Use of compounds in controlling or killing mites and treating xerophthalmia - Patents.com

Abstract

The present invention relates to methods of use of compounds, their salts, stereoisomers and solvates for killing mites and treating xerophthalmia.

Description

[Technical field]

[0001] The present invention is in the field of medicine, specifically, the use of compounds in controlling or killing mites and in the treatment of xerophthalmia (XEROPHTHALMIA). [Background technology]

[0002] Mite-related diseases (e.g., eye and skin diseases) have not yet received much clinical attention and are often misdiagnosed as bacterial diseases, and conventional antibiotic treatments are often ineffective. Summary of the Invention

[0003] To overcome the deficiencies of the prior art, the present invention provides the use of compounds, their salts, stereoisomers and solvates in the manufacture of products for controlling and / or killing mites.

[0004] In one embodiment of the invention, the compound has the formula: [ka] Rj 1 , Rj 2 , Rj 3 are each one or more optional independent substituents on the corresponding phenyl group, and each Rj 1 , Rj 2 , Rj 3 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O.2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from The A ring is a heterocyclyl group.

[0005] Specifically, the A ring may be a 5- or 6-membered heteroaryl group containing 1, 2 or 3 heteroatoms selected from N, O or S atoms.

[0006] In one embodiment of the present invention, the A ring is [ka] where X 1 , X 2 , X 3 , X 4 , X 5 are each independently CRj 4 , N; Rj 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 is selected from.

[0007] Specifically, the A ring is [ka] Each Rj 4 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group)2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 is selected from.

[0008] In one embodiment of the present invention, Rj 4 is H.

[0009] In another embodiment of the invention, the A ring is [ka] It is.

[0010] Here, Y 1 , Y 2 , Y 3 and Y 4 are each independently CRj 5 , N, and Y 5 is O, S, NRj 5 , C.R.j. 5 Rj 6 is selected from Rj 5 and Rj 6 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 is selected from.

[0011] Specifically, the A ring is [ka] may be selected from:

[0012] In one embodiment of the present invention, Rj 5 is H.

[0013] Specifically, Rj 1 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 is selected from.

[0014] In one embodiment of the present invention, R 1 is Cl.

[0015] Specifically, Rj 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, R 2 is H.

[0016] Specifically, Rj 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO2 In one embodiment of the present invention, R 3 is H.

[0017] In one embodiment of the invention, the compound has the structure:

[0018] [ka] In the formula, Rj 1 , Rj 2 , Rj 3 , X 1 , X 2 , X 3 , X 4 , X 5 has the corresponding definition above in the present invention.

[0019] Specifically, the compound has the following structure:

[0020] [ka] In the formula, Rj 1 , Rj 2 , Rj 3 , Rj 4 has the corresponding definition above in the present invention.

[0021] More specifically, the compound has the following structure:

[0022] [ka] In the formula, Rj 1 , Rj 4 has the corresponding definition above in the present invention.

[0023] In one embodiment of the invention, the compound has the following structure:

[0024] [ka]

[0025] In another embodiment of the invention, the compound has the structure:

[0026] [ka] In the formula, Rk 1 , Rk 2 , Rk 3 , Rk 4 , Rk 5 , Rk 6 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2, C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 or Rk 1 and Rk 2 form an aryl or heterocyclyl group together with the carbon atom to which they are bonded, Rk 3 , Rk 4 , Rk 5 , Rk 6 two of which together with the carbon atom to which they are attached form an aryl or heterocyclyl group; [ka] represents a single bond or a double bond, Rk 7 H, O, halogens, C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from Rk 8 , Rk 9 , Rk 10 , Rk 11 , Rk 12 , Rk 13 , Rk 14 , Rk 15 , Rk 16 , Rk 17 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C (C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from m is selected from an integer from 1 to 5.

[0027] Specifically, Rk 1 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 1 is H.

[0028] Specifically, Rk 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 2 is H.

[0029] Specifically, Rk 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 3 is H.

[0030] Specifically, Rk 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 4 is H.

[0031] Specifically, Rk 5 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 Specifically, R 5 is OH or O(C 1-8 alkyl groups), e.g., OCH 3 , O(C 2 alkyl group), O(C 3 alkyl group), O(C 4 alkyl group), O(C 5 alkyl group), O(C 6 alkyl group), O(C 7 alkyl group), O(C 8 In one embodiment of the present invention, Rk 5 is OCH 3 It is.

[0032] In one embodiment of the present invention, [ka] is a single bond.

[0033] Specifically, Rk 7 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 More specifically, R 7 is OH or O(C1-8 alkyl groups), e.g., OCH 3 , O(C 2 alkyl group), O(C 3 alkyl group), O(C 4 alkyl group), O(C 5 alkyl group), O(C 6 alkyl group), O(C 7 alkyl group), O(C 8 In one embodiment of the present invention, Rk 7 is OH.

[0034] Specifically, m is selected from 1, 2, 3, 4, and 5. In one embodiment of the invention, m is 2.

[0035] Specifically, Rk 8 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 8 is H.

[0036] Specifically, Rk 9 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 9 is H.

[0037] Specifically, Rk 10 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 10 is H.

[0038] Specifically, Rk 11 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 11 is H.

[0039] Specifically, Rk 12 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 12 is H.

[0040] Specifically, Rk 13 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 More specifically, R is selected from the group consisting of alkenyl groups. 13 is C 2-8 In one embodiment of the present invention, Rk is selected from the group consisting of alkenyl groups. 13 is a vinyl group.

[0041] Specifically, Rk 14 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 14 is H.

[0042] Specifically, Rk 15 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2In one embodiment of the present invention, Rk 15 is H.

[0043] Specifically, Rk 16 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 16 is H.

[0044] Specifically, Rk 17 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rk 17 is H.

[0045] In one embodiment of the invention, the compound has the structure:

[0046] [ka] In the formula, Rk 5 , Rk 7 , Rk 13 has the corresponding definition above in the present invention.

[0047] In one embodiment of the invention, the compound has the following structure:

[0048] [ka]

[0049] In one embodiment of the invention, the compound has the following structure:

[0050] [ka]

[0051] In one embodiment of the invention, the salt of the compound is its sulfate salt.

[0052] In another embodiment of the invention, the compound has the structure:

[0053] [ka] In the formula, Rq 1 , Rq 2 , Rq 3 , Rq 4 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from Rq 5 , Rq 6 , Rq 7 , Rq8 , Rq 9 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), NHC(=O)(C 6-18 aryl group), NHC(=O)(C 1-10 Aralkyl group), NHC(=O)(C 1-10Arylalkoxyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), NHC(=O)(C 1-8 Alkyl group)NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 or Rq 1 , Rq 2 , Rq 3 , Rq 4 , Rq 5 , Rq 6 , Rq 7 , Rq 8 , Rq 9 Two of them (e.g., Rq 5 and Rq 6 , Rq 6 and Rq 7 , Rq 7 and Rq 8 , Rq 8 and Rq 9 , Rq 9 and Rq 1 , Rq 9 and Rq 2 , Rq 5 and Rq 4 , Rq 5 and Rq 3 , Rq3 and Rq 2 , Rq 3 and Rq 1 , Rq 4 and Rq 2 , Rq 4 and Rq 1 ) form with the carbon atom to which they are attached an aryl group, a cycloalkyl group, or a heterocyclyl group; m is selected from an integer from 1 to 5.

