Granted Patent B2

US 10,011,601 · App. 15/300,762 · Granted Jul 3, 2018

Inventors: Lee Babiss (Waltham, MA); Matthew Clark (Waltham, MA); Anthony D. Keefe (Waltham, MA); Mark J. Mulvihill (Waltham, MA); Haihong Ni (Beijing, CN); Louis Renzetti (Waltham, MA); Frank Ruebsam (Beijing, CN); Ce Wang (Beijing, CN); Zhifeng Xie (Beijing, CN); Ying Zhang (Lexington, MA)

Assignee: X-Rx, Inc.

C07D471/10A61K31/435A61K31/437A61K31/444A61K31/498A61K31/517A61K31/538A61K31/69A61K45/06C07D519/00C07F5/025

Abstract

Claims (354)

1. A compound according to Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X 1 and X 2 are each independently selected from one or more of C 1-2 alkyl C═O, NR 3 , or O;

X 3 is independently selected from one or more of C 1-2 alkyl, C═O, NR 3 , O, or CR 10 R 11 ;

m and n are each independently selected from 0, 1 or 2;

R 1 is selected from C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, aryl-C 0-12 alkyl-, aryl-C 3-12 cycloalkyl-, heteroaryl-C 0-12 alkyl-, heteroaryl-C 3-12 cycloalkyl-, or heteroaryl-C 3-12 heterocycloalkyl-, any of which is optionally substituted with one or more independent G 1 substituents;

R 2 is selected from C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl, heteroaryl-C 3-12 cycloalkyl-, or heteroaryl-C 3-12 heterocycloalkyl-, any of which is optionally substituted with one or more independent G 2 substituents;

R 2a is selected from C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, heteroaryl-C 3-12 cycloalkyl-, or heteroaryl-C 3-12 heterocycloalkyl-, any of which is optionally substituted with one or more independent G 2a substituents;

R 2 and R 2a are each independently a linear structure, or, R 2 and R 2a are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m1 ;

R 3 is selected from C 1-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, aryl-C 0-12 alkyl-, aryl-C 3-12 cycloalkyl-, aryl-C 3-12 heterocycloalkyl-, heteroaryl-C 0-12 alkyl-, heteroaryl-C 3-12 cycloalkyl-, or heteroaryl-C 3-12 heterocycloalkyl-, any of which is optionally substituted with one or more independent G 3 substituents;

R 4 is selected from C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, aryl-C 0-12 alkyl-, aryl-C 3-12 cycloalkyl-, aryl-C 3-12 heterocycloalkyl-, heteroaryl-C 0-12 alkyl-, heteroaryl-C 3-12 cycloalkyl-, heteroaryl-C 3-12 heterocycloalkyl-, or pyridine-N-oxide, any of which is optionally substituted with one or more independent G 4 substituents;

G 1 , G 2 , G 2a , G 3 , and G 4 are each independently selected from one or more of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —B(OH) 2 , —PO(OR 12 ) 2 , —PO(OR 12 )R 13 , —CONR 12 OH, —C 0-12 alkyl, —C 2-12 alkenyl, —C 2-12 alkynyl, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, aryl-C 0-12 alkyl-, heteroaryl-C 0-12 alkyl-, —OC 0-12 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , —C(O)—C(O)NR 12 R 13 , —C(O)OR 12 , —C(O)—C(O)OR 12 , —OC(O)R 12 , —NR 12 C(O)R 13 , —NR 12 C(O)OR 13 , —NR 12 S(O) 2 R 13 , —(CR 14 R 15 )C(O)R 13 , —(CR 14 R 15 )C(O)OR 12 , —(CR 14 R 15 )C(O)NR 12 R 13 , —(CR 14 R 15 ) n1 S(O) 2 NR 12 R 13 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 S(O) n2 R 12 , —NR 16 C(O)NR 12 R 13 , —NR 16 S(O) 2 NR 12 R 13 or —NR 16 S(O)NR 12 R 13 , any of which is optionally substituted with one or more independent Q 1 substituents;

Q 1 is selected from H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NO 2 , —B(OH) 2 , —PO(OR 17 ) 2 , —PO(OR 17 )R 18 , NR 17 R 18 , —CONR 17 OH, C 0-12 alkyl-, —C 2-12 alkenyl, —C 2-12 alkynyl, aryl-C 0-12 alkyl-, heteroaryl-C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, aryl-C 0-12 cycloalkyl-, heteroaryl-C 3-12 cycloalkyl-, C 3-12 heterocycloalkyl-C 3-12 cycloalkyl-, C 3-12 cycloalkyl-C 3-12 cycloalkyl-, C 1-12 alkyl-C 3-12 heterocycloalkyl-, C 3-12 heterocycloalkyl-C 3-12 heterocycloalkyl-, aryl-C 3-12 heterocycloalkyl-, heteroaryl-C 3-12 heterocycloalkyl-, —OC 0-12 alkyl, —C(O)—C(O)NR 17 R 18 , —C(O)—C(O)OR 17 , —OC(O)R 17 , —NR 17 C(O)R 18 , —NR 17 S(O) 2 R 18 , —(CR 19 R 20 ) n3 C(O)R 17 , —(CR 19 R 20 ) n3 C(O)OR 17 , —(CR 19 R 20 ) n3 C(O)NR 17 R 18 , —(CR 19 R 20 ) n3 S(O) 2 NR 17 R 18 , —(CR 19 R 20 ) n3 NR 17 R 18 , —(CR 19 R 20 ) n3 OR 17 , —(CR 19 R 20 ) n3 S(O) n4 R 17 , —NR 21 C(O)NR 17 R 18 , —NR 21 S(O) 2 NR 17 R 18 or —NR 21 S(O)NR 17 R 18 , any of which is optionally substituted with one or more independent Q 2 substituents;

