Fused ring derivative having MGAT-2 inhibitory activity
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Publication Number
US-12454533-B2
Publication Date
2025-10-28
Expiration Date
Abstract
The present invention provides the compound represented by the following formula (I):wherein a moiety represented by formula: or the like; y is 0 or 1; R1 is hydrogen or the like; R2a and R2b are taken together with an adjacent carbon atom to form ring B; ring B is a substituted or unsubstituted non-aromatic carbocycle or the like; R3a is hydrogen or the like; R3b is hydrogen or the like; R4a is represented by formula: L1 is a single bond or the like; L2 is —C(═O)— or the like; La is a single bond or the like; R7 is substituted or unsubstituted alkyl or the like; R4b is substituted or unsubstituted alkyl or the like; R4c is each independently halogen or the like.
Core Innovation
The invention relates to compounds represented by formula (I), including pharmaceutically acceptable salts. The formula (I) scaffold is defined by a moiety in which Y is 1, X is C(=O), C(=S), or SO2, and m is 0 or 1, together with variable groups R1, R2a/R2b, R3a/R3b, R4a/R4b/R4c′, R5, R7, and n.
The compound definitions specify ring C as an aromatic carbocycle, an aromatic heterocycle, a non-aromatic carbocycle, or a non-aromatic heterocycle, and allow ring B formation when R2a and R2b are taken together with an adjacent carbon atom. Optional ring formation is also provided for R3a and R3b, including formation of a substituted or unsubstituted non-aromatic carbocycle or non-aromatic heterocycle. R1 is restricted to enumerated substituent classes and is not represented by a further specified formula.
The variable groups include extensive substituent sets for R4a, R4b, R4c′, R5, and R7, including halogen, hydroxy, cyano, carboxy, carbamoyl, thiocarbamoyl, amidino, amino, ureido, guanidino, pentafluorothio, sulfo, sulfamoyl, alkyl, alkenyl, alkyloxy, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, and aromatic or non-aromatic carbocyclyl and heterocyclyl options. The definition also includes sulfur- and nitrogen-containing group patterns linked through L, and n is an integer of 1 to 5.
The disclosed compounds are described in an MGAT2 inhibitory context. The partial content also states that the compounds are useful for prophylaxis and therapy of MGAT2-associated diseases, and includes pharmaceutical composition and treatment/use language, together with examples and compound tables illustrating substituent and ring variants.
Claims Coverage
The consolidated claim coverage centers on one independent compound claim for formula (I), with multiple structural feature groups and dependent refinements. Across the input items, the independent claim consistently includes the constrained moiety defined by Y, X, and m; the R1 exclusion; ring C and ring B definitions; optional ring formation through R2a/R2b and R3a/R3b; and extensive R4/R5/R7 substituent and sulfur-containing group definitions. MGAT2 inhibitory activity and therapeutic use claims also appear in the provided claim excerpts.
Formula (I) compound scaffold with constrained core parameters
A compound represented by formula (I) (or its pharmaceutically acceptable salt) in which Y is 1, X is C(=O), C(=S), or SO2, and m is 0 or 1.
Restricted R1 substitution with explicit exclusion
R1 is defined by an enumerated substitution set and is not represented by a further specified formula.
Ring C selection and ring B formation from R2a and R2b
Ring C is an aromatic carbocycle, aromatic heterocycle, non-aromatic carbocycle, or non-aromatic heterocycle, and R2a and R2b may be taken together with an adjacent carbon atom to form ring B, where ring B is a substituted or unsubstituted non-aromatic carbocycle or non-aromatic heterocycle.
Optional ring formation through R3a and R3b
R3a and R3b are defined by enumerated substituent sets and may be taken together with an adjacent carbon atom to form a substituted or unsubstituted non-aromatic carbocycle or non-aromatic heterocycle.
Extensive R4, R5, R7, and L-linked sulfur-containing group definitions
R4a, R4b, R4c′, R5, and R7 are defined through broad substituent sets, including sulfur- and nitrogen-containing group patterns linked through L; L is a single bond, alkylene, or C(=O); and n is an integer of 1 to 5.
Pharmaceutical composition having MGAT2 inhibitory activity
A pharmaceutical composition is provided that has MGAT2 inhibitory activity.
Method of treating specified diseases by administering the compound
A method of treating at least one specified disease by administering the compound or a pharmaceutically acceptable salt to a patient in need of treatment.
The consolidated claims coverage is directed to formula (I) compounds defined by constrained Y, X, and m parameters, an R1 exclusion, ring-forming and substituent limitations for R2a/R2b, R3a/R3b, R4 groups, R5, R7, and L-linked sulfur-containing motifs, with n fixed to 1 to 5. The claim set also includes pharmaceutical composition and treatment claims tied to MGAT2 inhibitory activity and treatment of specified diseases.
Stated Advantages
Inhibits MGAT2.
Useful for prophylaxis and therapy of MGAT2-associated diseases including obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyper-VLDL-triglyceridemia, hyperfattyacidemia, diabetes mellitus, and arteriosclerosis.
Condensing ring A to a dihydropyridone-like monocycle to avoid enone structure.
Suppressing toxicity.
Providing MGAT2 inhibitory activity.
Usefulness for MGAT2-associated diseases including obesity and related metabolic disorders.
Documented Applications
A pharmaceutical composition having MGAT2 inhibitory activity.
Treating at least one specified disease by administering the compound or a pharmaceutically acceptable salt to a patient in need of treatment, including obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyper-VLDL-triglyceridemia, hyperfattyacidemia, diabetes mellitus, and arteriosclerosis.
Prophylaxis and therapy of MGAT2-associated diseases including obesity, metabolic syndrome, dyslipidemias, diabetes mellitus, and arteriosclerosis.
MGAT2-associated diseases and metabolic disorders including obesity, hyperlipidemia, hypertriglyceridemia, hyper-VLDL-triglyceridemia, hyperfattyacidemia, diabetes mellitus, arteriosclerosis, and metabolic syndrome.
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