US 12,404,283 B2
c-MYC mRNA translation modulators and uses thereof in the treatment of cancer
Aviad Mandabi, Ramat Gan (IL); Boaz Inbal, Ramat Gan (IL); Scott Alexander Sadler, Ramat Gan (IL); Shuyu Chu, Ramat Gan (IL); David William Sheppard, Ramat Gan (IL); Jason Paul Tierney, Ramat Gan (IL); Iris Alroy, Ramat Gan (IL); Rina Wassermann, Ramat Gan (IL); Yoni Sheinberger, Ramat Gan (IL); Yaode Wang, Beijing (CN); Haitang Li, Beijing (CN); and Lothar Willms, Hillscheid (DE)
Assigned to Anima Biotech Inc., , NJ (US)
Appl. No. 18/868,756
Filed by Anima Biotech Inc., Bernardsville, NJ (US)
PCT Filed Jul. 2, 2023, PCT No. PCT/US2023/026828
§ 371(c)(1), (2) Date Nov. 24, 2024,
PCT Pub. No. WO2024/010762, PCT Pub. Date Jan. 11, 2024.
Application 18/868,756 is a continuation in part of application No. 17/856,998, filed on Jul. 3, 2022.
Claims priority of provisional application 63/358,134, filed on Jul. 3, 2022.
Prior Publication US 2025/0129100 A1, Apr. 24, 2025
Int. Cl. C07D 513/04 (2006.01); A61K 31/429 (2006.01); A61K 31/437 (2006.01); A61K 31/454 (2006.01); A61K 31/4545 (2006.01); A61K 31/4725 (2006.01); A61K 31/496 (2006.01); A61K 31/5377 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 513/14 (2006.01)
CPC C07D 513/04 (2013.01) [A61K 31/429 (2013.01); A61K 31/437 (2013.01); A61K 31/454 (2013.01); A61K 31/4545 (2013.01); A61K 31/4725 (2013.01); A61K 31/496 (2013.01); A61K 31/5377 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 513/14 (2013.01)] 38 Claims
 
1. A compound represented by the structure of formula I (j):

OG Complex Work Unit Chemistry
wherein
X2, X3, and X4, are each independently nitrogen or CH;
X10 is N, CH, C(R), C(CH2)OH, C(CH2)2OH, C(NH—CH2-cyclopropyl), C(CH3), C(cyclopropyl), C(isopropoxy), or C(COOH);
Ring W is a 3-10 membered single, fused, bridged or spiro, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring, morpholine, tetrahydrofuran, tetrahydropyran, oxetane, pyrrolidine, pyrrolidin-2-one, pyrrolidin-3-one, imidazole, pyrazole, isoxazolidine, piperazine, piperidine, piperidine-2-one, oxadiazole, triazole, 2-oxopyrrolidine, cyclopropyl, 2,2-dimethylpyrrolidine, 4-azaspiro [2.4]heptane, pyrrolidin-3-one-O-methyloxime, 2-oxa-5-azaspiro [3.4]octane, 1,4-dioxa-6-azaspiro [4.4]nonane, 3,3-dimethylmorpholine, 1-methylpiperazine, 4,7-diazaspiro [2.5]octane, bicyclo[1.1.1]pentane, 2,5-diazabicyclo [2.2.1]heptane, piperazine, or piperazine-2-one;
W1 is CH2, C═O, CH(R10), or CHCH3;
R7′ and R7″ are each independently H, F, Cl, Br, I, OH, O—R20, SH, R8—OH, R8—SH, —R8—O—R10, R8-(C3-C8 cycloalkyl), R8-(3-8 membered heterocyclic ring), CF3, CD3, OCD3, CN, NO2, —CH2CN, —R8CN, NH2, NHR, N(R)2, NH(R10), N(R10)(R11), R8—N(R10)(R11), R9-R8—N(R10)(R11), B(OH)2, —OC(O)CF3, —OCH2Ph, NHC(O)—R10, NHCO—N(R10)(R11), COOH, —C(O)Ph, C(O)O—R10, R8—C(O)-R10, C(O)H, C(O)-R10, C1-C5 linear or branched C(O)-haloalkyl, —C(O)NH2, C(O)NHR, C(O)N(R10)(R11), SO2R, SO2N(R10)(R11), CH(CF3)(NH—R10), C1-C5 linear or branched, substituted or unsubstituted alkyl, isopropyl, methyl, ethyl, C1-C5 linear or branched, substituted or unsubstituted alkenyl, C1-C5 linear or branched, or C3-C8 cyclic haloalkyl, CHF2, C1-C5 linear or branched, or C3-C8 cyclic alkoxy, methoxy, optionally wherein at least one methylene group (CH2) in the alkoxy is replaced with an oxygen atom, C1-C5 linear or branched thioalkoxy, C1-C5 linear or branched haloalkoxy, C1-C5 linear or branched alkoxyalkyl, substituted or unsubstituted C3-C8 cycloalkyl, cyclopropyl, cyclohexyl, substituted or unsubstituted 3-8 membered heterocyclic ring, morpholine, pyran, oxetane, pyrrolidine, 3,3-difluoropyrrolidine, imidazole, pyrazole, triazole, piperazine, piperidine, piperidin-2-one, piperidin-4-ol, dioxazole, 2-oxopyrrolidine, substituted or unsubstituted aryl, substituted or unsubstituted benzyl;
or R7′ and R7″ are joined to form a 3-8 membered substituted or unsubstituted, saturated, unsaturated or aromatic, carbocyclic or heterocyclic ring, cyclopentyl, cyclohexyl, piperidine, tetrahydrofuran, tetrahydropyran, or pyrrolidine;
R20 is represented by the following structure:

