Enantiomerically purified GPER agonist for use in treating disease states and conditions
Inventors
NATALE, Christopher • MOONEY, Patrick T. • Garyantes, Tina • LUKE, Wayne
Assignees
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Publication Number
US-11760749-B2
Publication Date
2023-09-19
Expiration Date
Abstract
The present disclosure provides 1) an enantiomerically purified compound SRR G-1, or a derivative thereof, including specific crystal forms, salts and co-crystals that modulates G protein-coupled estrogen receptor activity, 2) pharmaceutical and cosmetic compositions comprising an enantiomerically purified SRR G-1, or a derivative thereof, and 3) methods of treating or preventing disease states and conditions and cosmetic conditions mediated through these receptors and related methods thereof in humans and animals.
Core Innovation
The invention relates to a defined chiral compound of 1-((3aS,4R,9bR)-4-(6-bromobenzo[d][1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl)ethan-1-one, or a salt thereof, having chiral purity of about 90% or greater. The solid-state invention is focused on providing the compound in a selected crystalline form, where each form is identified by an XRPD pattern with specified 2θ peak positions (degrees) expressed with (±0.20).
The described thermal behavior and solid-state relationships distinguish crystalline Form B and crystalline Form C from crystalline Form A. Form B is a DCM mono-solvate that desolvates to Form C upon heating, while Form C is described as a desolvate with a melt onset of about 129°C.
The document further contrasts crystalline stability with amorphous behavior and establishes crystallization pathways. Amorphous SRR G-1 is described as unstable and crystallizing to Form A under heat or humidity, and relative stability between Form A and Form C is assessed using density/heat-of-fusion rules and supported by interconversion/competitive slurry results that favor Form A at room temperature and across temperatures.
Claims Coverage
The independent claim coverage includes one specified chiral ketone, or a salt thereof, with about 90% or greater chiral purity, limited to crystalline Form A, crystalline Form B, or crystalline Form C, each defined by XRPD peak patterns with specified 2θ positions (±0.20).
Chiral ketone with at least 90% chiral purity
A compound of the formula or a salt thereof, wherein the chiral purity of 1-((3aS,4R,9bR)-4-(6-bromobenzo[d][1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl)ethan-1-one, or a salt thereof, is about 90% or greater.
Crystalline Form A defined by XRPD peaks
The compound is in crystalline Form A that is characterized by an XRPD pattern having peaks expressed in degrees 2θ (±0.20) at about 5.75, about 20.54, about 20.71, about 21.25, and about 21.86.
Crystalline Form B defined by XRPD peaks
The compound is in crystalline Form B that is characterized by an XRPD pattern having peaks expressed in degrees 2θ (±0.20) at about 13.98, about 15.44, about 19.67, about 21.55, and about 22.05.
Crystalline Form C defined by XRPD peaks
The compound is in crystalline Form C that is characterized by an XRPD pattern having peaks expressed in degrees 2θ (±0.20) at about 10.73, about 12.77, about 13.49, about 16.09, and about 20.60.
Overall claim coverage is anchored on a defined chiral purity level for the specified chiral ketone, or salt, and crystalline-form selection enforced by XRPD fingerprint peak positions for crystalline Form A, crystalline Form B, and crystalline Form C.
Stated Advantages
Relative stability between Form A and Form C is assessed using density/heat-of-fusion rules and supported by interconversion/competitive slurry results that favor Form A at room temperature and across temperatures.
Amorphous SRR G-1 is described as unstable and crystallizing to Form A under heat or humidity.
Documented Applications
Pharmaceutical compositions mediated via GPER.
Cosmetic compositions mediated via GPER.
Treatment or prevention of multiple cancers and metabolic/cardiovascular/neuro/inflammatory disorders mediated via GPER, as listed in the partial content.
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