Q 2 is selected from one or more of H, D, halo, —CN, -oxo-, —CD 3 , —OCD 3 , —CF 3 , —OCF 3 , —OCHF 2 , —NO 2 , —B(OH) 2 , —PO(OR 27 ) 2 , —PO(OR 27 )R 28 , —CONR 27 OH, —CONR 27 R 28 C 0-12 alkyl-, —C 2-12 alkenyl, —C 2-12 alkynyl, —OC 0-12 alkyl, aryl-C 0-12 alkyl-, heteroaryl-C 0-12 alkyl-, C 3-12 cycloalkyl-C 0-12 alkyl-, C 3-12 heterocycloalkyl-C 0-12 alkyl-, aryl-C 0-12 cycloalkyl-, heteroaryl-C 3-12 cycloalkyl-, C 3-12 heterocycloalkyl-C 3-12 cycloalkyl-, C 3-12 cycloalkyl-C 3-12 cycloalkyl-, C 1-12 alkyl-C 3-12 heterocycloalkyl-, C 3-12 heterocycloalkyl-C 3-12 heterocycloalkyl-, aryl-C 3-12 heterocycloalkyl-, heteroaryl-C 3-12 heterocycloalkyl-, —C(O)—C(O)NR 27 R 28 , —C 0-12 alkylC(O)OR 27 , —C(O)—C(O)OR 27 , —OC(O)R 27 , —NR 27 C(O)R 28 , —NR 27 C(O)OR 28 , —NR 27 S(O) 2 R 28 , —(CR 29 R 30 ) n5 C(O)R 27 , —(CR 29 R 30 ) n5 C(O)OR 27 , —(CR 29 R 30 ) n5 C(O)NR 27 R 28 —(CR 29 R 30 ) n5 S(O) 2 NR 27 R 28 , —(CR 29 R 30 ) n5 NR 27 R 28 , —(CR 29 R 30 ) n5 OR 27 , —(CR 29 R 30 ) n5 S(O) n6 R 27 , —NR 30 C(O)NR 27 R 28 , —NR 30 S(O) 2 NR 27 R 28 , or —NR 30 S(O)NR 27 R 28 substituents, any of which may be optionally substituted;

R 5 , R 6 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , and R 16 are each independently selected from one or more of H, C 1-6 alkyl-, C 3-8 cycloalkyl-C 0-6 alkyl-, C 3-8 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, aryl-C 3-8 cycloalkyl-, aryl-C 3-8 heterocycloalkyl-, heteroaryl-C 1-6 alkyl-, heteroaryl-C 3-8 cycloalkyl- or heteroaryl-C 3-8 heterocycloalkyl-, any of which may be optionally substituted;

R 17 , R 18 , R 19 , R 20 , R 21 , R 27 , R 28 , R 29 , and R 30 are each independently selected from H, C 1-6 alkyl-, C 3-8 cycloalkyl-C 0-6 alkyl-, C 3-8 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, aryl-C 3-8 cycloalkyl-, aryl-C 3-8 heterocycloalkyl-, heteroaryl-C 1-6 alkyl-, heteroaryl-C 3-8 cycloalkyl- or heteroaryl-C 3-8 heterocycloalkyl-, any of which may be optionally substituted;

—NR 5 R 6 and —NR 12 R 13 are each independently a linear structure, or, R 5 and R 6 , or R 12 and R 13 , respectively, are taken together with the nitrogen atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m2 ;

—CR 10 R 11 and —CR 14 R 15 are each independently a linear structure, or, R 10 and R 11 , or R 14 and R 15 respectively, are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more heteroatoms selected from O, N, or S(O) m3 ;

—CR 19 R 20 is a linear structure, or, R 19 and R 20 are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m4 ;

—NR 17 R 18 is a linear structure, or, R 17 and R 18 are taken together with the nitrogen atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m5 ;

—CR 29 R 30 is a linear structure, or, R 29 and R 30 are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m6 ;

—NR 27 R 28 is a linear structure, or, R 27 and R 28 are taken together with the nitrogen atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m7 ;

wherein m1, m2, m3, m4, m5, m6, m7, n1, n2, n3, n4, n5 and n6 are each independently selected from 0, 1 or 2.

