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US-12624034-B2 - Non-covalent modifiers of AKT1 and uses thereof

US12624034B2US 12624034 B2US12624034 B2US 12624034B2US-12624034-B2

Abstract

Provided herein are non-covalent modifiers of AKT1 of Formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (V-A), (V-B), (VI), (VI-A), or (VI-B), and pharmaceutical compositions thereof. In some embodiments, the present disclosure provides methods of modulating wild-type AKT1 using a compound or salt of Formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (V-A), (V-B), (VI), (VI-A), or (VI-B), and pharmaceutical compositions thereof.

Inventors

  • Hang Chu
  • Kin S. Yang
  • Solomon H. Reisberg
  • Adam Zajdlik
  • Jordan D. Carelli
  • Brian P. Bestvater
  • Timothy R. Hansen
  • Peter A. Thompson

Assignees

  • TERREMOTO BIOSCIENCES, INC.

Dates

Publication Date
20260512
Application Date
20250602

Claims (20)

  1. 1 . A compound represented by the structure of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: Ring B is selected from: R 1 is selected from hydrogen, halogen, —OR 10 , —SR 10 , —N(R 10 ) 2 , —NO 2 , —CN, optionally substituted C 3-8 carbocycle, optionally substituted 4- to 8-membered heterocycle, and optionally substituted C 1-6 alkyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 10 , —SR 10 , —N(R 10 ) 2 , —NO 2 , and —CN; A 1 and A 2 are each independently selected from (i), (ii), and (iii): (i) hydrogen, halogen, C 1-4 haloalkyl, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —N(R 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , and —CN; (ii) C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 10 , —SR 10 , —N(R 10 ) 2 , —NO 2 , and —CN; C 3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11A , —N(R 11A ) 2 , —C(O)R 11A , —C(O)N(R 11A ) 2 , —N(R 11A )C(O)R 11A , —C(O)OR 11A , —OC(O)R 11A , —NO 2 , ═O, ═S, ═N(R 11A ), and —CN; and C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11A , —SR 11A , —N(R 11A ) 2 , —C(O)R 11A , —C(O)N(R 11A ) 2 , —N(R 11A )C(O)R 11A , —N(R 11A )S(O) 2 R 11A , —C(O)OR 11A , —OC(O)R 11A , —NO 2 , ═O, ═S, ═N(R 11A ), and —CN; and (iii) 5- to 10-membered heterocycle and C 3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NS(O) 2 N(R 11 ) 2 , —C(O)OR 11 , —OC(O)R 11 , —N(R 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , ═O, ═S, =N(R 11 ), and —CN; C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —N(R 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , ═O, =S, =N(R 11 ), and —CN; and C 3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —NO 2 , ═O, =S, =N(R 11 ), and —CN; and C 1-6 alkyl, C 2-6 alkenyl, C 3-6 alkynyl, C 3-8 carbocycle, and 4- to 8-membered heterocycle, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —C(O)OR 11 , —OC(O)R 11 , —NO 2 , ═O, ═S, ═N(R 11 ), and —CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 is independently selected at each instance from halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —NO 2 , and —CN; R 3 is independently selected at each instance from: halogen, —OR 13 , —SR 13 , —N(R 13 ) 2 , —C(O)R 13 , —C(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —NO 2 , and —CN; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 13 , —SR 13 , —N(R 13 ) 2 , —C(O)R 13 , —C(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —NO 2 , ═O, ═S, =N(R 13 ), and —CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 