IP Library › Granted Patent US 11,274,111
Granted Patent B2
US 11,274,111 · App. 16/973,623 · Granted Mar 15, 2022

Arginase inhibitors and methods of use

Inventors: Abdelghani Abe Achab (Melrose, MA); Jared N. Cumming (Winchester, MA); Christian Fischer (Natick, MA); Symon Gathiaka (Waltham, MA); Charles A. Lesburg (Newton, MA); Derun Li (West Roxbury, MA); Min Lu (Brookline, MA); Matthew J. Mitcheltree (Boston, MA); Anandan Palani (Needham, MA); Rachel L. Palte (Melrose, MA); David L. Sloman (Brookline, MA); Hongjun Zhang (Boston, MA)
Assignee: MERCK SHARP & DOHME CORP.
C07F5/025C07K16/2818
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 11,274,111
App. No.
16/973,623
Granted
Mar 15, 2022
Kind
B2
Abstract

Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula (I) act as arginase inhibitors and can be useful in preventing, treating or acting as a remedial agent for arginase-related diseases.

Claims (53)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Y is a straight or branched (C 2 -C 5 )alkylene, wherein one or more —CH 2 — groups in Y are optionally and independently replaced with a moiety selected from the group consisting of O, S and NH;

U is a bond, O, NR 15 or CR 7 R 8 ;

X is O, NR 15 or CR 9 R 10 , wherein U and X cannot be simultaneously O and NR 15 , respectively;

Z is a bond or CR 11 R 12 ;

R 1 is hydrogen, C 3 -C 6 cycloalkyl or C 1 -C 6 alkyl or, taken with R 2 forms a C 3 -C 8 cycloalkyl, wherein the C 3 -C 8 cycloalkyl is unsubstituted or substituted with one to four substituents selected from the group consisting of halogen, C 1 -C 6 alkyl or OH;

R 2 is hydrogen, C 3 -C 6 cycloalkyl or C 1 -C 6 alkyl or, taken with R 1 forms a C 3 -C 8 cycloalkyl, wherein the C 3 -C 8 cycloalkyl is unsubstituted or substituted with one to four substituents selected from the group consisting of halogen, C 1 -C 6 alkyl or OH;

R 3 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl;

R 4 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl;

R 5 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 6 forms a C 3 -C 6 cycloalkyl or heterocycle, wherein the C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 6 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 5 forms a C 3 -C 6 cycloalkyl or heterocycle, or taken with R 7 forms a C 1 -C 6 alkyl bridge, or taken with R 10 or R 12 forms an aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle or when taken with R 15 forms a heteroaryl or heterocycle, wherein the aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl;

R 7 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 6 , R 11 or R 12 forms a C 1 -C 6 alkyl bridge or when taken with R 8 forms a C 3 -C 6 cycloalkyl or heterocycle, wherein the C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 8 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 11 or R 12 forms a C 1 -C 6 alkyl bridge or when taken with R 7 forms a C 3 -C 6 cycloalkyl or heterocycle, or when taken with R 10 forms an aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle or when taken with R 15 forms a heteroaryl or heterocycle, wherein the aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 9 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 10 forms a C 3 -C 6 cycloalkyl or heterocycle, wherein the C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), —C 1 -C 6 alkylaryl, —C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 10 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 6 or R 8 forms an aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle, or taken with R 9 forms C 3 -C 6 cycloalkyl or heterocycle, or when taken with R 15 forms a heteroaryl or heterocycle, wherein the aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 11 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 7 or R 8 forms a C 1 -C 6 alkyl bridge or when taken with R 12 forms a C 3 -C 6 cycloalkyl or heterocycle, wherein the C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 12 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl or when taken with R 7 or R 8 forms a C 1 -C 6 alkyl bridge or when taken with R 6 forms an aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle or when taken with R 11 forms a C 3 -C 6 cycloalkyl or heterocycle, wherein the aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

R 13 is hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, COC 1 -C 6 alkylNH 2 , COC 1 -C 6 alkylNH(C 1 -C 6 alkyl), COC 1 -C 6 alkylN(C 1 -C 6 alkyl) 2 , C 1 -C 6 haloalkyl, C 1 -C 6 alkylOH or COC 1 -C 6 alkyl;

