2-pyrazole anilines and related analogs for inhibiting YAP/TAZ-TEAD

1. A compound of Formula I:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

is selected from the group consisting of:

wherein the bond marked with an “*” is attached to R 2 ;

X is selected from the group consisting of —CR 10a — and —N═; and X 1 is CR 1 ; or

X is CR 1 ; and X 1 is selected from the group consisting of —CR 10b ═ and —N═; or

X is selected from the group consisting of —CR 10a — and —N═; and X 1 is selected from the group consisting of —CR 10b ═ and —N═;

X 2 is selected from the group consisting of —CR 10c ═ and —N═;

X 3 is selected from the group consisting of —CR 10d ═ and —N═;

L 1 is selected from the group consisting of —NH— and —(CH 2 ) p —;

p is 0 or 1;

R 1 is selected from the group consisting of:

(i) hydrogen,

(ii) -L 2 -NR 4a R 4b , and

(iii) unsubstituted or substituted 4- to 8-membered heterocycle, wherein one or more substituents are selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) —C(═O)Z 2

(c) —C(═O)OZ 2 ,

(d) —C(═O)NZ 3 Z 4 ,

(e) —S(═O) 2 Z 8 ,

(f) —S(═O) 2 NZ 3 Z 4 ,

(g) cyano,

(h) —OZ 1 , and

(i) halogen;

(iv) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of —OZ 1 , —C(═O)Z 2 , halogen, C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl;

L 2 is selected from the group consisting —(CH 2 ) n — and C 3 -C 6 cycloalkylenyl

n is 0 or 1;

R 2 is selected from the group consisting of:

R 3a is selected from the group consisting of:

(i) hydrogen,

(ii) halogen,

(iii) cyano,

(iv) —OZ 1 ,

(v) —C(═O)NZ 3 Z 4 ,

(vi) —NZ 3 Z 4 ,

(vii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) cyano,

(b) —C(═O)NZ 3 Z 4 ,

(c) —OZ 1 ,

(d) —NZ 3 Z 4

(e) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

 (1) halogen,

 (2) cyano,

 (3) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of hydroxy, —OZ 1 , and —NZ 3 Z 4 ,

 (4) C 1 -C 6 haloalkyl,

 (5) C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy, and —NZ 3 Z 4 ,

 (6) —C(═O)NZ 3 Z 4 ,

 (7) —NZ 3 Z 4 ,

 (8) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

 (9) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halo, —OZ 1 , C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl,

 (10) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl,

 (11) —OZ 1 ,

 (12) —C(═O)OH,

 (13) hydroxy,

 (14) —NZ 5 C(═O)Z 2 ,

 (15) —NZ 5 S(═O) 2 Z 2 , and

 (16) —NZ 5 S(═O) 2 NZ 3 Z 4 ,

(f) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

 (1) C 1 -C 6 alkyl, and

 (2) C 1 -C 6 haloalkyl,

(g) unsubstituted or substituted 5- to 10-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:

 (1) halogen,

 (2) cyano,

 (3) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of hydroxy, —OZ 1 , and —NZ 3 Z 4 ,

 (4) C 1 -C 6 haloalkyl,

 (5) C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy, and —NZ 3 Z 4 ,

 (6) —C(═O)NZ 3 Z 4 ,

 (7) —NZ 3 Z 4 ,

 (8) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 ,

 (9) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halo, —OZ 1 , C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl,

 (10) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl,

 (11) —OZ 1 ,

 (12) —C(═O)OH,

 (13) hydroxy, and

 (14) —NZ 5 C(═O)Z 2 ,

(viii) C 1 -C 6 haloalkyl,

(ix) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of halogen and C 1 -C 6 alkyl;

(x) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) —C(═O)Z 2 , and

(c) —S(═O) 2 Z 8 ,

(xi) unsubstituted or substituted 5- to 10-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(c) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of hydroxy, —OZ 1 , and —NZ 3 Z 4 ,

(d) C 1 -C 6 haloalkyl,

(e) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy, and —NZ 3 Z 4 ,

(f) —C(═O)NZ 3 Z 4 ,

(g) —NZ 3 Z 4 ,

(h) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(i) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halo, —OZ 1 , C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl,

(j) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl,

(k) —OZ 1 ,

(l) —C(═O)OH,

(m) hydroxy, and

(n) —NZ 5 C(═O)Z 2 ;

R 3b , R 3c , and R 3d are independently selected from the group consisting of:

(i) hydrogen,

(ii) halogen,

(iii) cyano,

(iv) —C(═O)NZ 3 Z 4 ,

(v) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of hydroxy, —OZ 1 , and —NZ 3 Z 4 ,

(vi) C 1 -C 6 haloalkyl,

(vii) C 3 -C 6 cycloalkyl, and

(viii) OZ 1 ,

q is 0, 1, or 2;

