CROSS-REFERENCE TO RELATED APPLICATION

This application is a 371 of international application of PCT application serial no. PCT/CN2018/113811, filed on Nov. 2, 2018, which claims the priority benefit of China application no. 201711069917.7, filed on Nov. 3, 2017 and China application no. 201810219338.4, filed on Mar. 16, 2018. The entirety of each of the above mentioned patent applications is hereby incorporated by reference herein and made a part of this specification.

TECHNICAL FIELD

The present invention belongs to the field of heterocyclic compounds, and more particularly, relates to a fused heterocyclic compound, and an optical isomer, cis and trans isomers or an agromedically acceptable salt thereof, as well as a preparation method and use thereof.

BACKGROUND

New heterocyclic pesticides represented by nitrogen-containing heterocycles have the advantages of high insecticidal activity, wide insecticidal spectrum, low toxicity to mammals and appropriate field stability, so that heterocyclic compounds have become an important hotspot field in the development of new pesticides. In recent years, newly developed pesticides such as Flupyrimin, flupyradifurone, cycloxaprid, sulfoxaflor, flonicamid, spirotetramat, cyflumetofen, cyenopyrafen, cyantraniliprole and the like, all belong to the nitrogen-containing heterocyclic compounds (with reference to patents US2013150414, CN103960242, CN103254125, CN102892290, DE102006015467, WO2010069266, WO2007095229, EP580374, WO9805638, WO2002014263, JP2003201280 and WO2004067528).

However, the problems of serious resistance and cross resistance are caused due to excessive and frequent use of a single pesticide and a high toxicity of the existing insecticide to the environment while killing pests, which reduces an efficacy of the pesticide and greatly restricts use of the pesticide, thus restricting the development of agriculture and forestry. Therefore, how to develop a new pesticide that is more efficient and environmentally friendly and how to solve the problem of resistance become technical problems to be urgently solved in this field.

New structural molecules with big structural differences from previous pesticide molecules are believed to have no cross resistance with the existing pesticides, and may be used to control the development of pest resistance (Pestide Biochemistry and Physiology, 2015, 121: 22). In recent years, multiple series of fused heterocyclic compounds have been synthesized and reported to have an extensive bioactivity (such as Computational Biology and Chemistry, 2018, 74: 218; Bioorganic & Medicinal Chemistry Letters, 2017, 27: 3201; Journal of Medicinal Chemistry, 2017, 60: 9691; Journal of Heterocyclic Chemistry, 2017, 54: 2788; Organic & Biomolecular Chemistry, 2016, 14: 8721; Journal of Enzyme Inhibition and Medicinal Chemistry, 2015, 31: 195; New Journal of Chemistry, 2015, 39: 1060; Chemistry-A European Journal, 2015, 21: 16859; Bioorganic & Medicinal Chemistry Letters, 2014, 24: 2693; Journal of Medicinal Chemistry, 2013, 56: 7458; Bioorganic & Medicinal Chemistry Letters, 2009, 19: 4196; Chemistry & Biology, 2007, 14: 153; Journal of Biological Chemistry, 2003, 278: 25990; and Journal of Medicinal Chemistry, 2002, 45: 1035). Based on this, a large number of new fused heterocyclic compounds have been designed, synthesized and screened in this study. These compounds with novel structures have excellent control effects on a variety of pests and even on pests with resistance.

SUMMARY

According to an aspect of the invention, there is provided a nitrogen-containing fused tricyclic compound, and an optical isomer, cis and trans isomers or an agromedically acceptable salt thereof. The fused heterocyclic compound and the optical isomer, the cis and trans isomers or the agromedically acceptable salt thereof have a high killing activity on agroforestry pests and sanitary insect pests and sanitary pests, and more surprisingly, have a delayed working effect on pests such asSolenopsis invicta, thereby having a better killing effect.

According to another aspect of the invention, there is provided a method for preparing the fused tricyclic compound, and the optical isomer, the cis and trans isomers or the agromedically acceptable salt thereof.

According to another aspect of the invention, these is provided a method of using the fused heterocyclic compound and the optical isomer, the cis and trans isomers or the agromedically acceptable salt thereof in preparing an insecticide.

In order to achieve the above objects, the technical solutions adopted by the present invention are as follows.