[0054] Specifically, Rq 1 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 More specifically, Rq 1 NH 2 , NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 In one embodiment of the present invention, Rq 1 NH 2 It is.

[0055] Specifically, Rq 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 2 is H.

[0056] Specifically, m is selected from 1, 2, 3, 4, and 5. In one embodiment of the present invention, m is 1.

[0057] Specifically, each Rq 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 3 is H.

[0058] Specifically, each Rq 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 4 is H.

[0059] Specifically, Rq 5 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO2 In one embodiment of the present invention, Rq 5 is H.

[0060] Specifically, Rq 6 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 6 is H.

[0061] Specifically, Rq 7 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), NHC(=O)(C 6-18 aryl group), NHC(=O)(C 1-10 Aralkyl group), NHC(=O)(C 1-10 Arylalkoxyl group), OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 7 is H.

[0062] Specifically, Rq 8 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group)2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 8 is H.

[0063] Specifically, Rq 9 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rq 9 is H.

[0064] Specifically, the compound has the following structure:

[0065] [ka] In the formula, Rq 1 , Rq 2 , Rq 3 , Rq 4 , Rq 5 , Rq 6 , Rq 7 , Rq 8 , Rq 9 has the corresponding definition above in the present invention.

[0066] In one embodiment of the invention, the compound has the structure:

[0067] [ka] In the formula, Rq 1 , Rq2 has the corresponding definition above in the present invention.

[0068] In one embodiment of the invention, the compound has the following structure:

[0069] [ka]

[0070] In one embodiment of the invention, the compound has the following structure:

[0071] [ka]

[0072] In one embodiment of the invention, the salt of the compound is its hydrochloride salt.

[0073] In another embodiment of the invention, the compound has the structure:

[0074] [ka] In the formula, Rs. 1 , Rs. 2 , Rs. 3 , Rs. 4 , Rs. 5 , Rs. 6 , Rs. 7 , Rs. 8 , Rs. 9 , Rs. 10 are independently H, halogen, C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl groups, CH=CH 2 , CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from.

[0075] Furthermore, the compound has the following structure:

[0076] [ka] In the formula, Rs. 11 , Rs. 12 , Rs. 13 , Rs. 14 , Rs. 15 are independently H, halogen, C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl groups, CH=CH 2 , CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from.

[0077] Specifically, Rs. 1 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 1is H.

[0078] Specifically, Rs. 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 2 is H.

[0079] Specifically, Rs. 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 3 is H.

[0080] Specifically, Rs. 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H.2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 4 is H.

[0081] Specifically, Rs. 5 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 alkynyl groups.

[0082] Additionally, Rs. 5 is NH(C 1-8 In one embodiment of the present invention, Rs 5 ,NHCH 3 It is.

[0083] Specifically, Rs. 6 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 6 is H.

[0084] Specifically, Rs. 7 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 7 is H.

[0085] Specifically, Rs. 8 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 8 is H.

[0086] Specifically, Rs. 9 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 9 is H.

[0087] Specifically, Rs. 10 H, halogen, C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 alkynyl groups.

[0088] Additionally, Rs. 10 is selected from an aryl group and a heteroaryl group.

[0089] Specifically, Rs. 11 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 alkynyl groups.

[0090] Additionally, Rs. 11 is selected from H, F, Cl, Br, I. In one embodiment of the present invention, Rs 11 is Cl.

[0091] Specifically, Rs. 12 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 alkynyl groups.

[0092] Additionally, Rs. 12 is selected from H, F, Cl, Br, I. In one embodiment of the present invention, Rs 12 is Cl.

[0093] Specifically, Rs. 13 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 13 is H.

[0094] Specifically, Rs. 14 are H, F, Cl, Br, I, and C.1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 14 is H.

[0095] Specifically, Rs. 15 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C 2-8 Alkenyl group, C 2-8 In one embodiment of the present invention, Rs is selected from the group consisting of alkynyl groups. 15 is H.

[0096] In one embodiment of the invention, the compound has the structure:

[0097] [ka] In the formula, Rs. 5 , Rs. 11 , Rs. 12 has the corresponding definition above in the present invention.

[0098] In one embodiment of the invention, the compound has the following structure:

[0099] [ka]

[0100] In one embodiment of the invention, the compound has the following structure:

[0101] [ka]

[0102] In one embodiment of the invention, the salt of the compound is its hydrochloride salt.

[0103] In another embodiment of the invention, the compound has the structure:

[0104] [ka] In the formula, Rw 1 are one or more optional independent substituents on the phenyl group, and each Rw 1 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from Rw 2 , Rw 3 , Rw 4 , Rw 5 , Rw 6 , Rw 7 , Rw8 , Rw 9 , Rw 10 , Rw 11 , Rw 12 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 or Rw 3 and Rw 4 Or Rw 4 and Rw 5 form an aryl group, a cycloalkyl group, or a heterocyclyl group together with the carbon atom to which they are attached, Xw, Yw, Zw 1 , Zw 2 , Zw 3 are each independently CRw 13 Rw 14 ,O,S,NRw 13 is selected from m1 is selected from integers 1 to 5; Rw 13 and Rw 14 are independently H, halogen, C 1-8 Alkyl group, C 3-11 It is selected from a cycloalkyl group, an aryl group, and a heteroaryl group.

[0105] Specifically, Rw 1 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 1 is F.

[0106] Specifically, Rw 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 2 is H.

[0107] Specifically, Rw 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 3 is H.

[0108] Specifically, Rw 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 4 is H.

[0109] Specifically, Rw 5 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 5 is H.

[0110] Specifically, Rw 6 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 6 is H.

[0111] Specifically, Rw 7 and Rw 8 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 7 is H. In one embodiment of the present invention, Rw 8 is H.

[0112] Specifically, Rw 9 and Rw 10 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 9 is H. In one embodiment of the present invention, Rw 10 is H.

[0113] Specifically, Rw 11 Japanese Rw 12 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rw 11 is H. In one embodiment of the present invention, Rw 12 is H.

[0114] Specifically, m1 is selected from 1, 2, 3, 4, and 5. In one embodiment of the present invention, m1 is 1.

[0115] In one embodiment of the present invention, Xw is NRw 13 where Rw 13 , H, C 1-8 Alkyl group, C 3-11 In one embodiment of the present invention, Xw is NH.

[0116] In one embodiment of the present invention, Yw is O.

[0117] In one embodiment of the present invention, Zw 1 is O.

[0118] In one embodiment of the present invention, Zw 2 CRw 13 Rw 14 where Rw 13 and Rw 14 are independently H, halogen, C 1-8 Alkyl group, C 3-11 In one embodiment of the present invention, Zw may be selected from the group consisting of cycloalkyl, aryl and heteroaryl groups. 2 is CH 2 It is.

[0119] In one embodiment of the present invention, Zw 3 is O.

[0120] In one embodiment of the invention, the compound has the structure:

[0121] [ka] In the formula, Rw 1 , Rw 2 , Rw 3 , Rw 4 , Rw 5 , Rw6 , Rw 13 has the corresponding definition above in the present invention.