2. The compound or salt of claim 1 , wherein:

R 1 is selected from one of C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, or heteroaryl-C 0-8 alkyl-;

G 1 is selected from one of H, halo, —CN, -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —OC 0-8 alkyl, —S(O) n1 R 12 , —B(OH) 2 , —C 0-8 alkyl, —C 2-8 alkenyl, —C 2-8 alkynyl, C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, or heteroaryl-C 0-8 alkyl-.

3. The compound or salt of claim 1 , wherein G 1 is selected from 0 to 3 of H, halo, —CN, -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —OC 0-8 alkyl, —S(O) n1 R 12 , —B(OH) 2 , —C 0- 8 alkyl, —C 2-8 alkenyl, —C 2-8 alkynyl, C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, or heteroaryl-C 0-8 alkyl-.

4. The compound or salt of claim 1 , wherein:

R 2 is selected from C 0-8 alkyl-, C 3-8 cycloalkyl-C 0-8 alkyl-, or C 3-8 heterocycloalkyl-C 0-8 alkyl-;

R 2a is C 0-8 alkyl-;

G 2 is selected from one or more of H, halo, —CN, —CD 3 , —OCD 3 , —CF 3 , —OCF 3 , —OCHF 2 , or —OC 0-8 alkyl;

R 2 and R 2a are each independently a linear structure, or, R 2 and R 2a are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, or N.

5. The compound or salt of claim 1 , wherein G 2 is selected from 0 to 3 of H, halo, —CN, —CD 3 , —OCD 3 , —CF 3 , —OCF 3 , —OCHF 2 , or —OC 0-8 alkyl.

6. The compound or salt of claim 1 , wherein:

R 3 is selected from C 1-8 alkyl-, C 3-8 cycloalkyl-C 0-8 alkyl-, or C 3-8 heterocycloalkyl-C 0-8 alkyl-;

G 3 is selected from one or more of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —C 0-8 alkyl, —C 2-8 alkenyl, —C 2-8 alkynyl, —OC 0-8 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , or —C(O)OR 12 .

7. The compound or salt of claim 1 , wherein G 3 is selected from 0 to 3 of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —C 0-8 alkyl, —C 2-8 alkenyl, —C 2-8 alkynyl, —OC 0-8 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , or —C(O)OR 12 .

8. The compound or salt of claim 1 , wherein:

R 4 is selected from C 0-8 alkyl-, C 3-8 cycloalkyl-C 3-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, heteroaryl-C 0-8 alkyl-, heteroaryl-C 3-8 cycloalkyl-, heteroaryl-C 3-8 heterocycloalkyl-, or pyridine-N-oxide;

G 4 is selected from one or more of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —B(OH) 2 , —CONR 12 OH, —C 0-8 alkyl, C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, heteroaryl-C 0-8 alkyl-, —OC 0-8 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , —C(O)—C(O)NR 12 R 13 , —C(O)OR 12 , —C(O)—C(O)OR 12 , —OC(O)R 12 , —NR 12 C(O)R 13 , —NR 12 C(O)OR 13 , —(CR 14 R 15 )C(O)R 13 , —(CR 14 R 15 ) n1 S(O) 2 NR 12 R 13 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 S(O) n2 R 12 , or —NR 16 C(O)NR 12 R 13 .

9. The compound or salt of claim 1 , wherein G 4 is selected from 0 to 3 of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —B(OH) 2 , —CONR 12 OH, —C 0-8 alkyl, C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 alkyl-, heteroaryl-C 0-8 alkyl-, —OC 0-8 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , —C(O)—C(O)NR 12 R 13 , —C(O)OR 12 , —C(O)—C(O)OR 12 , —OC(O)R 12 , —NR 12 C(O)R 13 , —NR 12 C(O)OR 13 , —(CR 14 R 15 )C(O)R 13 , —(CR 14 R 15 ) n1 S(O) 2 NR 12 R 13 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 S(O) n2 R 12 , or —NR 16 C(O)NR 12 R 13 .

10. The compound or salt of claim 1 , wherein:

Q 1 is selected from H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , NR 17 R 18 , C 0-8 alkyl-, aryl-C 0-8 alkyl-, heteroaryl-C 0-8 alkyl-, C 3-8 cycloalkyl-C 0-8 alkyl-, C 3-8 heterocycloalkyl-C 0-8 alkyl-, aryl-C 0-8 cycloalkyl-, heteroaryl-C 3-8 cycloalkyl-, C 3-8 heterocycloalkyl-C 3-8 cycloalkyl-, C 3-8 cycloalkyl-C 3-8 cycloalkyl-, C 1-8 alkyl-C 3-8 heterocycloalkyl-, C 3-8 heterocycloalkyl-C 3-8 heterocycloalkyl-, aryl-C 3-8 heterocycloalkyl-, heteroaryl-C 3-8 heterocycloalkyl-, —OC 0-8 alkyl, —C(O)—C(O)NR 17 R 18 , —C(O)—C(O)OR 17 , —OC(O)R 17 , —NR 17 C(O)R 18 , —NR 17 S(O) 2 R 18 , —(CR 19 R 20 ) n3 C(O)R 17 , —(CR 19 R 20 ) n3 C(O)OR 17 , —(CR 19 R 20 ) n3 C(O)NR 17 R 18 , —(CR 19 R 20 ) n3 S(O) 2 NR 17 R 18 , —(CR 19 R 20 ) n3 NR 17 R 18 , —(CR 19 R 20 ) n3 OR 17 , —(CR 19 R 20 ) n3 S(O) n4 R 17 , —NR 21 C(O)NR 17 R 18 , —NR 21 S(O) 2 NR 17 R 18 , or —NR 21 S(O)NR 17 R 18 .

