Inhibitors of protein arginine deiminase 1 and methods of preparation and use thereof

Patent metadata

Field	Value
Publication number	US-12448358-B2
Application number	US-202017622200-A
Country	US
Kind code	B2
Filing date	Jun 26, 2020
Priority date	Jul 3, 2019
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

The invention provides novel inhibitors or inactivators of protein arginine deiminase 1, pharmaceutical compositions and methods of use thereof. The invention also relates to molecular probes based on such compounds and methods of use thereof.

First claim

What is claimed is:

1. A compound having the structural formula (I),

wherein
each of R a and R b is H or D;
X is a halogen atom;
R 2 is selected from the group consisting of: H, OH or OCH 3 ;
R 4 is selected from the group consisting of: H, halogen, ethynyl (HC≡C—)
each of R 3 and R 5 is I;
R 6 is H or R; and
each R is independently a C 1-6 alkyl,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein each of R a and R b is H.

3. The compound of claim 1 , wherein X is F.

4. The compound of claim 1 , wherein X is Cl.

5. The compound of claim 1 , wherein R 2 is OH.

6. The compound of claim 5 , wherein R 4 is H.

7. The compound of claim 6 , wherein R 6 is H.

8. The compound of claim 1 , wherein R 4 is a halogen atom.

9. The compound of claim 1 , in the form of a salt.

10. A pharmaceutical composition comprising a compound of claim 1 .

11. A unit dosage form comprising a pharmaceutical composition according to claim 10 .

12. A method for inhibiting or inactivating protein arginine deiminase 1 (PAD1), comprising administering to a subject in need thereof a pharmaceutical composition of claim 10 .

Assignees

• Univ Massachusetts

Inventors

• Thompson Paul R
• Mondal Santanu

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P15/18

  Feminine contraceptives · CPC title

• C07D235/16 Primary

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D235/14 Primary

  Radicals substituted by nitrogen atoms (by nitro radicals C07D235/10) · CPC title