Benzene-1,3,5-tricarboxamide derivatives and uses thereof

Patent metadata

Field	Value
Publication number	US-2018147166-A1
Application number	US-201615575919-A
Country	US
Kind code	A1
Filing date	May 20, 2016
Priority date	May 21, 2015
Publication date	May 31, 2018
Grant date	—

Abstract

The present invention relates to compounds, compositions, lipid-like nanoparticles, and methods for delivery of therapeutic, diagnostic, or prophylactic agents (for example, a polynucleotide).

First claim

1 . A compound of Formula I:

and salts thereof; wherein
each R 1 is independently substituted or unsubstituted alkyl;
each R 2 is independently substituted or unsubstituted alkyl;
each R 3 is independently hydrogen or substituted or unsubstituted alkyl; and
each m is independently 1, 2, 3, 4[[ ]], 5, 6, 7, or 8.

2 . The compound of claim 1 , wherein at least one R 1 is unsubstituted alkyl.

3 . The compound of claim 2 , wherein at least one R 1 is C 11 H 23 .

4 . The compound of claim 1 , wherein at least one R 2 is unsubstituted alkyl.

5 . The compound of claim 4 , wherein at least one R 2 is C 11 H 23 .

6 . The compound of claim 1 , wherein at least one R 3 is hydrogen.

7 . The compound of claim 1 , wherein at least one m=3.

8 . The compound of claim 1 , wherein
each R 1 is independently unsubstituted alkyl; each R 2 is independently unsubstituted alkyl; each R 3 is hydrogen; and each m is independently 1, 2, 3, 4, 5, 6, 7, or 8.

9 . The compound of claim 8 , wherein
each R 1 is independently unsubstituted alkyl; each R 2 is independently unsubstituted alkyl; each R 3 is hydrogen; and each m is 3.

10 . The compound of claim 1 , having the structure:

and salts thereof, wherein m=3.

11 .- 23 . (canceled)

24 . A nanoparticle comprising:
a compound of Formula I;

and salts thereof; wherein
each R 1 is independently or substituted or unsubstituted alkyl;
each R 2 is independently substituted or unsubstituted alkyl;
each R 3 is independently hydrogen or substituted or unsubstituted alkyl; and
each m is independently 1, 2, 3, 4, 5, 6, 7, or 8;
a non-cationic lipid;
a polyethylene glycol-lipid; and
a sterol.

25 . The nanoparticle of claim 24 , wherein the compound of Formula I is:

and salts thereof, wherein m=3.

26 . The nanoparticle of claim 24 , wherein the phosphatidylethanolamine lipid is selected from 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1- stearoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (SOPE), or combinations thereof.

27 . The nanoparticle of claim 26 , wherein the phosphatidylethanolamine lipid is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE).

28 . The nanoparticle of claim 24 , wherein the polyethylene glycol-lipid is selected from 1,2-dimyristoyl-sn-glycerol, methoxypolyethylene glycol (DMG-PEG), DLPE-PEGs, DMPE-PEGs, DPPC-PEGs, and DSPE-PEGs.

29 . The nanoparticle of claim 28 , wherein the polyethylene glycol-lipid is 1,2-dimyristoyl-sn-glycerol, methoxypolyethylene glycol (DMG-PEG).

30 . The nanoparticle of claim 24 , wherein the sterol is selected from cholesterol, campesterol, ergosterol, or sitosterol.

31 . The nanoparticle of claim 30 , wherein the sterol is cholesterol.

32 . A method for the delivery of an agent into a cell comprising;
introducing into the cell a composition comprising;
a nanoparticle comprising;
a compound of Formula I;

and salts thereof; wherein
each R 1 is independently substituted or unsubstituted alkyl;
each R 2 is independently substituted or unsubstituted alkyl;
each R 3 is independently hydrogen or substituted or unsubstituted alkyl; and
each m is independently 1, 2, 3, 4, 5, 6, 7, or 8;

a non-cationic lipid;
a polyethylene glycol-lipid;
a sterol; and
an agent.

33 . The method of claim 32 , wherein the agent is a polynucleotide.

34 .- 52 . (canceled)

Assignees

• Ohio State Innovation Foundation

Inventors

• Dong Yizhou
• Li Bin

Classifications

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• A61K31/166 Primary

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title

• A61K47/06

  Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title