[0122] More specifically, the compound has the following structure:

[0123] [ka] In the formula, Rw 1 , Rw 2 , Rw 3 , Rw 4 , Rw 5 , Rw 6 , Rw 13 has the corresponding definition above in the present invention.

[0124] More specifically, the compound has the following structure:

[0125] [ka] In the formula, Rw 1 , Rw 13 has the corresponding definition above in the present invention.

[0126] In one embodiment of the invention, the compound has the following structure:

[0127] [ka]

[0128] In one embodiment of the invention, the compound has the following structure:

[0129] [ka]

[0130] In one embodiment of the invention, the salt of the compound is its hydrochloride salt.

[0131] In another embodiment of the invention, the compound has the structure:

[0132] [ka] In the formula, Rt 1 are one or more optional independent substituents on the phenyl group, and each Rt 1 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH 2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C 1-8 (alkyl group) 2 is selected from Rt 2 , Rt 3 , Rt 4 , Rt 5 , Rt 6 are each independently H, halogen, or C 1-8 Alkyl group, O(C 1-8 alkyl group), S(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , C 3-11 Cycloalkyl groups, aryl groups, heteroaryl groups, C 3-11 Heterocycloalkyl groups, O(C 1-8 Cycloalkyl group), S(C 1-8 Cycloalkyl group), NH(C 1-8 Cycloalkyl group), N(C 1-8 Cycloalkyl group)(C 1-8 Alkyl group), OH, NH2 , SH, SO 2 (C 1-8 Alkyl group), C 2-8 Alkenyl group, C 2-8 Alkynyl group, CH=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=CH 2 , C(C 1-8 Alkyl group)=CH(C 1-8 alkyl group), C(C 1-8 Alkyl group)=C(C 1-8 (alkyl group) 2 ,OC(=O)(C 1-8 alkyl group), C(=O)(C 1-8 Alkyl group), (C 1-8 Alkyl group)CO 2 H, CO 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 , C(=O)NH(C 1-8 alkyl group), C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)C(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH(C 1-8 alkyl group), NHC(=O)N(C 1-8 (alkyl group) 2 , NHC(=O)NH 2 , N(C 1-8 Alkyl group)SO 2 NH(C 1-8 alkyl group), N(C 1-8 Alkyl group)SO 2 N(C 1-8 (alkyl group) 2 , N.H.S.O. 2 NH(C 1-8 alkyl group), NHSO 2 N(C1-8 (alkyl group) 2 is selected from Rt 7 , Rt 8 are independently H, C 1-8 Alkyl group, C 3-6 cycloalkyl groups, Yt is CRt 9 Rt 10 , O, S, NRt 9 is selected from Zt is C 1-8 is an alkylene group, Rt 9 and Rt 10 are each independently H, halogen, or C 1-8 Alkyl group, C 3-11 It is selected from a cycloalkyl group, an aryl group, and a heteroaryl group.

[0133] Specifically, each Rt 1 are independently H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rt 1 is H.

[0134] Specifically, Rt 2 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO2 In particular, Rt 2 , H, C 1-3 Alkyl groups (e.g., methyl, ethyl, n-propyl, isopropyl), CF 3 , CHF 2 , C.H. 2 In one embodiment of the present invention, Rt 2 is a methyl group.

[0135] Specifically, Rt 3 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rt 3 is H.

[0136] Specifically, Rt 4 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rt 4 is H.

[0137] Specifically, Rt 5 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8(alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rt 5 is H.

[0138] Specifically, Rt 6 are H, F, Cl, Br, I, and C. 1-8 Alkyl group, O(C 1-8 alkyl group), NH(C 1-8 alkyl group), N(C 1-8 (alkyl group) 2 , OH, NH 2 , S.H., C.O. 2 H, C.N., and C.F. 3 , CHF 2 , C.H. 2 F, NO 2 In one embodiment of the present invention, Rt 6 is H.

[0139] Specifically, Rt 7 , Rt 8 are independently H, C 1-3 In one embodiment of the present invention, Rt is selected from the group consisting of alkyl groups (e.g., methyl, ethyl, and n-propyl). 7 is a methyl group. 8 is a methyl group.

[0140] Specifically, Yt is CH 2 , O, S, NH. More particularly, Yt is O or S. In one embodiment of the invention, Yt is O.

[0141] Specifically, Zt is C 1-6 Alkylene groups, in particular C 1-3 Alkylene groups, for example, -CH 2 -, -CH 2 CH 2 -, -CH 2CH 2 CH 2 In one embodiment of the present invention, Zt is -CH 2 CH 2 -It is.

[0142] In some embodiments of the invention, the compound has the structure:

[0143] [ka] In the formula, Rt 2 , Rt 7 , Rt 8 , Yt, Zt have the corresponding definitions above of the present invention.

[0144] More specifically, the compound has the following structure:

[0145] [ka] In the formula, Rt 2 , Rt 7 , Rt 8 , Yt have the corresponding definitions above of the present invention.

[0146] In one embodiment of the invention, the compound has the following structure:

[0147] [ka] In one embodiment of the invention, the salt of the compound is its citrate salt.

[0148] Specifically, the salts, stereoisomers and solvates are pharma- ceutically acceptable salts, stereoisomers and solvates.

[0149] Specifically, the compounds, or salts, stereoisomers and solvates thereof, may be the sole active ingredient or may be used in combination with other, same or different, active ingredients to control or kill mites.

[0150] In particular, the acaricidal products according to the invention may be used for therapeutic and / or preventive purposes, but also for non-therapeutic and / or preventive purposes.

[0151] Specifically, the mite according to the invention may be one or more of Demodex, House dust mite, Sarcoptes scabiei, etc. In one embodiment of the invention, the mite according to the invention is Demodex, such as Demodex folliculorum and Demodex sebaceus.

[0152] In one embodiment of the invention, the mite controlling and / or killing product according to the invention is a pharmaceutical composition.

[0153] Specifically, the pharmaceutical composition further comprises a pharma- ceutically acceptable excipient.

[0154] In particular, the pharmaceutical compositions according to the present invention can be used for the prevention and / or treatment of diseases caused by tick infection.

[0155] In one embodiment of the invention, said use is the use of said compound, or a salt, stereoisomer or solvate thereof, in the manufacture of a medicament for the prevention and / or treatment of a disease caused by a tick infestation.

[0156] Specifically, the disease may be an eye disease, a skin disease, an allergic disease, or the like.

[0157] Specifically, the eye disease may be one or more of blepharitis, blepharokeratoconjunctivitis, meibomian gland dysfunction, eyelash loss, abnormal eyelash arrangement, conjunctivitis and blepharoconjunctivitis, pterygium, keratitis, eyelid basal cell carcinoma, xerophthalmia, chalazion, etc., and may have one or more symptoms selected from redness and itching of the eye, dry eye, burning sensation in the eye, foreign body sensation, photophobia, increased eye discharge, eyelash loss, blurred vision, decreased vision, etc.

[0158] Specifically, the skin disease may be one or more of seborrheic dermatitis, acne, rosacea-like dermatitis, pityriasis follicularis, perioral dermatitis, demodex, scabies mites, basal cell carcinoma, and the like.

[0159] Specifically, the allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, allergic conjunctivitis, and the like.

[0160] Specifically, the pharmaceutical composition may be in any dosage form suitable for administration, such as a topical preparation, in particular an ophthalmic preparation, a skin topical preparation, and the like.

