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US 2024/0409556 A1Published application
Benzopiperazine and related analogs for inhibiting yap/taz-tead
AssigneesSpringworks Therapeutics, Inc., Katholieke Universiteit Leuven, Vib Vzw
InventorsBrian LAWHORN, Stephen L. GWALTNEY, II, Arnaud MARCHAND, Bart VANDERHOYDONCK
Life of this patent
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Abstract
The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.
Claims71
A compound of Formula I:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
- Z is selected from —O—, —N—, —S—, —S(O)— or —S(O)2—,
- with the proviso that:
- when Z is —O—, —S—, —S(O)— or —S(O)2—, R3 is absent;
- X1 and X2 are independently selected from the group consisting of:
- (i) hydrogen,
- (ii) halogen,
- (iii) hydroxyl,
- (iv) cyano,
- (v) C1-C6 alkyl,
- (vi) C1-C6 haloalkyl,
- (vii) C2-C6 alkenyl, and
- (viii) carbonyl, or
- X1 and X2 are taken together with the carbon atoms they are bound to form an:
- (i) unsubstituted or substituted C3-C6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- (ii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- (iii) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2, or
- (iv) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- with the provisos that:
- (i) represents a double bond when X1 and X2 are taken together to form an aryl or heteroaryl, and
- (ii) represents a single bond when X1 and X2 are otherwise
- R1 is selected from the group consisting of:
- (i) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- (a) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) C1-C6 alkyl,
- (4) C3-C6 cycloalkyl,
- (5) C1-C6 haloalkyl,
- (6) —OZ1,
- (7) C2-C6 alkenyl, and
- (8) C2-C6 alkynyl,
- (b) unsubstituted or substituted C3-C6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) C1-C6 alkyl,
- (4) C3-C6 cycloalkyl,
- (5) C1-C6 haloalkyl, and
- (6) —OZ1,
- (c) C2-C6 alkynyl, and
- (d) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, C2-C8 alkenyl, and C1-C6 alkyl,
- (ii) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) C1-C6 alkyl,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl,
- (f) —OZ1, and
- (g) unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C1-C6 haloalkyl, and —OZ1,
- (iii) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) C1-C6 alkyl,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl,
- (f) —OZ1, and
- (g) unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C1-C6 haloalkyl, and —OZ1,
- (iv) unsubstituted or substituted C3-C6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) C1-C6 alkyl,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl, and
- (f) —OZ1,
- (v) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) C1-C6 alkyl,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl, and
- (f) —OZ1,
- (vi) —S(═O)2Z2, and
- (vii) —C(═O)Z2;
- R2 and R3 are independently selected from the group consisting of:
- (i) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z5,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —C(═O)Z1,
- g. —NZ3Z4,
- h. halogen,
- i. hydroxy,
- j. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- k. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- l. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (ii) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- a. halogen,
- b. cyano,
- c. C1-C6 alkyl,
- d. C3-C6 cycloalkyl,
- e. C1-C6 haloalkyl,
- f. —OZ1, and
- g. —C(═O)Z1,
- (iii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- a. halogen,
- b. cyano,
- c. C1-C6 alkyl,
- d. C3-C6 cycloalkyl,
- e. C1-C6 haloalkyl,
- f. —OZ1, and
- g. —C(═O)Z1,
- (iv) hydrogen,
- (v) —C(═O)Z1, and
- (vi) —S(═O)2Z5, or
- R2 and R3 are taken together with the carbon and nitrogen atom they are respectively bound to form an:
- (i) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- (1) cyano,
- (2) C3-C8 cycloalkyl,
- (3) —C(═O)OH,
- (4) —S(═O)2Z1,
- (5) —NZ3Z4,
- (6) halogen, and
- (7) unsubstituted or substituted C3-C6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- a. halogen,
- b. cyano,
- c. hydroxy,
- d. C1-C6 alkyl,
- e. C3-C6 cycloalkyl,
- f. C1-C6 haloalkyl,
- g. —OZ1,
- h. —C(═O)Z1, and
- i. S(═O)2Z5,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl,
- (f) —OZ1,
- (g) —C(═O)Z1,
- (h) —S(═O)2Z1,
