US 12,240,837 B2
Chemokine receptor modulators and uses thereof
Parcharee Tivitmahaisoon, South San Francisco, CA (US); David J. Wustrow, Los Gatos, CA (US); Mikhail Zibinsky, Redwood City, CA (US); and Omar Robles, Redwood City, CA (US)
Assigned to RAPT Therapeutics, Inc., South San Francisco, CA (US)
Filed by RAPT THERAPEUTICS, INC., South San Francisco, CA (US)
Filed on Apr. 5, 2023, as Appl. No. 18/131,314.
Claims priority of provisional application 63/328,214, filed on Apr. 6, 2022.
Prior Publication US 2023/0322741 A1, Oct. 12, 2023
Int. Cl. C07D 403/14 (2006.01); C07D 401/14 (2006.01)
CPC C07D 403/14 (2013.01) [C07D 401/14 (2013.01)] 42 Claims
 
1. A compound having Formula (IVb), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
X2 is CR9;
n1, n2, n3.2, n3.3, n4, n7, n9, and n44 are independently an integer from 0 to 4;
m1, m2, m3.2, m3.3, m4, m7, m9, v1, v2, v3.2, v3.3, v4, v7, v9, and v44 are independently 1 or 2;
z4 is 1;
L7 is a bond, —O—, —S—, —NR7.2B—, —C(O)—, —C(O)O—, —S(O)—, —S(O)2—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
R1 is hydrogen, halogen, —CX1.13, —CHX1.12, —CH2X1.1, —CN, —N3, —SOn1R1A, —SOv1NR1BR1C, —NHNR1BR1C, —ONR1BR1C, —NHC(O)NHNR1BR1C, —NHC(O)NR1BR1C, —N(O)m1, —NR1BR1C, —C(O)R1D, —C(O)OR1D, —C(O)NR1BR1C, —OR1A, —NR1BSO2R1A, —NR1BC(O)R1D, —NR1BC(O)OR1D, —NR1BOR1D, —OCX1.13, —OCHX1.12, —OCH2X1.1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R2 is hydrogen, halogen, —CX2.13, —CHX2.12, —CH2X2.1, —CN, —N3, —SOn2R2A, —SOv2NR2BR2C, —NHNR2BR2C, —ONR2BR2C, —NHC(O)NHNR2BR2C, —NHC(O)NR2BR2C, —N(O)m2, —NR2BR2C, —C(O)R2D, —C(O)OR2D, —C(O)NR2BR2C, —OR2A, —NR2BSO2R2A, —NR2BC(O)R2D, —NR2BC(O)OR2D, —NR2BOR2D, —OCX2.13, —OCHX2.12, —OCH2X2.1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R3.2 is hydrogen, halogen, —CX3.23, —CHX3.22, —CH2X3.2, —CN, —N3, —SOn3.2R3.2A, —SOv3.2NR3.2BR3.2C, —NHNR3.2BR3.2C, —ONR3.2BR3.2C, —NHC(O)NHNR3.2BR3.2C, —NHC(O)NR3.2BR3.2C, —N(O)m3.2, —NR3.2BR3.2C, —C(O)R3.2D, —C(O)OR3.2D, —C(O)NR3.2BR3.2C, —OR3.2A, —NR3.2BSO2R3.2A, —NR3.2BC(O)R3.2D, —NR3.2BC(O)OR3.2D, —NR3.2BOR3.2D, —OCX3.23, —OCHX3.22, —OCH2X3.2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R3.3 is hydrogen, halogen, —CX3.33, —CHX3.32, —CH2X3.3, —CN, —N3, —SOn3.3R3.3A, —SOv3.3 NR3.3BR3.3C, —NHNR3.3BR3.3C, —ONR3.3BR3.3C, —NHC(O)NHNR3.3BR3.3C, —NHC(O)NR3.3BR3.3C, —N(O)m3.3, —NR3.3BR3.3C, —C(O)R3.3D, —C(O)OR3.3D, —C(O)NR3.3BR3.3C, —OR3.3A, —NR3.3BSO2R3.3A, —NR3.3BC(O)R3.3D, —NR3.3BC(O)OR3.3D, —NR3.3BOR3.3D, —OCX3.33, —OCHX3.32, —OCH2X3.3, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted, heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R4 is hydrogen, halogen, —CX4.13, —CHX4.12, —CH2X4.1, —CN, —N3, —SOn4R4A, —SOv4NR4BR4C, —NHNR4BR4C, —ONR4BR4C, —NHC(O)NHNR4BR4C, —NHC(O)NR4BR4C, —N(O)m4, —NR4BR4C, —C(O)R4D, —C(O)OR4D, —C(O)NR4BR4C, —OR4A, —NR4BSO2R4A, —NR4BC(O)R4D, —NR4BC(O)OR4D, —NR4BOR4D, —OCX4.13, —OCHX4.12, —OCH2X4.1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, or R4 and R9 may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R7 is hydrogen, halogen, —CX7.13, —CHX7.12, —CH2X7.1, —CN, —N3, —SOn7R7A, —SOv7NR7BR7C, —NHNR7BR7C, —ONR7BR7C, —NHC(O)NHNR7BR7C, —NHC(O)NR7BR7C, —N(O)m7, —NR7BR7C, —C(O)R7D, —C(O)OR7D, —C(O)NR7BR7C, —OR7A, —NR7BSO2R7A, —NR7BC(O)R7D, —NR7BC(O)OR7D, —NR7BOR7D, —OCX7.13, —OCHX7.12, —OCH2X7.1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R9 is hydrogen, halogen, —CX9.13, —CHX9.12, —CH2X9.1, —CN, —N3, —SOn9R9A, —SOv9 NR9BR9C, —NHNR9BR9C, —ONR9BR9C, —NHC(O)NHNR9BR9C, —NHC(O)NR9BR9C, —N(O)m9, —NR9BR9C, —C(O)R9D, —C(O)OR9D, —C(O)NR9BR9C, —OR9A, —NR9BSO2R9A, —NR9BC(O)R9D, —NR9BC(O)OR9D, —NR9BOR9D, —OCX9.13, —OCHX9.12, —OCH2X9.1, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R4 and R9 may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R44 is hydrogen, —CX44.13, —CHX44.12, —CH2X44.1, —SOn44R44A, —SOv44NR44BR44C, —C(O)R44D, —C(O)OR44D, —C(O)NR44BR44C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3.2A, R3.2B, R3.2C, R3.2D, R3.3A, R3.3B, R3.3C, R3.3D, R4A, R4B, R4C, R4D, R7A, R7B, R7C, R7D, R9A, R9B, R9C, R9D, R44A, R44B, R44C, and R44D are independently hydrogen, halogen, —CF3, —CCl3, —CBr3, —CI3, —COOH, —CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R1B, R1C, R2B, R2C, R4B, R4C, R7B, R7C, R9B, R9C, R44B, and R44C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; and
X1.1, X2.1, X3.2, X3.3, X4.1, X7.1, X9.1, and X44.1 are independently —Cl, —Br, —I or —F.