N-arylated analogues and uses thereof

Patent metadata

Field	Value
Publication number	US-11419335-B2
Application number	US-201716467461-A
Country	US
Kind code	B2
Filing date	Dec 7, 2017
Priority date	Dec 7, 2016
Publication date	Aug 23, 2022
Grant date	Aug 23, 2022

Abstract

The present invention provides novel compounds of Formula (I′) and (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for killing a microorganism (e.g., bacteria, fungi, viruses, protozoa, or multicellular parasites), the prevention and/or treatment of infectious diseases (e.g., infections by microorganisms, bacterial infection, cystic fibrosis infection, foreign body infection, urinary tract infection (UTI), or infections leading to biofilms), controlling and/or eradicating biofilms (e.g., bacterial biofilms), preventing biofilm formation, sterilizing a surface, and/or eradicating persister cells (e.g., in a subject in need thereof or in a subject involving a biofilm).

First claim

What is claimed is:

1. A compound of Formula (I′):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:
R 1 is C 1 -C 6 alkyl;
R 2 is optionally substituted C 5 -C 24 alkyl;

R 5 is of the formula:
wherein a is 1, 2, 3, 4, or 5;
each instance of R 3B is independently —CN, —SCN, —NO 2 , —N 3 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, —OR a1 , —N(R b1 ) 2 , or —SR a1 ;
each instance of R a1 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and
each instance of R b1 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of R b1 are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;
each instance of R 4′ is independently hydrogen, halogen, —CN, —SCN, —NO 2 , —N 3 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted acyl, sulfonyl, —OR a , —N(R b ) 2 , or —SR a , or optionally two instances of R 4′ are joined together with the intervening atoms to form optionally substituted aryl;
each instance of R a is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom;
each instance of R b is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of R b are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl; and
b1 is 0, 1, or 2.

2. The compound of claim 1 , wherein the compound is of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:
R 1 is C 1 -C 6 alkyl;
R 2 is optionally substituted C 5 -C 24 alkyl;
each instance of R 3B is independently —CN, —SCN, —NO 2 , —N 3 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, —OR a1 , —N(R b1 ) 2 , or —SR a1 ;
each instance of R 4 is independently hydrogen, halogen, —CN, —SCN, —NO 2 , —N 3 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, sulfonyl, —OR a , —N(R b ) 2 , or —SR a ;
each instance of R a1 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and
each instance of R b1 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of R b1 are joined together with the intervening atoms to form optionally substituted heterocyclyl or optionally substituted heteroaryl;
a is 1, 2, 3, 4, or 5; and
b is 0, 1, or 2.

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

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

4. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R 2 is optionally substituted C 12 -C 16 alkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R 5 is of formula

and
a is 1 or 2;
each instance of R 3B is independently —CN, —NO 2 , optionally substituted alkyl, optionally substituted acyl, optionally substituted alkenyl, optionally substituted alkynyl, —OR a1 , or —N(R b1 ) 2 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein at least one instance of R 3B is —OR a1 , wherein R a1 is optionally substituted C 1 -C 6 alkyl or optionally substituted aryl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein b1 is 0.

8. The compound of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

9. The compound of claim 1 , wherein the compound is of formula:

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

10. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R 5 is of formula

and at least one instance of R 3B is —OMe, —NO 2 , —CF 3 , —OPh, or —OCF 3 .

11. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein R 1 is methyl.

12. A compound of formula:

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

13. The compound of claim 1 , or

Assignees

• Univ Florida

Inventors

• Huigens Iii Robert William
• Abouelhassan Yasmeen
• Basak Akash

Classifications

• A01N43/52

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• C07D233/58

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms · CPC title

• C07D249/04

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A01N43/50 Primary

  1,3-Diazoles; Hydrogenated 1,3-diazoles · CPC title