[0161] Specifically, the ophthalmic preparation may be eye drops, eye ointments, eye gels, eye emulsions, eye suspensions, eye films, eye washes, intraocular injections, and the like.

[0162] Specifically, the topical skin preparation may be an aerosol, a powder, a detergent, a tincture, a liniment, a coating, an ointment, a gel, a paste, an emulsion, or the like.

[0163] Specifically, various dosage forms of the pharmaceutical composition according to the present invention can be prepared according to conventional methods in the pharmaceutical field.

[0164] Specifically, the pharmaceutical compositions according to the present invention may contain 0.01-99.5% by weight of the active ingredient (specifically, for example, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%).

[0165] Specifically, the pharmaceutical composition can be used for humans, and can also be used as an animal drug for non-human animals, such as non-human mammals, for example, pet animals (e.g., dogs, cats, rabbits, mice, etc.), livestock animals (e.g., horses, cows, sheep, pigs, etc.), etc.

[0166] In another embodiment of the invention, the acaricidal product according to the invention is a cosmetic product.

[0167] In particular, the cosmetic product further comprises additives acceptable in the cosmetic field.

[0168] Specifically, the cosmetic product according to the present invention may be a cosmetic product used on the face, such as a facial cleanser, soap, smoothing toner, cleansing lotion, skin care lotion, gel, face cream, sunscreen, essence, face mask, gel, liquid foundation, scrub cream, etc.

[0169] Specifically, the cosmetic product according to the present invention may be a cosmetic product to be used on parts of the body other than the face, such as neck cream, shampoo, body soap, soap, conditioner, body lotion, scrub cream, etc.

[0170] Specifically, the cosmetic product according to the present invention may be a cosmetic product used on or around the eyes, such as an eye cream, mascara, eyeliner powder, eyeliner cream, eyeliner pencil, eyeshadow powder, eyeshadow cream, eyebrow pencil, eyebrow powder, etc.

[0171] Specifically, the various forms of the cosmetic product according to the present invention can be produced according to conventional methods in the cosmetic field.

[0172] Specifically, the cosmetic product according to the present invention may contain 0.01-99.5% by weight of the active ingredient (specifically, for example, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%).

[0173] In another embodiment of the present invention, the acaricidal product according to the present invention is a miticide and can be used to kill and suppress mites that can infest items in the living environment (e.g., pillowcases, pillow inserts, sheets, futons, mattresses, clothing, carpets, cushions, sofas, mats, stuffed toys, air conditioners, etc.).

[0174] Specifically, the miticide may contain any suitable additive capable of achieving the desired performance.

[0175] Specifically, the miticide may be in the form of a spray, a detergent, a patch, a small packet, or the like.

[0176] Specifically, the various forms of the acaricide according to the present invention can be prepared according to conventional methods in the field of daily care products.

[0177] Specifically, the miticide according to the present invention may contain 0.01-99.5% by weight of active ingredient (specifically, for example, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%).

[0178] The present invention further provides a method for preventing and / or treating a disease caused by a tick infestation comprising the step of administering to a subject in need thereof a compound according to the present invention, or a salt, stereoisomer or solvate thereof, pharmaceutical composition.

[0179] Specifically, in said methods, the disease, the compound, or its salts, stereoisomers and solvates, pharmaceutical compositions have the above corresponding definitions of the present invention.

[0180] In particular, the subject may be any animal, in particular a mammalian animal, such as a human, cat, dog, rabbit, rat, horse, cow, sheep, pig, etc. In one embodiment of the invention, the subject is a human. In another embodiment of the invention, the subject is a non-human animal.

[0181] Specifically, the dosage of the compound, or its salts, stereoisomers and solvates, or pharmaceutical compositions may vary depending on factors such as the route of administration, the age and weight of the subject, and the type and severity of the disease being treated.

[0182] The present invention further provides a cosmetic method comprising the step of administering to a subject in need thereof a compound represented by formula IA, IB, IC, ID, IE, IF, or a salt, stereoisomer, or solvate thereof, to improve skin problems, such as rough skin, increased scaly skin, itching, etc., caused by mites in the subject in need thereof.

[0183] Specifically, in said method, the subject is a human.

[0184] Specifically, said compounds have the corresponding definitions as defined above in the present invention.

[0185] The present invention further provides the use of compounds of formula IA, IB, IC, ID, IE, I-, salts, stereoisomers and solvates thereof in the manufacture of a medicament for preventing and / or treating dry eye syndrome.

[0186] Specifically, the compounds represented by formulae IA, IB, IC, ID, IE, I-, salts, stereoisomers and solvates thereof have the above corresponding definitions of the present invention.

[0187] Specifically, the compounds represented by the formulas IA, IB, IC, ID, IE, I-, their salts, stereoisomers and solvates may be used as the sole active ingredient or in combination with other identical or different active ingredients for the prevention and / or treatment of dry eye syndrome.

[0188] Specifically, the dry eye syndrome has one or more symptoms selected from itchy eyes, foreign body sensation, burning sensation, photophobia, blurred vision, fluctuation in vision, dry eyes, tired eyes, viscous secretions, sensitivity to external stimuli, red and swollen eyes, congestion, keratinization, damage to the corneal epithelium and adhesion of thread-like substances, etc.

[0189] In one embodiment of the invention, said xerophthalmia is xerophthalmia caused by or associated with a mite infestation.

[0190] Specifically, the drug can be used in humans, and can also be used as a veterinary medicine in non-human animals, such as non-human mammals, including pet animals (e.g., dogs, cats, rabbits, mice, etc.), livestock animals (e.g., horses, cows, sheep, pigs, etc.), etc.

[0191] In particular, the drug may further comprise suitable pharma- ceutically acceptable excipients.

[0192] In particular, the drug may be in any suitable dosage form for administration, such as a topical formulation, in particular an ophthalmic formulation.

[0193] Specifically, the ophthalmic preparation may be eye drops, eye ointments, eye gels, eye emulsions, eye suspensions, eye films, eye washes, intraocular injections, and the like.

[0194] The present invention further provides a method for preventing and / or treating xerophthalmia, comprising the step of administering to a subject in need thereof a compound of formula IA, IB, IC, ID, IE, I-, a salt thereof, a stereoisomer or a solvate thereof, a medicament thereof as described in the present invention.

[0195] Specifically, in the method, the dry eye syndrome, the compounds represented by formula IA, IB, IC, ID, IE, I-, salts, stereoisomers and solvates thereof, drugs have the above corresponding definitions of the present invention.

[0196] In particular, the subject may be any animal, in particular a mammalian animal, such as a human, cat, dog, rabbit, rat, horse, cow, sheep, pig, etc. In one embodiment of the invention, the subject is a human. In another embodiment of the invention, the subject is a non-human animal.

[0197] Specifically, the dosage of the compound represented by the formula IA, IB, IC, ID, IE, I-, its salt, stereoisomer and solvate, or drug may vary depending on factors such as the administration route, the age and weight of the subject, the type and severity of the disease being treated, etc.

