CXCR7 antagonists

Patent metadata

Field	Value
Publication number	US-11834452-B2
Application number	US-202117331750-A
Country	US
Kind code	B2
Filing date	May 27, 2021
Priority date	Nov 29, 2012
Publication date	Dec 5, 2023
Grant date	Dec 5, 2023

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.

First claim

What is claimed is:

1. 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 X a , X b and X c is independently selected from the group consisting of N, NH, N(R 2 ), O, CH and C(R 2 );
the subscript n is 0, 1 or 2;
Z is selected from the group consisting of

R 1 is a member selected from the group consisting of H and C 1-8 alkyl, wherein the alkyl portion is optionally substituted with halogen, —NR a R b , —OR a , —CO 2 R a and —CONR a R b ;
each R 2 is independently selected from the group consisting of H and C 1-4 alkyl;
R 3 is a member selected from the group consisting of H, C 1-8 alkyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl, —CO 2 R a , —X—CO 2 R a , —CONR a R b and —X—CONR a R b ;
each R 4 , when present, is a member independently selected from the group consisting of C 1-8 alkyl, C 1-8 haloalkyl, C 1-8 hydroxyalkyl, —OR a , —CO 2 R a , —X—CO 2 R a , —NR a R b , —CONR a R b and —X—CONR a R b ;
R 5 is selected from the group consisting of substituted aryl, heteroaryl, cycloalkyl, and heterocycloalkyl optionally further substituted with 1-3 R a ;
each R a and R b is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy, C 1-8 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylalkyl, amino, C 1-8 alkylamino, di C 1-8 alkylamino, carboxamide, carboxy C 1-4 alkyl ester, carboxylic acid, and —SO 2 — C 1-8 alkyl;
each X is a C 1-4 alkylene linking group or a linking group having the formula —(CH 2 ) m O(CH 2 ) 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.

2. The compound of claim 1 , wherein Z is monocyclic heteroaryl selected from the group consisting of imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, thiazole, oxazole, oxadiazole, pyrimidine, pyrazine, and pyridazine, each of which is optionally substituted with 1 R 5 substituents.

3. The compound of claim 1 , wherein R 1 is H.

4. The compound of claim 1 , wherein R 3 is selected from the group consisting of H, CH 2 OH and C(O)NH 2 .

5. The compound of claim 1 , having the structure:

6. The compound of claim 5 , wherein the bicyclic portion having X a , X b and X c as ring vertices is selected from the group consisting of:

7. The compound of claim 5 , wherein Z has the formula:

wherein each Q is independently selected from the group consisting of N, and CH.

8. The compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 8 , wherein R a is selected from the group consisting of selected from the group consisting of hydrogen, halogen, cyano, C 1-8 alkyl and —SO 2 — C 1-8 alkyl.

10. The compound of claim 8 , wherein R 2 is selected from the group consisting of H and C 1-4 alkyl.

11. The compound of claim 8 , wherein R a is selected from the group consisting of hydrogen, halogen, cyano, C 1-8 alkyl and —SO 2 — C 1-8 alkyl; and R 2 is selected from the group consisting of H and C 1-4 alkyl.

12. A compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

13. A compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

14. A compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

Assignees

• Chemocentryx Inc

Inventors

• Fan Junfa
• Krasinski Antoni
• Lange Christopher W
• Lui Rebecca M
• Mcmahon Jeffrey P
• Powers Jay P
• Zeng Yibin
• Zhang Penglie

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K51/0459

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title

• G01N33/57492

  Physics · mapped topic

• G01N2333/7158

  for chemokines · CPC title