11. The compound or salt of claim 1 , wherein:

R 1 is selected from one of C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, or heteroaryl-C 0-6 alkyl-;

G 1 is selected from one of H, halo, —CN, -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —OC 0-6 alkyl, —S(O) n1 R 12 , —B(OH) 2 , —C 0-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, or heteroaryl-C 0-6 alkyl-.

12. The compound or salt of claim 1 , wherein G 1 is selected from 0 to 2 of H, halo, —CN, -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —OC 0-6 alkyl, —S(O) n1 R 12 , —B(OH) 2 , —C 0- 6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, or heteroaryl-C 0-6 alkyl-.

13. The compound or salt of claim 1 , wherein:

R 2 is selected from C 0-6 alkyl-, C 3-6 cycloalkyl-C 0-6 alkyl-, or C 3-6 heterocycloalkyl-C 0-6 alkyl-;

R 2a is C 0-6 alkyl-;

G 2 is selected from one or more of H, halo, —CN, —CD 3 , —OCD 3 , —CF 3 , —OCF 3 , —OCHF 2 , or —OC 0-6 alkyl;

R 2 and R 2a are each independently a linear structure, or, R 2 and R 2a are taken together with the carbon atom to which they are attached to form a 3-12 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, or N.

14. The compound or salt of claim 1 , wherein: R 2 and R 2a are each independently a linear structure, or, R 2 and R 2a are taken together with the carbon atom to which they are attached to form a 4-6 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, or N.

15. The compound or salt of claim 1 , wherein G 2 is selected from 0 to 2 of H, halo, —CN, —CD 3 , —OCD 3 , —CF 3 , —OCF 3 , —OCHF 2 , or —OC 0-6 alkyl.

16. The compound or salt of claim 1 , wherein:

R 3 is selected from C 1-6 alkyl-, C 3-6 cycloalkyl-C 0-6 alkyl-, or C 3-6 heterocycloalkyl-C 0-6 alkyl-;

G 3 is selected from one or more of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —C 0-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —OC 0-6 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , or —C(O)OR 12 .

17. The compound or salt of claim 1 , wherein G 3 is selected from 0 to 2 of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —C 0-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —OC 0-6 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , or —C(O)OR 12 .

18. The compound or salt of claim 1 , wherein:

R 4 is selected from C 0-6 alkyl-, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, heteroaryl-C 0-6 alkyl-, heteroaryl-C 3-6 cycloalkyl-, heteroaryl-C 3-6 heterocycloalkyl-, or pyridine-N-oxide;

G 4 is selected from one or more of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —B(OH) 2 , —CONR 12 OH, —C 0-6 alkyl, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, heteroaryl-C 0-6 alkyl-, —OC 0-6 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , —C(O)—C(O)NR 12 R 13 , —C(O)OR 12 , —C(O)—C(O)OR 12 , —OC(O)R 12 , —NR 12 C(O)R 13 , —NR 12 C(O)OR 13 , —(CR 14 R 15 )C(O)R 13 , —(CR 14 R 15 ) n1 S(O) 2 NR 12 R 13 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 S(O) n2 R 12 , or —NR 16 C(O)NR 12 R 13 .

19. The compound or salt of claim 1 , G 4 is selected from 0 to 2 of H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , —NR 5 R 6 , —NO 2 , —B(OH) 2 , —CONR 12 OH, —C 0-6 alkyl, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 alkyl-, heteroaryl-C 0-6 alkyl-, —OC 0-6 alkyl, —S(O) n1 R 12 , —C(O)R 12 , —C(O)NR 12 R 13 , —C(O)—C(O)NR 12 R 13 , —C(O)OR 12 , —C(O)—C(O)OR 12 , —OC(O)R 12 , —NR 12 C(O)R 13 , —NR 12 C(O)OR 13 , —(CR 14 R 15 )C(O)R 13 , —(CR 14 R 15 ) n1 S(O) 2 NR 12 R 13 , —(CR 14 R 15 ) n1 NR 12 R 13 , —(CR 14 R 15 ) n1 OR 12 , —(CR 14 R 15 ) n1 S(O) n2 R 12 , or —NR 16 C(O)NR 12 R 13 .