[0198] The present inventors have found through experiments that the compounds represented by formulas IA, IB, IC, ID, IE, I-, their salts, stereoisomers and solvates (particularly the compound represented by formula V) can be used to inhibit and kill mites, effectively shorten the survival time of Demodex mites, and can be used in products for killing and inhibiting mites (such as medicines, cosmetics, daily necessities, etc.).The present inventors have also found that the compounds represented by formulas IA, IB, IC, ID, IE, I-, their salts, stereoisomers and solvates (particularly the compound represented by formula VA) can be used to treat xerophthalmia, and can effectively alleviate and improve the symptoms of xerophthalmia. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0199] Unless otherwise defined, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0200] The term "alkyl group" refers to a straight or branched hydrocarbon chain free radical that contains no unsaturated bonds and is attached to the rest of the molecule through a single bond. 1-8 The alkyl group is C 1 Alkyl groups (i.e., mercury groups), C 2 Alkyl group (i.e., ethyl group), C 3 Alkyl groups (e.g., n-propyl, isopropyl), C 4 Alkyl groups (e.g., n-butyl, isobutyl, tert-butyl), C 5 Alkyl group, C 6 Alkyl group, C 7 Alkyl group, C 8 Contains an alkyl group.

[0201] The term "alkenyl group" refers to a straight or branched hydrocarbon chain free radical containing at least two carbon atoms, at least one unsaturated bond, which is connected to the rest of the molecule through a single bond. 2-8 The alkenyl group is C 2 Alkenyl group (i.e., vinyl group), C 3 Alkenyl groups (e.g., 1-propenyl, 2-propenyl, 1-methylvinyl), C 4 Alkenyl groups (e.g., 1-butenyl, 2-butenyl, 3-butenyl), C 5 Alkenyl group, C 6 Alkenyl group, C 7 Alkenyl group, C 8 Contains an alkenyl group.

[0202] The term "alkynyl group" refers to a straight or branched hydrocarbon chain free radical containing at least two carbon atoms, at least one carbon-carbon triple bond, which is attached to the rest of the molecule through a single bond. 2-8 The alkynyl group is C 2 Alkynyl group (i.e., ethynyl group), C 3 Alkynyl groups (e.g., 1-propynyl group, 2-propynyl group), C 4 Alkynyl groups (e.g., 1-butyl, 2-butyl, 3-butyl), C 5 Alkynyl group, C 6 Alkynyl group, C 7 Alkynyl group, C 8 Contains alkynyl groups.

[0203] The term "cycloalkyl group" refers to an alicyclic hydrocarbon group, such as, for example, a cyclopropyl group, a cyclohexyl group, or an adamantyl group.

[0204] The term "aryl group" refers to a monocyclic or polycyclic free radical, including monoaryl and / or polycyclic free radicals containing fused aryl groups, such as, for example, a phenyl, naphthyl, biphenyl, indenyl, phenanthryl, or anthracenyl group.

[0205] The term "heterocyclyl group" includes heteroaromatic and heteroalicyclic groups containing 1-3 single and / or fused rings, and 3 to about 18 ring atoms. Heterocyclyl groups of the invention contain one, two or three types of heteroatoms. The heteroatoms are selected from N, O or S atoms. Heteroaryl groups include coumarinyl (including 8-coumarinyl), quinolinyl (including 8-quinolinyl), isoquinolinyl, pyridyl, pyrazinyl, pyrazolyl, pyrimidinyl, furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, imidazolyl, indolyl, isoindolyl, indazolyl, indolyl, ... pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyridyl, pyr These include, but are not limited to, linyl, phthalazinyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazolyl, pyridazinyl, triazinyl, cinnolinyl, benzimidazole, benzofuranyl, benzofurazanyl, benzothienyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl and furopyridyl groups. Examples of the heteroalicyclic group include a pyrrolidinyl group, a tetrahydrofuryl group, a dihydrofuryl group, a tetrahydrothiophenyl group, a tetrahydrothiopyranyl group, a piperidinyl group, a morpholinyl group, a thiomorpholinyl group, an oxathianyl group, a piperazinyl group, an azetidinyl group, an oxetanyl group, a thietanyl group, a homopiperidinyl group, an oxiranyl group, a thiiranyl group, an azepinyl group, an oxazacycloheptyl group, a diazepinyl group, a triazepinyl group, a 1,2,3,6-tetraphenylene group, a ... Examples of such groups include hydropyridyl, 2-pyrrolinyl, 3-pyrrolinyl, indolyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, 3H-indolyl, and quinolinyl.

[0206] The above groups may be substituted at one or more positions with one or more suitable groups.

[0207] The term "halogen" includes fluorine, chlorine, bromine and iodine.

[0208] The term "salt" should be understood to mean any form of a compound used herein. The compound is in ionic form, charged and bound to oppositely charged ions (cations or anions), or exists in solution. This definition also includes quaternary ammonium salts, as well as complexes of this molecule with other molecules and ions, particularly complexes formed by ionic interactions. This definition particularly includes physiologically acceptable salts. This term should be understood to be equivalent to "pharmacologically acceptable salts" or "pharmacologically acceptable salts".

[0209] Specifically, pharma- ceutically acceptable salts include acid addition salts and base addition salts.

[0210] Acid addition salts include, but are not limited to, salts derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, and phosphonic acid, and salts derived from organic acids such as aliphatic monocarboxylic acids, aliphatic dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedicarboxylic acids, aromatic acids, aliphatic sulfonic acids, and aromatic sulfonic acids. Thus, these salts include, but are not limited to, sulfate, pyrosulfate, hydrogen sulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, hydrochloride, hydrobromide, iodate, formate, acetate, propionate, octanoate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, amygdalate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, and methanesulfonate. Further included are salts of amino acids such as arginate, glutamate, glycinate, gluconate, galacturonate, and the like. Acid addition salts can be prepared by contacting the free base form with a sufficient amount of the desired acid to form the salt in a conventional manner. The salt form is contacted with a base to form the newly formed free base form, which can be isolated by conventional methods.

[0211] Base addition salts form hydroxides of alkali and alkaline earth metals with metals or amines, or organic amines. Examples of metals used as cations include, but are not limited to, sodium, potassium, magnesium, and calcium. Examples of suitable amines include, but are not limited to, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine (ethane-1,2-diamine), N-methylglucosamine, and procaine. Base addition salts can be prepared by contacting the free acid form with a sufficient amount of the desired base to form the salt in a conventional manner. The salt form can be contacted with an acid to newly form the free acid form, and the free acid can be isolated in a conventional manner.

[0212] In one embodiment of the invention, the pharma- ceutically acceptable salt is a hydrochloride salt, for example paroxetine hydrochloride.

[0213] The term "solvate" should be understood to refer to any form of the compound of the present invention, which is bound to other molecules (usually polar solvents) through non-covalent bonds, and includes in particular hydrates and alcoholates (e.g., methanolates).Preferably, the solvate is a hydrate.

[0214] Any compound described herein is intended to represent such a specific compound and several variations or forms thereof. In particular, the compounds described herein may have asymmetric centers, and therefore exist in different enantiomeric or diastereomeric forms. Therefore, any given compound described herein may represent any one of the racemates, one or more enantiomeric forms, one or more diastereomeric forms, and mixtures thereof. Similarly, stereoisomers or geometric isomers of double bonds may exist. In some cases, a molecule may exist as an (E) isomer or a (Z) isomer (trans and cis isomers). When a molecule contains multiple double bonds, each double bond has its own stereoisomerism, which may be the same or different from the stereoisomerism of other double bonds of the molecule. Furthermore, the compounds described herein may have atropisomers. All stereoisomers of the compounds described herein include enantiomers, diastereomers, geometric isomers, atropisomers, and mixtures thereof, all of which are included within the scope of the present invention.

