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US 9,169,261 B2Granted
CXCR7 antagonists
AssigneeChemoCentryx, Inc.
InventorsJunfa Fan, Antoni Krasinski, Christopher W. Lange, Rebecca M. Lui, Jeffrey P. McMahon, Jay P. Powers, Yibin Zeng, Penglie Zhang
Life of this patent
Estimating the term…
Abstract
Compounds having formula I, or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.
Claims26
A compound having formula I
- or a pharmaceutically acceptable salt, hydrate, N-oxide, isotopically enriched or enantiomerically enriched version or a rotamer thereof, wherein
- each of ring vertices Xa, Xb and Xc is independently selected from the group consisting of N, NH, N(R2), O, CH and C(R2);
- the subscript n is 0, 1 or 2;
- Z is selected from the group consisting of
- (i) monocyclic or fused-bicyclic aryl and heteroaryl, wherein the heteroaryl group has from 1-4 heteroatoms as ring members selected from N, O and S;
- and wherein said aryl and heteroaryl groups are optionally substituted with from 1 to 5 R5 substituents;
- (ii) monocyclic four-, five-, six- or seven-membered ring selected from the group consisting of cycloalkane, and heterocycloalkane, wherein the heterocycloalkane rings have from 1-3 heteroatoms as ring members selected from N, O and S;
- and wherein each of said monocyclic Z rings are optionally substituted with from 1 to 3 R5 substituents;
- R1 is a member selected from the group consisting of H and C1-8 alkyl, wherein the alkyl portion is optionally substituted with halogen, —NRaRb, —ORa, —CO2Ra, and —CONRaRb;
- each R2 is independently selected from the group consisting of H, halogen, CN, C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb and —X—CONRaRb;
- R3 is a member selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —CO2Ra, —X—CO2Ra, —CONRaRb and —X—CONRaRb;
- each R4, when present, is a member independently selected from the group consisting of C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb and —X—CONRaRb;
- each R5 is a member independently selected from the group consisting of halogen, CN, —X—CN, C1-8 alkyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, C3-5 spirocycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8
- hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb, —X—CONRaRb, aryl, 5- or 6-membered heteroaryl, and 3-, 4-, 5- or 6-membered heterocyclic wherein the heteroatoms present as ring vertices of the heteroaryl and heterocyclic rings are selected from N, O and S, and wherein the aryl, heteroaryl and hetereocyclic portions of R5 are optionally further substituted with 1-3 Ra;
- each Ra and Rb is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkylalkyl, amino, C1-8 alkylamino, di C1-8 alkylamino, carboxamide, carboxy C1-4 alkyl ester, carboxylic acid, and —SO2— C1-8 alkyl;
- each X is a C1-4 alkylene linking group or a linking group having the formula —(CH2)mO(CH2)p—, wherein the subscripts m and p are integer of from 0 to 5, and m+p is from 0 to 6, wherein any of the methylene portions of X are optionally substituted with one or two methyl groups.
13 more elements
Dependencies are inferred from the claim text.