IP Library › Patent Application 17909153

Patent Application

App. No. 17/909,153

STAT INHIBITORY COMPOUNDS AND COMPOSITIONS

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US None
App. No.: 17/909,153

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for the inhibition of Signal Transducer and Activator of Transcription 5a and 5b (STAT5). Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as, for example, breast cancer and pancreatic cancer.

Claims (228)

1 . A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 1 is substituted or unsubstituted phenyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted naphthyl, or substituted or unsubstituted mono- or bi-cyclic heteroaryl, wherein the mono- or bi-cyclic heteroaryl contains 1 to 4 heteroatoms selected from O, N, and S;

R 2 is substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 3 -C 7 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, or substituted or unsubstituted mono- or bi-cyclic heteroaryl, wherein the mono- or bi-cyclic heteroaryl contains 1 to 4 heteroatoms selected from O, N, and S;

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

R 4 is —OR 11 , —C 0-6 alkylene-R 41 , sulfonic acid, sulfinic acid, tetrazole, acyl-sulfonamide, C(O)N(R 11 ) 2 , C(O)OR 11 , S(O) 2 N(R 11 ) 2 , or carboxylic acid or an isostere thereof, wherein the alkylene is substituted or unsubstituted and wherein R 41 is sulfonic acid, sulfinic acid, tetrazole, acyl-sulfonamide, C(O)N(R 11 ) 2 , C(O)OR 11 , S(O) 2 N(R 11 ) 2 , or carboxylic acid or an isostere thereof;

each of R 7 and R 8 is independently selected from the group consisting of H, F, amino, —OR 11 , substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, or R 7 and R 8 , taken together with the carbon to which they are attached form a substituted or unsubstituted 3, 4, 5, or 6-membered ring;

each of R 5 and R 6 is independently selected from hydrogen, F, —CN, —OR 11 , —SR 11 , —N(R 11 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, and substituted or unsubstituted C 3 -C 7 heterocycloalkyl, or R 5 and R 6 , taken together form an oxo, oxime, or with the carbon to which they are attached form a substituted or unsubstituted spirocyclic 3, 4, 5, or 6-membered ring,

wherein each of R 9 and R 10 is independently selected from the group consisting of H, F, amino, —OR 11 , substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, or R 9 and R 10 , taken together with the carbon to which they are attached form a substituted or unsubstituted 3, 4, 5, or 6-membered ring; or

R 5 and R 9 , taken together with the intervening atoms to which they are attached form a 4, 5 or 6-membered ring,

wherein R 6 is selected from hydrogen, F, —CN, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(═O)R 11 , —C(═O)R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, and substituted or unsubstituted C 3 -C 7 heterocycloalkyl,

wherein R 10 is selected from the group consisting of H, F, amino, —OR 11 , substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, wherein the alkyl, haloalkyl or heteroalkyl is optionally substituted with hydroxy, amino, or methoxy,

provided that p is 1 and q is 1;

each of R B and R B1 is independently halogen, D, —CN, —NO 2 , —OR 11 , —SR 11 , —N(R 11 ) 2 , —NR 11 S(═O) 2 R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl;

X is O, NR 11 , or absent;

each R 11 is independently H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl;

each of n and q is independently 0, 1, 2, or 3;

p is 1, 2, or 3; and

m is 0, 1, 2, or 3.

2 . The compound of claim 1 , wherein each R 6 is independently selected from H, F, —CN, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, and substituted or unsubstituted C 1 -C 6 alkoxy.

3 . The compound of claim 1 , wherein each R 6 is independently selected from H, F, methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 F, —OCF 3 , —OH, —OCH 3 , —OC 2 CH 3 , —OC 2 OMe, and —OC 2 C 2 OH.

4 . The compound of claim 1 , wherein each R 6 is H.

5 . The compound of claim 1 , wherein X is O.

6 . The compound of claim 1 , wherein p is 1; n is 0 or 1; and q is 0 or 1.