R 4a is selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) hydroxy,

(c) cyano,

(d) —OZ 1 ,

(e) —SZ 1 ,

(f) —NZ 3 Z 4 ,

(g) —C(═O)Z 2 ,

(h) —C(═O)OH,

(i) —C(═O)OZ 2 ,

(j) —C(═O)NZ 3 Z 4 ,

(k) —NZ 5 C(═O)Z 2 ,

(l) —NZ 5 C(═O)OZ 2 ,

(m) —NZ 5 C(═O)NZ 3 Z 4 ,

(n) —S(═O) 2 Z 8 ,

(o) —S(═O) 2 NZ 3 Z 4 ,

(p) —S(═O)(═NZ 6 )Z 2 ,

(q) —S(═Z 6 )(═NZ 7 )Z 2 ,

(r) —S(═O)(═NZ 6 )NZ 3 Z 4 ,

(s) —NZ 5 S(═O) 2 Z 2 ,

(t) —NZ 5 S(═O) 2 NZ 3 Z 4 ,

(u) —NZ 5 S(═O)(═NZ 6 )Z 2 ,

(v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 , and

(w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 ,

(iii) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) hydroxy,

(c) cyano,

(d) —OZ 1 ,

(e) —SZ 1 ,

(f) —NZ 3 Z 4 ,

(g) —C(═O)Z 2

(h) C(═O)OH,

(i) —C(═O)OZ 2 ,

(j) —C(═O)NZ 3 Z 4 ,

(k) —NZ 5 C(═O)Z 2 ,

(l) —NZ 5 C(═O)OZ 2 ,

(m) —NZ 5 C(═O)NZ 3 Z 4 ,

(n) —S(═O) 2 Z 8 ,

(o) —S(═O) 2 NZ 3 Z 4 ,

(p) —S(═O)(═NZ 6 )Z 2 ,

(q) —S(═Z 6 )(═NZ 7 )Z 2 ,

(r) —S(═O)(═NZ 6 )NZ 3 Z 4 ,

(s) —NZ 5 S(═O) 2 Z 2 ,

(t) —NZ 5 S(═O) 2 NZ 3 Z 4 ,

(u) —NZ 5 S(═O)(═NZ 6 )Z 2 ,

(v) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 ,

(w) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 ,

(x) C 1 -C 6 alkyl,

(y) C 1 -C 6 haloalkyl, and

(z) C 3 -C 6 cycloalkyl,

(iv) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of —C(═O)OZ 2 , halogen, and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(v) —C(═O)Z 2

(vi) —C(═O)OZ 2 ,

(vii) —C(═O)NZ 3 Z 4 ,

(viii) —S(═O) 2 Z 8 ,

(ix) —S(═O) 2 NZ 3 Z 4 ,

(x) —S(═O)(═NZ 6 )Z 2 ,

(xi) —S(═Z 6 )(═NZ 7 )Z 2 , and

(xii) —S(═O)(═NZ 6 )NZ 3 Z 4 ,

R 4b is selected from the group consisting of:

(i) hydrogen, and

(ii) C 1 -C 6 alkyl;

each Z 1 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(iv) C 2 -C 6 alkynyl,

(v) C 3 -C 6 cycloalkyl,

(vi) C 3 -C 6 cycloalkenyl, and

(vii) C 1 -C 6 haloalkyl;

each Z 2 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(iv) C 2 -C 6 alkynyl,

(v) C 3 -C 6 cycloalkyl,

(vi) C 3 -C 6 cycloalkenyl, and

(vii) C 1 -C 6 haloalkyl;

each Z 3 is independently selected from the group consisting of:

(i) hydrogen;

(ii) C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(iv) C 2 -C 6 alkynyl,

(v) C 3 -C 6 cycloalkyl,

(vi) C 3 -C 6 cycloalkenyl,

(vii) C 1 -C 6 haloalkyl,

(viii) cyano, and

(ix) —C(═O)Z 2 ;

each Z 4 , Z 5 , Z 6 and Z 7 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl, and

(iii) C 3 -C 6 cycloalkyl;

each Z 8 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(iv) halogen, and

(v) hydroxy;

R 3b and R 3c are independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) C 1 -C 6 haloalkyl, and

(iv) C 3 -C 6 cycloalkyl;

is selected from the group consisting of:

(i) C 3 -C 6 cycloalkyl,

(ii) 4- to 10-membered heterocycle,

(iii) C 6 -C 10 aryl, and

(iv) 5- to 10-membered heteroaryl;

each R 5 is independently selected from the group consisting of:

