# US 10,370,385 B2 · Tricyclic mosquitocides and methods of making and using thereof

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- Number: US 10,370,385 B2
- Document ID: US10370385B2
- Status: Granted
- Kind: B2
- Application number: 15/325,320
- Filed: 2015-07-10
- Published: 2017-06-15
- Granted: 2019-08-06
- Earliest claimed: 2014-07-10
- Assignees: Arizona Board of Regents on Behalf of the University of Arizona
- Applicants: The Arizona Board of Regents on Behalf of the University of Arizona
- Inventors: Jon Njardarson; Jun Isoe; Roger Miesfeld
- Web page: https://patentgrep.com/patent/US10370385B2

## CPC

- C07D 495/04: Ortho-condensed systems
- A01N 43/90: having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compounds that inhibit digestion in blood-ingesting pests are described herein. In one embodiment, the compounds described herein block entry of blood into the midgut and thereby inhibit digestion and nutrient processing. In another embodiment, the compounds described herein prevent pathogens contained in the blood meal from entering the midgut where they could cross the epithelial cell layer and infect the mosquito. The compounds can be administered to a population of blood-ingesting pests, such as mosquitos, directly or indirectly in an effective amount to prevent mosquitoes from transmitting diseases such as malaria, dengue fever, West Nile virus and lymphatic filariasis. Preferably, the compounds are lethal to blood-ingesting pests. The compounds can be combined with one or more excipients to prepare compositions.

## Claims

### Claim 1

A composition comprising a compound having the formula:
wherein
X is O, S, CR10R11, SiR10R11, or NR10;
Y is O, S, CR10R11;
Z is O, S, CR10R11;
R1-R11 are each independently selected from the group consisting of hydrogen, hydroxyl, cyano, nitro, halogen, NH2, SH, SR12, OR12, N(R12)2, OCON(R12)2, C(═O)R12, OC(═O)R12, C(═O)OR12, COOH, COO−M+, CONH2, CON(R12)2, C(═O)H, substituted or unsubstituted linear, branched, or cyclic alkyl, alkenyl, or alkynyl; substituted or unsubstituted linear, branched, or cyclic heteroalkyl, heteroalkenyl, or heteroalkynyl, substituted or unsubstituted aryl or heteroaryl, SOR12, SOOR12, SO3R12, SO4R12, NR12COR13, phosphoryl, sulfamoyl, and sulfonamido; wherein each occurrence of R12 or R13 is selected from the group consisting of hydrogen, substituted or unsubstituted linear, branched, or cyclic alkyl, alkenyl, or alkynyl; substituted or unsubstituted linear, branched, or cyclic heteroalkyl, heteroalkenyl, or heteroalkynyl, and substituted or unsubstituted aryl or heteroaryl;
wherein the dotted line represents a bond that is either present or absent;
and
wherein the compound is in an effective amount to inhibit digestion or nutrient processing in at least 40% of a population of blood-ingesting pests, reduce follicle size in female blood-ingesting pests compared to the follicle size when the pests are not exposed to the compound, or provide a lethal concentration against pest larvae, or a combination thereof, and
wherein the compound is in a concentration of less than 0.25 mM.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the compound has the following stereochemistry

### Claim 3 (depends on 1)

The composition of claim 1, wherein
X is sulfur;
Y is oxygen;
Z is oxygen; or
X is sulfur and Y and Z are both oxygen.

### Claim 4 (depends on 1)

The composition of claim 1, wherein R1 is a substituted or unsubstituted alkyl.

### Claim 5 (depends on 4)

The compound of claim 4, wherein
R1 is methyl;
R2 is hydrogen;
R3 is hydrogen;
R6 is hydrogen;
R7 is hydrogen; or
R4 and R5 are hydrogen.

### Claim 6 (depends on 1)

The composition of claim 1, wherein R8 is a substituted or unsubstituted aryl.

### Claim 7 (depends on 6)

The composition of claim 6, wherein R8 is a substituted or unsubstituted phenyl.

### Claim 8 (depends on 7)

The composition of claim 7, wherein R8 is an unsubstituted phenyl.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the compound is:

### Claim 10 (depends on 1)

The composition of claim 1, wherein the compound has the formula:

### Claim 11 (depends on 1)

The composition of claim 1, in the form of a liquid is selected from the group consisting of a solution, suspension, dispersion, and an emulsion.

### Claim 12 (depends on 1)

The composition of claim 1, wherein the effective amount of the compound is non-toxic to plants, animals, and/or arthropods that do not function as vectors of human pathogens.

### Claim 13

A method of preventing the spread of mosquito-borne illnesses, comprising administering to a site or region containing one or more mosquitoes an effective amount of a composition comprising a compound having the formula:
wherein
X is O, S, CR10R11, SiR10R11, or NR10;
Y is O, S, CR10R11;
Z is O, S, CR10R11;
R1-R11 are each independently selected from the group consisting of hydrogen, hydroxyl, cyano, nitro, halogen, NH2, SH, SR12, OR12, N(R12)2, OCON(R12)2, C(═O)R12, OC(═O)R12, C(═O)OR12, COOH, COO−M+, CONH2, CON(R12)2, C(═O)H, substituted or unsubstituted linear, branched, or cyclic alkyl, alkenyl, or alkynyl; substituted or unsubstituted linear, branched, or cyclic heteroalkyl, heteroalkenyl, or heteroalkynyl, substituted or unsubstituted aryl or heteroaryl, SOR12, SOOR12, SO3R12, SO4R12, NR12COR13, phosphoryl, sulfamoyl, and sulfonamido; wherein each occurrence of R12 or R13 is selected from the group consisting of hydrogen, substituted or unsubstituted linear, branched, or cyclic alkyl, alkenyl, or alkynyl; substituted or unsubstituted linear, branched, or cyclic heteroalkyl, heteroalkenyl, or heteroalkynyl, and substituted or unsubstituted aryl or heteroaryl;
wherein the dotted line represents a bond that is either present or absent; and
wherein the compound is in an effective amount to inhibit digestion or nutrient processing in at least 40% of a population of blood-ingesting pests, reduce follicle size in female blood-ingesting pests compared to the follicle size when the pests are not exposed to the compound, or provide a lethal concentration against pest larvae, or a combination thereof, and
wherein the compound is in a concentration of less than 0.25 mM.

### Claim 14 (depends on 13)

The method of claim 13, wherein the site or region is a body of water or contains standing water.

### Claim 15 (depends on 13)

The method of claim 13, wherein the compound is:

### Claim 16 (depends on 1)

The composition of claim 1, wherein the composition formed by introducing pellets comprising the compound into a continuous aqueous phase.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the composition formed by introducing flakes comprising the compound into a continuous aqueous phase.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the composition is in the form of a liquid, and wherein the compound is dispersed or dissolved in an aqueous continuous phase.

### Claim 19 (depends on 1)

The composition of claim 1, further comprising a wetting agent, surfactant, or carrier, or a combination thereof.

### Claim 20 (depends on 19)

The compound of claim 19, wherein the composition comprises a surfactant, and wherein the surfactant is an anionic, cationic, amphoteric, or nonionic surface-active agent.