7 . The compound of claim 1 , wherein the compound is

8 . The compound of claim 1 , wherein the compound has a structure of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

each of R 7 and R 8 is independently selected from the group consisting of H, F, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, or R 7 and R 8 , taken together with the carbon to which they are attached form a substituted or unsubstituted 3, 4, 5, or 6-membered ring;

R 5 is selected from hydrogen, F, —CN, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, and substituted or unsubstituted C 3 -C 7 heterocycloalkyl,

wherein each of R 9 and R 10 is independently selected from the group consisting of H, F, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, or R 9 and R 10 , taken together with the carbon to which they are attached form a substituted or unsubstituted 3, 4, 5, or 6-membered ring; or

R 5 and R 9 , taken together with the intervening atoms to which they are attached form a 4, 5 or 6-membered ring, and R 10 is selected from the group consisting of H, F, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, wherein the alkyl, haloalkyl or heteroalkyl is optionally substituted with hydroxy, amino, or methoxy;

each of R B and R B1 is independently halogen, D, —CN, —NO 2 , —OR 11 , —SR 11 , —N(R 11 ) 2 , NR 11 S(═O) 2 R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl;

m is 0, 1, 2, or 3.

9 . The compound of claim 1 or 8 , wherein the compound has a structure of Formula (IIa), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

R 5 and R 9 , taken together with the intervening atoms to which they are attached form a 4, 5 or 6-membered ring, and R 10 is selected from the group consisting of H, F, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C1-C6heteroalkyl, wherein the alkyl, haloalkyl or heteroalkyl is optionally substituted with hydroxy, amino, or methoxy;

m is 0, 1, 2, or 3.

10 . The compound of claim 1 or 8 , wherein the compound has a structure of Formula (IIb), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

m is 0, 1, 2, or 3.

11 . The compound of claim 1 , wherein each of R 5 is independently selected from the group consisting of H, F, —OR 11 , —SR 11 , -N(R 11 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, and substituted or unsubstituted C 3 -C 7 heterocycloalkyl.

12 . The compound of claim 1 , wherein each of R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of H, amino, F, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, wherein the alkyl, haloalkyl, and heteroalkyl is optionally substituted with hydroxy, amino, or methoxy.

13 . The compound of claim 1 , wherein each of R 7 , R 8 , R 9 , and R 10 is H.

14 . The compound of claim 1 , wherein the compound has a structure of Formula (III), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

m is 0, 1, 2, or 3.

15 . The compound of claim 1 , wherein R B1 is halogen.

16 . The compound of claim 15 , wherein R B1 is F or Cl.

17 . The compound of claim 1 , wherein R B1 is a linear or branched, substituted or unsubstituted C 1 -C 6 alkyl.

18 . The compound of claim 17 , wherein R B1 is methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, linear or branched pentyl, linear or branched hexyl, —CF 3 , —C 2 NH 2 , —CH 2 CF 3 , —CH 2 CHNH 2 , —CH 2 C 2 F, —CH 2 OH, or —CH 2 C 2 OH.

19 . The compound of claim 1 , wherein R B1 is substituted or unsubstituted —C 0-3 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-3 alkylene-C 3-7 heterocycloalkyl.

20 . The compound of claims 19 , wherein R B1 is C 3-6 cycloalkyl, —CH 2 -C 3-6 cycloalkyl, —(C 2 ) 2 —C 3-6 cycloalkyl, —(C 2 ) 3 —C 3-6 cycloalkyl, C 3-5 heterocycloalkyl, —CH 2 —C 3-5 heterocycloalkyl, —(C 2 ) 2 —C 3-5 heterocycloalkyl, or —(C 2 ) 3 —C 3-5 heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl is substituted or unsubstituted.

21 . The compound of claim 18 , wherein the cycloalkyl or heterocycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl is optionally substituted, and wherein 0 to 2 of the ring carbon atoms are optionally and independently replaced by nitrogen, oxygen and sulfur.

