US 11,702,429 B2
mTORC modulators and uses thereof
Stelios T. Tzannis, Corte Madera, CA (US); Ian J. Massey, Los Altos, CA (US); Alexandre Froidbise, Gardouch (FR); and Guillaume Eppe, Toulouse (FR)
Assigned to AEOVIAN PHARMACEUTICALS, INC., Berkeley, CA (US)
Filed by Aeovian Pharmaceuticals, Inc., Walnut Creek, CA (US)
Filed on May 21, 2021, as Appl. No. 17/326,633.
Application 17/326,633 is a continuation of application No. 17/024,470, filed on Sep. 17, 2020, granted, now 11,021,492.
Application 17/024,470 is a continuation of application No. PCT/US2020/014671, filed on Jan. 22, 2020.
Claims priority of provisional application 62/795,482, filed on Jan. 22, 2019.
Prior Publication US 2023/0013344 A1, Jan. 19, 2023
Int. Cl. C07D 498/18 (2006.01); C07D 519/00 (2006.01); A61K 31/436 (2006.01)
CPC C07D 498/18 (2013.01) [A61K 31/436 (2013.01); C07D 519/00 (2013.01)] 20 Claims
 
1. A compound represented by the structure of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from

OG Complex Work Unit Chemistry
R2 is selected from hydrogen and an optionally substituted C1-C6 alkoxy group, wherein substituents are independently selected at each occurrence from hydroxy, halogen, cyano, nitro, C2-C6 alkoxy group, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, wherein cycloalkyl, aryl, heterocyloalkyl, and heteroaryl, are each optionally substituted with one or more substituents independently selected from hydroxy, halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkoxy, and alkoxyalkyl;
R3 is selected from hydrogen and an optionally substituted C1-C6 alkoxy group, wherein the substituents independently selected at each occurrence from hydroxy, halogen, cyano, nitro, C2-C6 alkoxy group, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl, wherein cycloalkyl, aryl, heterocyloalkyl, and heteroaryl, are each optionally substituted with one or more substituents independently selected from hydroxy, halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkoxy, and alkoxyalkyl;
R4 is selected from

OG Complex Work Unit Chemistry
z is 2, 3, 4, or 5;
each R′ and R″ are independently selected from hydrogen, halogen, —OR31, and C1-3 alkyl optionally substituted with one or more substituents independently selected from halogen and —OR31;
R25 is selected from —OR31;
R31 is independently selected at each occurrence from hydrogen, —Si(C1-C6 alkyl)3; and C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OSi(C1-C6 alkyl)3, —CN, —NO2, —NH2, ═O, ═S, C1-10 alkyl, —C1-10 haloalkyl, —C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle;
R22 is selected from C3-C6 alkyl substituted with one or more substituents selected from;
halogen, —OR30, —N(R30)2, —(O—CH2—(CH2)p)n—W, —SR30, —C(O)R30, —C(O)N(R30)2, —N(R30)C(O)R30, —C(O)OR30, —OC(O)R30, —S(O)R30, —S(O)2R30, —P(O)(OR30)2, —OP(O)(OR30)2, —NO2, ═O, ═S, ═N(R30), —CN;
C2-10 alkenyl, C2-10 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR30, —SR30, —N(R30)2, —C(O)R30, —C(O)N(R30)2, —N(R30)C(O)R30, —C(O)OR30, —OC(O)R30, —S(O)R30, —S(O)2R30, —P(O)(OR30)2, —OP(O)(OR30)2, —NO2, ═O, ═S, ═N(R30), —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
C3-10 carbocycle which is optionally substituted with one or more substituents independently selected from halogen, —OR30, —SR30, —N(R30)2, —C(O)R30, —C(O)N(R30)2, —N(R30)C(O)R30, —C(O)OR30, —OC(O)R30, —S(O)R30, —S(O)2R30, —P(O)(OR30)2, —OP(O)(OR30)2, —NO2, ═O, ═S, ═N(R30), —CN, C1-6 alkyl, C1-6 alkyl-R30, C2-6 alkenyl, and C2-6 alkynyl;
each p is selected from 1 or 2;
n is selected from 1-4;
W is selected from —OH and —CH3
R30 is independently selected at each occurrence from hydrogen, —Si(C1-C6 alkyl)3; and C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OH, —OSi(C1-C6 alkyl)3, —CN, —NO2, —NH2, ═O, ═S, C1-10 alkyl, —C1-10 haloalkyl, —O—C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, and 3- to 12-membered heterocycle.