Binary compositions as disruptors of orco-mediated odorant sensing

Patent metadata

Field	Value
Publication number	US-2018092359-A1
Application number	US-201615561427-A
Country	US
Kind code	A1
Filing date	Mar 24, 2016
Priority date	Mar 25, 2015
Publication date	Apr 5, 2018
Grant date	—

Abstract

In one aspect, the invention relates to binary compositions that disrupt ORco-mediated odorant sensing. In particular, compounds and compositions are provided that can inhibit sensory (e.g., host targeting) functions in organisms that express ORco receptors such as airborne insects, e.g., mosquitoes, and ticks. Method of employing such agents, and articles incorporating the same, are also provided. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1 . A method of disrupting odor sensing behavior in an organism having an ORco ion channel, comprising exposing the organism to a composition comprising:
(a) a first compound having the structure:

wherein R 5 is optionally substituted aryl or optionally substituted (≤C6) heteroaryl;
wherein L 1 is a divalent organic groups having from 1 to 8 non-hydrogen members;
wherein p is 0 or 1;
wherein Q 1 is hydrogen, OR 20 , SR 20 , or NR 21a R 21b ,
wherein R 20 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;
wherein each of R 21a and R 21b is independently hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;

wherein Q 2 is O, S, or NR 4
wherein R 4 is hydrogen or alkyl (C≤5) ; and

(b) a second compound having the structure:

wherein each of R 1a and R 1b is independently hydrogen, optionally substituted C1-C4 alkyl, or an alkyloxy carbonyl group; and
wherein R 7 is optionally substituted and selected from monocyclic aryl, bicyclic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and tricyclic heteroaryl.

2 . The method of claim 1 , wherein the organism is an insect.

3 . The method of claim 1 , wherein the first compound has the structure:

wherein R 4 is methyl, ethyl, isopropyl, or cyclopropyl.

4 . The method of claim 1 , wherein the second compound has the structure:

wherein R 1b is hydrogen or optionally substituted C1-C4 alkyl; wherein R 2 is hydrogen or methyl; and wherein R 3 is hydrogen, halo, hydroxy, nitro, halo, cyclopropyl, alkyl (C≤5) , substituted alkyl (C≤5) , alkenyl (C≤5) , or substituted alkenyl (C≤5) .

5 - 9 . (canceled)

10 . The method of claim 1 , wherein L 1 is selected from:

11 - 12 . (canceled)

13 . The method of claim 1 , wherein the first compound has the structure:

and
the second compound has the structure:

14 . The method of claim 1 , wherein the composition is formed as a water-soluble tablet, formulated as an aerosol, or formulated as a sprayable liquid.

15 - 17 . (canceled)

18 . The method of claim 1 , wherein the composition further comprises an insect repellant.

19 - 20 . (canceled)

21 . A method of agonizing an ORco ion channel, comprising exposing the ORco ion channel to a composition comprising:
(a) a first compound having the structure:

wherein R 5 is optionally substituted aryl or optionally substituted (≤C6) heteroaryl;
wherein L 1 is a divalent organic groups having from 1 to 8 non-hydrogen members;
wherein p is 0 or 1;
wherein Q 1 is hydrogen, OR 20 , SR 20 , or NR 21a R 21b ,
wherein R 20 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;
wherein each of R 21a and R 21b is independently hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;

wherein Q 2 is O, S, or NR 4
wherein R 4 is hydrogen or alkyl (C≤5) ; and

(b) a second compound having the structure:

wherein each of R 1a and R 1b is independently hydrogen, optionally substituted C1-C4 alkyl, or an alkyloxy carbonyl group; and
wherein R 7 is optionally substituted and selected from monocyclic aryl, bicyclic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and tricyclic heteroaryl.

22 . The method of claim 21 , wherein the first compound has the structure:

wherein R 4 is methyl, ethyl, isopropyl, or cyclopropyl.

23 . The method of claim 21 , wherein the second compound has the structure:

wherein R 1b is hydrogen or optionally substituted C1-C4 alkyl; wherein R 2 is hydrogen or methyl; and wherein R 3 is hydrogen, halo, hydroxy, nitro, halo, cyclopropyl, alkyl (C≤5) , substituted alkyl (C≤5) , alkenyl (C≤5) , or substituted alkenyl (C≤5) .

24 . The method of claim 21 , wherein the first compound has the structure:

and
the second compound has the structure:

25 . A composition for disrupting odorant sensing comprising
(a) a first compound having the structure:

wherein R 5 is optionally substituted aryl or optionally substituted (≤C6) heteroaryl;
wherein L 1 is a divalent organic groups having from 1 to 8 non-hydrogen members;
wherein p is 0 or 1;
wherein Q 1 is hydrogen, OR 20 , SR 20 , or NR 21a R 21b ,
wherein R 20 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;
wherein each of R 21a and R 21b is independently hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, i-butyl, s-butyl, t-butyl, or CH 2 -isopropyl;

wherein Q 2 is O, S, or NR 4
wherein R 4 is hydrogen or alkyl (C≤5) ; and

(b) a second compound having the structure:

wherein each of R 1a and R 1b is independently hydrogen, optionally substituted C1-C4 alkyl, or an alkyloxy carbonyl group; and
wherein R 7 is optionally substituted and selected from monocyclic aryl, bicyclic aryl, monocyclic heteroaryl, bicyclic heteroaryl, and tricyclic heteroaryl.

26 . The composition of claim 25 , wherein the first compound has the structure:

wherein R 4 is methyl, ethyl, isopropyl, or cyclopropyl.

27 . The composition of claim 25 , wherein the second compound has the structure:

wherein R 1b is hydrogen or optionally substituted C1-C4 alkyl; wherein R 2 is hydrogen or methyl; and wherein R

Assignees

• Univ Vanderbilt

Inventors

• Zwiebel Laurence J
• Romaine Ian M
• Ochieng Sam
• Waterson Alex Gregory
• Sulikowski Gary A

Classifications

• A01N43/653 Primary

  1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles · CPC title

• A01N33/06 Primary

  Nitrogen directly attached to an aromatic ring system · CPC title

• A01N2300/00

  Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48 · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A01N25/18

  Vapour or smoke emitting compositions with delayed or sustained release · CPC title