22 . The compound of claim 19 , wherein R B1 is

23 . The compound of claim 19 , wherein R B1 is

24 . The compound of claim 1 , wherein R B1 is —OR 11 .

25 . The compound of claim 24 , wherein R B1 is OH.

26 . The compound of claim 24 , wherein R B1 is substituted or unsubstituted —O—C 1 -C 6 alkyl.

27 . The compound of claim 26 , wherein R B1 is

28 . The compound of claim 1 , wherein R B1 is substituted or unsubstituted —O—C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —O—C 0-6 alkylene-C 3-7 heterocycloalkyl.

29 . The compound of claim 28 , wherein R B1 is

30 . The compound of claim 1 , wherein R B1 is —N(R 11 ) 2 .

31 . The compound of claim 30 , wherein R B1 is —N(CH 3 ) 2 , —NHCH 3 , —N(C 2 CH 3 ) 2 , —NHCH 2 CH 3 , or —N(C 2 C 2 CH 3 ) 2 .

32 . The compound of claim 1 , wherein R B1 is —NR 11 S(═O) 2 R 11 .

33 . The compound of claim 32 , wherein R B1 is —NCH 3 S(═O) 2 CH 3 .

34 . The compound of claims 1 , wherein m is 0 or 1.

35 . The compound of claim 1 , wherein each R B is independently halogen, D, —CN, —OR 11 , —SR 11 , —N(R 11 ) 2 , —NR 11 S(═O) 2 R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted —C 0-3 alkylene-C 3-6 cycloalkyl, or substituted or unsubstituted —C 0-3 alkylene-C 3-5 heterocycloalkyl.

36 . The compound of claim 35 , wherein each R B is independently a halogen selected from F and Cl.

37 . The compound of claim 35 , wherein each R B is independently linear or branched, substituted or unsubstituted C 1 -C 6 alkyl.

38 . The compound of claim 37 , wherein each C 1 -C 6 alkyl is independently methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, linear or branched pentyl, linear or branched hexyl, —CF 3 , —CH 2 NH 2 , —CH 2 CF 3 , —CH 2 CHNH 2 , —CH 2 C 2 F, —CH 2 OH, or —CH 2 C 2 OH.

39 . The compound of claim 35 , wherein each of R B is independently substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl.

40 . The compound of claim 39 , wherein each of R B is independently C 3-6 cycloalkyl, —CH 2 —C 3-6 cycloalkyl, —(C 2 ) 2 —C 3-6 cycloalkyl, —(C 2 ) 3 —C 3-6 cycloalkyl, C 3-5 heterocycloalkyl, —C 2 —C 3-5 heterocycloalkyl, —(C 2 ) 2 —C 3-5 heterocycloalkyl, or —(C 2 ) 3 —C 3 -sheterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl is substituted or unsubstituted.

41 . The compound of claim 39 , wherein the cycloalkyl or heterocycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl is optionally substituted, and wherein 0 to 2 of the ring carbon atoms are optionally and independently replaced by nitrogen, oxygen and sulfur.

42 . The compound of claim 39 , wherein each of the cycloalkyl is independently

43 . The compound of claim 39 , wherein each of the heterocycloalkyl is independently

44 . The compound of claim 35 , wherein each R B is independently —OR 11 .

45 . The compound of claim 44 , wherein each —OR 11 is independently OH, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, —O—C 1 -C 6 heteroalkyl, —O—C 0-6 alkylene-C 3-8 cycloalkyl, or —O—C 0-6 alkylene-C 3-7 heterocycloalkyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is substituted or unsubstituted.

46 . The compound of claim 44 , wherein each R B is independently

47 . The compound of claim 44 , wherein each R B is independently

48 . The compound of claim 35 , wherein each R B is independently —N(R 11 ) 2 .

49 . The compound of claim 48 , wherein each R B is independently —N(CH 3 ) 2 , —NHCH 3 , —N(C 2 CH 3 ) 2 , —NHC 2 CH 3 , or —N(C 2 C 2 CH 3 ) 2 .