- (i) unsubstituted or substituted C3-C6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) hydroxy,
- (4) C1-C6 alkyl,
- (5) C3-C6 cycloalkyl,
- (6) C1-C6 haloalkyl,
- (7) —OZ1,
- (8) —C(═O)Z1, and
- (9) S(═O)2Z5, and
- (j) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) C1-C6 alkyl,
- (4) C3-C6 cycloalkyl,
- (5) C1-C6 haloalkyl,
- (6) —OZ1,
- (7) —C(═O)Z1, and
- (8) S(═O)2Z5;
- each Z1 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) hydroxyl,
- (iii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z5,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —NZ3Z4,
- g. halogen,
- h. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- i. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- j. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (iv) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. —S(═O)2Z5,
- c. halogen, and
- d. unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- i. cyano,
- ii. —S(═O)2Z5,
- iii. C3-C8 cycloalkyl,
- iv. —C(═O)OH,
- v. —NZ3Z4,
- vi. halogen,
- vii. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- viii. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- ix. unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, cyano, —S(═O)2Z5, —NZ3Z4 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl,
- (viii) C1-C6 haloalkyl,
- (ix) —OZ2,
- (x) —C(═O)Z2,
- (xi) —NHZ2,
- (xii) unsubstituted or substituted C3-C8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xiii) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xiv) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and
- (xv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl;
- each Z2 is independently selected from the group consisting of:
- (i) C1-C6 alkyl,
- (ii) —NHZ3,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle,
- (iv) C2-C6 alkynyl,
- (v) C3-C6 cycloalkyl,
- (vi) C3-C6 cycloalkenyl,
- (vii) C1-C6 haloalkyl, and
- (viii) hydrogen;
- each Z3 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of C2-C6 alkenyl, cyano, —C(═O)OH, —S(═O)2Z5, halogen, —NZ3Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) —C(═O)Z7,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl, and
- (viii) C1-C6 haloalkyl;
- each Z4 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) C1-C6 alkyl, and
- (iii) C3-C6 cycloalkyl;
- each Z5 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C1-C6 alkyl,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) halogen, and
- (v) hydroxy;
- each Z6 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of C2-C6 alkenyl, cyano, —C(═O)OH, —S(═O)2H, —S(═O)2(unsubstituted or substituted C1-C6 alkyl), —S(═O)2(unsubstituted or substituted C2-C6 alkenyl), —S(═O)2(halogen), —S(═O)2OH, —NHZ4, —N(unsubstituted or substituted C1-C6 alkyl)Z4, —N(unsubstituted or substituted C2-C6 alkenyl)Z4, —N(—C(═O)Z7)Z4, —N(C2-C6 alkynyl)Z4, —N(C3-C6 cycloalkyl)Z4, —N(C3-C6 cycloalkenyl)Z4, —N(C1-C6 haloalkyl)Z4, and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2H, —S(═O)2(unsubstituted or substituted C1-C6 alkyl), —S(═O)2(unsubstituted or substituted C2—C6 alkenyl), —S(═O)2(halogen), —S(═O)2OH, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NHZ4, —N(unsubstituted or substituted C1-C6 alkyl)Z4, —N(unsubstituted or substituted C2-C6 alkenyl)Z4, —N(—C(═O)Z7)Z4, —N(C2-C6 alkynyl)Z4, —N(C3-C6 cycloalkyl)Z4, —N(C3-C6 cycloalkenyl)Z4, —N(C1-C6 haloalkyl)Z4, and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) —C(═O)Z7,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl, and
- (viii) C1-C6 haloalkyl;
- and
- each Z7 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) hydroxyl,
- (iii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z9,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —NHZ8,
- g. —N(unsubstituted or substituted C1-C6 alkyl)Z8,
- h. —N(unsubstituted or substituted C2-C6 alkenyl)Z8,
- i. —N(—C(═O) unsubstituted or substituted C3-C6 cycloalkyl)Z8,
- j. —N(—C(═O) unsubstituted or substituted C3-C6 cycloalkenyl)Z8,
- k. —N(—C(═O) unsubstituted or substituted C1-C6 haloalkyl)Z8,
- l. —N(C2-C6 alkynyl)Z8,
- m. —N(C3-C6 cycloalkyl)Z8,
- n. —N(C3-C6 cycloalkenyl)Z8,
- o. —N(C1-C6 haloalkyl)Z8,
- p. halogen,
- q. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- r. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- s. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (iv) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. —S(═O)2Z9,
