Granted Patent
B2
US 12,351,597 · App. 17/617,642 · Granted Jul 8, 2025
Substituted biphenyl or phenylheteroaryl-mannosides as antagonists of FimH
Inventors:
Michael Joseph Bishop (Collegeville, PA); James Walter Janetka (Saint Louis, MO); Laurel Kathryn McGrane (Saint Louis, MO); Katherine Louisa Widdowson (Collegeville, PA)
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Abstract
Disclosed herein are new O-biphenyl- and O-phenylheteroarylmannoside compounds and compositions and their application as pharmaceuticals for use in the treatment of human disease. Methods of inhibition of FimH activity in human subjects are also provided for the treatment of diseases such as urinary tract infection.
Claims (23)
1. A compound of formula I, or a pharmaceutically acceptable salt thereof,
in which
Z is
wherein:
X is CH 3 , Cl, or CF 3 ;
Y is H or F; and
each R 1 , R 2 , R 3 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 22 , R 23 , and R 24 are independently selected from the group consisting of hydrogen, CN, F, C 3-6 cycloalkyl, C 1-6 alkyl, —N(C 1-6 alkyl) 2 , —OC 1-6 alkyl, CF 3 , and
2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Z is:
wherein one of R 1 , R 2 and R 3 are selected from the group consisting of CN, F, C 3-6 cycloalkyl, C 1-6 alkyl, —N(C 1-6 alkyl) 2 , —OC 1-6 alkyl, CF 3 , and
and the others are hydrogen.
3. A compound or pharmaceutically acceptable salt according to claim 2 , wherein one of R 1 , R 2 and R 3 are selected from the group consisting of cyclopropyl, —CH 3 , CF 3 , and
and the others are hydrogen.
4. A compound or pharmaceutically acceptable salt according to claim 3 , wherein R 1 and R 3 are both hydrogen and R 2 is selected from the group consisting of cyclopropyl, —CH 3 , CF 3 , and
5. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein either:
X is CH 3 and Y is H; or
X is CF 3 and Y is F or H; or
X is Cl and Y is H.
6. A compound or pharmaceutically acceptable salt thereof according to claim 5 , wherein X is CH 3 and Y is H.
7. A compound of claim 1 selected from the group consisting of:
(2R,3S,4S,5S,6R)-2-(Hydroxymethyl)-6-(2-methyl-4-(5-(trifluoromethyl) pyrazin-2-yl) phenoxy) tetrahydro-2H-pyran-3,4,5-triol,
(2R,3S,4S,5S,6R)-2-(2-Fluoro-6-(trifluoromethyl)-4-(5-(trifluoromethyl) pyrazin-2-yl) phenoxy)-6-(hydroxymethyl) tetrahydro-2H-pyran-3,4,5-triol, and
(2R,3S,4S,5S,6R)-2-(Hydroxymethyl)-6-(2-(trifluoromethyl)-4-(5-(trifluoromethyl) pyrazin-2-yl) phenoxy) tetrahydro-2H-pyran-3,4,5-triol,
or a pharmaceutically acceptable salt thereof.
Assignments (4)
CHANGE OF ADDRESS
Recorded Oct 8, 2025
From: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Reel/Frame 073032/0390 →
CHANGE OF ADDRESS
Recorded Jun 17, 2025
From: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Reel/Frame 071649/0432 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 31, 2025
From: BISHOP, MICHAEL JOSEPH; WIDDOWSON, KATHERINE LOUISA
To: GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED
Reel/Frame 070676/0399 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 31, 2025
From: MCGRANE, LAUREL KATHRYN; JANETKA, JAMES EALTER
To: FIMBRION THERAPEUTICS, INC.
Reel/Frame 070676/0449 →
Continuity (2)
Provisional Application
62863479
· Jun 19, 2019
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