50 . The compound of claim 35 , wherein at least one R B is —NR 11 S(═O) 2 R 11 .

51 . The compound of claim 50 , wherein the -NR 11 S(═O)2R 11 is —NCH 3 S(═O) 2 CH 3 .

52 . The compound of claim 1 , wherein R 4 is COOH or an isostere thereof.

53 . The compound of claim 1 , wherein R 4 is SO 2 H.

54 . The compound of claim 1 , wherein R 4 is —OR 11 .

55 . The compound of claim 54 , wherein R 4 is

56 . The compound of claim 1 , wherein

57 . The compound of claim 1 , wherein R 1 is substituted or unsubstituted phenyl.

58 . The compound of claim 57 , wherein R 1 is substituted phenyl, and wherein the phenyl is substituted with 1 to 5 substituents independently selected from halogen, D, —CN, —NO 2 , —OR 11 , —N(R 11 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, and substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl.

59 . The compound of claim 58 , wherein R 1 is substituted phenyl, and wherein the phenyl is substituted with F or Cl.

60 . The compound of claim 58 , wherein R 1 is substituted phenyl, wherein the phenyl is substituted with —O—C 1 -C 6 alkyl, and wherein the alkyl is substituted or unsubstituted.

61 . The compound of claim 58 , wherein R 1 is substituted phenyl, and wherein the phenyl is substituted with one or two C 1 -C 6 alkyl, and wherein the alkyl is linear or branched, substituted or unsubstituted.

62 . The compound of claim 58 , wherein R 1 is substituted phenyl, and wherein the phenyl is substituted with one or two C 3-8 cycloalkyl, and wherein the cycloalkyl is substituted or unsubstituted.

63 . The compound of claim 58 , wherein R 1 is

64 . The compound of claim 58 , wherein R 1 is

65 . The compound of claim 64 , wherein R 1 is

66 . The compound of claim 58 , wherein Ris naphthyl.

67 . The compound claim 1 , wherein R 1 is substituted or unsubstituted C 3 -C 8 cycloalkyl.

68 . The compound of claim 67 , wherein R 1 is

69 . The compound of claim 1 , wherein R 1 is substituted or unsubstituted monocyclic heteroaryl containing 1, 2, or 3 nitrogen(s).

70 . The compound of claim 69 , wherein R 1 is substituted or unsubstituted pyridinyl, pyridazinyl, or pyrimidinyl.

71 . The compound of claim 1 , wherein R 1 is substituted or unsubstituted bicyclic heteroaryl comprising 1 to 2 N.

72 . The compound of claim 71 , wherein R 1 is

73 . A compound of Formula (IV), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

each of R 7 and R 8 is independently selected from the group consisting of H, F, amino, —OR 11 , substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, wherein the alkyl is optionally substituted with hydroxy, amino, or methoxy, or R 7 and R 8 , taken together with the carbon to which they are attached form a substituted or unsubstituted 3, 4, 5, or 6-membered ring;

R 5 and R 9 , taken together with the intervening atoms to which they are attached form a 4, 5 or 6-membered ring,

provided that p is 1 and q is 1;

each of R A1 , R A2 , R A3 , R A4 , and R A5 is independently selected from hydrogen, halogen, —CN, —NO 2 , —OR 11 , —N(R 11 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, and substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl, wherein

at least one of R A1 and R A3 is substituted or unsubstituted —C 3 -C 8 cycloalkyl, substituted or unsubstituted —C 3 -C 7 heterocycloalkyl, substituted or unsubstituted —O—C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —O—C 0-6 alkylene-C 3-7 heterocycloalkyl;

each of R B is independently halogen, D, —CN, —NO 2 , —OR 11 , —SR 11 , —N(R 11 ) 2 , —NR 11 S(═O) 2 R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl;

X is O, NR 11 , or absent;

each of n and q is independently 0, 1, 2, or 3;

p is 1, 2, or 3; and

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

provided that when (i)

(ii) each of n, p, and q is 1, (iii) R 2 is phenyl substituted with 1-5 halogens, and (iv) R A1 and R A3 are both C 3 -C 5 unsubstituted cycloalkyl, or one of R A1 and R A3 is C 3 -C 5 unsubstituted cycloalkyl and the other is hydrogen or unsubstituted t-butyl,

then R A4 and R A5 are not the same.