OG Complex Work Unit Chemistry
R is H, F, Cl, Br, I, OH, SH, alkoxy, NH(R10), NH—CH2-cyclopropyl, N(R10)(R11), CF3, CN, NO2, COOH, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, ethyl, CH2—OH, CH2—CH2—OH, CH2—CH2—O—CH2—CH2—O—CH3, CH2—O—CH2—CH2—O—CH3, C3-C8 substituted or unsubstituted cycloalkyl, cyclopropyl, C1-C5 linear or branched alkoxy, isopropoxy, C1-C5 linear or branched haloalkyl, CHF2, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH (CH3)2, CF(CH3)—CH(CH3)2), R8-aryl, CH2-Ph,-R8—O—R8—O—R10, (CH2)2—O—(CH2)2—O—CH3), —R8—O—R10 (CH2—OH, CH2—CH2—OH), —R8-R10, (CH2)2—O—CH3, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, or pyridine;
R200 is H, R20, F, Cl, Br, I, OH, SH, alkoxy, NH2, N(R)2, NH(R10), N(R10)(R11), CF3, CN, NO2, C1-C5 linear or branched, substituted or unsubstituted alkyl, methyl, ethyl, CH2—CH2—O—CH2—CH2—O—CH3, CH2—O—CH2—CH2—O—CH3, C1-C5 linear or branched alkoxy, methoxy, C1-C5 linear or branched haloalkyl, CHF2, CF3, CF2CH3, CH2CF3, CF2CH2CH3, CH2CH2CF3, CF2CH(CH3)2, CF(CH3)—CH(CH3)2, R8-aryl, CH2-Ph, —R8—O—R8—O—R10, (CH2)2—O—(CH2)2—O—CH3, —R8—O—R10, —R8-R10, (CH2)2—O—CH3, substituted or unsubstituted aryl, phenyl, substituted or unsubstituted heteroaryl, or pyridine;
or R200 and the carbon atom to which it is connected are C═O, C═N—O(R), C═N—O—CH3 or C(R)2, C(CH3)2, or CF2;
each R8 is independently [CH2]p
wherein p is between 1 and 10;
R9 is [CH]q, [C]q
wherein q is between 2 and 10;
R10 and R11 are each independently H, C1-C5 substituted or unsubstituted linear or branched alkyl, methyl, ethyl, CH2-cyclopropyl, CH2—CH2—O—CH3, C1-C5 substituted or unsubstituted linear or branched haloalky, CH2CF3, C1-C5 linear or branched alkoxy, O—CH3, R20, C(O)R, or S (O)2R;
or R10 and R11 are joined to form a substituted or unsubstituted 3-8 membered heterocyclic ring, piperazine, or piperidine,
n is an integer between 0 and 4;
or its pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, N-oxide, reverse amide analog, prodrug, isotopic variant, deuterated analog, pharmaceutical product or any combination thereof.