- c. halogen, and
- (v) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. —S(═O)2Z9,
- c. C3-C8 cycloalkyl,
- d. —C(═O)OH,
- (vi) —NHZ8,
- (vii) —N(unsubstituted or substituted C1-C6 alkyl)Z8,
- (viii) —N(unsubstituted or substituted C2-C6 alkenyl)Z8,
- (ix) —N(unsubstituted or substituted C2-C6 alkynyl)Z8,
- (x) —N(unsubstituted or substituted C3-C6 cycloalkyl)Z8,
- (xi) —N(unsubstituted or substituted C3-C6 cycloalkenyl)Z8,
- (xii) —N(C1-C6 haloalkyl)Z8,
- (xiii) halogen,
- (xiv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 akyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xv) unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- (xvi) unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, cyano, —S(═O)2Z9, —NZ6Z8 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,
- (xvii) C2-C6 alkynyl,
- (xviii) C3-C6 cycloalkyl,
- (xix) C3-C6 cycloalkenyl,
- (xx) C1-C6 haloalkyl,
- (xxi) —OZ10,
- (xxii) —C(═O)Z10,
- (xxiii) —NHZ10,
- (xxiv) unsubstituted or substituted C3-C8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xxv) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xxvi) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl,
- (xxvii) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl;
- and
- each Z8 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) C1-C6 alkyl, and
- (iii) C3-C6 cycloalkyl;
- each Z9 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C1-C6 alkyl,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) halogen, and
- (v) hydroxy;
- and
- each Z10 is independently selected from the group consisting of:
- (i) C1-C6 alkyl,
- (ii) —NH2,
- (iii) —NH(C1-C6 alkyl),
- (iv) —N(C1-C6 alkyl)2,
- (v) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle,
- (vi) C2-C6 alkynyl,
- (vii) C3-C6 cycloalkyl,
- (viii) C3-C6 cycloalkenyl,
- (ix) C1-C6 haloalkyl, and
- (x) hydrogen.
334 more elements
A compound of Formula VIII:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
- each of Q1, Q2, Q3, and Q4 are independently ═N— or ═CH—;
- Z is selected from —O—, —N—, —S—, —S(O)— or —S(O)2—,
- with the proviso that:
- when Z is —O—, —S—, —S(O)— or —S(O)2—, R3 is absent;
- X1 and X2 are independently selected from the group consisting of:
- (i) hydrogen,
- (ii) halogen,
- (iii) hydroxyl,
- (iv) cyano,
- (v) C1-C6 alkyl,
- (vi) C1-C6 haloalkyl,
- (vii) C2-C6 alkenyl, and
- (viii) carbonyl, or
- X1 and X2 are taken together with the carbon atoms they are bound to form an:
- (i) unsubstituted or substituted C3-C6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- (ii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- (iii) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2, or
- (iv) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- i. halogen,
- ii. cyano,
- iii. C1-C6 alkyl,
- iv. C3-C6 cycloalkyl,
- v. C1-C6 haloalkyl, and
- vi. —OZ1,
- vii. —N(Z1)2, and
- viii. —C(O)N(Z1)2,
- with the provisos that:
- (i) represents a double bond when X1 and X2 are taken together to form an aryl or heteroaryl;
- and
- (ii) represents a single bond when X1 and X2 are otherwise;
- R2 and R3 are independently selected from the group consisting of:
- (i) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z5,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —C(═O)Z1,
- g. —NZ3Z4,
- h. halogen,
- i. hydroxy,
- j. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- k. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- l. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (ii) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- a. halogen,
- b. cyano,
- c. C1-C6 alkyl,
- d. C3-C6 cycloalkyl,
- e. C1-C6 haloalkyl,
- f. —OZ1, and
- g. —C(═O)Z1,
- (iii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- a. halogen,
- b. cyano,
- c. C1-C6 alkyl,
- d. C3-C6 cycloalkyl,
- e. C1-C6 haloalkyl,
- f. —OZ1, and
- g. —C(═O)Z1,
- (iv) hydrogen,
- (v) —C(═O)Z1, and
- (vi) —S(═O)2Z5, or
- R2 and R3 are taken together with the carbon and nitrogen atom they are respectively bound to form an:
- (i) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (a) halogen,
- (b) cyano,
- (c) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- (1) cyano,
- (2) C3-C8 cycloalkyl,
- (3) —C(═O)OH,
- (4) —S(═O)2Z1,
- (5) —NZ3Z4, and
- (6) halogen,
