US 2026/0209247 A1 · Substituted Tricyclic Compounds

Abstract

Disclosed are compounds of the general formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its polymorph, or solvate thereof, wherein, ring A, ring B, R1 to R4, and n are as defined herein, for use as SOS1 inhibitors in the treatment of proliferative, infectious and RASopathy diseases or disorders. Also disclosed are methods of synthesizing the compound of formula I, pharmaceutical compositions containing the compound of formula I, method of treatment of proliferative, infectious and RASopathy diseases or disorder, for example, a cancer, by administering the said compound and combinations of the compound of formula I with other active ingredients.

A compound of the general formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its polymorph, or solvate thereof,
wherein,
Ring A is selected from aryl, heteroaryl, and heterocyclyl;
Ring B is selected from substituted or unsubstituted 5 or 6 membered carbocyclic ring and substituted or unsubstituted 5 or 6 membered heterocyclic ring containing 1 to 3 heteroatoms independently selected from S, O, and N;
when ring B is carbocyclic ring, it is substituted with 1 to 8 substituents independently selected from Rc and Rd;
when ring B is heterocyclic ring, it is substituted with 1 to 7 substituents;
when it is substituted on a ring nitrogen atom, it is substituted with substituents selected from Ra and Rb;
and when it is substituted on a ring carbon atom, it is substituted with substituents selected from Rc and Rd;
Ra and Rb are independently selected from hydrogen, —C(═O)Rg, —C(═O)NRh(Ri), substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl;
Rc and Rd are independently selected from hydrogen, halogen, oxo, —C(═O)Rg, —NRh(Ri), —C(═O)NRh(Ri), —ORj, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl;
optionally Rc and Rd groups together with the carbon atom which they are attached forming a substituted or unsubstituted carbocyclic ring and substituted or unsubstituted heterocycle;
R1 is selected from hydrogen, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl.
R2 and R3 are independently selected from hydrogen, halogen, cyano, substituted or unsubstituted alkyl, and substituted or unsubstituted cycloalkyl;
R4 is selected from halogen, cyano, —NReRf, —ORj, —C(═O)Rg, —C(═O)NRh(Ri), substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, cycloalkyl substituted with substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and heterocyclyl substituted with substituted alkyl;
Re and Rf are independently selected from hydrogen, —C(═O)Rg, —C(═O)NRh(Ri), substituted or unsubstituted alkyl, alkyl substituted with substituted or unsubstituted heterocyclyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl;
Rg is selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl;
Rh and Ri are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocyclyl;
optionally Rh and Ri groups together with the nitrogen atom to which they are attached forming a substituted or unsubstituted heterocycle;
Rj is selected from hydrogen, substituted or unsubstituted alkyl, alkyl substituted with substituted or unsubstituted cycloalkyl, and substituted or unsubstituted cycloalkyl;
‘n’ is an integer selected from 0, 1, 2, and 3;
when an alkyl group is substituted, it is substituted with 1 to 5 substituents independently selected from oxo (═O), halogen, cyano, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR5, —C(═O)OH, —C(═O)O(alkyl), —NR6R6a, —NR6C(═O)R7, and —C(═O)NR6R6a;
when an cycloalkyl group is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (═O), halogen, alkyl, hydroxyalkyl, cyano, aryl, heteroaryl, heterocyclyl, —OR5, —C(═O)OH, —C(═O)O(alkyl), —NR6R6a, —NR6C(═O)R7, and —C(═O)NR6R6a;
when the aryl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, nitro, cyano, alkyl, perhaloalkyl, cycloalkyl, heterocyclyl, heteroaryl, —OR5, —NR6R6a, —NR6C(═O)R7, —C(═O)R7, —C(═O)NR6R6a, —SO2-alkyl, —C(═O)OH, —C(═O)O-alkyl, and haloalkyl;
when the heteroaryl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, nitro, cyano, alkyl, haloalkyl, perhaloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR5, —NR6R6a, —NR5C(═O)R7, —C(═O)R7, —C(═O)NR6R6a, —SO2-alkyl, —C(═O)OH, and —C(═O)O-alkyl;
when the heterocycle group is substituted, it is substituted either on a ring carbon atom or on a ring hetero atom, and when it is substituted on a ring carbon atom, it is substituted with 1 to 4 substituents independently selected from oxo (═O), halogen, cyano, alkyl, alkoxyalkyl, hydroxyalkyl, cycloalkyl, perhaloalkyl, —OR5, —C(═O)NR6R6a, —C(═O)OH, —C(═O)O-alkyl, —N(H)C(═O)(alkyl), —N(H)R6, and —N(alkyl)2;
and when the heterocycle group is substituted on a ring nitrogen, it is substituted with substituents independently selected from alkyl, cycloalkyl, aryl, heteroaryl, —SO2(alkyl), —C(═O)R7, and —C(═O)O(alkyl);
when the heterocycle group is substituted on a ring sulfur, it is substituted with 1 or 2 oxo (═O) group(s);
R5 is selected from hydrogen, alkyl, perhaloalkyl, and cycloalkyl;
R6 and R6a are each independently selected from hydrogen, alkyl, and cycloalkyl;
or R6 and R6a together with nitrogen to which they are attached form a heterocyclyl ring;
and
R7 is selected from alkyl and cycloalkyl.

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Substituted Tricyclic Compounds

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Substituted Tricyclic Compounds

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Abstract

Claims22