Shikimate analogues and methods of use

Patent metadata

Field	Value
Publication number	US-2019038579-A1
Application number	US-201716077389-A
Country	US
Kind code	A1
Filing date	Feb 14, 2017
Priority date	Feb 15, 2016
Publication date	Feb 7, 2019
Grant date	—

Abstract

The present disclosure, in at least certain embodiments, is directed to shikimate (shikimic acid) analogues and compositions thereof, kits which contain the shikimate analogues or compositions thereof, and methods of use of the compounds and compositions for treating epithelial surfaces before or following exposure to irritants, allergens, and toxic agents (for example, urushiol).

First claim

What is claimed is:

1 . A composition comprising at least one shikimate analogue, and at least one secondary compound, the at least one shikimate analogue comprising Structural Formula I or Structural Formula II:

wherein,
X is O, N, S, or is absent;
R 1 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, phenylmethyl, and substituted naphthalenyl;
R 2 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, phenylmethyl, and substituted naphthalenyl, or is absent;
R 3 is selected from the group consisting of fluoro, chloro, bromo, iodo, hydroxyl, substituted phosphate, —O-tosyl, —O-mesyl, (C1-C8)alkoxy, (C2-C8)acyloxy, substituted phenoxy, substituted naphthalenyloxy, substituted naphthalenylmethoxy, (C1-C12)primary amino, (C1-C12)secondary amino, (C1-C12)tertiary amino, and (C1-C12)cyclic amino, (C1-C8)ammonio, (C1-C8)carboxamino, (C1-C8)imino, azido, (C1-C8)azo, cyanato, isocyanato, nitrooxy, cyano, isocyano, nitrosooxy, nitro, nitroso, (C1-C8)substituted carbamoyl, hydroxyamino, morpholino, anilino, indol, pyrrol, imidazole, benzimidazol, pyrazol, guanidino, piperazino, polyamino, and N-methylated polyamino;
R 4 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy;
R 5 selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy; and
R 6 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy.

2 . The composition of claim 1 , comprising a plurality of shikimate analogues.

3 . The composition of claim 1 , wherein the at least one secondary compound is selected from the group consisting of propylene glycol, sodium metasilicate, chlorhexidine, diethanolamine, borates, zinc pyrithione, ammonia, trimethyl ammonia, 3-(N-morpholino)propane sulfonic acid (MOPS), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethanolamine, morpholine, barium hydroxide, 9-Azajulolidine, sodium iodide, potassium iodide, Lugol's Iodine, iodine tincture, povidone-iodine, benzalkonium chloride, cetrimonium bromide, Brilliant Green, triarylmethane dyes, Malachite green, octenidine dihydrochloride, phenoxyethanol, USP Tincture of Iodine, USP Strong Iodine Tincture, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), methyl cellulose, and methyl ethyl cellulose.

4 . The composition of claim 1 , wherein the at least one secondary compound is selected from the group consisting of glycols, polyols, alditols, and saccharides.

5 . The composition of claim 1 , wherein the at least one secondary compound is a polysaccharide.

6 . The composition of claim 1 , wherein the at least one secondary compound is selected from the group consisting of pharmaceutically-acceptable excipients, diluents, carriers, and vehicles.

7 . The composition of claim 1 , wherein the at least one secondary compound is selected from the group consisting of sticks, bars, soaps, balms, creams, pastes, gums, lotions, gels, foams, ointments, emulsions, suspensions, aqueous solutions, eye drops, aerosols, sprays, inhalants, body washes, face washes, rinses, and oral tinctures.

8 . The composition of claim 1 , wherein the at least one secondary compound is water and/or an alcohol.

9 . The composition of claim 1 , wherein the at least one secondary compound is selected from the group consisting of fragrances, preservatives, and surfactants.

10 . The composition of claim 1 , comprising about 0.01 to about 1000 milligrams of said at least one shikimate analogue per ml of said at least one secondary compound.

11 . The composition of claim 1 , comprising about 1 wt % to about 90 wt % of said at least one shikimate analogue and about 10 wt % to about 99 wt % of said at least one secondary compound.

12 . A method of treating an epithelial condition of a subject in need of such treatment, comprising applying a composition comprising at least one shikimate analogue to an area of the subject affected by the epithelial condition, the at least one shikimate analogue comprising Structural Formula I or Structural Formula II:

wherein,
X is O, N, S, or is absent;
R 1 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, phenylmethyl, and substituted naphthalenyl;
R 2 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, phenylmethyl, and substituted naphthalenyl, or is absent;
R 3 is selected from the group consisting of fluoro, chloro, bromo, iodo, hydroxyl, substituted phosphate, —O-tosyl, —O-mesyl, (C1-C8)alkoxy, (C2-C8)acyloxy, substituted phenoxy, substituted naphthalenyloxy, substituted naphthalenylmethoxy, (C1-C 12)primary amino, (C1-C12)secondary amino, (C1-C12)tertiary amino, and (C1-C12)cyclic amino, (C1-C8)ammonio, (C1-C8)carboxamino, (C1-C8)imino, azido, (C1-C8)azo, cyanato, isocyanato, nitrooxy, cyano, isocyano, nitrosooxy, nitro, nitroso, (C1-C8)substituted carbamoyl, hydroxyamino, morpholino, anilino, indol, pyrrol, imidazole, benzimidazol, pyrazol, guanidino, piperazino, polyamino, and N-methylated polyamino;
R 4 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy;
R 5 selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C 1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy; and
R 6 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C8)alkenyl, (C1-C8)alkynyl, cyano, halo, nitro, thio, substituted phenyl, hydroxyl, (C1-C8)alkoxy, (C2-C8)acyloxy, (C1-C8)carboxamino, substituted phenoxy, phenylmethoxy, [1-(methoxycarbonyl)ethenyl]oxy, and (1-carboxyethenyl)oxy.

13 . The method of claim 12 , wherein the composition comprises a plurality of shikimate analogues.

14 . The method of claim 12 , wherein the composition comprises at least one secondary compound.

15 . The method of claim 14 , wherein the at least one secondary compound is selected from the group consisting of propylene glycol, sodium metasilicate, chlorhexidine, diethanolamine, borates, zinc pyrithione, ammonia, trimethyl ammonia, 3-(N-morpholino)propane sulfonic acid (MOPS), 1,4-diazabicyclo[2.2.2]octane (DABCO), triethanolamine, morpholine, barium hydroxide, 9-Azajulolidine, sodium iodide, potassium iodide, Lugol's Iodine, iodine tincture, povidone

Assignees

• Univ Oklahoma

Inventors

• Du Lin
• Cichewicz Robert
• Nicholas Ken
• You Jianlan

Classifications

• A61K31/336

  having three-membered rings, e.g. oxirane, fumagillin · CPC title

• A61P17/04

  Antipruritics · CPC title

• A61K31/365

  Lactones · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K31/4418

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine · CPC title