Modulation of chemosensory receptors and ligands associated therewith

摘要

The present invention includes methods for identifying modifiers of chemosensory receptors and their ligands, e.g., by determining whether a test entity is suitable to interact with one or more interacting sites within the Venus flytrap domains of the chemosensory receptors, and modifiers capable of modulating chemosensory receptors and their ligands. The present invention also includes modifiers of chemosensory receptors and their ligands having Formula (I), its subgenus, and specific compounds. Furthermore, the present invention includes ingestible compositions comprising the modifiers of chemosensory receptors and their ligands and methods of using the modifiers of chemosensory receptors and their ligands to enhance the sweet taste of an ingestible composition or treat a condition associated with a chemosensory receptor. In addition, the present invention include processes for preparing the modifiers of chemosensory receptors and their ligands.

主权项

1. An ingestible composition comprising a compound having structural Formula (IIIb), or a tautomer, salt, solvate, and/or ester thereof; and an ingestible carrier;wherein
A is hydrogen, halo, —CN, —NO2, —OR9, —S(O)cR9, —NR9COR10, —NHOR9, —NR9R10, —NOR9, —CONR9R10, —CO2R9, —NR9CO2R10, —NR9CONR10R11, —NR9CSNR10R11, —NR9C(═NH)NR10R11; R9, R10, and R11 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; or alternatively, R9 and R10, or R10 and R11, together with the atoms to which they are bonded, form a cycloheteroalkyl or substituted cycloheteroalkyl ring; H is —C(R35)— or —N—; I is —C(R36) or —N—; J is —C(R37)— or —N—; K is —C(R38)— or —N—; R17 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl; R35 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —NO2, —OR39, —S(O)jR39, —OCOR39, —NR39R40, —CONR39R40, —CO2R39, —SO2NR39R40, or —NR39SO2R40; R36 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —NO2, —OR41, —S(O)kR41, —OCOR41, —NR41R42, —CONR41R42, —CO2R41, —SO2NR41R42, or —NR41SO2R42; R37 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —NO2, —OR43, —S(O)lR43, —OCOR43, —NR43R44, —CONR43R44, —CO2R43, —SO2NR43R44, or —NR43SO2R44; R38 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, halo, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —CN, —NO2, —OR45, —S(O)mR45, —OCOR45, —NR45R46, —CONR45R46, —COR45, —CO2R45, —SO2NR45R46, or —NR45SO2R46; or alternatively R36 and R37, or R37 and R38, taken together with the atom to which they are bonded, form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring; j, k, l and m are independently 0, 1 or 2; and R39, R40, R41, R42, R43, R44, R45, and R46 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, acyl, substituted acyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, or substituted heteroarylalkyl; or alternatively R39 and R40, R41 and R42, R43 and R44, or R45 and R46, together with the atoms to which they are bonded, form a cycloheteroalkyl or substituted cycloheteroalkyl ring; with the proviso that at most, two of H, I, J and K are —N—.