R 14 is hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, COC 1 -C 6 alkylNH 2 , COC 1 -C 6 alkylNH(C 1 -C 6 alkyl), COC 1 -C 6 alkylN(C 1 -C 6 alkyl) 2 , C 1 -C 6 haloalkyl, C 1 -C 6 alkylOH or COC 1 -C 6 alkyl; and

R 15 is hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ) or COC 1 -C 6 alkyl or when taken with R 6 or R 8 forms a heteroaryl or heterocycle, wherein the aryl, heteroaryl, C 3 -C 6 cycloalkyl or heterocycle is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), heteroaryl, C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl;

wherein the structure of Formula I comprises a bridged ring or multiple rings.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are both hydrogen.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is propylenyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is COOH.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is NH 2 or NHCH 3 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein U is a bond.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is hydrogen and R 6 , when taken with R 10 , forms a heterocycle.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6 , when taken with R 10 , forms

wherein

A is NH or CH 2 ;

E is a bond, NH or CHR 21 ;

V is NR 22 or CHR 23 , wherein A and V cannot be simultaneously NH and NR 22 , and wherein E and V cannot be simultaneously NH and NR 22 ;

R 21 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy, COOC 1 -C 6 alkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ) or heteroaryl;

R 22 hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, C 1 -C 6 alkylN(R 13 )(R 14 ), COOC 1 -C 6 alkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ) or heteroaryl; and

R 23 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy, COOC 1 -C 6 alkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ) or heteroaryl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 , when taken with R 10 , forms

wherein

V is NR 22 or CHR 23 ;

R 22 is hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, C 1 -C 6 alkylN(R 13 )(R 14 ), COOC 1 -C 6 alkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ) or heteroaryl; and

R 23 is hydrogen, halogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl, haloC 1 -C 6 alkyl, OH, C 1 -C 6 alkylOH, C 1 -C 6 alkylOC 1 -C 6 alkyl, COOH, N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkoxy, COOC 1 -C 6 alkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ) or heteroaryl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is hydrogen and R 6 , when taken with R 10 , forms a pyrrolidine.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CR 9 R 10 and wherein R 10 , when taken with R 9 , forms a heterocycle.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CR 9 R 10 and wherein R 10 , when taken with R 9 , forms a pyrrolidine.

13. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein the pyrrolidine is substituted with a substituent selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), C 1 -C 6 alkoxy or COOC 1 -C 6 alkyl.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CR 9 R 10 and wherein R 9 is hydrogen and R 10 when taken with R 8 forms a heterocycle.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CR 9 R 10 and wherein R 9 is hydrogen and R 10 when taken with R 8 forms a pyrrolidine.

16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the pyrrolidine is substituted with a substituent selected from the group consisting of halogen, OH, C 1 -C 6 alkylOH, C 3 -C 6 cycloalkyl, C 1 -C 6 alkylOC 1 -C 6 alkyl, oxo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, COC 1 -C 6 alkyl, COC 1 -C 6 alkylN(R 13 )(R 14 ), COC 1 -C 6 alkyl(OH)N(R 13 )(R 14 ), C 1 -C 6 alkylCON(R 13 )(R 14 ), CON(R 13 )(R 14 ), SO 2 C 1 -C 6 alkyl, SO 2 N(R 13 )(R 14 ), N(R 13 )(R 14 ), —C 1 -C 6 alkylN(R 13 )(R 14 ), C 1 -C 6 alkylaryl, C 1 -C 6 alkylhaloaryl, C(NH)N(R 13 )(R 14 ), C 1 -C 6 alkoxy and COOC 1 -C 6 alkyl, wherein R 13 is hydrogen, C 3 -C 6 cycloalkyl, C 1 -C 6 alkyl or COC 1 -C 6 alkyl; and

R 14 is hydrogen, C 3 -C 6 cycloalkyl or C 1 -C 6 alkyl.

17. A compound which is:

or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

19. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 9, 2020
From: ACHAB, ABDELGHANI ABE; CUMMING, JARED N.; FISCHER, CHRISTIAN; GATHIAKA, SYMON; LESBURG, CHARLES A.; LI, DERUN; LU, MIN; MITCHELTREE, MATTHEW J.; PALANI, ANANDAN; PALTE, RACHEL L.; SLOMAN, DAVID L.; ZHANG, HONGJUN
To: MERCK SHARP & DOHME CORP.
Reel/Frame 054595/0293 →