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-10934277-B2
Publication Date
2021-03-02
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 is directed to SRR G-1 crystalline Form A, or a pharmaceutically acceptable salt thereof, 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. The crystalline Form A is further characterized as anhydrous, with low hygroscopicity, a melt onset of about 176 °C, and a calculated density of about 1.485 g cm−3.
The document provides single-crystal and solid-state characterization for SRR G-1 crystalline Form A, including an orthorhombic P212121 unit cell and absolute configuration determination reported using a Flack parameter. It also includes XRPD pattern generation and comparison for Form A, together with chiral center assignments based on the described characterization.
The document relates crystalline Form A to other solid-state forms of SRR G-1, including crystalline Forms B and C and an amorphous form, and describes their polymorph relationships. Thermal behaviors are reported for the different forms, including solvate and desolvate behavior, with Form B described as a mono dichloromethane solvate and Form C described as a desolvate.
Claims Coverage
The independent claim defines the claimed compound or pharmaceutically acceptable salt by a combination of XRPD peak positions plus multiple solid-state property constraints. The inventive features are XRPD-defined crystalline Form A, melt onset, anhydrousness, low hygroscopicity, and calculated density.
Crystalline form A defined by specific XRPD peaks
The crystalline Form A 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 A with melt onset
The crystalline Form A has a melt onset of about 176 °C.
Anhydrous crystalline form A
The crystalline Form A is anhydrous.
Low hygroscopicity crystalline form A
The crystalline Form A exhibits low hygroscopicity.
Crystalline form A with calculated density
The crystalline Form A exhibits a calculated density of about 1.485 g cm−3.
Overall, the claim coverage is anchored on an XRPD-defined crystalline Form A further limited by melt onset, anhydrousness, low hygroscopicity, and calculated density.
Stated Advantages
Crystalline Form A exhibits low hygroscopicity.
There is no form change in pH/bio-relevant buffers.
SRR G-1 shows enhanced inhibition of YUMM1.7 melanoma cell growth versus the racemate and opposite enantiomer.
Documented Applications
Therapeutic use for GPER-mediated diseases, including cancer.
Therapeutic use for metabolic, cardiovascular, and neuroinflammatory indications.
Pharmaceutical compositions.
Cosmetic compositions.
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