Substituted biphenyl or phenylheteroaryl-mannosides as antagonists of FimH

Patent metadata

Field	Value
Publication number	US-12351597-B2
Application number	US-202017617642-A
Country	US
Kind code	B2
Filing date	Jun 17, 2020
Priority date	Jun 19, 2019
Publication date	Jul 8, 2025
Grant date	Jul 8, 2025

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.

First claim

We claim:

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.

Assignees

• Glaxosmithkline Ip Dev Ltd
• Fimbrion Therapeutics Inc

Inventors

• Bishop Michael Joseph
• Janetka James Walter
• Mcgrane Laurel Kathryn
• Widdowson Katherine Louisa

Classifications

• C07H15/23

  with only two saccharide radicals in the molecule, e.g. ambutyrosin, butyrosin, xylostatin, ribostamycin · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P13/02

  of urine or of the urinary tract, e.g. urine acidifiers · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P31/04

  Antibacterial agents · CPC title