[0215] Unless otherwise specified, the compounds of the present invention also include isotopically enriched forms, i.e., compounds that differ only in the presence of one or more isotopically enriched atoms. For example, at least one hydrogen atom is replaced with only deuterium or tritium, or at least one carbon atom is replaced with only deuterium or tritium. 13 C or 14 C-rich carbon or at least one nitrogen 15Any compound having an existing structure that is substituted with an N-rich nitrogen is within the scope of the present invention.

[0216] The term "xerophthalmia" refers to an eye disease caused by many factors, characterized by dry eyes as the main symptom, and is always accompanied by phenomena such as itching of both eyes, foreign body sensation, burning sensation or photophobia, blurred vision, and fluctuations in vision. Common symptoms include dry eyes, eye fatigue, itchy eyes, foreign body sensation, painful burning sensation, viscous secretion, phobia, photophobia, and sensitivity to external stimuli. Eyes may become too dry and tear production may be insufficient, stimulating tear secretion and causing frequent tearing. In severe cases, the eyes may become red and swollen, bloodshot, keratinized, and the corneal epithelium may be damaged and thread-like material may adhere to the eye, which may cause keratoconjunctivitis over time and affect vision. The xerophthalmia of the present invention includes keratoconjunctivitis sicca (KCS), and further includes either one of the types of xerophthalmia with reduced tear secretion and increased tear evaporation.

[0217] Dry eye syndrome with reduced tear secretion is divided into dry eye syndrome with Sjögren's syndrome and dry eye syndrome without Sjögren's syndrome. Dry eye syndrome with Sjögren's syndrome includes cases with lacrimal gland disease such as congenital alacrimal gland disease, sarcoidosis, and graft-versus-host disease (GVHD) due to bone marrow transplantation, cases with lacrimal obstruction due to ocular pemphigoid, Stevens-Johnson syndrome, and trachoma, and cases with reduced reflex secretion due to diabetes and corneal refractive surgery (LASIK: Laser (assisted) in situ keratomileusis).

[0218] In addition, xerophthalmia with increased tear evaporation may include cases accompanied by a decrease in the oil layer due to meibomian gland dysfunction, blepharitis, etc.; cases accompanied by insufficient blinking or eyelid closure due to exophthalmos, lagophthalmos, etc.; cases accompanied by decreased tear stability due to contact lens wear; cases accompanied by decreased mucin secretion from free goblet cells; and cases accompanied by VDT work.

[0219] The terms "prevention" or "treatment" include therapeutic or prophylactic treatments or measures aimed at preventing or delaying the targeted pathological condition or disease state. A subject is shown to have been successfully "prevented" or "treated" by the methods of the invention if, after receiving a therapeutically effective amount of a CYP450 inhibitor, pharmaceutical composition or drug described in the invention, one or more observable and / or measurable signs and symptoms of a particular disease are reduced or eliminated in the subject.

[0220] In the present invention, the term "animal" generally refers to vertebrates, particularly mammals, including humans. The term "non-human animals" refers to any vertebrate other than humans, particularly mammals. In some embodiments of the present invention, the non-human animals described in the present invention are animals kept at home (i.e., animals kept and tamed by humans, whose reproduction can be controlled by humans, and used for functions such as food, labor, fur, pets, experiments, etc.), such as economic animals, pet animals, and laboratory animals. Economic animals (e.g., livestock) include, for example, pigs, cows, sheep, horses, donkeys, foxes, raccoon dogs, minks, and camels. Pet animals include, for example, dogs, cats, rabbits, and mice (e.g., guinea pigs, hamsters, gerbils, chinchillas, squirrels, etc.). Laboratory animals include, for example, monkeys, dogs, rabbits, cats, and mice (e.g., rats, mice).

[0221] Various publications, patents, and published patent specifications cited herein are hereby incorporated by reference in their entirety.

[0222] The following embodiments of the present invention will clearly and completely describe the technical solutions of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and are not all of the embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts are all included in the protection scope of the present invention. EXAMPLES

[0223] Example 1: Miticidal experiment 1. Experimental subjects This study was conducted in accordance with the ethical principles of the Declaration of Helsinki, "Ethical Guidelines for Life Science and Medical Research Involving Human Subjects." Demodex mites were collected from patients with a confirmed diagnosis of ophthalmic Demodex infection. Those who met the inclusion criteria were informed and agreed to participate in the study after signing a written informed consent.

[0224] 2. Demodex detection Demodex detection was performed by standard eyelash microscopy. Three eyelashes were plucked from each eyelid, for a total of 12 eyelashes. Three plucked eyelashes were immediately placed on a glass slide and observed under a standard light microscope. Demodex mites of all stages were counted and classified based on morphology (specific criteria: head-to-body ratio of 1:1 for sebaceous Demodex mites, and head-to-body ratio of 1:3-1:4 for follicular Demodex mites). Only adults fully exposed to the field of view were used as experimental subjects (larvae and eggs were not studied because they tend to die in the early stages of life).

[0225] 3. In Vitro Cultivation of Demodex mites Based on the Demodex detection, 50μl of different solutions were added to each slide, and the survival of the parasites was observed every hour. The movement of the parasites (body, limbs, etc.) was observed under a microscope to determine whether they died. During the experiment, two experienced Demodex-related experimenters observed and judged them separately, and if the judgment results differed, a third experienced experimenter judged them independently. In vitro culture was performed in an artificial climate chamber at a temperature of 20℃ and a humidity of 96%. The slides were transported in a humid chamber during observation, and a high humidity state was ensured by adding the solution appropriately before the solution evaporated and bubbles were generated.

[0226] 4. Screening of Anti-mite Compounds (1) Preparation of compound solutions: Compounds (structures are represented by VA, IV-B, VC, VD, VI-E, and IV-F below) or their salts and 0.9% NaCl solution were used to prepare solutions. The final concentrations of the compounds were as shown in Table 1. (2) 50 μl of each compound solution was dropped onto the mites, and a cover glass was placed over the mites. (3) To the control group, 50 μl of the solute of this compound, i.e., 0.9% NaCl solution, was dropped and a cover glass was placed on it. (4) The number of mites and the administration time were recorded, and the mites were then placed in an artificial incubation chamber and cultured. (5) The mites' ability to move was periodically observed under a microscope until they died. (6) The time of tick death was recorded. (7) The anti-mite activity of the compounds was statistically determined.

[0227] [ka]

[0228] The experimental results are shown in Table 1.