74 . The compound of claim 73 , wherein the compound is

75 . The compound of claim 73 , wherein each of R 5 and R 6 is independently selected from the group consisting of H, F, —OR 11 , —SR 11 , —N(R 11 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, and substituted or unsubstituted C 3 -C 7 heterocycloalkyl.

76 . The compound of claim 73 , wherein each of R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of H, amino, F, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted mono-C 1 -C 6 alkylamino, substituted or unsubstituted di-C 1 -C 6 alkylamino, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, and substituted or unsubstituted C 1 -C 6 heteroalkyl, wherein the alkyl, haloalkyl, and heteroalkyl is optionally substituted with hydroxy, amino, or methoxy.

77 . The compound of claim 76 , wherein each of R 7 , R 8 , R 9 , and R 10 is H.

78 . The compound of claim 73 , wherein X is 0.

79 . The compound of claim 73 , wherein the compound has a structure of Formula (V), or a pharmaceutically acceptable salt or solvate thereof:

wherein,

R 3 is pentafluorophenyl, or substituted or unsubstituted 5 or 6 membered heteroaryl;

wherein at least one of R A1 and R A3 is substituted or unsubstituted —C 3 -C 8 cycloalkyl, substituted or unsubstituted 1 'C 3 -C 7 heterocycloalkyl, substituted or unsubstituted —O—C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —O—C 0-6 alkylene-C 3-7 heterocycloalkyl;

each R 11 is independently H, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or

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

provided that when (i)

then R A4 and R A5 are not the same.

80 . The compound of claim 73 , wherein

81 . The compound of claim 73 , wherein m is 0, 1, or 2.

82 . The compound of claim 73 , wherein R 4 is COOH.

83 . The compound of claim 73 , wherein R 4 is SO 2 H.

84 . The compound of claim 73 , wherein R 4 is —OR 11 .

85 . The compound of claim 84 , wherein R 4 is

86 . The compound of claim 73 , wherein each R B is independently halogen, D, —CN, —OR 11 , ——SR 11 , —N(R 11 ) 2 , —NR 11 S(═O) 2 R 11 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl.

87 . The compound of claim 86 , wherein at least one R B is a halogen selected from F and Cl.

88 . The compound of claim 86 , wherein at least one R B is a linear or branched, substituted or unsubstituted C 1 -C 6 alkyl.

89 . The compound of claim 88 , wherein each C 1 -C 6 alkyl is independently methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, linear or branched pentyl, linear or branched hexyl, —CF 3 , —CH 2 NH 2 , —CH 2 CF 3 , —CH 2 CHNH 2 , —CH 2 C 2 F, —CH 2 OH, or —CH 2 C 2 OH.

90 . The compound of claim 86 , wherein at least one R B is C 3-6 cycloalkyl, —CH 2 -C 3-6 cycloalkyl, —(C 2 ) 2 —C 3-6 cycloalkyl, —(C 2 ) 3 —C 3-6 cycloalkyl, C 3-5 heterocycloalkyl, —CH 2 —C 3-5 heterocycloalkyl, —(C 2 ) 2 —C 3-5 heterocycloalkyl, or —(C 2 ) 3 —C 3-5 heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl is substituted or unsubstituted.

91 . The compound of claim 86 , wherein the cycloalkyl or heterocycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein the cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl is optionally substituted, and wherein 0 to 2 of the ring carbon atoms are optionally and independently replaced by nitrogen, oxygen and sulfur.

92 . The compound of claim 86 , wherein each of the cycloalkyl is independently

93 . The compound of claim 86 , wherein each of the heterocycloalkyl is independently

94 . The compound of claim 86 , wherein at least one R B is —OR 11 .

