APPLICATION OF COMPOUNDS IN CONTROLLING OR KILLING MITES

Abstract

An application of a series of compounds in controlling or killing mites. It has been found by comparison that the compounds, when compared with a control group, can reduce the survival time of mites; in particular, taraxerol, diosmetin, and taraxasteryl acetate can significantly shorten the survival time of mites, and can be used for miticide and mite control products (such as drugs, cosmetic products, daily products and so on).

Claims

1. Use of a compound of formula I or a salt, an isomer or a solvate thereof in preparing a product for controlling or killing mites, wherein the compound of formula I is: ##STR00009## wherein, R.sub.1 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH.sub.2, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)=CH.sub.2, C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2, or when the bond between R.sub.1 and carbon atom at position 5 is a double bond, R.sub.1 is selected from O and S; R.sub.2, R.sub.3, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2; R.sub.4 is selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2, or when the bond between carbon atoms at positions 1 and 4 is a double bond, R.sub.4 is absent; R.sub.5 is selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2, or when the bond between carbon atoms at positions 2 and 3 is a double bond, R.sub.5 is absent; the bond between carbon atoms at positions 6 and 7 is a double bond or single bond; R.sub.10 and R.sub.13 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.1-8 alkynyl, CH═CH(C.sub.1-8 alkyl), CH═CH.sub.2, C(C.sub.1-8 alkyl)=CH.sub.2, C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; and R.sub.11 and R.sub.12 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.1-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2, or R.sub.11 and R.sub.12 are carbon atoms and together with carbon atoms therebetween form a 5- to 8-membered ring, wherein H on any carbon atom on the ring may be substituted with C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH, NH.sub.2, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH.sub.2, C(C.sub.1-8 alkyl)=CH.sub.2, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl) or C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2.

2. The use according to claim 1, wherein the compound of formula I is a compound of formula I-1: ##STR00010## wherein, when the bond between R.sub.14 and carbon atom at position 8 is a single bond, R.sub.14 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2, and hydrogen atom on the carbon atom at position 8 is optionally substituted with R.sub.14; when the bond between R.sub.14 and the carbon atom on position 8 is a double bond, R.sub.14 is selected from O, S, CH.sub.2, CH(C.sub.1-8 alkyl) and C(C.sub.1-8 alkyl).sub.2; R.sub.15 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; and n is an integer of 1-4, such as 1, 2, 3 or 4.

3. The use according to claim 1, wherein R.sub.1 is selected from H, C.sub.1-3 alkyl, OH, OC(═O)(C.sub.1-3 alkyl), (C.sub.1-3 alkyl)CO.sub.2H, CF.sub.3, CHF.sub.2 and CH.sub.2F, or when the bond between R.sub.1 and carbon atom at position 5 is a double bond, R.sub.1 is O; R.sub.2, R.sub.3, R.sub.6, R.sub.7, R.sub.5 and R.sub.9 are independently selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, OH and NH.sub.2; the bond between carbon atoms at positions 1 and 4 is a single bond, and R.sub.4 is selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, O(C.sub.1-3 cycloalkyl) and OH; the bond between carbon atoms at positions 2 and 3 is a single bond, and R.sub.5 is selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, O(C.sub.1-3 cycloalkyl) and OH; the bond between carbon atoms at positions 6 and 7 is a single bond; R.sub.10 and R.sub.13 are independently selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, OH and NH.sub.2; when bond between R.sub.14 and the carbon atom at position 8 is a single bond, R.sub.14 is selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, OH and NH.sub.2, and similarly, the hydrogen atom on the carbon atom at position 8 is substituted with R.sub.14; when bond between R.sub.14 and the carbon atom at position 8 is a double bond, R.sub.14 is selected from CH.sub.2, CH(C.sub.1-3 alkyl) and C(C.sub.1-3 alkyl).sub.2; and R.sub.15 is selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, OH, NH.sub.2, CH═CH(C.sub.1-3 alkyl), C(C.sub.1-3 alkyl)=CH.sub.2, C(C.sub.1-3 alkyl)═CH(C.sub.1-3 alkyl) and C(C.sub.1-3 alkyl)═C(C.sub.1-3 alkyl).sub.2; preferably, R.sub.15 is selected from H, C.sub.1-3 alkyl and C(CH.sub.3)═CH.sub.2.