20. The compound or salt of claim 1 , wherein:

Q 1 is selected from H, D, halo, —CN, —CD 3 , —OCD 3 , -oxo-, —CF 3 , —OCF 3 , —OCHF 2 , NR 17 R 18 , C 0-6 alkyl-, aryl-C 0-6 alkyl-, heteroaryl-C 0-6 alkyl-, C 3-6 cycloalkyl-C 0-6 alkyl-, C 3-6 heterocycloalkyl-C 0-6 alkyl-, aryl-C 0-6 cycloalkyl-, heteroaryl-C 3-6 cycloalkyl-, C 3-6 heterocycloalkyl-C 3-6 cycloalkyl-, C 3-6 cycloalkyl-C 3-6 cycloalkyl-, C 1-6 alkyl-C 3-6 heterocycloalkyl-, C 3-6 heterocycloalkyl-C 3-6 heterocycloalkyl-, aryl-C 3-6 heterocycloalkyl-, heteroaryl-C 3-6 heterocycloalkyl-, —OC 0-6 alkyl, —C(O)—C(O)NR 17 R 18 , —C(O)—C(O)OR 17 , —OC(O)R 17 , —NR 17 C(O)R 18 , —NR 17 S(O) 2 R 18 , —(CR 19 R 20 ) n3 C(O)R 17 , —(CR 19 R 20 ) n3 C(O)OR 17 , —(CR 19 R 20 ) n3 C(O)NR 17 R 18 , —(CR 19 R 20 ) n3 S(O) 2 NR 17 R 18 , —(CR 19 R 20 ) n3 NR 17 R 18 , —(CR 19 R 20 ) n3 OR 17 , —(CR 19 R 20 ) n3 S(O) n4 R 17 , —NR 21 C(O)NR 17 R 18 , —NR 21 S(O) 2 NR 17 R 18 , or —NR 21 S(O)NR 17 R 18 .

21. The compound or salt of claim 1 , wherein:

R 2 is selected from methyl, ethyl, propyl, isopropyl, or one of the following groups:

and R 2a is selected H, methyl, ethyl, propyl, isopropyl; or

R 2 and R 2a are taken together with the carbon atom to which they are attached to form one of the following groups:

22. The compound or salt of claim 1 , wherein:

R 1 is selected from one of C 6 cycloalkyl-C 0-6 alkyl-, C 6 heterocycloalkyl-C 0-6 alkyl-, 6-membered-aryl-C 0-6 alkyl-, or 6-membered-heteroaryl-C 0-6 alkyl-,

wherein the 4-position of R 1 is hydrogen, and wherein R 1 is optionally substituted by one or more G 1 substituents at the 2, 3, 5 and 6 positions.

23. The compound or salt of claim 1 , wherein:

—NR 5 R 6 and —NR 12 R 13 are each independently a linear structure, or, R 5 and R 6 , or R 12 and R 13 , respectively, are taken together with the nitrogen atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m2 ;

—CR 10 R 11 and —CR 14 R 15 are each independently a linear structure, or, R 10 and R 11 , or R 14 and R 15 respectively, are taken together with the carbon atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more heteroatoms selected from O, N, or S(O) m3 ;

—CR 19 R 20 is a linear structure, or, R 19 and R 20 are taken together with the carbon atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m4 ;

—NR 17 R 18 is a linear structure, or, R 17 and R 18 are taken together with the nitrogen atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m5 ;

—CR 29 R 30 is a linear structure, or, R 29 and R 30 are taken together with the carbon atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m6 ;

—NR 27 R 28 is a linear structure, or, R 27 and R 28 are taken together with the nitrogen atom to which they are attached to form a 4-8 membered saturated or unsaturated ring, wherein said ring optionally includes one or more additional heteroatoms selected from O, N, or S(O) m7 ;

wherein m2, m3, m4, m5, m6, and m7 are each independently selected from 0, 1 or 2.

24. The compound or salt of claim 1 , which is represented by the Formula Ia:

wherein X 3 is selected from C═O, or CR 10 R 11 .

25. The compound or salt of claim 24 , wherein R 2a is hydrogen.

26. The compound or salt of claim 24 , wherein R 2 is C 1-12 alkyl-, C 3-12 cycloalkyl-, or C 1-12 heteroalkyl any of which is optionally substituted with one or more independent G 2 substituents.

27. The compound or salt of claim 24 , wherein R 1 is aryl or heteroaryl, any of which is optionally substituted with one or more independent G 1 substituents.

28. The compound or salt of claim 27 , wherein R 1 is aryl.

29. The compound or salt of claim 28 , wherein the 4-position of said aryl is H, and wherein the 2, 3, 5 and 6 positions of said aryl are optionally substituted by one or more G 1 substituents.

30. The compound or salt of claim 29 , wherein said 2, 3, 5, and 6 positions are optionally substituted with halo, C 1-6 alkyl, C 1-6 heteroalkyl, or C 3-8 cycloalkyl.

31. The compound or salt of claim 24 , wherein R 3 is C 1-12 alkyl or C 1-12 heteroalkyl.

32. The compound or salt of claim 24 , wherein R 4 is C 1-12 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl, aryl-C 1-6 alkyl, heteroaryl-C 1-6 alkyl, or C 3-12 heterocycloalkyl, any of which is optionally substituted with one or more independent Q 1 substituents.

33. The compound or salt of claim 24 , wherein X 3 is C═O.

34. The compound of salt of claim 24 , wherein X 3 is CR 10 R 11 wherein R 10 is hydrogen and R 11 is hydrogen or methyl.