[0229] [Table 1]

[0230] Example 2: Clinical study on the treatment of dry eye caused by mite infestation

[0231] (1) Inclusion and Exclusion Criteria 1.Case Selection Criteria (1) Patients who met the diagnostic criteria for dry eye based on their medical history (2) Age: 18-70 years (3) Regardless of gender (4) People who can cooperate with treatment 2.Case Exclusion Criteria (1) Patients with iridocyclitis diagnosed by slit lamp (2) Patients with high or low intraocular pressure (3) Patients with ulcerated wounds on the eyelid skin and corneal epithelial infiltration lesions on the corneal surface (4) Patients with systemic diseases, e.g., Sjögren's syndrome and liver / renal dysfunction, were excluded. (5) Those under 18 years of age or over 70 years of age (6) Individuals who are unable to cooperate with the evaluation due to their mental condition (7) Pregnant or breastfeeding women 3. Dropout and Exclusion Criteria (1) Those who are unable or do not wish to continue treatment due to the development of other diseases during the course of treatment (2) Patients who are unable to cooperate with the treatment process or whose symptoms have worsened and who do not wish to continue treatment. (3) Those who violate the study plan and use drugs not used in the study. (4) Those whose final data are incomplete and therefore the effectiveness of treatment cannot be determined

[0232] (2) End point indicator Patients were scored for ocular surface discomfort, had a general eye examination (visual acuity, intraocular pressure, slit lamp examination), had three dry eye tests (conjunctival injection scoring, BUT test, Schirmer I test), had an ocular surface disease index score (OSDI), and had dry eye instrument and ocular Demodex folliculorum tests before and every week after treatment.

[0233] (3) Statistics 1. Estimation of sample content Considering that dry eye is a common clinical disease of the ocular surface and the positive rate of ocular Demodex mites is 23.8%-90.0%, the sample size calculation formula for quantitative data superiority test was used to calculate that the experimental and control groups had 30 patients each.

[0234] 2. Statistics and analysis of research data Statistical processing was performed using SPSS20.0 software and excel. Count data were analyzed using paired sample t-test for normal distribution data, quantitative data using chi-square test, and non-normal distribution data using non-parametric test. The results are shown as mean ± standard deviation x + s), and there is a statistically significant difference when P<0.05.

[0235] The above description is merely a preferred embodiment of the present invention, and does not limit the present invention. Any modifications, equivalent replacements, etc. made within the scope of the spirit and principle of the present invention should be included within the protection scope of the present invention.

[0236] The embodiments and methods described herein may be modified according to the capabilities, experience and preferences of those skilled in the art.

[0237] The method steps specified in a certain order in the present invention do not constitute any limitation on the order of the method steps.

Claims

A pharmaceutical composition comprising a compound, or a salt, ester, stereoisomer or solvate thereof, for suppressing and / or killing Demodex mites in a subject and / or for preventing and / or treating a disease of the subject caused by Demodex mite infection, wherein the compound is a cytochrome P450 inhibitor selected from the group consisting of compounds represented by the following formula, pharmaceutical composition. 【Chemical 1】 (In the formula, one or more Rj1, one or more Rj2, and one or more Rj3 are provided, Each Rj1, each Rj2, and each Rj3 are one or more arbitrary independent substituents on the corresponding phenyl group, and each Rj1, Rj2, Rj3 are each independently H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and are selected from, Ring A is a heterocyclyl group.) [Chemical Formula 2] (wherein, Rk1, Rk2, Rk3, Rk4, Rk5, and Rk6 are each independently H, halogen, a C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, a C3-11 cycloalkyl group, an aryl group, a heteroaryl group, a C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), a C2-8 alkenyl group, a C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and are selected from, or Rk1 and Rk2 together with the carbon atom to which they are attached form an aryl group or a heterocyclyl group, or two of Rk3, Rk4, Rk5, and Rk6 together with the carbon atom to which they are attached form an aryl group or a heterocyclyl group, [Chemical Formula 3] represents a single bond or a double bond, Rk7 is selected from H, O, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NH(C=O)NH(C1-8 alkyl group), NH(C=O)N(C1-8 alkyl group)2, NH(C=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, Rk8, Rk9, Rk10, Rk11, Rk12, Rk13, Rk14, Rk15, Rk16, Rk17 are each independently selected from H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, m is selected from integers of 1 - 5. ) 【Chemical Formula 4】 (wherein, Rq1, Rq2, each Rq3, and each Rq4 are each independently H, halogen, a C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, a C3-11 cycloalkyl group, an aryl group, a heteroaryl group, a C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), a C2-8 alkenyl group, a C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and are selected from Rq5, Rq6, Rq7, Rq8, Rq9 are each independently selected from H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), NHC(=O)(C6-18 aryl group), NHC(=O)(C1-10 aralkyl group), NHC(=O)(C1-10 arylalkoxyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), NHC(=O)(C1-8 alkyl group)NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, or Two of Rq1, Rq2, Rq3, Rq4, Rq5, Rq6, Rq7, Rq8, and Rq9 form a carbon atom and an aryl group, a cycloalkyl group, or a heterocyclyl group bonded thereto. m is selected from integers of 1 - 5. [Chemical Formula 5] (wherein Rs1, Rs2, Rs3, Rs4, Rs5, Rs6, Rs7, Rs8, Rs9, and Rs10 are independently H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH2, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and are selected from.) [Chemical Formula 6] (wherein one or more Rw1 are provided, and each Rw1 is independently H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and is selected from Rw2, Rw3, Rw4, Rw5, Rw6, Rw7, Rw8, Rw9, Rw10, Rw11, Rw12 are each independently H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and are selected from, or Rw3 and Rw4 or Rw4 and Rw5 form an aryl group, a cycloalkyl group or a heterocyclyl group with the carbon atom to which they are attached, Xw, Yw, Zw1, Zw2, Zw3 are each independently selected from CR13R14, O, S, NRw13, m1 is selected from integers from 1 to 5, Rw13 and Rw14 are each independently selected from H, halogen, C1-8 alkyl group, C3-11 cycloalkyl group, aryl group, heteroaryl group. 【Chemical Formula 7】 (wherein one or more Rt1 are provided, and each Rt1 is independently H, halogen, a C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, a C3-11 cycloalkyl group, an aryl group, a heteroaryl group, a C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), a C2-8 alkenyl group, a C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, and is selected from Rt2, Rt3, Rt4, Rt5, and Rt6 are each independently selected from H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), NHS02N(C1-8 alkyl group)2, Rt7 and Rt8 are each independently selected from H, C1-8 alkyl group, and C3-6 cycloalkyl group, Yt is selected from CRt9Rt10, O, S, and NRt9, Zt is a C1-8 alkylene group, Rt9 and Rt10 are each independently selected from H, halogen, a C1-8 alkyl group, a C3-11 cycloalkyl group, an aryl group, and a heteroaryl group.)

2. The pharmaceutical composition according to claim 1, wherein the A ring is selected from the group consisting of the following. 【Chemical Formula 8】 (In the formula, X1, X2, X3, X4, and X5 are each independently selected from CRj4 or N, Rj4 is selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2.) 【Chemical Formula 9】 (In the formula, Y1, Y2, Y3, and Y4 are each independently selected from CRj5 or N, Y5 is selected from O, S, NRj5, or CRj5Rj6, Rj5 and Rj6 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2.)

3. The A ring is 【Chemical Formula 10】 selected from and Rj4 and Rj5 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, the pharmaceutical composition according to claim 1.