- (d) C3-C6 cycloalkyl,
- (e) C1-C6 haloalkyl,
- (f) —OZ1,
- (g) —C(═O)Z1,
- (h) —S(═O)2Z1,
- (i) unsubstituted or substituted C3-C6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) hydroxy,
- (4) C1-C6 alkyl,
- (5) C3-C6 cycloalkyl,
- (6) C1-C6 haloalkyl,
- (7) —OZ1,
- (8) —C(═O)Z1, and
- (9) S(═O)2Z5, and
- (j) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:
- (1) halogen,
- (2) cyano,
- (3) C1-C6 alkyl,
- (4) C3-C6 cycloalkyl,
- (5) C1-C6 haloalkyl,
- (6) —OZ1,
- (7) —C(═O)Z1, and
- (8) S(═O)2Z5;
- each Z1 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) hydroxyl,
- (iii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z5,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —NZ3Z4,
- g. halogen,
- h. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- i. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- j. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (iv) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. —S(═O)2Z5,
- c. halogen, and
- d. unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- i. cyano,
- ii. —S(═O)2Z5,
- iii. C3-C8 cycloalkyl,
- iv. —C(═O)OH,
- v. —NZ3Z4,
- vi. halogen,
- vii. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- viii. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- ix. unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, cyano, —S(═O)2Z5, —NZ3Z4 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl,
- (viii) C1-C6 haloalkyl,
- (ix) —OZ2,
- (x) —C(═O)Z2,
- (xi) —NHZ2,
- (xii) unsubstituted or substituted C3-C8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xiii) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xiv) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and
- (xv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl;
- each Z2 is independently selected from the group consisting of:
- (i) C1-C6 alkyl,
- (ii) —NHZ3,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle,
- (iv) C2-C6 alkynyl,
- (v) C3-C6 cycloalkyl,
- (vi) C3-C6 cycloalkenyl,
- (vii) C1-C6 haloalkyl, and
- (viii) hydrogen;
- each Z3 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of C2-C6 alkenyl, cyano, —C(═O)OH, —S(═O)2Z5, halogen, —NZ3Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) —C(═O)Z7,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl, and
- (viii) C1-C6 haloalkyl;
- each Z4 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) C1-C6 alkyl, and
- (iii) C3-C6 cycloalkyl;
- each Z5 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C1-C6 alkyl,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) halogen, and
- (v) hydroxy;
- each Z6 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of C2-C6 alkenyl, cyano, —C(═O)OH, —S(═O)2H, —S(═O)2(unsubstituted or substituted C1-C6 alkyl), —S(═O)2(unsubstituted or substituted C2-C6 alkenyl), —S(═O)2(halogen), —S(═O)2OH, —NHZ4, —N(unsubstituted or substituted C1-C6 alkyl)Z4, —N(unsubstituted or substituted C2-C6 alkenyl)Z4, —N(—C(═O)Z7)Z4, —N(C2-C6 alkynyl)Z4, —N(C3-C6 cycloalkyl)Z4, —N(C3-C6 cycloalkenyl)Z4, —N(C1-C6 haloalkyl)Z4, and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2H, —S(═O)2(unsubstituted or substituted C1-C6 alkyl), —S(═O)2(unsubstituted or substituted C2-C6 alkenyl), —S(═O)2(halogen), —S(═O)2OH, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NHZ4, —N(unsubstituted or substituted C1-C6 alkyl)Z4, —N(unsubstituted or substituted C2-C6 alkenyl)Z4, —N(—C(═O)Z7)Z4, —N(C2-C6 alkynyl)Z4, —N(C3-C6 cycloalkyl)Z4, —N(C3-C6 cycloalkenyl)Z4, —N(C1-C6 haloalkyl)Z4, and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) —C(═O)Z7,
- (v) C2-C6 alkynyl,
- (vi) C3-C6 cycloalkyl,
- (vii) C3-C6 cycloalkenyl, and
- (viii) C1-C6 haloalkyl;
- each Z7 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) hydroxyl,
- (iii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. C1-C6 alkyl,
- c. —S(═O)2Z9,
- d. C3-C8 cycloalkyl,
- e. —C(═O)OH,
- f. —NHZ8,
- g. —N(unsubstituted or substituted C1-C6 alkyl)Z8,
- h. —N(unsubstituted or substituted C2-C6 alkenyl)Z8,
- i. —N(—C(═O) unsubstituted or substituted C3-C6 cycloalkyl)Z8,
- j. —N(—C(═O) unsubstituted or substituted C3-C6 cycloalkenyl)Z8,
- k. —N(—C(═O) unsubstituted or substituted C1-C6 haloalkyl)Z8,
- l. —N(C2-C6 alkynyl)Z8,
- m. —N(C3-C6 cycloalkyl)Z8,
- n. —N(C3-C6 cycloalkenyl)Z8,
- o. —N(C1-C6 haloalkyl)Z8,
- p. halogen,