35. The compound or salt of claim 1 , which is represented by the Formula Ih:

wherein X 3 is selected from C═O, or CR 10 R 11 .

36. The compound or salt of claim 35 , wherein the 4-position of the phenyl ring in Formula Ih is H, and wherein the 2, 3, 5 and 6 positions of the phenyl ring in Formula Ih are optionally substituted by one or more G 1 substituents.

37. The compound or salt of claim 35 , wherein R 3 is selected from methyl, ethyl, propyl, isopropyl, —(CH 2 ) 1-3 -cyclopropyl, C 3-8 cycloalkyl, —(CH 2 ) 1-3 CN, —(CH 2 ) 1-3 C(O)OH, or —(CH 2 ) 1-3 S(O) 2 Me.

38. The compound or salt of claim 35 , wherein:

X 1 is selected from C 1-2 alkyl or C═O;

X 2 is selected from C 1-2 alkyl, NR 3 , or O;

X 3 is selected from C═O or CR 10 R 11 ;

R 10 and R 11 are each independently equal to H or C 1-6 alkyl;

m and n are each equal to 1.

39. The compound or salt of claim 1 , wherein the compounds of Formula I are inhibitors of ATX.

40. A compound selected from:

(R)-N-(1-Cyclohexyl-2-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-3-methylbenzamide;

(R)-3-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-3-methyl-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

2-Fluoro-3-methyl-N-((2R,3R)-3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxopentan-2-yl)benzamide;

(R)-N-(1-(3-(Cyanomethyl)-1-(4-methoxyphenyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-2-Fluoro-N-(1-(1-(3-fluoro-4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-Cyanophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3-Cyanophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methylsulfonyl)phenyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(3-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-1H-indazol-5-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(2-methyl-2H-indazol-5-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(imidazo[1,2-a]pyridin-6-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(3-(methylsulfonyl)phenyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-1H-pyrazol-3-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-1H-pyrazol-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-1-(3-methylimidazo[1,5-a]pyridin-6-yl)-2,4-dioxo-1,3,8triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(2-methyl-1H-benzo[d]imidazol-6-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3,4-Dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(6-oxo-1,6-dihydropyridin-3-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclopentyl-2-(3-methyl-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(6-methoxypyridin-3-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(4-(trifluoromethoxy)phenyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(5-benzofuran)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-N-(1-(1-(1H-Benzo[d][1,2,3]triazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(3-Methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-3-(trifluoromethyl)benzamide;

(R)-3-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3,4-Dichloro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2, 5-Dichloro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

5-Ethyl-2-fluoro-N-((2R,3S)-3-methoxy-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

3-Ethyl-5-fluoro-N-((2R,3S)-3-methoxy-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

5-Ethyl-2-fluoro-N-((2R,3R)-3-methoxy-1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

3-Fluoro-N-((2R,3R)-1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxopentan-2-yl)-5-methylbenzamide;

(R)-5-Cyclopropyl-2-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Chloro-2-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-5-Cyclopropyl-2-fluoro-N-(1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)benzamide;

(R)-3-Ethyl-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3-Ethyl-5-fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3,5-Dichloro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

5-Cyclopropyl-2-fluoro-N-((2R,3R)-3-methoxy-1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-N-(1-(1-(4-methoxyphenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-6-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-cyclopropyl-2-fluorobenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-methylbenzamide;

(R)-N-(2-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-cyclopentyl-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(2-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-cyclobutyl-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-chloro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-methyl-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethoxy)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-methoxybenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(difluoromethoxy)-2-fluorobenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2,5-dichlorobenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2, 5-difluorobenzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-1-admantanecarboxyl amide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-chloro-5-(trifluoromethyl)benzamide;

(S)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

N-(2-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carbonyl)cyclopropyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxopropan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

N-(3-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carbonyl)oxetan-3-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-2-methyl-1-oxopropan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(Cyclopropylmethyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-Cyclopropyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(tetrahydro-2H-pyran-4-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

2-Fluoro-N-((R)-3-methyl-1-(3-methyl-2,4-dioxo-1-((S)-1-phenylethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-((tetrahydro-2H-pyran-4-yl)methyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

2-Fluoro-N-((R)-3-methyl-1-(3-methyl-2,4-dioxo-1-((R)-1-phenylethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-(Azetidin-3-ylmethoxy)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-N-(1-(1-(4-(cyanomethoxy)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(oxetan-3-ylmethoxy)phenyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(4-(2-hydroxyethoxy)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-(2-(Dimethylamino)ethoxy)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-N-(1-(1-(4-(Azetidin-3-ylamino)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(oxetan-3-ylamino)phenyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-Cyanobenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-Benzyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(4-fluorobenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(4-methoxybenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