4. Rk1, Rk2, Rk3, Rk4, and Rk6 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Rk5 and Rk7 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Rk8, Rk9, Rk10, Rk11, Rk12, Rk14, Rk15, Rk16, Rk17 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, and / or Rk13 is selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, NO2, or a C2-8 alkenyl group, the pharmaceutical composition according to claim 1. **Claim 5**: Rq1 is selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Rq7 is selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, NHC(=O)(C1-8 alkyl group), NHC(=O)(C6-18 aryl group), NHC(=O)(C1-10 aralkyl group), NHC(=O)(C1-10 arylalkoxyl group), OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, and / or, Rq2, each Rq3, each Rq4, Rq5, Rq6, Rq8, Rq9 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, the pharmaceutical composition according to claim 1. **Claim 6**: The compound of formula (I-D) is the compound of formula (II-D), the pharmaceutical composition according to claim 1. **Chemical Formula 11** (In the formula, Rs11, Rs12, Rs13, Rs14, and Rs15 are independently selected from H, halogen, C1-8 alkyl group, O(C1-8 alkyl group), S(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, C3-11 cycloalkyl group, aryl group, heteroaryl group, C3-11 heterocycloalkyl group, O(C1-8 cycloalkyl group), S(C1-8 cycloalkyl group), NH(C1-8 cycloalkyl group), N(C1-8 cycloalkyl group)(C1-8 alkyl group), OH, NH2, SH, SO2(C1-8 alkyl group), C2-8 alkenyl group, C2-8 alkynyl group, CH=CH2, CH=CH(C1-8 alkyl group), C(C1-8 alkyl group)=CH2, C(C1-8 alkyl group)=CH(C1-8 alkyl group), C(C1-8 alkyl group)=C(C1-8 alkyl group)2, OC(=O)(C1-8 alkyl group), C(=O)(C1-8 alkyl group), (C1-8 alkyl group)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C1-8 alkyl group), C(=O)N(C1-8 alkyl group)2, N(C1-8 alkyl group)C(=O)NH(C1-8 alkyl group), N(C1-8 alkyl group)C(=O)N(C1-8 alkyl group)2, NHC(=O)NH(C1-8 alkyl group), NHC(=O)N(C1-8 alkyl group)2, NHC(=O)NH2, N(C1-8 alkyl group)SO2NH(C1-8 alkyl group), N(C1-8 alkyl group)SO2N(C1-8 alkyl group)2, NHS02NH(C1-8 alkyl group), or NHS02N(C1-8 alkyl group)2.) **Claim 7**: Rs1, Rs2, Rs3, Rs4, Rs6, Rs7, Rs8, Rs9, Rs13, Rs14, and Rs15 are independently selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, NO2, C2-8 alkenyl group, or C2-8 alkynyl group, Rs5 is selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, NO2, C2-8 alkenyl group, or C2-8 alkynyl group, and / or Rs11 and Rs12 are each independently selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, NO2, C2-8 alkenyl group, or C2-8 alkynyl group, the pharmaceutical composition according to claim 6. **Claim 8**: Rw1 is selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Rw2, Rw3, Rw4, Rw5, Rw6, Rw7, Rw8, Rw9, Rw10, Rw11, Rw12 are each independently selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Xw is NRw13, where Rw13 in the NRw13 is selected from H, C1-8 alkyl group, or C3-11 cycloalkyl group, Yw is O, Zw1 and / or Zw3 is O, Zw2 is CRw13Rw14, where Rw13 and Rw14 in the CRw13Rw14 are independently selected from H, halogen, C1-8 alkyl group, C3-11 cycloalkyl group, aryl group, or heteroaryl group, and / or The pharmaceutical composition according to claim 1, wherein the compound of formula (I-E) is a compound of formula (II-E). [Chemical Formula 12]

9. Each of Rt1, Rt2, Rt3, Rt4, Rt5, Rt6 is independently selected from H, F, Cl, Br, I, C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, Rt7, Rt8 are each independently selected from H or C1-3 alkyl group, Yt is selected from CH2, O, S or NH, and / or The pharmaceutical composition according to claim 1, wherein Zt is a C1-6 alkylene group. **Claim 10**: The pharmaceutical composition according to claim 1, wherein the compound is selected from the group consisting of a compound represented by formula (III-A), a compound represented by formula (II-B), a compound represented by formula (II-C), a compound represented by formula (III-D), a compound represented by formula (III-E), and a compound represented by formula (II-F). 【Chemical 13】 (In the formula, Rj4 is selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, or NO2, and Rs11 and Rs12 are each independently selected from H, F, Cl, Br, I, a C1-8 alkyl group, O(C1-8 alkyl group), NH(C1-8 alkyl group), N(C1-8 alkyl group)2, OH, NH2, SH, CO2H, CN, CF3, CHF2, CH2F, NO2, a C2-8 alkenyl group, or a C2-8 alkynyl group.) **Claim 11**: The pharmaceutical composition according to claim 10, wherein the compound is selected from the group consisting of a compound represented by formula (IV-A), a compound represented by formula (II-B), a compound represented by formula (III-C), a compound represented by formula (III-D), a compound represented by formula (IV-E), and a compound represented by formula (III-F). 【Chemical 14】 **Claim 12**: The pharmaceutical composition according to claim 1, wherein the compound is selected from the group consisting of a compound represented by formula (V-A), a compound represented by formula (III-B), a compound represented by formula (IV-C), a compound represented by formula (IV-D), a compound represented by formula (V-E), and a compound represented by formula (IV-F). 【Chemical 15】

13. The pharmaceutical composition according to claim 1, wherein the compound is selected from the group consisting of a compound represented by formula (V-A), a compound represented by formula (IV-B), a compound represented by formula (V-C), a compound represented by formula (V-D), a compound represented by formula (VI-E), and a compound represented by formula (IV-F). 【Chemical Formula 16】

14. The pharmaceutical composition according to any one of claims 1 to 13, wherein the compound, or a salt, ester, stereoisomer or solvate thereof, is in the form of a topical preparation.

15. The pharmaceutical composition according to any one of claims 1 to 13, wherein the compound, or a salt, ester, stereoisomer or solvate thereof, is in the form of an ophthalmic preparation or a topical skin preparation.

16. The ophthalmic preparation is selected from the group consisting of eye drops, eye ointments, ophthalmic gels, ophthalmic emulsions, ophthalmic suspensions, ophthalmic film agents, eye washes, and intraocular injections, or the skin preparation is selected from the group consisting of aerosols, powders, detergents, tinctures, liniments, coating agents, ointments, gels, pastes, and emulsions, and the pharmaceutical composition according to claim 15.

17. The pharmaceutical composition according to claim 1, wherein the disease is selected from the group consisting of eye diseases, skin diseases, and allergic diseases.

18. The eye disease is selected from the group consisting of blepharitis, blepharokeratoconjunctivitis, meibomian gland dysfunction, eyelash loss, abnormal eyelash arrangement, conjunctivitis and eyelid conjunctivitis, pterygium, keratitis, eyelid basal cell carcinoma, dry eye, and chalazion, the skin disease is selected from the group consisting of seborrheic dermatitis, acne, rosacea-like dermatitis, follicular pityriasis, perioral dermatitis, acne mite disease, scabies mite disease, and basal cell carcinoma, or, the allergic disease is selected from the group consisting of allergic asthma, allergic rhinitis, allergic dermatitis, and allergic conjunctivitis, and the pharmaceutical composition according to claim 17.

19. The pharmaceutical composition according to claim 1, wherein the disease is keratoconjunctivitis sicca. The pharmaceutical composition according to claim 1, wherein the subject is a human or a non-human animal.

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