is independently selected at each instance from: halogen, —OR 14 , —SR 14 , —N(R 14 ) 2 , —C(O)R 14 , —C(O)N(R 14 ) 2 , —N(R 14 )C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 , —NO 2 , and —CN; and C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from halogen, —OR 14 , —SR 14 , —N(R 14 ) 2 , —C(O)R 14 , —C(O)N(R 14 ) 2 , —N(R 14 )C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 , —NO 2 , —O, —S, —N(R 14 ), and —CN; or two R 4 attached to the same atom are taken together to form a group selected from: ═O, ═S, and =N(R 14 ); or two R 4 attached to the same atom or to adjacent atoms are taken together with the carbons to which they are attached to form a group selected from 4- to 8-membered heterocycle and C 3-8 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 14 , —SR 14 , —N(R 14 ) 2 , —NO 2 , and —CN; L is represented by —L 1 —L 2 —L 3 —L 4 —, wherein L 1 , L 2 , L 3 , and L 4 are each independently selected from (a) and (b): (a) —O—, —N(R 15 )—, —S—, —S(O)—, —S(O) 2 —, —S(O)(NR 15 )—, —N(R 15 )C(O)—, —N(R 15 )C(O)O—, —N(R 15 )S(O) 2 —, and —(R 15 )NC(O)N(R 15 )N(R 15 )N(r 15 )—; and (b) C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 3-8 carbocyclene, and 4- to 8-membered heterocyclene, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 15 , —SR 15 , ═O, ═S, and —CN; wherein L 1 , L 2 , L 3 , and L 4 are each optionally absent; wherein no more than two of L 1 , L 2 , L 3 , and L 4 are selected from (a) and the two selected are not adjacent; R 5 is selected from 4- to 10-membered heterocycle and C 3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 16 , —SR 16 , —N(R 16 ) 2 , —C(O)N(R 16 ) 2 , —C(O)OR 16 , —OC(O)R 16 , —N(R 16 )C(O)R 16 , —N(R 16 )S(O) 2 R 16 , —S(O) 2 N(R 16 ) 2 , —N(R 16 )C(O)N(R 16 ) 2 , —N(R 16 )C(O)OR 16 , —OC(O)N(R 16 ) 2 , —S(O)R 16 , —S(O) 2 R 16 , —NO 2 , —O, ═S, and =N(R 16 ), and CN; C 1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 16 , —SR 16 , —N(R 16 ) 2 , and —NO 2 , and CN; and 4- to 6-membered heterocycle and C 3-8 carbocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 16 , —SR 16 , —N(R 16 ) 2 , and —NO 2 ; R 10 , R 11 , R 11A , R 12 , R 13 , R 14 , and R 15 are each independently selected at each occurrence from: hydrogen, C 1-4 alkyl, C 3-8 carbocycle, 4- to 8-membered heterocycle, and C 1-4 haloalkyl; R 16 is independently selected at each occurrence from (iv), (v), and (vi): (iv) hydrogen; (v) C 1-4 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —OC(O)R 20 , —C(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , —N(R 20 )S(O) 2 R 20 , —S(O) 2 N(R 20 ) 2 , and —NO 2 ; and C 3-8 carbocycle and 4- to 8-membered heterocycle, either of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —OC(O)R 20 , —C(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , —N(R 20 )S(O) 2 R 20 , —S(O) 2 N(R 20 ) 2 , and —NO 2 ; and (vi) C 3-8 carbocycle and 4- to 8-membered heterocycle, either of which is optionally substituted with one or more substituents independently selected from halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)N(R 20 ) 2 , —C(O)OR 20 , —OC(O)R 20 , —N(R 20 )C(O)R 20 , —N(R 20 )S(O) 2 R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , —NO 2 , C 3-8 carbocycle, and 4- to 8-membered heterocycle, wherein the C 3-8 carbocycle and 4- to 8-membered heterocycle are each optionally further substituted with one or more substituents independently selected from halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)N(R 20 ) 2 , —C(O)OR 20 , —OC(O)R 20 , —N(R 20 )C(O)R 20 , —N(R 20 )S(O) 2 R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , and —NO 2 ; and R 20 is independently selected at each occurrence from hydrogen, C 1-4 alkyl, C 1-4 haloalkyl, C 3-8 carbocycle, and 4- to 8-membered heterocycle.