2-Fluoro-N-((2R)-3-methyl-1-(3-methyl-2,4-dioxo-1-(1-phenylethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methylsulfonyl)benzyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-((2-methoxypyridin-4-yl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((2-methylpyridin-4-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-((6-methoxypyridin-3-yl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-((1H-Indazol-5-yl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-Chlorobenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(quinoxalin-6-ylmethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3-Cyanobenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(imidazo[1,2-a]pyridin-7-ylmethyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(3-(methylsulfonyl)benzyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3-Chlorobenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((2-methyl-1H-benzo[d]imidazol-6-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(2-fluoro-5-methoxybenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(2-fluoro-4-methoxybenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclopropyl-2-(3-methyl-2,4-dioxo-1-(quinoxalin-6-ylmethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclobutyl-2-(3-methyl-2,4-dioxo-1-(quinoxalin-6-ylmethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(pyrimidin-2-ylmethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclopentyl-2-(3-methyl-2,4-dioxo-1-(quinoxalin-6-ylmethyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclopentyl-2-(3-methyl-1-((2-methyl-[,2,4]triazolo[, 5-a]pyridin-7-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((2-methyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((2-methylbenzo[d]oxazol-5-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((4-methylthiazol-2-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((2-methylbenzo[d]oxazol-6-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(2-Chloro-4-methoxybenzyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-((1-methyl-6-oxo-1, 6-dihydropyridin-3-yl)methyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-((1-Acetylazetidin-3-yl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1,3-Dimethyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-Ethyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-isopentyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-Cyclopentyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-Methyl-4-(8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)phenylcarbamate;

(R)-N-(1-(1-(4-(Cyclopropanecarboxamido)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-3-Methyl-N-(2-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide;

(S)-3-Methyl-N-(2-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethyl)benzamide;

(R)-N-(1-Cyclohexyl-2-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-6-methylpicolinamide trifluoroacetic acid salt;

(R)-N,3-Dimethyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

5-Ethyl-2-fluoro-N-((2R,3S)-3-methoxy-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-yl)-1-oxobutan-2-yl)benzamide;

N-((2R,3S)-3-Methoxy-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-3-methylbenzamide;

3-Ethyl-N-((2R,3S)-3-methoxy-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

3-Ethyl-5-fluoro-N-((2R,3S)-3-methoxy-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Methyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)isonicotinamide;

(R)-3-Ethyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-4-Fluoro-3-methyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3-Fluoro-5-methyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-5-methyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3-Cyclopropyl-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-3-Chloro-4-cyano-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-N-(1-(1-(4-Carbamoylphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-3-methylbenzamide;

(R)-N-(1-(1-(3-Carbamoylphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-3-methylbenzamide;

(R)-4-(8-(2-(2-Fluoro-3-methylbenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)phenylboronic acid;

(R)-3-(8-(2-(2-Fluoro-3-methylbenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)phenylboronic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-3-methylbenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)-2-methoxybenzoic acid;

(R)-4-(8-(2-(5-Ethyl-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(5-Cyclopropyl-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-2-Chloro-4-(8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(3-(Cyclopropylmethyl)-8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-Cyclopentyl-2-(2-fluoro-5-(trifluoromethyl)benzamido)acetyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-N-(1-(1-(4-Carbamoylphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)-2-methylbenzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3,3-dimethylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(3-Chloro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(3-Methyl-8-(3-methyl-2-(2-methyl-5-(trifluoromethyl)benzamido)butanoyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethoxy)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-methoxybenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(1-Admantanecarboxamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(5-(Difluoromethoxy)-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(5-(Difluoromethoxy)-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethoxy)benzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-2-(4-(8-(2-(5-Ethyl-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)phenoxy)acetic acid;

(R)-N-(1-(1-(4-(2-Amino-2-oxoethoxy)phenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-N-(1-(1-(4-(Cyanomethoxy)phenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-N-(1-(1-(4-(2-(Dimethylamino)ethoxy)phenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-N-(1-(1-(4-Acetamidophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methylsulfonamido)phenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methylsulfonamido)phenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-Methyl-4-(8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)phenylcarbamate;

(R)-2-(8-(2-(3-Fluoro-5-methylbenzamido)-3-methylbutanoyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid;

(R)-2-Fluoro-3-methyl-N-(3-methyl-1-(3-(3-(methyl sulfonyl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-N-(1-(3-(Cyanomethyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-N-(1-(1-(4-Cyanophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-3-methylbenzamide;

(R)-N-(1-(1-(3-Cyanophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-3-methylbenzamide;

(R)-N-(1-(1-(4-Chlorophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(4-fluorophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3,4-Dichlorophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-p-tolyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(4-(trifluoromethyl)phenyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3-Chlorophenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(pyridin-2-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(pyridin-3-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(4-deuterium-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(Benzo[d][1,3]dioxol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(3-Chlorophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-N-(1-(1-(4-Chlorophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-N-(1-(1-(3-Bromophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-3-Methyl-N-(3-methyl-1-(3-methyl-4-oxo-1-(pyridin-3-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-N-(1-(1-(2-Chlorophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-N-(1-(1-(4-Methoxyphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-N-(1-(1-(3-Methoxyphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-N-(1-(1-(4-Bromophenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-3-methylbenzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methyl sulfonyl)phenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(1-(1-(4-methoxyphenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)benzamide;

