# US 2022/0033385 A1 · Enantiomerically purified gper agonist for use in treating disease states and conditions

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- Number: US 2022/0033385 A1
- Document ID: US20220033385A1
- Status: Published application
- Kind: A1
- Application number: 17/184,870
- Filed: 2021-02-25
- Published: 2022-02-03
- Earliest claimed: 2018-07-21
- Assignees: Linnaeus Therapeutics, Inc.
- Applicants: Linnaeus Therapeutics, Inc.
- Inventors: Christopher NATALE; Patrick T. MOONEY; Tina GARYANTES; Wayne LUKE
- Web page: https://patentgrep.com/patent/US20220033385A1

## CPC

- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- A61P 35/00: Antineoplastic agents
- C07C 309/19: of a saturated carbon skeleton containing rings
- C07C 309/29: of non-condensed six-membered aromatic rings
- C07C 309/35: Naphthalene sulfonic acids
- C07B 2200/07: Optical isomers
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## 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.

## Claims

### Claim 1

A compound comprising the formula 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 derivative 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 derivative thereof, is about 90% or greater.

### Claim 2 (depends on 1)

The compound of claim 1. (New), wherein the compound is crystalline as evidenced by XRPD analysis or amorphous as evidenced by XRPD analysis or a mixture of crystalline and amorphous material.

### Claim 3 (depends on 1)

The compound of claim 1. (New), 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 derivative thereof, is substantially free of its opposite enantiomer.

### Claim 4 (depends on 1)

The compound of claim 1. (New) wherein the form 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 is selected from 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 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 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; is amorphous; or combinations thereof.

### Claim 5 (depends on 1)

The compound of claim 1. (New) wherein the crystalline form 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 is selected from 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 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 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; or combinations thereof.

### Claim 6 (depends on 5)

The compound of claim 5. (New) wherein the crystalline form 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 is 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.

### Claim 7 (depends on 6)

The compound of claim 6. (New) wherein the crystalline form 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 is crystalline Form A that is further characterized by an XRPD pattern having peaks expressed in degrees 2θ (±0.20) at about 5.75, about, 9.56, about 10.53, about 17.03, about 20.54, about 20.71, about 21.25, about 21.86, about 24.67, and about 28.06.

### Claim 8 (depends on 7)

The compound of claim 7. (New) wherein the crystalline form 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 is crystalline Form A that is further characterized by an XRPD pattern having peaks expressed in degrees 2θ (±0.20) at about 5.75, about, 9.56, about 10.53, about 10.81, about 13.02, about 14.66, about 14.79, about 16.23, about 17.03, about 20.54, about 20.71, about 21.25, about 21.86, about 24.67, and about 28.06.

### Claim 9 (depends on 1)

The compound of claim 1. (New) wherein the derivative thereof is a salt or co-crystal.

### Claim 10 (depends on 1)

The compound of claim 1. (New) wherein the derivative thereof is selected from salts or co-crystals formed with benzenesulfonic acid, with (+)-(1S)-camphor-10-sulfonic acid, with ethane-1,2-disulfonic acid, with hydrochloric acid, with methanesulfonic acid, with naphthalene-2-sulfonic acid, with naphthalene-1,5-disulfonic acid, with sulfuric acid, with p-toluenesulfonic acid, or combinations thereof.

### Claim 11 (depends on 10)

The compound of claim 10. (New) wherein the derivative thereof is a salt or co-crystal formed with benzenesulfonic acid.

### Claim 12 (depends on 10)

The compound of claim 10. (New) wherein the derivative thereof is a salt or co-crystal formed with (+)-(1S)-camphor-10-sulfonic acid.

### Claim 13 (depends on 10)

The compound of claim 10. (New) wherein the derivative thereof is a salt or co-crystal formed with naphthalene-2-sulfonic acid.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1. (New) and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

### Claim 15 (depends on 1)

A cosmetic composition comprising a therapeutically effective amount of the compound of claim 1. (New) and a cosmetically acceptable carrier, adjuvant, or vehicle.

### Claim 16 (depends on 1)

A method of treating or preventing a disease or disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound of claim 1. (New), or a derivative thereof.

### Claim 17 (depends on 16)

The method of claim 16. (New) wherein the disease or disorder is selected from the group consisting of cancer, endometritis, prostatitis, polycystic ovarian syndrome, urinary incontinence, hormone-related disorders, hearing disorders, hot flashes, profuse sweating, hypertension, stroke, ischemia, myocardial infarction, dilated cardiomyopathy, obesity, insulin resistance, osteoporosis, atherosclerosis, symptoms of menopause, inflammation, rheumatoid arthritis, osteoarthritis, lymphoproliferative disorders, myeloproliferative disorders, eosinophilia, histiocytosis, paroxysmal nocturnal hemoglobinuria, systemic mastocytosis, venous thrombosis, embolisms, depression, insomnia, anxiety, neuropathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, inflammatory bowel disease, Crohn's disease, celiac disease, proteinuric renal disease, vascular disease, and thymic atrophy.

### Claim 18 (depends on 14)

A method of preventing or reducing the likelihood of pregnancy after intercourse comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 14. (New).

### Claim 19 (depends on 16)

The method of claim 16. (New), wherein the subject is a human or an animal.

### Claim 20 (depends on 1)

A method of treating or preventing type 2 diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound of claim 1. (New), or a derivative thereof.