A fused heterocyclic compound, and an optical isomer, cis and trans isomers or an agromedically acceptable salt thereof, wherein the fused heterocyclic compound has a structure shown in formula (I):



wherein R11and R12are each independently hydrogen, halogen, —NO2, —CN, —COR17, —CO2R17, —CONR17R18, —S(O) R17, —S(O)2R17, —N R17R18, —N R17CO R18, —N R17CON R18R19, —N R17CO2R18, —N R17S(O)2R18, alkyl, heteroalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the alkenyl, the cycloalkyl, the cycloalkenyl, the aryl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10; and

R13is hydrogen, —COR17, —CO2R17, —S(O)2R17, —CONR17R18, alkyl, heteroalkyl, alkenyl, cycloalkyl, cycloalkenyl and aryl; wherein the alkyl, the alkenyl, the cycloalkyl, the cycloalkenyl and the aryl are unsubstituted or substituted with one or more substituents R10;

R14and R15are each independently hydrogen, halogen, —CN, —OH, —N R17R18, —O R17, —CO R17, —CO2R17, —CONR17R18, —N R17CO R18, —NR17CON R18R19, —NR17CO2R18, —NR17S(O)2R18, —S(O)R17, —S(O)2R17, alkyl, heteroalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the alkenyl, the cycloalkyl, the cycloalkenyl, the aryl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10, and R14and R15are not hydrogen at the same time;

Y is N or CH;

Z1, Z2, Z3and Z4are each independently C or N, under conditions that at most two of Z1to Z4are N, and a ring containing Z1to Z4is aromatic;

R16represents a substituent on the ring containing Z1to Z4, one or more R16are provided, and each R16is independently hydrogen, halogen, —CN, alkyl, heteroalkyl, —CO R17, —CO2R17, —N R17R18, —CONR17R18, —N R17CO R18, —NR17CON R18R19, —NR17CO2R18or —NR17S(O)2R18;

R17, R18and R19are each independently hydrogen, alkyl, heteroalkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl; wherein the alkyl, the alkenyl, the cycloalkyl, the cycloalkenyl, the aryl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10; and

R10is halogen, C1-C6alkyl, C2-C6alkenyl, substituted or unsubstituted cycloalkyl, cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, —CN, —NH2, —OR′″, —NR′″R″″, —COR′″, —CO2R′″, —CONR′″R″″, —NR′″COR″″, —NR′″CONR′″R″″, —NR′″CO2R″″, —S(O)2R′″ or —NR′″S(O)2R″″, wherein R′″ and R″″ are each independently hydrogen, C1-C6alkyl, C2-C6alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocyclyl.

Preferably, when Y is N or CH;

R11is halogen, —CN, —COR17, —CONR17R18, —S(O) R17, —N R17R18, —N R17CO R18, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R12is hydrogen, —COR17, —CONR17R18, —S(O)R17, —S(O)2R17, —N R17R18, —N R17CO R18, —NR17CONR18R19, —NR17CO2R18, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R13is hydrogen, —COR17, alkyl, heteroalkyl or alkenyl;

R14is halogen, —CN, —N R17R18, —O R17, —CO R17, —CO2R17, —CONR17R18, —N R17CO R18, —NR17CO2R18, alkyl, heteroalkyl or alkenyl; wherein the alkyl, the heteroalkyl or the alkenyl is unsubstituted or substituted with one or more substituents R10; and

R15is hydrogen, halogen, —CN, —N R17R18, —O R17, —CO R17, —CO2R17, —CONR17R18, —N R17CO R18, —NR17CO2R18, alkyl, heteroalkyl or alkenyl; wherein the alkyl, the heteroalkyl or the alkenyl is unsubstituted or substituted with one or more substituents R10.

Preferably, when Z1, Z2, Z3and Z4are all C, one or more R16are provided, and each R16is independently hydrogen, halogen, alkyl, heteroalkyl, alkenyl, —S(O) R17, —S(O)2R17, —COR17, —N R17R18, —CONR17R18, —N R17CO R18or —NR17S(O)2R18;

R11is halogen, —CN, —COR17, —CONR17R18, —S(O) R17, —N R17R18, —N R17CO R18, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R12is —CONR17R18, —S(O) R17, —S(O)2R17, —N R17R18, —N R17CO R18, —N R17CON R18R19, aryl, heterocyclyl or heteroaryl; wherein the alkyl, the heterocyclyl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R13is hydrogen, —COR17, alkyl or alkenyl; and

R14and R15are each independently halogen, —CN, —N R17R18, —O R17, —CO R17, —CO2R17, —CONR17R18, —N R17CO R18, —NR17CO2R18, alkyl, heteroalkyl and alkenyl; wherein the alkyl, the heteroalkyl and the alkenyl are unsubstituted or substituted with one or more substituents R10.

More preferably,

when Y is N or CH;

R11is halogen, —CN, —COR17, —CONR17R18, —S(O) R17, —N R17R18or —N R17CO R18;

R12is —S(O) R17, —S(O)2R17, —N R17R18, —N R17CO R18, aryl or heteroaryl; wherein the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R13is hydrogen, —COR17, alkyl or alkenyl;

R14and R15are each independently halogen, —CN, —N R17R18, —O R17, —CO R17, —CO2R17, —CONR17R18, —N R17CO R18, —NR17CO2R18, alkyl, heteroalkyl or alkenyl; wherein the alkyl or the alkenyl is unsubstituted or substituted with one or more substituents R10; and

Z1, Z2, Z3and Z4are all C, one or more R16are provided, and each R16is independently halogen, alkyl, heteroalkyl, —S(O) R17, —S(O)2R17, —COR17, —N R17R18, —N R17CO R18or —NR17S(O)2R18.

