Macrocycles as factor XIa inhibitors
The present invention provides compounds of Formula (Ia): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
1. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
2. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
3. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
4. A compound having the following formula:
wherein R is selected from:
5. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
6. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R and R l are selected from:
R
R 1
Me
Me
Me
Me
Me
7. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R and X are selected from:
X
R
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
8. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
9. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
and H.
10. A compound having the following formula:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein R is selected from:
11. A compound selected from the group consisting of:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof.