IP Library Granted Patent US 12,291,504
Granted Patent B2
US 12,291,504 · App. 17/299,733 · Granted May 6, 2025

Small molecule inhibition of sulfotransferase SULT1A3

Inventors: Alexander Deiters (Pittsburgh, PA); Kristie E. Darrah (Pittsburgh, PA); Mary Frances Cacace (Pittsburgh, PA); Ian Cook (Bronx, NY); Thomas Leyh (Bronx, NY); Ting Wang (Bronx, NY)
Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education; Albert Einstein College of Medicine
C07D219/06C07D215/04C07D215/48C07D249/06C07D401/04C07D471/04
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Quick Facts
Patent No.
US 12,291,504
App. No.
17/299,733
Granted
May 6, 2025
Kind
B2
Abstract

Provided herein are small molecule compounds and methods inhibiting human sulfotransferase 1A3 (SULT1A3) using these small molecule compounds. Methods of manufacturing and treatment are also disclosed.

Claims (31)

1. A compound having the structure of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

is a naphthalene or a quinoline;

X is selected from a bond and an optionally substituted alkyl or alkene;

Y is selected from —OR′, —CONR′ 2 , —COOR′ and optionally substituted heteroaryl;

R′ is H or an optionally substituted alkyl;

Z is independently selected from H, optionally substituted alkyl, and —X-Y, or two Z together form an optionally substituted cycloalkyl, wherein when Z 1 and Z 2 are both H, then Y is heteroaryl, or wherein Z 1 and Z 2 are not both H;

a is 0 or an integer of 1-4; and

wherein the compound of formula (I) is selected from:

2. A compound having the structure of formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

X is selected from a —C 0 -C 6 alkyl or a —C 2 -C 6 alkene;

Y is selected from —OR', —COOR′, —CONR′ 2 , and heteroaryl;

R′ is H or C 1 -C 6 alkyl;

Z 1 is selected from H and —OR′; and

Z 2 is selected from H, —C 1 -C 6 alkyl, and —C 0 -C 6 -COOR′, or

Z 1 and Z 2 together form a substituted cycloalkyl,

wherein when Z 1 and Z 2 are both H, then Y is heteroaryl and

wherein the compound of formula (II) is selected from:

3. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

4. A method of inhibiting SULT1A3 in a subject in need thereof, comprising administering a compound of claim 1 , or a composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier to the subject.

5. The method of claim 4 , wherein the subject is a human.

6. A method inhibiting SULT1A3 in a cell, comprising contacting a cell with a compound of claim 1 .

7. The method of claim 6 , wherein the cell is a mammalian cell, and optionally wherein the mammalian cell is a human cell.

8. A method of inhibiting the activity of SULT1A3, comprising providing a SULT1A3 enzyme, and contacting the SULT1A3 enzyme with a compound of claim 1 .

9. The method of claim 8 , wherein:

(a) the contacting of SULT1A3 is performed in vitro; or

(b) the contacting of SULT1A3 is performed in vivo.

10. A method of prolonging therapeutic efficacy of a catecholic drug or lowering the effective concentration of a catecholic drug in a subject in need, comprising administering a compound of claim 1 , or a composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier, to the subject.

11. A method of preventing metabolization of dopamine in a subject in need comprising administering a compound of claim 1 , or a composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier, to the subject.

12. A method of retarding tumor progression of hepatocellular carcinoma in a subject in need comprising administering a compound of claim 1 , or a composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier, to the subject.

Assignments (3)
CONFIRMATORY LICENSE Recorded Dec 5, 2023
From: UNIVERSITY OF PITTSBURGH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065774/0720 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 25, 2023
From: COOK, IAN; LEYH, THOMAS; WANG, TING
To: ALBERT EINSTEIN COLLEGE OF MEDICINE
Reel/Frame 062480/0387 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 25, 2023
From: DEITERS, ALEXANDER; DARRAH, KRISTIE E.; CACACE, MARY FRANCES
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 062481/0319 →
Continuity (2)
Provisional Application 62777644 · Dec 10, 2018
Related Publication 20220024876A1 · Jan 27, 2022
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