95 . The compound of claim 94 , wherein each -OR 11 is independently OH, —O—C 1 -C 6 alkyl, —O—C 1 -C 6 haloalkyl, —O—C 1 -C 6 heteroalkyl, —O—C 0-6 alkylene-C 3-8 cycloalkyl, or —O—C 0-6 alkylene-C 3-7 heterocycloalkyl, wherein the alkyl, haloalkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is substituted or unsubstituted.

96 . The compound of claim 95 , wherein at least one R B is

97 . The compound of claim 95 , wherein at least one R B is OH.

98 . The compound of claim 95 , wherein at least one R B is

99 . The compound of claim 86 , wherein at least one R B is —N(R 11 ) 2 .

100 . The compound of claim 99 , wherein at least one R B is —N(CH 3 ) 2 , —NHCH 3 , —N(C 2 CH 3 ) 2 , —NHC 2 CH 3 , or —N(C 2 C 2 CH 3 ) 2 .

101 . The compound of claim 86 , wherein at least one R B is —NR 11 S(O) 2 R 11 , wherein each R 11 is independently H or C 1 -C 3 alkyl.

102 . The compound of claim 101 , wherein the —NR 11 S(═O) 2 R 11 is —NCH 3 S(═O) 2 CH 3 .

103 . The compound of claim 73 , wherein

104 . The compound of claim 73 , wherein

105 . The compound of claim 104 , wherein at least one of R A1 and R A3 is substituted or unsubstituted —C 3 -C 6 cycloalkyl.

106 . The compound of claim 105 , wherein at least one of R A1 and R A3 is

107 . The compound of claim 104 , wherein at least one of R A1 and R A3 is substituted or unsubstituted —C 3 -C 5 heterocycloalkyl.

108 . The compound of claim 107 , wherein at least one of R A1 and R A3 is

109 . The compound of claim 104 , wherein at least one of R A1 and R A3 is substituted or unsubstituted —O—C 0-3 alkylene-C 3-6 cycloalkyl, or substituted or unsubstituted —O—C 0-3 alkylene-C 3-5 heterocycloalkyl.

110 . The compound of claim 73 , wherein each of R A2 , R A3 , R A4 , and R A5 is independently halogen, C 1 -C 6 alkyl, —C 0-3 alkylene-C 3-6 cycloalkyl, —C 0-3 alkylene-C 3-5 heterocycloalkyl, —O—C 1 -C 6 alkyl, -0—C 0-3 alkylene-C 3-6 cycloalkyl, or —O—C 0-3 alkylene-C 3-5 heterocycloalkyl, and wherein the alkyl, cycloalkyl, and heterocycloalkyl is substituted or unsubstituted.

111 . The compound of claim 110 , wherein each of R A2 , R A3 , R A4 , and R A5 is independently F, Cl, methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, —CF 3 , —CH 2 CF 3 , —C 2 C 2 F, —OCF 3 , —OH, −OCH 3 , —OC 2 CH 3 , —OC 20 Me, —OC 2 C 2 OH, —OC(CH 3 ) 3 , —OC 2 C 2 OCH 3 ,

112 . The compound of claim 73 , wherein

113 . The compound of claim 1 or 73 , wherein R 2 is phenyl or substituted phenyl.

114 . The compound of claim 113 , wherein R 2 is phenyl substituted with 1 to 5 R c , and wherein each R c is independently D, halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —CN, —NO 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl.

115 . The compound of claim 114 , wherein R 2 is phenyl substituted with 1 to 5 R c , and wherein each R c is independently D, F, Cl, Br, —CN, OH, methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, —CF 3 , —CH 2 CF 3 , —CH 2 C 2 F, —OCF 3 , —OH, —OCH 3 , —OC 2 CH 3 , —OC 2 OMe, —OC 2 C 2 OH, —OC(CH 3 ) 3 , —OC 2 C 2 OCH 3 ,

116 . The compound of claim 114 , wherein R 2 is

117 . The compound of claims 116 , wherein R 2 is

118 . The compound of claim 1 or 73 , wherein R 2 is substituted or unsubstituted 5-membered or 6-membered monocyclic heteroaryl.