4. The use according to claim 1, wherein the compound of formula I is taraxasterol, taraxerol, taraxerone, roburic acid, taraxasterol acetate, taraxeryl acetate, lupenone, or a salt, an isomer or a solvate thereof.

5. Use of a compound of formula II or a salt, an isomer or a solvate thereof in preparing a product for controlling or killing mites, wherein the compound of formula II is: ##STR00011## wherein, R.sub.16, R.sub.18, R.sub.20, R.sub.23 and R.sub.24 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; and R.sub.17, R.sub.19, R.sub.21 and R.sub.22 are independently selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl) and a group of formula II-1, II-2 or II-3: ##STR00012##

6. The use according to claim 5, wherein R.sub.16, R.sub.18, R.sub.20, R.sub.23 and R.sub.24 are independently selected from H, halogen, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), NH(C.sub.1-3 alkyl), N(C.sub.1-3 alkyl).sub.2, C.sub.3-11 cycloalkyl, OH, NH.sub.2, OC(═O)(C.sub.1-3 alkyl), C(═O)(C.sub.1-3 alkyl), (C.sub.1-3 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C.sub.2-3 alkenyl, C.sub.2-3 alkynyl, CH═CH(C.sub.1-3 alkyl), C(C.sub.1-3 alkyl)═CH(C.sub.1-3 alkyl) and C(C.sub.1-3 alkyl)═C(C.sub.1-3 alkyl).sub.2; and R.sub.17, R.sub.19, R.sub.21 and R.sub.22 are independently selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl) and a group of formula II-1 or II-2.

7. The use according to claim 5, wherein the compound of formula II is diosmetin or a salt, an isomer or a solvate thereof.

8. Use of a compound of formula III or a salt, an isomer or a solvate thereof in preparing a product for controlling or killing mites, wherein the compound of formula III is: ##STR00013## wherein R.sub.25 is selected from ##STR00014## R.sub.26 is a carbon atom and together with at least one of R.sub.27 and R.sub.28 forms a 5- to 8-membered ring, and the one of R.sub.27 and R.sub.28 that does not form the ring with R.sub.26 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; and R.sub.29 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2.

9. The use according to claim 8, wherein the compound of formula III is a compound of formula III-1 or III-2: ##STR00015## wherein, R.sub.30, R.sub.31, R.sub.33, R.sub.34 and R.sub.35 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; in formula III-1, the bond between carbon atom at positions 1 and 2 is selected from a double bond and a single bond, when in formula III-1 the bond between carbon atoms at positions 1 and 2 is a double bond, R.sub.32 is absent; when in formula III-1 the bond between carbon atoms at positions 1 and 2 is a single bond, R.sub.32 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2.

10. The use according to claim 9, wherein R.sub.25 is selected from ##STR00016## the one of R.sub.27 and R.sub.28 that does not form the ring with R.sub.26 is selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), O(C.sub.1-3 cycloalkyl), C.sub.2-3 alkenyl, C.sub.2-3 alkynyl, CH═CH(C.sub.1-3 alkyl), C(C.sub.1-3 alkyl)═CH(C.sub.1-3 alkyl), C(C.sub.1-3 alkyl)═C(C.sub.1-3 alkyl).sub.2, OC(═O)(C.sub.1-3 alkyl), C(═O)(C.sub.1-3 alkyl), (C.sub.1-3 alkyl)CO.sub.2H and CO.sub.2H; R.sub.30, R.sub.31, R.sub.33, R.sub.34 and R.sub.35 are independently selected from H, C.sub.1-3 alkyl, O(C.sub.1-3 alkyl), C.sub.3-6 cycloalkyl, OH, NH.sub.2, CH═CH(C.sub.1-3 alkyl), C(C.sub.1-3 alkyl)=CH.sub.2, C(C.sub.1-3 alkyl)═CH(C.sub.1-3 alkyl) and C(C.sub.1-3 alkyl)═C(C.sub.1-3 alkyl).sub.2; preferably, R.sub.30, R.sub.31, R.sub.33, R.sub.34 and R.sub.35 are independently selected from H, methyl and OH; and in formula III-1, the bond between carbon atom at positions 1 and 2 is a double bond, and R.sub.32 is absent.

