US 2024/0182415 A1Published application

Acetal, ketal, and hemiaminal analogs of psilocin, processes for the preparation thereof, and methods of use

OwnerJeffrey O'MEARA, Harpreet KAUR +1inventors

InventorsJeffrey O'MEARA, Harpreet KAUR, Ahmed Magdy ALI

Life of this patent

Estimating the term…

Abstract

This disclosure relates to compounds, compositions, methods and uses relating to activation of one or more serotonin receptors (i.e., 5-HT2 receptors). Specifically, the disclosure provides derivatives of psilocin and related tryptamines, and methods for treating neurological diseases or disorders, including neurodegenerative diseases, pain, and/or psychiatric disorders that comprise the compounds or compositions thereof. Also provided are methods for preparing the compounds described herein.

Claims47

Dependent claims

A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, heteroaryl, —(C═O)—R6, or —(C═S)—R6, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R6 is hydrogen, halogen, —C(CH3)3, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R2 and R3 are independently hydrogen, deuterium, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R2 and R3 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, or C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R′ and R″ are independently hydrogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or R′ and R″ together with the nitrogen atom to which they are attached form a C3-C12 heterocyclyl or heteroaryl;
X1 is N(R1), O, or S;
and
each Rx is independently hydrogen, —OH, methyl, methoxy, C1-C3 haloalkyl, deuterated C1-C3 alkyl, C1-C3 alkyl, C1-C3 alkoxy, —COOH, —CONR2R3, or halogen;
wherein the compound is not

8 more elements

A compound of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, heteroaryl, —(C═O)—R6, —(C═O)—OR6, —(C═O)—NR6R7, or —(C═S)—R6, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R6 and R7 are independently hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R2 and R3 are independently hydrogen, deuterium, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R2 and R3 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R′ and R″ are independently hydrogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or R′ and R″ together with the nitrogen atom to which they are attached form a C3-C12 heterocyclyl or heteroaryl;
X1 is N(R1), O, or S;
and
each Rx is independently hydrogen, —OH, methyl, methoxy, C1-C3 haloalkyl, deuterated C1-C3 alkyl, C1-C3 alkyl, C1-C3 alkoxy, —COOH, —CONR2R3, or halogen.

7 more elements

A compound of Formula (III):

or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, heteroaryl, —(C═O)—R6, —(C═O)—OR6, —(C═O)—NR7R8, or —(C═S)—R7, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R7 and R8 are independently hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R4 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, heteroaryl, —(C═O)—R8, —(C═O)—OR8, —(C═O)—N(R9R10), or —(C═S)—R9, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R9 and R10 are independently hydrogen, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl,
R2 and R3 are independently hydrogen, deuterium, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R2 and R3 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, or C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R8 and R6 are independently hydrogen, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R8 and R6 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, or C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R′ and R″ are independently hydrogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or R′ and R″ together with the nitrogen atom to which they are attached form a C3-C12 heterocyclyl or heteroaryl;
X1 is N(R1), O, or S;
X2 is N(R4), O, or S;
and
each Rx is independently hydrogen, —OH, methyl, methoxy, C1-C3 haloalkyl, deuterated C1-C3 alkyl, C1-C3 alkyl, C1-C3 alkoxy, —COOH, —CONR2R3, or halogen.

13 more elements

A compound of Formula (IV):

or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, heteroaryl, —(C═O)—R6, —(C═O)—OR6, —(C═O)—NR6R7, or —(C═S)—R6, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R6 and R7 are independently hydrogen, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl,
R2 and R3 are independently hydrogen, deuterium, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R2 and R3 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, or C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R′ and R″ are independently H, C1-C6 alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or together with the N to which they are attached form a C3-C12 heterocyclyl or heteroaryl;
X1 is N(R1), O, or S;
and
each Rx is independently hydrogen, —OH, methyl, methoxy, C1-C3 haloalkyl, deuterated C1-C3 alkyl, C1-C3 alkyl, C1-C3 alkoxy, —COOH, —CONR2R3, or halogen.

7 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R1 is hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, heteroaryl, —(C═O)—R6, or —(C═S)—R6, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
wherein R6 is hydrogen, halogen, —C(CH3)3, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R2 and R3 are independently hydrogen, deuterium, halogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 haloalkyl, C3-C20 cycloalkyl, C3-C20 heterocyclyl, aryl, or heteroaryl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
or
R2 and R3 together with the carbon atom to which they are attached form a C3-C20 cycloalkyl, or C3-C20 heterocyclyl, any of which is optionally substituted with one or more halogen, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C3-C12 cycloalkyl, C3-C12 heterocyclyl, aryl, or heteroaryl;
R′ and R″ are independently hydrogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or R′ and R″ together with the nitrogen atom to which they are attached form a C3-C12 heterocyclyl or heteroaryl;
X1 is N(R1), O, or S;
and
each Rx is independently hydrogen, —OH, methyl, methoxy, C1-C3 haloalkyl, deuterated C1-C3 alkyl, C1-C3 alkyl, C1-C3 alkoxy, —COOH, —CONR2R3, or halogen;
wherein the compound is not

8 more elements