EP2 antagonist
Inventors
Watanabe, Akio • Yoshida, Atsushi • Hirooka, Yasuo • Yang, Michael G. • Li, Ning
Assignees
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Publication Number
US-12630510-B2
Publication Date
2026-05-19
Expiration Date
Abstract
A drug containing, as an active ingredient, a compound having an antagonistic activity against an EP2 receptor in the prevention and/or treatment of a disease associated with the activation of an EP2 receptor, of formula (I-A): wherein all symbols have the same meanings as those described in the specification, or a pharmaceutically acceptable salt thereof.
Core Innovation
The document describes medicaments and active compounds having antagonistic activity against the EP2 receptor, including an (1R,2S)-cyclopropanecarboxylic acid EP2 antagonist and compounds of formulae (I-A), (I-1), and related sub-formulae. The compounds are presented for prophylaxis and/or treatment of diseases associated with EP2 activation, with technical objectives stated as potent EP2 antagonism and favorable pharmacokinetic properties, including solubility and liver microsomal stability.
The disclosure provides extensive chemical structural definitions using variable substituents and linkage groups, including R1 to R7, L1/L2, Y, ring A, and the stereodefined cyclopropanecarboxylic acid examples within the defined structural scope. Representative excluded compounds are listed, and specific sub-formulae such as (I-C) are also described with constrained substituent options.
The document further includes a brief note regarding anti-tumor activity in an allogenic mouse colorectal cancer cell line CT26 transplantation model and a mouse allogenic CT26 colorectal cancer transplant model, where administration of the test compound is described as suppressing tumor growth. A tablet formulation containing the (1R,2S)-cyclopropanecarboxylic acid EP2 antagonist is also described, including formulation components listed in the document.
Claims Coverage
The claim coverage centers on a family of compounds defined by extensive substituent and linkage options for formula (I-1), with further structural narrowing via formula (I-C). Independent and associated claim members also cover treating colorectal cancer by administration of the compound and a pharmaceutical composition that is an EP2 receptor antagonist.
Formula-defined substituted compound class
A compound of formula (I-1) with substituent and linkage definitions for R38, R40, L2, Y, R1, R10, R2, R3, R4, R5, X, and ring A, optionally as a pharmaceutically acceptable salt thereof.
Substitution constrained sub-formula variant
A compound according to claim 1, or a pharmaceutically acceptable salt thereof, defined as a compound of formula (I-C) with specific substituent options and constrained selections for X^a, CR6a, NR7a, R6a, R7a, R3a, R3b, R3c, R32, R35, and p.
Colorectal cancer treatment by administration of the compound
A method of treating colorectal cancer by administering the compound of formula (I-1), or a pharmaceutically acceptable salt, to a patient in need.
EP2 receptor antagonist pharmaceutical composition
A pharmaceutical composition that is an EP2 receptor antagonist.
Combination cancer treatment regimen with selected therapeutic agents
A cancer treatment regimen comprising the pharmaceutical composition and at least one selected therapeutic agent from specified therapeutic agent classes.
The core coverage is a family of compounds defined by extensive substituent and linkage options for formula (I-1), with further narrowing via formula (I-C). The claims also include treating colorectal cancer by administration of the compound, defining an EP2 receptor antagonist pharmaceutical composition, and combining the composition with selected therapeutic agents in a cancer treatment regimen.
Stated Advantages
Potent EP2 antagonism.
Favorable pharmacokinetic properties, including solubility and liver microsomal stability.
Suppressing tumor growth in a mouse allogenic CT26 colorectal cancer transplant model.
EP2 antagonistic activity as shown by inhibition of PGE2-stimulated cAMP in CHO cells expressing human EP2 with IC50 values for multiple examples.
Provides industrial applicability for preventing or treating EP2-activation-associated diseases.
Anti-tumor activity reported in an allogenic mouse colorectal cancer cell line CT26 transplantation model.
Documented Applications
Prophylaxis and/or treatment of diseases associated with EP2 activation using EP2 receptor antagonists.
Use of EP2 receptor antagonists in colorectal cancer treatment.
Treating colorectal cancer by administering a compound, with mouse allogenic CT26 colorectal cancer transplant model evidence of tumor growth suppression.
Formulating an (1R,2S)-cyclopropanecarboxylic acid EP2 antagonist as a tablet formulation.
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