  2. 2 . The compound or salt of claim 1 , wherein Ring B is
  3. 3 . The compound or salt of claim 1 , wherein Ring B is
  4. 4 . The compound or salt of claim 1 , wherein the structure of Formula (I) is represented by the structure of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: R 1 is selected from hydrogen, halogen, —OR 10 , —SR 10 , —N(R 10 ) 2 , —NO 2 , and —CN; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 10 , —SR 10 , —N(R 10 ) 2 , —NO 2 , and —CN; A 1 and A 2 are each independently selected from (i), (ii), and (iii): (i) hydrogen, halogen, C 1-4 haloalkyl, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —N(R 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , and —CN; (ii) C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 11 , —SR 11 , —N(R 11 ) 2 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —N(R 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , ═O, ═S, =N(R 11 ), and —CN; and (iii) 5- to 10-membered heterocycle and C 3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 ,—SR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O) 11 , —N(R 11 )S(O) 2 R 11 , —C(O)OR 11 , —OC(O)R 11 , —N( 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —S(O) 2 N(R 11) 2 , —NO 2 , =O, =S, =N(R 11 ), and —CN; C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 ,—SR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O) 11 , —C(O)OR 11 , —OC(O)R 11 , —N( 11 )C(O)OR 11 , —OC(O)N(R 11 ) 2 , —N(R 11 )C(O)N(R 11 ) 2 , —S(O)R 11 , —S(O) 2 R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , =O, =S, =N(R 11 ), and —CN; and C 3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , C(O)OR 11 —OC(O)R 11 —NO 2 , ═O, ═S, ═N(R 11 ), and —CN; and C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —C(O)OR 11 , —OC(O)R 11 , —NO 2 , =O, =S, =N(R 11 ), and —CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2, and 3; R 2 is independently selected at each instance from halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 12 , —SR 12 , —N(R 12 ) 2 , —NO 2 , and —CN; R 3 is independently selected at each instance from: halogen, —OR 13 , —SR 13 —N(R 13 ) 2 , —C(O)R 13 , —C(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —NO 2 , and —CN; and C 1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 13 , —SR 13 , —N(R 13 ) 2 , —C(O)R 13 , —C(O)N(R 13 ) 2 , —N(R 13 )C(O)R 13 , —C(O)OR 13 , —OC(O)R 13 , —NO 2 , ═O, ═S, =N(R 13 ), and —CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 is independently selected at each instance from: halogen, —OR 14 , —SR 14 , —N(R 14 ) 2 , —C(O)R 14 , —C(O)N(R 14 ) 2 , —N(R 14 )C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 , —NO 2 , and —CN; and C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from halogen, —OR 14 , —SR 14 , —N(R 14 ) 2 , —C(O)R 14 , —C(O)N(R 14 ) 2 , —N(R 14 )C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 —NO 2 , ═O, ═S, ═N(R 14 ), and —CN; or two R 4 attached to the same atom are taken together to form a group selected from: ═O, ═S, and ═N(R 14 ); or two R 4 attached to the same atom or to adjacent atoms are taken together with the carbons to which they are attached to form a group selected from 4- to 8-membered heterocycle and C 3-8 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 14 , —SR 14 , —N(R 14 ) 2 , —NO 2 , and —CN; L is represented by —L 1 —L 2 —L 3 —L 4 —, wherein L 1 , L 2 , L 3 , and L 4 are each independently selected from (a) and (b): (a) —O—, —N(R 15)—, —S—, —S(O)—, —S(O) 2 , —S(O)(NR 15 )—, —N(R 15 )C(O)—, —N(R 15 )C(O)O—, —N(R 15 )S(O) 2 —, —N(R 15 )S(O) 2 N(R 15 )—, —S(O)(NR 15 )N(R 15 )—, —N(R 15 )N(R 15 )—, —(R 15 )NC(O)N(R 15 )—, and —(R 15 )NC(O)N(R 15 )N(R 15 )—; and (b) C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 3-8 carbocyclene, and 4- to 8-membered heterocyclene, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 15 , —SR 15 , ═O, and ═S, and —CN; wherein L 2 , L 3 , and L 4 are each optionally absent; wherein no more than two of L 1 , L 2 , L 3 , and L 4 are selected from (a) and the two selected are not adjacent; R 5 is selected from 4- to 10-membered heterocycle and C 3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 16 , —SR 16 , —N(R 16 ) 2 , —C(O)N(R 16 ) 2 , —C(O)OR 16 , —OC(O)R 16 , —N(R 16 )C(O)R 16 , —N(R 16 )S(O) 2 R 16 , —S(O) 2 N(R 16 ) 2 , —N(R 16 )C(O)N(R 16 ) 2 , —N(R 16 )C(O)OR 16 , —OC(O)N(R 16 ) 2 , —S(O)R 16 , —S(O) 2 R 16 , —NO 2 , ═O, ═S, and —N(R 16 ); C 1-4 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 16 , —SR 16 , —N(R 16 ) 2 , and —NO 2 ; and 4- to 6-membered heterocycle and C 3-8 carbocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 16 , —SR 16 , —N(R 16 ) 2 , and —NO 2 ; R 10 , R 11 , R 12 , R 13 , R 14 , and R 15 are each independently selected at each occurrence from: hydrogen, C 1-4 alkyl, C 3-8 carbocycle, 4- to 8-membered heterocycle, and C 1-4 haloalkyl; R 16 is independently selected at each occurrence from (iv), (v), and (vi): (iv) hydrogen; (v) C 1-4 alkyl optionally substituted with one or more substituents independently selected from: halogen, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —OC(O)R 20 , —C(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , —N(R 20 )S(O) 2 R 20 , —S(O) 2 N(R 20 ) 2 , and —NO 2 ; and C 3-8 carbocycle and 4- to 8-membered heterocycle, either of which is optionally substituted with one or more substituents independently selected from: halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)OR 20 , —OC(O)R 20 , —C(O)N(R 20 ) 2 , —N(R 20 )C(O)R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , —N(R 20 )S(O) 2 R 20 , —S(O) 2 N(R 20 ) 2 , and —NO 2 ; and (vi) C 3-8 carbocycle and 4- to 8-membered heterocycle, either of which is optionally substituted with one or more substituents independently selected from halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 20 , —SR 20 , —N(R 20 ) 2 , —C(O)R 20 , —C(O)N(R 20 ) 2 , —C(O)OR 20 , —OC(O)R 20 , —N(R 20 )C(O)R 20 , —N(R 20 )S(O) 2 R 20 , —N(R 20 )C(O)N(R 20 ) 2 , —N(R 20 )C(O)OR 20 , —OC(O)N(R 20 ) 2 , —S(O)R 20 , —S(O) 2 R 20 , and —NO 2 ; and R 20 is independently selected at each occurrence from hydrogen, C 1-4 alkyl, C 1-4 haloalkyl, C 3-8 carbocycle, and 4- to 8-membered heterocycle.
  5. 5 . The compound or salt of claim 1 , wherein A 1 is selected from hydrogen, halogen, C 1-4 alkyl, C 1-4 haloalkyl, —OR 11 , —N(R 11 ) 2 , and —CN.