11. The use according to claim 8, wherein the compound of formula III is swertiamarin, sweroside, gentiopicroside, loganic acid or a salt, an isomer or a solvate thereof.

12. The use according to claim 1, wherein the mites are one or more of Demodex spp., Dermatophagoides pteronyssinus and Sarcoptes scabiei.

13. The use according to claim 1, wherein the product for controlling or killing mites is a pharmaceutical composition, a cosmetic product or an acaricide.

14. The use according to claim 13, wherein the pharmaceutical composition is a pharmaceutical composition for preventing and/or treating a disease caused by mite infestation; the disease is selected from: an ocular disease, a skin disease and an allergic disease; preferably, the ocular disease is selected from: blepharitis marginalis, meibomian gland dysfunction, tarsitis, madarosis, abnormal eyelash alignment, glaucoma, cataract, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, keratitis, eyelid laxity and ectropion, basal cell carcinoma of eyelid, xerophthalmia and chalazion; preferably, the skin disease is selected from: seborrhoeic dermatitis, acne, acne rosacea, pityriasis folliculorum, perioral dermatitis, demodicosis, gaile and basal cell carcinoma; and preferably, the allergic disease is selected from: allergic asthma, allergic rhinitis and allergic dermatitis.

15. The use according to claim 13, wherein the pharmaceutical composition is a topical preparation, preferably an ophthalmic preparation or a skin topical preparation; preferably, the ophthalmic preparation is selected from: an eye drop, an eye ointment, an ophthalmic gel, an ophthalmic emulsion, an ophthalmic suspension, an ophthalmic film, a collyrium and an intraocular injection; preferably, the skin topical preparation is selected from: an aerosol, a powder, a lotion, a tincture, a liniment, a film coating agent, an ointment, a gel, a paste and an emulsion.

16. The use according to claim 13, wherein the pharmaceutical composition is a human pharmaceutical composition or a veterinary pharmaceutical composition.

17. The use according to claim 13, wherein the cosmetic product is in a form selected from: a facial cleanser, a soap, a skin softener, a toner, a skin care lotion, a jelly lotion, a facial cream, a sunscreen cream, an essence, a facial mask, a gel, a foundation, a scrub, a neck cream, a shampoo, a shower gel, a hair conditioner, a body lotion, an eye cream, a mascara, an eyeliner powder, a cream eyeliner, an eyeliner pencil, an eye shadow powder, an eye shadow cream, an eyebrow pencil and a brow powder.

18. The use according to claim 13, wherein the acaricide is in a form selected from: a spray, a lotion, a paster and a small packet.

