SO2Ra, —X1—SO2Ra, —X1—SO2NRaRb, —X1—SO3Ra, —X1—CN, —X1—Y1 and —X1—Y1—Y1a wherein each X1 is a bond or C1-6 alkylene and is optionally further substituted with from 1 to 3 substituents independently selected from the group consisting of OH, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8alkyl and CO2H, and each Y1 and Y1a is independently selected from the group consisting of C3-10 cycloalkyl, 4- to 8-membered heterocycloalkyl, 5- to 6-membered heteroaryl, and aryl, wherein each heterocycloalkyl and heteroaryl have 1 to 3 heteroatom ring vertices selected from O, N and S; and each Y1 and Y1a is optionally further substituted with one to four substituents independently selected from the group consisting of halogen, oxo, CN, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 hydroxyalkoxy, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, SO2NH2, CONH2, C(O)NHOH, PO3H2, CO—C1-8alkyl, COO—C1-8alkyl, and CO2H;
R2 is a member selected from the group consisting of halogen, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, —Y2, —X2—C(O)2Ra, —X2—ORa, —X2—NRaRb, —X2—CONRaRb, —X2—SO2Ra, —X2—N(Ra)SO2Ra, —X2—SO2NRaRb, —X2—SO3Ra, —O—X2—Y2 and —X2—Y2 wherein each X2 is a bond or C1-6 alkylene and is optionally further substituted with from 1 to 3 substituents independently selected from the group consisting of OH, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8 alkyl and CO2H, and each Y2 is selected from the group consisting of C3-6 cycloalkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl, wherein each heterocycloalkyl and heteroaryl have 1 to 3 heteroatom ring vertices selected from O, N and S; and each Y2 is optionally further substituted with one to four substituents independently selected from the group consisting of halogen, oxo, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 hydroxyalkoxy, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8alkyl, and CO2H;
R3 is a member selected from the group consisting of C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkylC1-3 alkyl, C1-6 hydroxyalkyl, C1-6 haloalkyl and —X3—Y3 wherein each X3 is a bond, C1-6 alkylene or C1-6 haloalkylene and is optionally further substituted with OH, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8 alkyl or CO2H, and each Y3 is selected from the group consisting of C3-6 cycloalkyl, 4- to 8-membered heterocycloalkyl, and 5- to 6-membered heteroaryl, wherein each heterocycloalkyl and heteroaryl have 1 to 3 heteroatom ring vertices selected from O, N and S; and each Y3 is optionally further substituted with one to four substituents independently selected from the group consisting of halogen, oxo, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 hydroxyalkoxy, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8alkyl, and CO2H;
R4a and R4b are each a member independently selected from the group consisting of H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C1-6 hydroxyalkyl;
each Ra is independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylene-CO2H, C1-6 alkylene-SO3H, C3-6 cycloalkyl, C3-6 cycloalkylC1-3 alkyl, C1-3 alkylC3-6 cycloalkyl, phenyl and 3- to 7-membered heterocycloalkyl having from one to three heteroatom ring vertices selected from O, N and S; and each Ra is optionally further substituted with one or two members independently selected from halogen, OH, C1-4 alkoxy, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8alkyl and CO2H; and
each Rb is independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylene-CO2H, and C1-6 alkylene-SO3H, each of which is optionally further substituted with one or two members independently selected from OH, SO2NH2, CONH2, C(O)NHOH, PO3H2, COO—C1-8alkyl and CO2H.