  6. 6 . The compound or salt of claim 1 , wherein A 2 is selected from: C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 11 , —N(R 11 ) 2 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —S(O) 2 N(R 11 ) 2 , —NO 2 , ═O, and —CN; and 5- to 10-membered heterocycle and C 3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 , ═O, and —CN; C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 , —NO 2 , ═O, and —CN; and C 3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —NO 2 , ═O, —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, the C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 , ═O, and —CN.
  7. 7 . The compound or salt of claim 1 , wherein A 2 is selected from pyrazolyl, triazolyl, oxazolyl, thiazolyl, morpholinyl, phenyl, and cyclopropyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 , ═O, and —CN; C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 ; ═O, and —CN; and C 3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —NO 2 , ═O, —CN, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, the C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, —OR 11 , —N(R 11 ) 2 , —C(O)R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )S(O) 2 R 11 , —NO 2 , ═O, and —CN.
  8. 8 . The compound or salt of claim 1 , wherein A 2 is selected from:
  9. 9 . The compound or salt of claim 1 , wherein R 1 is selected from hydrogen, halogen, —OR 10 , —N(R 10 ) 2 , —NO 2 , —CN, and C 1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR 10 , and —N(R 10 ) 2 .
  10. 10 . The compound or salt of claim 1 , wherein R 1 is selected from hydrogen, fluoro, methoxy, —CN, methyl, ethyl, (methoxy) methyl, and
  11. 11 . The compound or salt of claim 1 , wherein q is 1.
  12. 12 . The compound or salt of claim 1 , wherein n is 0.
  13. 13 . The compound or salt of claim 1 , wherein p is selected from 0, 1, and 2.
  14. 14 . The compound or salt of claim 1 , wherein R 4 is independently selected at each instance from halogen, —OR 14 , —SR 14 , —N(R 14 ) 2 , —C(O)R 14 , —C(O)N(R 14 ) 2 , —N(R 14 )C(O)R 14 , —C(O)OR 14 , —OC(O)R 14 , —NO 2 , and —CN.
  15. 15 . The compound or salt of claim 1 , wherein L 1 , L 2 , L 3 , and L 4 are each independently selected from (a) and (b): (a) —O—, —N(R 15 )—, —S—, —N(R 15 )C(O)—, —N(R 15 )C(O)O—, —N(R 15 )S(O) 2 , —N(R 15 ) N(R 15 )—, and —(R 15 )NC(O)N(R 15 )—; and (b) C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 3-6 carbocyclene, and 4- to 6-membered heterocyclene, any of which is optionally substituted with one or more substituents independently selected from halogen, —OR 15 , —O, and —CN; wherein L 2 , L 3 , and L 4 are each optionally absent; wherein no more than two of L 1 , L 2 , L 3 , and L 4 are selected from (a) and the two selected are not adjacent; and R 15 is selected from hydrogen and C 1-4 alkyl.
  16. 16 . The compound or salt of claim 1 , wherein L 4 is absent.
  17. 17 . The compound or salt of claim 1 , wherein L 3 is absent, —O—, ethynyl, or methylene substituted with ═O.
  18. 18 . The compound or salt of claim 1 , wherein L 2 is absent, methylene, (methyl)methylene, ethylene, or —O—.
  19. 19 . The compound or salt of claim 1 , wherein L 1 is selected from —N(R 15 )C(O)—, —N(R 15 )—, —N(R 15 )S(O) 2 —, —(R 15 )NC(O)N(R 15 )—, and 4- to 6-membered heterocyclene optionally substituted with one or more halogen atoms.
  20. 20 . The compound or salt of claim 1 , wherein L is selected from