19. A method for treating and/or preventing an ocular disease caused by mites, comprising administering to eyes of a subject in need thereof a compound of formula I, wherein the compound of formula I is: ##STR00017## wherein, R.sub.1 is selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH.sub.2, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)=CH.sub.2, C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2, or when the bond between R.sub.1 and carbon atom at position 5 is a double bond, R.sub.1 is selected from O and S; R.sub.2, R.sub.3, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2; R.sub.4 is selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2, or when the bond between carbon atoms at positions 1 and 4 is a double bond, R.sub.4 is absent; R.sub.5 is selected from H, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH and NH.sub.2, or when the bond between carbon atoms at positions 2 and 3 is a double bond, R.sub.5 is absent; the bond between carbon atoms at positions 6 and 7 is a double bond or single bond; R.sub.10 and R.sub.13 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.1-8 alkynyl, CH═CH(C.sub.1-8 alkyl), CH═CH.sub.2, C(C.sub.1-8 alkyl)=CH.sub.2, C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2; and R.sub.11 and R.sub.12 are independently selected from H, halogen, C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), S(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, aryl, heteroaryl, C.sub.3-11 heterocycloalkyl, O(C.sub.1-8 cycloalkyl), S(C.sub.1-8 cycloalkyl), NH(C.sub.1-8 cycloalkyl), N(C.sub.1-8 cycloalkyl)(C.sub.1-8 alkyl), OH, NH.sub.2, SH, SO.sub.2(C.sub.1-8 alkyl), C.sub.2-8 alkenyl, C.sub.1-8 alkynyl, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2, OC(═O)(C.sub.1-8 alkyl), C(═O)(C.sub.1-8 alkyl), (C.sub.1-8 alkyl)CO.sub.2H, CO.sub.2H, CN, CF.sub.3, CHF.sub.2, CH.sub.2F, NO.sub.2, C(═O)NH(C.sub.1-8 alkyl), C(═O)N(C.sub.1-8 alkyl).sub.2, N(C.sub.1-8 alkyl)C(═O)NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)C(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH(C.sub.1-8 alkyl), NHC(═O)N(C.sub.1-8 alkyl).sub.2, NHC(═O)NH.sub.2, N(C.sub.1-8 alkyl)SO.sub.2NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl)SO.sub.2N(C.sub.1-8 alkyl).sub.2, NHSO.sub.2NH(C.sub.1-8 alkyl) and NHSO.sub.2N(C.sub.1-8 alkyl).sub.2, or R.sub.11 and R.sub.12 are carbon atoms and together with carbon atoms therebetween form a 5- to 8-membered ring, wherein H on any carbon atom on the ring may be substituted with C.sub.1-8 alkyl, O(C.sub.1-8 alkyl), NH(C.sub.1-8 alkyl), N(C.sub.1-8 alkyl).sub.2, C.sub.3-11 cycloalkyl, O(C.sub.1-8 cycloalkyl), OH, NH.sub.2, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, CH═CH.sub.2, C(C.sub.1-8 alkyl)=CH.sub.2, CH═CH(C.sub.1-8 alkyl), C(C.sub.1-8 alkyl)═CH(C.sub.1-8 alkyl) or C(C.sub.1-8 alkyl)═C(C.sub.1-8 alkyl).sub.2.

Description

DETAILED DESCRIPTION

[0095] Unless otherwise defined, all scientific and technical terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention relates.

[0096] In the present invention, the term “animal” generally refers to vertebrates, in particular, mammals, including humans. The term “non-human animal” refers to any vertebrate except human beings, in particular, mammals. In some embodiments of the present invention, the non-human animal described herein is a domestic animal, i.e., an animal raised and domesticated by humans with artificially controlled reproduction for purposes such as food, labor, fur, companionship and experiment, such as an economic animal, a companion animal and a laboratory animal. The economic animal may be, for example, a livestock animal such as a pig, a cow, a sheep, a horse, a donkey, a fox, a raccoon dog, a mink, a camel and the like. The companion animal may be, for example, a dog, a cat, a rabbit, a murine (such as a guinea pig, a hamster, a gerbil, a chinchilla, a squirrel, etc.) and the like. The laboratory animal may be, for example, a monkey, a dog, a rabbit, a cat, a murine (such as a rat and a mouse) and the like.

[0097] The technical schemes of the present invention will be clearly and completely described below with reference to the examples of the present invention, and it is obvious that the described examples are only a part of the examples of the present invention but not all of them. Based on the examples of the present invention, all other examples obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of the present invention.

Example 1: Preliminary Screening In Vitro of Compounds for Effect on Survival Time of Demodex Mites

Methodology:

1. Monomer Compound

[0098] The following monomer compounds were selected. The names and molecular formulas are shown in Table 1 below.

[0099] The monomer compounds were purchased from Chengdu Herbpurify Co., Ltd., as standard references.

