Sulfinylaminobenzamide and sulfonylaminobenzamide derivatives
Inventors
Farand, Julie • Kaplan, Joshua A. • Notte, Gregory • Olen, Casey Lockwood • Sangi, Michael • Sperandio, David
Assignees
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Publication Number
US-12049439-B2
Publication Date
2024-07-30
Expiration Date
Abstract
Provided is a compound of Formula (I):wherein the variable groups are defined herein.
Core Innovation
The invention provides methods of treating NAFLD, NASH, ASH, or lipodystrophy by administering to a patient in need thereof an effective amount of a compound of Formula I, Formula II, Formula III, or Formula IV, or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof. In each formula, Q is defined as —S(O)2—, and the compound framework is characterized by multiple substituent variables, including R1, R2, R3, R4, R5, R6, R7, and R8, as well as the corresponding R-group sets for the related formulas. The variables are limited to enumerated chemical groups and optional further substitution patterns.
The defined scaffold includes substituent-parameter constraints that specify allowed functional groups and substitution patterns, including halo, —CN, —OH, oxo, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups, together with sulfonamide/sulfone-related patterns such as —S(O)(NH)R14, —S(O)(NR8)R14, and —S(O)0-2R14. The claim language further sets options for ring-forming relationships among substituents and includes a substituted 5-10 membered carbobicyclic ring for R6 that may be fused, bridged, or spiro. Across the formula families, the substituent choices are constrained by multiple provisos and optional further substitution rules.
The invention further extends the treatment method to related Formula II, Formula III, and Formula IV compounds, each retaining Q as —S(O)2—. Across these formulas, the substituent frameworks are controlled by multiple variables, including x, y, and z for Formula II, with enumerated selections for substituent variables such as R21, R22, R23, R24, R27, R28, R31, R41, R42, R43, R44, R47, R48, R49, R61, R62, R63, R64, R67, R68, R69, R73, R74, R75, and R76. The disclosed invention centers on administering defined sulfonamide-linkage-containing benzamide derivatives with specified bicyclic carbobicyclic ring features for treating NAFLD, NASH, ASH, or lipodystrophy.
Claims Coverage
The independent claims are directed to treating NAFLD, NASH, ASH, or lipodystrophy by administering an effective amount of a Formula I, Formula II, Formula III, or Formula IV compound, each with Q defined as —S(O)2—. The inventive features mainly lie in the administering methods tied to the highly specific formula scaffolds and the constrained substituent-variable selections, with multiple provisos and optional ring-forming relationships narrowing allowable combinations.
Treating NAFLD, NASH, ASH, or lipodystrophy with Formula I compounds
A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof an effective amount of a compound of Formula I (or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof) wherein Q is —S(O)2— and R1 and other substituent variables are selected from enumerated groups with optional substitution patterns, including constraints on R6 as a 5-10 membered carbobicyclic ring that may be fused, bridged, or spiro and may be substituted with one or more R7.
Treating NAFLD, NASH, ASH, or lipodystrophy with Formula II compounds
A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof an effective amount of a compound of Formula II (or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof) wherein x, y, and z are independently 1, 2, 3, or 4, Q is S(O)2, and substituent variables including R21, R22, R23, R24, R27, and R28 are selected from enumerated groups with optional substitution and provisos that further restrict allowable combinations.
Treating NAFLD, NASH, ASH, or lipodystrophy with Formula III compounds
A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof an effective amount of a compound of Formula III (or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof) wherein Q is —S(O)2— and substituent variables including R41, R42, R43, R44, R47, R48, and R49 are selected from enumerated groups with optional substitution and provisos that restrict substituent choices.
Treating NAFLD, NASH, ASH, or lipodystrophy with Formula IV compounds
A method of treating NAFLD, NASH, ASH, or lipodystrophy comprising administering to a patient in need thereof an effective amount of a compound of Formula IV (or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, tautomer, or deuterated analog thereof) wherein Q is —S(O)2— and substituent variables including R61, R62, R63, R64, R67, R68, R69, R73, R74, R75, and R76 are selected from enumerated groups with optional substitution and provisos that restrict substituent choices and ring-forming relationships.
Across the independent claims, the core coverage is treatment of NAFLD, NASH, ASH, or lipodystrophy through administration of Formula I, Formula II, Formula III, or Formula IV compounds in which Q is —S(O)2— and the remaining structure is defined by constrained substituent-variable selections, optional substitution patterns, ring-forming options, and provisos.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating NAFLD, NASH, ASH, or lipodystrophy by administering an effective amount of a Formula I, Formula II, Formula III, or Formula IV compound to a patient in need thereof.
Examples describe synthesis and characterization of fluorinated sulfonamide/benzamide derivatives containing a bicyclo[1.1.1]pentane (and related) amine motif and various aryl sulfonyl or sulfonamide groups, with characterization by 1H NMR and LCMS-ESI.
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