Granted Patent B2

US 12,559,486 · App. 18/486,668 · Granted Feb 24, 2026

Inventors: Andrew P. Crew (Guilford, CT); Michael Berlin (Flemington, NJ); Angela M. Cacace (Haddam Neck, CT); Julian T. Chandler (Old Lyme, CT)

Assignee: ARVINAS OPERATIONS, INC.

C07D417/14A61K47/54C07D401/04C07D487/04A61K45/06

Abstract

Claims (38)

1 . A compound having the chemical structure:

PTM-L-ULM,

or a pharmaceutically acceptable salt thereof,

wherein:

the PTM is:

wherein:

X PTM7 and X PTM8 are independently nitrogen or carbon;

each R 7 is independently H or halogen;

each R 9 is independently halogen, H, or C 1-3 fluoroalkyl when R 9 is bonded to a carbon atom;

or each R 9 is independently absent when R 9 is bonded to a nitrogen atom; and

is the point of attachment of the L;

the ULM is:

wherein:

Q 1 is N or CR′;

W is CH 2 or C═O;

A is H or C 1-3 alkyl;

n is 1, 2, 3, or 4;

G is H or C 1-3 alkyl;

each R is independently selected from H, OH, NH 2 , —Cl, —F, —Br, C 1-3 alkyl, C 1-3 fluoroalkyl, or C 1-3 alkoxy, wherein one R is modified to be covalently joined to the L;

R′ is H, halogen, C 1-3 alkyl, or C 1-3 alkoxy; and

represents a bond that is stereospecific or non-stereospecific; and

the L is selected from:

wherein each * is a site of attachment of the PTM or the ULM.

2 . The compound according to claim 1 , wherein the PTM is selected from:

wherein is the point of attachment of the L.

3 . The compound of claim 1 , wherein the ULM is:

4 . The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

5 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6 . The compound of claim 1 , wherein the PTM is:

7 . The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

8 . A pharmaceutical composition comprising the compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9 . A pharmaceutical composition comprising the compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10 . A method of treating a disease state or condition associated with Tau aggregation and accumulation in a patient comprising administering to said patient an effective amount of the compound according to claim 4 .

11 . The method of claim 10 , wherein the disease is Alzheimer's disease.

12 . A method of treating a disease state or condition associated with Tau aggregation and accumulation in a patient comprising administering to said patient an effective amount of the compound according to claim 7 .

13 . The method of claim 12 , wherein the disease is Alzheimer's disease.

Assignments (1)

Continuity (3)

References Cited (286)