TABLE-US-00001 TABLE 1 Names and molecular formulas of monomer compounds Molecular No. Chinese name English name formula 1 Taraxasterol C30H50O 2 Taraxerol C30H50O 3 Gentiopicroside C16H20O9 4 Taraxerone C30H48O 5 Diosmetin C16H12O6 6 Sweroside C16H22O9 7 Roburic acid C30H48O2 8 Taraxasterol acetate C32H52O2 9 Taraxeryl acetate C32H52O2 10 Lupenone C30H48O 11 Swertiamarine C16H22O10 12 Loganic acid C16H24O10

2. Preparation of Solutions

[0100] The powders of the reference compounds shown in Table 1 were separately dissolved in dimethyl sulfoxide (DMSO), and then diluted with sterilized double-distilled water to make the final concentration of DMSO 10%, which could not shorten the survival time of Demodex mites as per a controlled study. The negative control group received DMSO mixed with sterilized water at a final concentration of 10%.

3. In-Vitro Culture of Demodex Mites

[0101] 35 μL of each solution was added to a glass slide, and the survival of the mites was observed under an optical microscope every 2 hours. During the experiment, the Demodex mites were observed by two skilled operators separately for the activities (bodies, limbs and the like) through the microscope to determine whether they were dead or not. If the two operators gave different results, the survival status was determined independently by a third skilled operator. The in-vitro culture was conducted in a climatic chamber at a temperature of 20° C. and a humidity of 96%. During the observation, the glass slides were transported in a wet box to ensure the high humidity.

4. Statistics

[0102] In this experiment, statistical analysis was conducted using SPSS22.0 statistical software, normality test was conducted using Shapiro-Wilk test, and homogeneity of variance test was conducted using Bartlett's test. The data with normal distribution and homogeneous variance were subjected to One-way ANOVA, and when there was statistical significance, Bonferroni's method was used for pairwise comparison among the groups; when the data did not converge to normal distribution, the Kruskal-Wallis test was adopted for statistical analysis with a test criterion a of 0.05.

5. Results:

[0103] Effects of compounds on survival time of D. folliculorum The in-vitro culture of the Demodex mites was conducted in an environment at a humidity of 96% and a temperature of 20° C. The survival of the Demodex mites was observed dynamically and the survival time was recorded. The results are shown in Table 2. Compared with the negative control group receiving 10% DMSO, the survival time of the Demodex mites in vitro was significantly shorter in the taraxerol group (37.91±20.96 vs. 80.79±25.34, P=0.006), the diosmetin group (35.92±14.82 vs. 80.79±25.34, P=0.001), the taraxasterol acetate group (37.91±20.96 vs. 80.79±25.34, P<0.001) and the gentiopicroside group (37.31±36.06 vs. 80.79±25.34, P<0.001), while the survival time of the Demodex mites in the groups of other monomer compounds did not show significant differences (P>0.05) as compared with the control group.

TABLE-US-00002 TABLE 2 Effects of compounds on survival time of D. folliculorum in vitro Number of Survival time Demodex No. Monomer compound (hours) mites (N) Control 10% DMSO 80.79 ± 25.34 36 1 Taraxasterol 68.28 ± 31.30 6 2 Taraxerol  37.91 ± 20.96** 11 3 Gentiopicroside   37.31 ± 36.06*** 15 4 Taraxerone 62.06 ± 28.97 8 5 Diosmetin  35.92 ± 14.82** 10 6 Loganic acid 61.56 ± 22.84 8 7 Sweroside 60.79 ± 25.98 7 8 Roburic acid 63.41 ± 12.20 9 9 Taraxasterol acetate   34.14 ± 22.96*** 13 10 Taraxeryl acetate 70.57 ± 27.45 12 11 Lupenone 66.25 ± 31.22 5 12 Swertiamarin 59.68 ± 10.97 7 Multiple comparisons were conducted using Duncan's test; as compared with the control group, P*: p < 0.05, P**: p < 0.01, P***: p < 0.001.

[0104] The above description is only for the purpose of illustrating the preferred example of the present invention, and is not intended to limit the scope of the present invention. Any modifications, equivalents and the like made without departing from the spirit and principle of the present invention shall fall within the protection scope of the present invention.

[0105] The foregoing examples and methods described herein may vary based on the abilities, experience, and preferences of those skilled in the art.

[0106] The certain order in which the procedures are described in the present invention does not constitute any limitation to the order of the procedures.