- q. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- r. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- s. unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, and cyano,
- (iv) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:
- a. cyano,
- b. —S(═O)2Z9,
- c. halogen, and
- (v) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of:
- e. cyano,
- f. —S(═O)2Z9,
- g. C3-C8 cycloalkyl,
- h. —C(═O)OH,
- (vi) —NHZ8,
- (vii) —N(unsubstituted or substituted C1-C6 alkyl)Z8,
- (viii) —N(unsubstituted or substituted C2-C6 alkenyl)Z8,
- (ix) —N(unsubstituted or substituted C2-C6 alkynyl)Z8,
- (x) —N(unsubstituted or substituted C3-C6 cycloalkyl)Z8,
- (xi) —N(unsubstituted or substituted C3-C6 cycloalkenyl)Z8,
- (xii) —N(C1-C6 haloalkyl)Z8,
- (xiii) halogen,
- (xiv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 akyl, and C2-C6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xv) unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 Alkyl, and C2-C6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and
- (xvi) unsubstituted or substituted C6-C10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 haloalkyl, cyano, —S(═O)2Z9, —NZ6Z8 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,
- (xvii) C2-C6 alkynyl,
- (xviii) C3-C6 cycloalkyl,
- (xix) C3-C6 cycloalkenyl,
- (xx) C1-C6 haloalkyl,
- (xxi) —OZ10,
- (xxii) —C(═O)Z10,
- (xxiii) —NHZ10,
- (xxiv) unsubstituted or substituted C3-C8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xxv) unsubstituted or substituted C6-C10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (xxvi) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl,
- (xxvii) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C1-C6 alkyl, and C2-C6 alkenyl;
- and
- each Z8 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) C1-C6 alkyl, and
- (iii) C3-C6 cycloalkyl;
- each Z9 is independently selected from the group consisting of:
- (i) hydrogen,
- (ii) unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C1-C6 alkyl,
- (iii) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ6Z4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,
- (iv) halogen, and
- (v) hydroxy;
- and
- each Z10 is independently selected from the group consisting of:
- (i) C1-C6 alkyl,
- (ii) —NH2,
- (iii) —NH(C1-C6 alkyl),
- (iv) —N(C1-C6 alkyl)2,
- (v) unsubstituted or substituted C2-C6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, halogen and unsubstituted or substituted C1-C6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O)2Z5, —NZ3Z4 and 4- to 8-membered heterocycle,
- (vi) C2-C6 alkynyl,
- (vii) C3-C6 cycloalkyl,
- (viii) C3-C6 cycloalkenyl,
- (ix) C1-C6 haloalkyl, and
- (x) hydrogen.
273 more elements
A compound of Formula IX:
- or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
- each of Q1, Q2, Q3, and Q4 are independently ═N— or ═CH—;
- each of Q5, Q6, Q7, and Q8 are independently ═N— or ═CR—, wherein each R is, individually, H or C1-C6 alkyl;
- L is —O— or —NR2, wherein R2 is H or C1-C6 alkyl (e.g., Me);
- each of Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh are independently H or C1-C6 alkyl (e.g., Me), or one or more of Ra and Rb, Rc and Rd, Re and Rf, and/or Rg and Rh, together with the carbon atom to which they are attached, for a carbonyl (—C(═O)) group;
- and
- R1 is H or C1-C6 alkyl.
4 more elements
A compound or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:
- 8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;
- (R)-8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;
- (S)-8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;
- N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;
- (R)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;
- (S)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;
- 1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;
- (R)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;
- (S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;
- N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;
- (6aR,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;
- (6aR,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;
- and
- (6aR,8S)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid.
11 more elements
(canceled)
(canceled)
(canceled)
(canceled)
(canceled)
Dependencies are inferred from the claim text.