(R)-5-Ethyl-2-fluoro-N-(3-methyl-1-(3-methyl-1-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(methyl sulfonyl)phenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-(imidazo[1,2-a]pyridin-6-yl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide trifluoroacetic acid salt;

(R)-3-Chloro-N-(3-methyl-1-(3-methyl-1-(1-methyl-6-oxo-1, 6-dihydropyridin-3-yl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-Cyclopentyl-2-(3-methyl-1-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-2-oxoethyl)-2-fluoro-5-(trifluoromethyl)benzamide;

2-Fluoro-N-((2R)-1-(1-(4-methoxyphenyl)-2,3-dimethyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

4-((R)-8-((R)-2-(5-Ethyl-2-fluorobenzamido)-3-methylbutanoyl)-2,3-dimethyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

4-((S)-8-((R)-2-(5-Ethyl-2-fluorobenzamido)-3-methylbutanoyl)-2,3-dimethyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

4-((R)-8-((R)-2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-2,3-dimethyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

4-((S)-8-((R)-2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-2,3-dimethyl-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-N-(1-(1-(1H-Benzo[d]imidazol-6-yl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-ethyl-2-fluorobenzamide;

(R)-3-Methyl-N-(3-methyl-1-oxo-1-(2-oxo-1-phenyl-3-oxa-1,8-diazaspiro[4.5]decan-8-yl)butan-2-yl)benzamide;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-1-(4-(oxetan-3-ylamino)phenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-2-Fluoro-N-(1-(1-((3-methoxycyclobutyl)methyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-(1H-1,2,4-Triazol-3-yl)phenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-Methyl-4-(8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoate;

(R)-4-(8-(2-(5-Cyclopropyl-2-fluorobenzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid;

(R)-N-(1-(1-(4-(2H-Tetrazol-5-yl)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(4-(2H-Tetrazol-5-yl)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethoxy)benzamide;

(R)-N-(1-(1-(4-(2H-Tetrazol-5-yl)phenyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(difluoromethoxy)-2-fluorobenzamide;

(R)-N-(1-(1-(4-(2H-Tetrazol-5-yl)phenyl)-3-methyl-4-oxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)picolinamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)nicotinamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)cyclohexanecarboxamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)isonicotinamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)pivalamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)benzamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)thiazole-2-carboxamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-4-(trifluoromethyl)thiazole-2-carboxamide;

(R)-N-(1-(1-(1H-Indazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-N-methyl-5-(trifluoromethyl)benzamide;

(R)-4-(3-(2-(Dimethylamino)ethyl)-8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid trifluoroacetic acid salt;

(R)-4-(3-(2-(Dimethylamino)ethyl)-8-(2-(2-fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-1-yl)benzoic acid trifluoroacetic acid salt;

(R)-2-Fluoro-N-(3-methyl-1-(3-methyl-2,4-dioxo-1-(pyridin-4-yl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-4-(8-(2-(2-Fluoro-5-(trifluoromethyl)benzamido)-3-methylbutanoyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-1-yl)pyridine 1-oxide;

(R)-2-Fluoro-N-(1-(1-(4-methoxycyclohexyl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-5-(trifluoromethyl)benzamide;

(R)-N-(1-(1-Cyclohexyl-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

(R)-N-(3-Methyl-1-(3-methyl-2,4-dioxo-1-(4-methoxy-d3-phenyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-3-(trifluoromethyl)-5-fluorobenzamide;

(R)-N-(3-Methyl-1-(3-methyl-2,4-dioxo-1-(4-ethoxyphenyl)-1,3,8-triazaspiro[4.5]decan-8-yl)-1-oxobutan-2-yl)-3-(trifluoromethyl)-5-fluorobenzamide;

(R)-N-(1-(1-(Benzo[d]oxazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide; and

(R)-N-(1-(1-(2-Methylbenzo[d]oxazol-5-yl)-3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)-3-methyl-1-oxobutan-2-yl)-2-fluoro-5-(trifluoromethyl)benzamide;

or a pharmaceutically acceptable salt thereof.

41. A pharmaceutical composition comprising the compound or salt of a compound according to claim 1 , formulated with or without one or more pharmaceutical carriers.

42. A method for inhibiting autotaxin (ATX) comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

43. The method of claim 42 , wherein the compound binds to and inhibits ATX providing a reduction in LPA levels.

44. The method according to claim 42 , comprising administering to the subject one or more additional therapeutically active agents selected from: corticosteroids, immunosuppressants, analgesics, anti-cancer agents, anti-inflammatories, non-steroidal anti-inflammatories, dual cyclooxygenase-1 and -2 inhibitors, cyclooxygenase-2 selective inhibitors, TNFα blockers, kinase inhibitors, chemokine receptor antagonists, bronchodilators, leukotriene receptor antagonists, leukotriene formation inhibitors, prostaglandin receptor antagonists, prostaglandin formation inhibitors, monoacylglycerol kinase inhibitors, phospholipase A1 inhibitors, phospholipase A2 inhibitors, lysophospholipase D (lyso PLD) inhibitors, autotaxin inhibitors, and LPA receptor antagonists.

Assignments (9)

Continuity (2)