(i) halogen,

(ii) hydroxy,

(iii) cyano,

(iv) —OZ 1 ,

(v) —SZ 1 ,

(vi) —NZ 3 Z 4 ,

(vii) —C(═O)Z 2

(viii) —C(═O)OH,

(ix) —C(═O)OZ 2 ,

(x) —C(═O)NZ 3 Z 4 ,

(xi) —NZ 5 C(═O)Z 2 ,

(xii) —NZ 5 C(═O)OZ 2 ,

(xiii) —NZ 5 C(═O)NZ 3 Z 4 ,

(xiv) —S(═O) 2 Z 8 ,

(xv) —S(═O) 2 NZ 3 Z 4 ,

(xvi) —S(═O)(═NZ 6 )Z 2 ,

(xvii) —S(═Z 6 )(═NZ 7 )Z 2 ,

(xviii) —S(═O)(═NZ 6 )NZ 3 Z 4 ,

(xix) —NZ 5 S(═O) 2 Z 2 ,

(xx) —NZ 5 S(═O) 2 NZ 3 Z 4 ,

(xxi) —NZ 5 S(═O)(═NZ 6 )Z 2 ,

(xxii) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 2 ,

(xxiii) —NZ 5 S(═O)(═NZ 6 )NZ 3 Z 4 ,

(xxiv) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of hydroxy, —OZ 1 , and —NZ 3 Z 4 ,

(xxv) C 1 -C 6 haloalkyl,

(xxvi) C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy, and —NZ 3 Z 4 ,

(xxvii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(xxviii) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halo, —OZ 1 , C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl, and

(xxix) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl and C 1 -C 6 haloalkyl,

R 6a is selected from the group consisting of:

(i) hydrogen, and

(ii) C 1 -C 6 alkyl;

R 6b is selected from the group consisting of:

(i) hydrogen, and

(ii) C 1 -C 6 alkyl,

m is 0, 1, 2, 3, or 4,

R 10a , R 10b , R 10c , and R 10d are independently selected from the group consisting of:

(i) hydrogen,

(ii) cyano,

(iii) hydroxy

(iv) —OZ 1 ,

(v) —SZ 1 ,

(vi) —NZ 3 Z 4 ,

(vii) C 1 -C 6 alkyl, and

(viii) C 1 -C 6 haloalkyl.

2. The compound of claim 1 of Formula III:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

3. The compound of claim 1 of Formula IV:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

4. The compound of claim 1 of Formula V:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

5. The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 1 is -L 2 -NR 4a R 4b .

6. The compound of claim 5 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein L 2 is —(CH 2 ) n —.

7. The compound of claim 6 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein n is 0.

8. The compound of claim 7 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein n is 1.

9. The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 4a is selected from the group consisting of —C(═O)Z 2 , —C(═O)OZ 2 , —C(═O)NZ 3 Z 4 , —S(═O) 2 Z 8 , and —S(═O) 2 NZ 3 Z 4 .

10. The compound of claim 9 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z 2 is selected from the group consisting of C 1 -C 6 alkyl and C 2 -C 6 alkenyl;

Z 3 is selected from the group consisting of C 1 -C 6 alkyl and C 2 -C 6 alkenyl; and

Z 4 is hydrogen.

11. The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 1 is unsubstituted or substituted 4-to 8-membered heterocycle.

12. The compound of claim 11 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 1 is:

13. The compound of claim 1 of Formula VI:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

X is selected from the group consisting of —CR 10a — and —N═; and

X 1 is selected from the group consisting of —CR 10b ═ and —N═.

14. The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein X, X 1 , X 2 , and X 3 are —CH═.

15. The compound of claim 1 of Formula VII:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

16. The compound of claim 1 of Formula VIII:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

17. The compound of claim 1 of Formula IX:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof.

18. The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

(S)-1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one; and

(R)-1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one.

19. A pharmaceutical composition comprising a compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, and a pharmaceutically acceptable carrier.

20. The compound of claim 1 selected from

1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

(S)-1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

(R)-1-(3-(4-(1-(difluoromethyl)-1H-pyrazol-3-yl)-6-(4-fluorophenyl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl)pyridazin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

1-(3-(6-(4-fluorophenyl)-2-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)pyrrolidin-1-yl)prop-2-en-1-one;

1-(3-(5-(4-fluorophenyl)-3-(1-methyl-1H-pyrazol-3-yl)pyrazin-2-yl)pyrrolidin-1-yl)prop-2-en-1-one;

1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-hydroxypyrrolidin-1-yl)prop-2-en-1-one;

(3R,4S)-1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-hydroxypyrrolidin-1-yl)prop-2-en-1-one;

(3S,4R)-1-(3-(6-(4-fluorophenyl)-4-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-4-hydroxypyrrolidin-1-yl)prop-2-en-1-one; and

1-(3-(4-(1-methyl-1H-pyrazol-3-yl)-2-(3,3,4,4-tetrafluoropyrrolidin-1-yl)pyrimidin-5-yl)pyrrolidin-1-yl)prop-2-en-1-one;

or a tautomer or pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a compound of claim 20 and a pharmaceutically acceptable carrier.