Description

CROSS-REFERENCE This application is a continuation application of International Patent Application No. PCT/US2024/040866, filed Aug. 2, 2024, which claims the benefit of U.S. Provisional Application No. 63/517,760 filed Aug. 4, 2023, and U.S. Provisional Application No. 63/650,658 filed May 22, 2024, each of which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION The AKT or Protein Kinase B (PKB) family of serine/threonine protein kinases is comprised of 3 highly homologous members, AKT1, AKT2 and AKT3. The family of AKT proteins are involved in signal transduction pathways that regulate cellular processes including apoptosis, proliferation, differentiation, and metabolism. The AKT1 pathway is the most frequently dysregulated signaling pathways in human cancers. Enhanced activation of all the isoforms can be implicated in tumor development and progression, and has been demonstrated in breast, ovarian, pancreatic, and prostate cancers among others (Song et al., 2019). In cancer cells, AKT1 is involved in proliferation and growth, promoting tumor initiation, and suppressing apoptosis, whereas AKT2 regulates cytoskeleton dynamics, favoring local tissue invasion and metastasis. The role of AKT3 hyperactivation in cancer is hypothesized to be involved with possible stimulation of cell proliferation (Hinz et al., Cell Commun Signal 2019, 17(1), 154; Pascual et al., Ann. Oncol. 2019, 30(7), 1051-1060). Expression of these AKT family members is altered in many human malignant carcinomas including gastric, breast, prostate, ovarian, and pancreatic. AKT family members are rarely mutated however, the most common mutation is AKT1 E17K which has been reported in 6-8% of breast cancers, 2-6% of colorectal cancers, and in 6% of meningiomas, in humans (Yu et al., PLoS One 2015, 10 (10), No. e0140479). Thus, there is a need to develop new treatments for the modulation of AKT1 and mutants thereof. SUMMARY OF THE INVENTION In one aspect, the present disclosure provides a compound represented by the structure of Formula (I): or a pharmaceutically acceptable salt thereof, wherein:Ring B is selected from: R1 is selected from hydrogen, halogen, —OR10, —SR10, —N(R10)2, —NO2, and —CN; and C1-6 alkyl optionally substituted with one or more substituents independently selected from: halogen, C3-8 carbocycle which is optionally substituted with one or more substituents independently selected from: halogen, C1-4 alkyl, C1-4 haloalkyl, —OR20, —SR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)N(R20)2, —N(R20)C(O)OR20, —OC(O)N(R20)2, —S(O)R20, —S(O)2R20, —N(R20)S(O)2R20, —S(O)2N(R20)2, —NO2, and —CN, 4- to 8-membered heterocycle, which is optionally substituted with one or more substituents independently selected from: halogen, C1-4 alkyl, C1-4 haloalkyl, —OR20, —SR20, —N(R20)2, —C(O)R20, —C(O)OR20, —OC(O)R20, —C(O)N(R20)2, —N(R20)C(O)R20, —N(R20)C(O)N(R20)2, —N(R20)C(O)OR20, —OC(O)N(R20)2, —S(O)R20, —S(O)2R20, —N(R20)S(O)2R20, —S(O)2N(R20)2, —NO2, and —CN;A1 and A2 are each independently selected from (i), (ii), and (iii): (i) hydrogen, halogen, C1-4 haloalkyl, —OR11, —SR11, —N(R11)2, —C(O)N(R11)2, —N(R11)C(O)R11, —C(O)OR11, —OC(O)R11, —N(R11)C(O)OR11, —OC(O)N(R11)2, —N(R11)C(O)N(R11)2, —S(O)R11, —S(O)2R11, —N(R11)S(O)2R11, —S(O)2N(R11)2, —NO2, and —CN;(ii) C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR11, —SR11, —N(R11)2, —C(O)N(R11)2, —N(R11)C(O)R11, —C(O)OR11, —OC(O)R11, —N(R11)C(O)OR11, —OC(O)N(R11)2, —N(R11)C(O)N(R11)2, —S(O)R11, —S(O)2R11, —N(R11)S(O)2R11, —S(O)2N(R11)2, —NO2, ═O, ═S, ═N(R11), and —CN; and C3-10 carbocycle and 4- to 10-membered heterocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR11A, —N(R11A)2—C(O)R11A, —C(O)N(R11A)2—N(R11A)C(O)R11A, —C(O)OR11A, —OC(O)R11A, —NO2, ═O, ═S, ═N(R11A), —CN; andC1-6 alkyl C2-6 alkenyl, and C2-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR11A, —SR11A, —N(R11A)2—C(O)R11A, —C(O)N(R11A)2—N(R11A)C(O)R11A, —N(R11A)S(O)2R11A, —C(O)OR11A, —OC(O)R11A—NO2, ═O, ═S, ═N(R11A), and —CN; and (iii) 5- to 10-membered heterocycle and C3-10 carbocycle, any of which is optionally substituted with one or more substituents independently selected from: halogen, —OR11, —SR11, —N(R11)2, —C(O)R11, —C(O)N(R11)2, —N(R11)C(O)R11, —N(R11)S(O)2R11, —NS(O)2N(R11)2, —C(O)OR11, —OC(O)R11, —N(R11)C(O)OR11, —OC(O)N(R11)2, —N(R11)C(O)N(R11)2, —S(O)R11, —S(O)2R11, —S(O)2N(R11)2, —NO2, ═O, ═S, ═N(R11), and —CN; andC1-6 alkyl, C2-6 alkenyl, and C3-6 alkynyl, any one of which is optionally substituted with one or more substituents independently selected from: halogen, —OR11, —SR11, —N(R11)2, —C(O)R11, —C(O)N(R11)2, —N(R11)C(O)R11,