US 12,234,224 B2
Pyrimidine and pyridine amine compounds and usage thereof in disease treatment
Graham Beaton, Vista, CA (US); Fabio Tucci, San Diego, CA (US); Satheesh Ravula, San Diego, CA (US); Suk Joong Lee, San Diego, CA (US); and Chandravadan Shah, San Diego, CA (US)
Assigned to EPIGEN Biosciences, Inc., San Diego, CA (US)
Filed by Epigen Biosciences, Inc., San Diego, CA (US)
Filed on Dec. 6, 2023, as Appl. No. 18/531,575.
Application 18/531,575 is a division of application No. 17/334,921, filed on May 31, 2021, granted, now 11,866,421.
Prior Publication US 2024/0124423 A1, Apr. 18, 2024
Int. Cl. C07D 403/04 (2006.01); C07D 401/04 (2006.01); C07D 405/14 (2006.01)
CPC C07D 403/04 (2013.01) [C07D 401/04 (2013.01); C07D 405/14 (2013.01)] 18 Claims
 
1. A method for treating a S6K-dependent or S6K-mediated disease or condition in a subject, comprising administering an effective amount of a compound, or a pharmaceutically acceptable salt thereof, to the subject, wherein the compound has the structure of Formula I:

OG Complex Work Unit Chemistry
wherein X is ═N— or a carbon atom that is substituted or unsubstituted;
RA is —H, —CN, C1-C4 alkyl, C1-C4 fluoroalkyl, —C(O)RD or —SO2RD;
RA′ is —H, C1-C4alkyl, C1-C4 fluoroalkyl, or —C(O)RD;
RB is substituted phenyl or C5-C6 heteroaryl (Ar, or HetAr), either of which is unsubstituted or substituted by up to three RE independently of one another;
L1 is a bond, or a C1-C4 unbranched alkylene, a C3-C6 cycloalkylene or a 3-6-membered heterocycloalkylene, either one of which is unsubstituted or substituted by one or two RF independently of one another and/or having one, two or three of its —CH2— groups independently replaced by —O—, —NH—, or —CO— or, L1 is a C3-C7 branched alkylene, which is unsubstituted or substituted by one or two RF independently of one another, and/or having one, two or three of its —CH2— groups independently replaced by —O—, —NH—, or —CO— and/or having one of its —CH— groups replaced by —N—;
RC is a C6 or C10 aryl or C5-C10 heteroaryl, either of which is unsubstituted or substituted by up to three RG independently of one another,
Ring A is a pyrazole moiety having the structure of:

OG Complex Work Unit Chemistry
wherein the pyrazole moiety is unsubstituted or substituted with one or two RH substituents at its aromatic carbon atom(s), wherein each RH, if present, is independently selected from the group consisting of a monovalent C-linked moiety, —OH, —CN, C1-C4 alkoxy, —OC1-C4 fluoroalkyl, C1-C20 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, and halogen;
RD is —H or an unsubstituted or substituted C1-C4 alkyl or an amino acid moiety;
each RE, if present, is independently selected from the group consisting of halogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, —OH, —SH, C1-C4 alkoxy, C3-C6 cycloalkyloxy, —SC1-C4alkyl, —S(O)C1-C4alkyl, —SO2C1-C4alkyl, —NH2, —NHC1-C4 alkyl, —N(C1-C4 alkyl)2, —NO2, —CN, —OCN, —COOH, —COO(C1-C4 alkyl), —CONH2, —CONH(C1-C4 alkyl), —CON(C1-C4 alkyl)2, —NHCO(C1-C4 alkyl), —NHCONH(C1-C4 alkyl), —NHCONH2, —CHO and —CO(C1-C4 alkyl), or is independently selected from the group consisting of halogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C3-C6 cycloalkyloxy, —SC1-C4alkyl, —SO2C1-C4alkyl, —N(C1-C4 alkyl)2, —CN, or at least two adjacent RE are present that taken together define a substituted or unsubstituted C5-C6 carbocycle or heterocycle, and the remaining RE, if present, is as previously defined;
each RF, if present, is independently selected from the group consisting of halogen, —OH, —CN, —NH2, —NMe2, —CONH2, —CONHMe, —CONMe2, —COOH, —CH3 and —CF3;
each RG, if present, is independently selected from the group consisting of halogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, —OH, —SH, C1-C4 alkoxy, C3-C6 cycloalkyloxy, —SC1-C4alkyl, —S(O)C1-C4alkyl, —SO2C1-C4alkyl, —NH2, —NHC1-C4 alkyl, —N(C1-C4 alkyl)2, —NO2, —CN, —OCN, —COOH, —COO(C1-C4 alkyl), —CONH2, —CONH(C1-C4 alkyl), —CON(C1-C4 alkyl)2, —NHCO(C1-C4 alkyl), —NHCONH(C1-C4 alkyl), —NHCONH2, —CHO and —CO(C1-C4 alkyl), or is independently selected from the group consisting of halogen, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C3-C6 cycloalkyloxy, —SC1-C4alkyl, —SO2C1-C4alkyl, —N(C1-C4 alkyl)2, —CN, or at least two adjacent RG are present that taken together define a substituted or unsubstituted C5-C6 carbocycle or heterocycle, and the remaining RG, if present, is as previously defined;
wherein the remaining aromatic carbon atom(s) of the pyrimidine or pyridine ring of formula I is unsubstituted or independently substituted by RJ; and
wherein each RJ, if present is independently selected from the group consisting of C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, —OH, —SH, C1-C4 alkoxy, C3-C6 cycloalkyloxy, —SC1-C4alkyl, —S(O)C1-C4alkyl, —SO2C1-C4alkyl, —NH2, —NHC1-C4 alkyl, —N(C1-C4 alkyl)2, and —CN, or is selected from the group consisting of C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, halogen, —CN, —NH2, and —OH.