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US 10,329,314 B2Granted
Soluble C5aR antagonists
AssigneeChemoCentryx, Inc.
InventorsPingchen Fan, Antoni Krasinski, Venkat Reddy Mali, Shichang Miao, Sreenivas Punna, Yang Song, Valentino J. Stella, Yibin Zeng, Penglie Zhang
Life of this patent
Estimating the term…
Abstract
Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Claims21
A compound of Formula (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is selected from the group consisting of H, —O—CH2—O—P(O)ORaORb, —O—C(O)—C1-6 alkylene-L2-X1, O—P(O)ORaORb, and —O—C(O)-A1-(C1-3 alkylene)n-C4-7 heterocyclyl wherein the C4-7 heterocyclyl is optionally substituted with 1 to 6 Rc groups;
- A1 is selected from the group consisting of C6-10 aryl, C3-10 cycloalkyl, C5-10 heteroaryl and C5-10 heterocyclyl, each of which is optionally substituted with 1 to 5 Rx which can be the same or different;
- n=0 or 1;
- L2 is independently selected from the group consisting of a bond, —O—C(O)—C1-6 alkylene-, and —NRd—C(O)—C1-6 alkylene-;
- X1 is independently selected from the group consisting of —NReRf, —P(O)ORaORb, —O—P(O)ORaORb, and —CO2H;
- R2 is selected from the group consisting of H, -L3-C1-6 alkylene-L4-X2, -L3-(C1-6 alkylene)m-A2-X2, —P(O)ORaOC(O)—C1-6 alkyl, —P(O)ORaNRgRh and —P(O)ORaORb;
- L3 is independently selected from the group consisting of —C(O)—O—, and —C(O)—;
- L4 is independently selected from the group consisting of a bond, —O—C(O)—C2-6 alkenylene-, —O—C(O)—C1-6 alkylene-, and —NRd—C(O)—C1-6 alkylene- wherein the C1-6 alkylene in —NRd—C(O)—C1-6 alkylene- and —O—C(O)—C1-6 alkylene- is optionally substituted with NReRf;
- X2 is independently selected from the group consisting of —NRkRl, —P(O)ORaORb, —O—P(O)ORaORb, and —CO2H;
- m=0 or 1;
- A2 is selected from the group consisting of C6-10 aryl, C3-10 cycloalkyl, C5-10 heteroaryl and C5-10 heterocyclyl, each of which is optionally substituted with 1 to 5 Rx which can be the same or different;
- R3 is H or -L5-P(O)ORaORb wherein L5 is independently selected from the group consisting of a bond and —CH2—O—;
- each Rx is independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, C1-6heteroalkyl, CN, NRyRz, SRy and ORy;
- each Rc is independently selected from the group consisting of halogen, C1-6alkyl, C1-6haloalkyl, C1-6heteroalkyl, CN, NRyRz, SRy and ORy;
- each Ra, Rb, Rd, Re, Rf, Rg, Rk, Rl, Ry and Rz is independently selected from the group consisting of H and C1-6 alkyl;
- each Rh is independently selected from the group consisting of H and C1-6 alkyl wherein the C1-6 alkyl is optionally substituted with 1 to 5 substituents independently selected from CO2H, NRiRj, C6-10 aryl, C3-10 cycloalkyl, C5-10 heteroaryl and C5-10 heterocyclyl, wherein each Ri and Rj is independently H or C1-6 alkyl;
- wherein two of R1, R2 and R3 are H, and one of R1, R2 and R3 is other than H.
15 more elements
Dependencies are inferred from the claim text.