US 12,448,373 B2
Azetidinyl-acetamides as CXCR7 inhibitors
Pingchen Fan, Hayward, CA (US); Christopher W. Lange, Hayward, CA (US); Rebecca M. Lui, Mountain View, CA (US); Darren J. McMurtrie, Vancouver (CA); Ryan J. Scamp, Fremont, CA (US); Ju Yang, Palo Alto, CA (US); Yibin Zeng, Foster City, CA (US); and Penglie Zhang, Foster City, CA (US)
Assigned to AMGEN INC., Thousand Oaks, CA (US)
Filed by CHEMOCENTRYX, INC., San Carlos, CA (US)
Filed on Apr. 18, 2022, as Appl. No. 17/722,491.
Claims priority of provisional application 63/176,451, filed on Apr. 19, 2021.
Prior Publication US 2022/0348568 A1, Nov. 3, 2022
Int. Cl. C07D 413/14 (2006.01); C07D 413/12 (2006.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01); G01N 33/68 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 413/12 (2013.01); C07D 417/12 (2013.01); C07D 417/14 (2013.01); G01N 33/6863 (2013.01); G01N 2333/7158 (2013.01); G01N 2458/00 (2013.01)] 30 Claims
 
1. A compound having formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, hydrate, N-oxide, isotopically enriched or enantiomerically enriched version or a rotamer thereof, wherein
HAr is a five-membered heteroaryl ring;
Ar1 is selected from the group consisting of phenyl, pyridyl, pyrimidinyl, and pyrazinyl;
Ar2 is aryl or heteroaryl, each of which is independently monocyclic or fused-bicyclic;
the subscript m is 0, 1 or 2;
the subscript n is 0, 1, 2 or 3;
the subscript p is 0, 1, 2 or 3;
the subscript q is 0, 1, 2, 3 or 4;
each R1 is a member independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, —NRaRb, —ORa, —CO2Ra, and —C(O)NRaRb;
each R2 is a member independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, —NRaRb, —ORa, —CO2Ra, and —C(O)NRaRb;
each R3 is a member selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, —CO2Ra, —X—CO2Ra, —C(O)NRaRb and —X—C(O)NRaRb;
each of R4a and R5a, is a member independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, —X—ORa, —CO2Ra, —X—CO2Ra, —X—NRaRb, —C(O)NRaRb and —X—C(O)NRaRb,
each of R4 and R5, is a member independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, —X—ORa, —CO2Ra, —X—CO2Ra, —X—NRaRb, —C(O)NRaRb and —X—C(O)NRaRb; or R4 and R5 are combined to form a three- to five-membered ring having 0 or 1 heteroatom ring vertex selected from O, S or N, wherein said three- to five-membered ring is unsubstituted or substituted with 1-4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
each R6 is a member independently selected from the group consisting of halogen, CN, —X—CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —X—NRaRb, —C(O)NRaRb, and —X—C(O)NRaRb,
R7 is a member selected from the group consisting of C1-8 alkyl, C3-8 hydroxyalkyl, C1-4 alkoxy-C2-4 alkyl, —C(O)NH—C1-8 alkyl, —C(O)—C1-8 alkyl, —S(O)2—C1-8 alkyl, C3-8 cycloalkyl, —X—C3-8 cycloalkyl, C6-9 spirocycloalkyl, —X—C6-9 spirocycloalkyl, 4- to 7-membered heterocycloalkyl, —X-4- to 7-membered heterocycloalkyl, 7- to 11-membered spiroheterocycloalkyl, and —X-7- to 11-membered spiroheterocycloalkyl, wherein each R7 is substituted with zero to four substituents independently selected from the group consisting of hydroxy, methyl, ethyl, hydroxymethyl, fluoro, chloro, methoxy, ethoxy and cyclopropyl;
each Ra and Rb is independently selected from the group consisting of H, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl-C1-4 alkyl;
each X is a C1-4 alkylene linking group wherein any of the methylene portions of X are unsubstituted or substituted with one or two methyl groups.