119 . The compound of claim 118 , wherein R 2 is pyridinyl, pyridazinyl, pyrimidinyl, triazinyl, wherein the pyridinyl, pyridazinyl, pyrimidinyl, or triazinyl is substituted with 1 to 4 R c , and wherein each R c is independently D, halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —CN, —NO 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 haloalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted —C 0-6 alkylene-C 3-8 cycloalkyl, or substituted or unsubstituted —C 0-6 alkylene-C 3-7 heterocycloalkyl.

120 . The compound of claim 119 , wherein each R c is independently D, F, Cl, Br, —CN, OH, methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, —CF 3 , —CH 2 CF 3 , —C 2 C 2 F, —OCF 3 , —OH, —OCH 3 , —OC 2 CH 3 , —OC 2 OMe, —OC 2 C 2 OH, —OC(CH 3 ) 3 , —OC 2 C 2 OCH 3 ,

121 . The compound of claim 116 , wherein R 2 is

122 . The compound of claim 1 or 73 , wherein R 2 is substituted or unsubstituted 5-6, 6-6, or 6-5 fused bicyclic heteroaryl containing 1-3 hetero ring atoms selected from O, N and S.

123 . The compound of claim 1 or 73 , wherein R 3 is substituted heteroaryl.

124 . The compound of claim 123 , wherein R 3 is pentafluorophenyl.

125 . A compound or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from a compound of Table 1 or Table 2.

126 . A compound or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is

127 . A pharmaceutical composition comprising a compound of any one of claims 1 to 125 , a pharmaceutically acceptable salt, solvate, ester, hydrate, or polymorph thereof, and a pharmaceutically acceptable excipient or carrier.

128 . A method of modulating signal transducer and activator of transcription 5a and 5b (STAT5) proteins in a subject in need thereof, comprising administering to a subject a therapeutically effective amount of a compound of any one of claims 1 to 125 , or a pharmaceutically acceptable salt or solvate thereof.

129 . The method of claim 128 , wherein the subject has cancer.

130 . A method of treating cancer in a subject in need thereof, comprising administering to a subject with cancer a therapeutically effective amount of a compound of any one of claims 1 to 125 , or a pharmaceutically acceptable salt or solvate thereof

131 . The method of claim 130 , wherein the cancer is a solid tumor or hematologic cancer.

132 . The method of claim 130 , wherein the cancer is breast cancer, head and neck squamous cell carcinoma, non-small cell lung cancer, hepatocellular cancer, colorectal cancer, gastric adenocarcinoma, melanoma, or advanced cancer.

Assignments (4)

RELEASE OF SECURITY INTEREST Recorded Jun 24, 2026

From: OXFORD FINANCE LLC

To: CENTESSA PHARMACEUTICALS (UK) LIMITED

Reel/Frame 075069/0879 →

SECURITY INTEREST Recorded Dec 31, 2024

From: CENTESSA PHARMACEUTICALS (UK) LIMITED

To: OXFORD FINANCE LLC

Reel/Frame 069708/0039 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 29, 2023

From: JANPIX LIMITED

To: CENTESSA PHARMACEUTICALS (UK) LIMITED

Reel/Frame 065695/0341 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 10, 2023

From: FLECK, ROMAN; PROUDFOOT, JOHN; OMEARA, JEFF; GNANASEKARAN, KRISHNA KUMAR; GUNNING, PATRICK THOMAS; JOHN, ALFORD ANTOINE; PALERM, ANGEL SAMPEDRO; DARWISH, ALLA; KRASKOUSKAYA, DZIYANA; ALI, AHMED MAGDY AHMED MOHAMED

To: JANPIX LIMITED

Reel/Frame 062326/0859 →