US 12,018,016 B2
Aryl sulfonyl (hydroxy) piperidines as CCR6 inhibitors
Penglie Zhang, Foster City, CA (US); Daniel R. Marshall, San Mateo, CA (US); Howard S. Roth, Sunnyvale, CA (US); Aubrie Harland, Redwood City, CA (US); Ju Yang, Palo Alto, CA (US); Christopher W. Lange, Hayward, CA (US); Rebecca M. Lui, Mountain View, CA (US); and Antoni Krasinski, Sunnyvale, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US)
Filed by CHEMOCENTRYX, INC., San Carlos, CA (US)
Filed on Aug. 17, 2022, as Appl. No. 17/820,271.
Claims priority of provisional application 63/354,906, filed on Jun. 23, 2022.
Claims priority of provisional application 63/234,271, filed on Aug. 18, 2021.
Prior Publication US 2023/0133406 A1, May 4, 2023
Int. Cl. C07D 401/14 (2006.01); C07D 401/12 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 487/10 (2006.01); C07D 491/107 (2006.01); C07D 491/20 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 401/12 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/10 (2013.01); C07D 491/107 (2013.01); C07D 491/20 (2013.01)] 59 Claims
 
1. A compound having formula (Ia):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, hydrate, solvate, N-oxide, optically enriched form, or rotamer thereof,
wherein
each R1 is independently selected from the group consisting of halogen, CN, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORa, and —NRaRb;
each Ra and Rb is independently selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, and C3-6 cycloalkyl;
Ar2 is selected from the group consisting of:
i) monocyclic 5- or 6-membered aromatic or heteroaromatic ring having 0 to 3 heteroatoms as ring vertices selected from N, O and S, and which is substituted with 0 to 5 R2; and
ii) bicyclic 9- or 10-membered fused aromatic or heteroaromatic ring having 0 to 4 heteroatoms as ring vertices selected from N, O and S, and which is substituted with 0 to 5 R2;
each R2 is independently selected from the group consisting of halogen, CN, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORc, —SRc, —CORc, —CO2Rc, —NRcRd, —CONRcRd, —CO(NRc)2CORd, —SO2Rc, —SO2NRcRd, —X2—CONRcRd, —X2—NRcSO2Rd, —X2—NRcCO2Rd, —X2—P(═O)(ORd)2, —X2—O—P(═O)(ORd)2, —N(Rc)—Rd—X2—NRcRd, oxo, 4- to 6-membered heterocyclyl, 7- to 10-membered spiroheterocyclyl and 5- or 6-membered heteroaryl; and wherein the heterocyclyl, spiroheterocyclyl and heteroaryl rings of R2 have from 1 to 3 heteroatoms selected from N, O, and S, and are each unsubstituted or substituted with one or two members independently selected from the group consisting of halogen, hydroxyl, oxo, C1-4 alkyl, amino, C1-4 alkylamino, di-C1-4 alkylamino, C1-4 alkoxy, C1-4 hydroxalkyl, and C1-4 haloalkyl; and wherein two R2 groups attached to the same carbon atom are optionally combined to form a 3- to 6-membered spirocyclic ring or a 3- to 6-membered spiroheterocyclic ring having from 1 to 3 heteroatoms selected from N, O, and S;
Rc is independently selected from the group consisting of hydrogen, hydroxyl, C1-4 alkyl, C1-4 haloalkyl, and C1-4 hydroxyalkyl;
Rd is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C3-6 cycloalkyl, 4- to 6-membered heterocyclyl, and 5- or 6-membered heteroaryl; and wherein the C3-6 cycloalkyl, 4- to 6-membered heterocyclyl, and 5- or 6-membered heteroaryl rings of Rd have from 1 to 3 heteroatoms selected from N, O, and S, and are each unsubstituted or substituted with one or two members independently selected from the group consisting of halogen, hydroxyl, oxo, C1-4 alkyl, amino, C1-4 alkylamino, di-C1-4 alkylamino, C1-4 alkoxy, C1-4 hydroxalkyl, and C1-4 haloalkyl;
or Rc and Rd, when attached to the same nitrogen atom are joined to form a 4- to 7-membered heterocyclic ring having from 0 to 2 additional heteroatoms as ring vertices selected from O, S, S(O), S(O)2, NH, and N(C1-4 alkyl); and
X2 is C1-4 alkylene.