# US 11,999,694 B2 · Delivery of therapeutic alkaloid compounds

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- Number: US 11,999,694 B2
- Document ID: US11999694B2
- Status: Granted
- Kind: B2
- Application number: 17/976,150
- Filed: 2022-10-28
- Published: 2023-05-25
- Granted: 2024-06-04
- Earliest claimed: 2021-10-29
- Assignees: Sensorium Therapeutics, Inc.
- Applicants: Sensorium Therapeutics, Inc.
- Inventors: Jacob M. Hooker; Michael S. Placzek
- Web page: https://patentgrep.com/patent/US11999694B2

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 209/12: Radicals substituted by oxygen atoms
- A61P 25/22: Anxiolytics
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 475/04: with a nitrogen atom directly attached in position 2
- C07D 487/04: Ortho-condensed systems
- C07D 487/10: Spiro-condensed systems
- C07D 491/113: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- C07D 491/20: Spiro-condensed systems
- C07D 495/04: Ortho-condensed systems
- C07D 495/10: Spiro-condensed systems
- C07D 497/10: Spiro-condensed systems
- C07D 498/10: Spiro-condensed systems
- C07D 513/10: Spiro-condensed systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07F 7/1804: {Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Disclosed are prodrug compounds that can be converted to mesembrine under biologically relevant conditions, such as hydrolysis in vivo; and related methods of preparing and using these compounds. Stable preparations of isolated mesembrine stereoisomers are also provided.

## Claims

### Claim 1

A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
R1is or C1-C7alkyl or H; and
ring A
wherein * denotes the attachment points of ring A to the compound of formula (I), and wherein
R3 is —OSi(C1-C6 alkyl)3, —OC(O)C1-C6 alkyl, —OC(O)C2-C6 alkenyl, —OC(O)C3-C10 cycloalkyl, —OC(O)phenyl, —OC(O)-5- to 7-membered heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C3-C10 cycloalkyl, phenyl, and 5- to 7-membered heteroaryl is optionally substituted by halogen, C1-C6 alkyl, C1-C3 alkoxy, nitro, —N(C1-C3 alkyl)2, C1-C3 haloalkyl, cyano, phenyl, phenoxy or —O(CH2)pOCH3; and
p is 2, 3, or 4.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the compound is of formula (IIIb-1)
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R3 is —OC(O)C1-C6 alkyl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein R3 is —OC(O)CH3.

### Claim 5 (depends on 1)

The compound of claim 1, wherein R3 is

### Claim 6 (depends on 1)

The compound of claim 1, wherein R3 is —OC(O)—C2-C6 alkenyl; wherein the C2-C6 alkenyl is isopropenyl or butenyl.

### Claim 7 (depends on 1)

The compound of claim 1, wherein the compound is a compound of formula (IIIb-1)
or a pharmaceutically acceptable salt thereof, wherein:
R1 is methyl; and
R3 is —OC(O)C1-C6 alkyl, —OC(O)(cyclohexyl), —OC(O)phenyl, or —OC(O)-(6-membered heteroaryl), wherein each hydrogen atom in C1-C6 alkyl, cyclohexyl, phenyl, and 6-membered heteroaryl is optionally substituted by C1-C6 alkyl, C1-C3 alkoxy, or —O(CH2)pOCH3; and
p is 2, 3, or 4.

### Claim 8 (depends on 7)

The compound of claim 7, wherein R3 is —OC(O)C1-C6 alkyl, and the C1-C6 alkyl is unsubstituted.

### Claim 9 (depends on 7)

The compound of claim 7, wherein the C1-C6 alkyl is substituted by methoxy.

### Claim 10

A compound of formula (IIIb-1)
or a pharmaceutically acceptable salt thereof, wherein:
R1 is methyl; and
R3 is —OC(O)C1-C6 alkyl, wherein the C1-C6 alkyl is unsubstituted; or
R3 is —OC(O)phenyl, wherein the phenyl is optionally monosubstituted with an unsubstituted C1-C6 alkyl.

### Claim 11 (depends on 10)

The compound of claim 10, wherein R3 is —OC(O)C1-C6 alkyl.

### Claim 12 (depends on 1)

The compound of claim 1, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The compound of claim 1, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The compound of claim 1, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

The compound of claim 1, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The compound of claim 1, wherein the compound is
or a pharmaceutically acceptable salt thereof.

### Claim 17

A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein R3 is —OC(O)alkyl optionally substituted by alkoxy, —OH, halogen, or −O(CH2)pCH3; and p is 2, 3, or 4.

### Claim 18 (depends on 17)

The compound of claim 17, wherein R3 is —OC(O)alkyl substituted by fluoro, —OH, methoxy or −O(CH2)pOCH3; and p is 2, 3, or 4.

### Claim 19 (depends on 18)

The compound of claim 18, wherein R3 is —OC(O)alkyl substituted by fluoro, methoxy, or —O(CH2)2OCH3.

### Claim 20 (depends on 17)

The compound of claim 17, selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 17)

The compound of claim 17, selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.