More preferably,

R11is halogen, —CN, —COR17or —CONR17R18;

R12is —S(O)R17, —S(O)2R17, —NR17COR18, aryl or heteroaryl; wherein the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R10;

R13is hydrogen, —COR17or alkyl; and

Z1, Z2, Z3and Z4are all C, one or more R16are provided, and each R16is independently halogen, heteroalkyl, —S(O)R17, —NR17R18or —NR17COR18.

More preferably,

R11is —CN or —COR17;

R12is —S(O)R17or aryl; wherein the aryl is substituted with one or more substituents R10;

R13is hydrogen, —COR17, methyl or ethyl;

R14and R15are each independently halogen, —OR17, —COR17, —CO2R17, —CONR17R18, —NR17COR18, —NR17CO2R18, alkyl, heteroalkyl or alkenyl; wherein the alkyl or the alkenyl is unsubstituted or substituted with one or more substituents R10; and

Z1, Z2, Z3and Z4are all C, one or more R16are provided, and each R16is independently halogen or heteroalkyl.

More preferably,

R11is —CN or —COR17, and R17is alkyl or heteroalkyl;

R12is —S(O)R17, and R17is alkyl or heteroalkyl;

R13is hydrogen, —COR17, methyl or ethyl, and R17is alkyl;

R14and R15are each independently halogen, —OR17, —COR17, —CO2R17, —CONR17R18, —NR17COR18, —NR17CO2R18, alkyl, heteroalkyl or alkenyl; wherein the alkyl or the alkenyl is unsubstituted or substituted with one or more substituents R10; and

Z1, Z2, Z3and Z4are all C, one or more R16are provided, and each R16is independently halogen or heteroalkyl.

The present invention further discloses a pyrazole-ring-containing fused heterocyclic compound, and an optical isomer, cis and trans isomers or an agromedically acceptable salt thereof, wherein the pyrazole-ring-containing fused heterocyclic compound has a structure shown in formula (II):



wherein R1is hydrogen, halogen, —CN, alkyl, heteroalkyl, aryl or heteroaryl; wherein the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9; and

R2is hydrogen, halogen, —CN, —S(O)R7, —S(O)2R7, alkyl, heteroalkyl, aryl or heteroaryl; wherein the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9; and

R3is hydrogen, —COR7, alkyl or heteroalkyl;

R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted by one or more substituents R9, and R4and R5are not hydrogen at the same time;

Z1and Z2are independently C or N, and are not N at the same time, and a ring containing Z1and Z2is an aromatic ring;

R6represents a substituent on the ring containing Z1and Z2, one or more R6are provided, and each R6is independently hydrogen, halogen, —NO2, —CN, alkyl, heteroalkyl, —OR7, —COR7, —CO2R7or —NR7R8;

R7and R8are each independently hydrogen, hydroxyl, amino, C1-C6alkyl, heteroalkyl, aryl or heteroaryl; wherein the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9; and

R9is halogen, C1-C6alkyl, heteroalkyl, —CN, —NH2, —OH, —COR′, —CO2R′ or —CONR′R11, wherein R′ and R″ are each independently hydrogen, C1-C6alkyl or heteroalkyl.

Preferably, when Z1is N and Z2is C, R6is a monosubstituent —CF3at a 5-position of a pyridine ring, and a general formula of the compound is shown in formula (a):


wherein R3is hydrogen, methyl or chloromethyl; R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9;

or,

when Z2is N and Z1is C, R6is a monosubstituent chlorine at a 5-position of the pyridine ring, and a general formula of the compound is shown in formula (b):


wherein R3is hydrogen, methyl or chloromethyl; R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9;

or,

when Z1and Z2are both C, and R6is disubstituents at a 3-position and a 5-position of a benzene ring, a general formula of the compound is shown in formula (c):


wherein R1is —CN or —CF3, and R2is —CN, —CF3, —OCF3, —SOCF3or —SOCH2CH3; R3is hydrogen, —CH3, —Ac or —CH2CH2Cl; a substituent of R6at the 3-position of the benzene ring is —Cl, —Br, —CF3, —CH3, —CN, —CO2CH3or —NO2, and a substituent of R6at the 5-position of the benzene ring is —Cl, —CF3, —OCF3or —NO2; R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9;

or,

when Z1and Z2are both C, R6is disubstituents at a 4-position and a 6-position of the benzene ring, and R3is hydrogen, the general formula of the compound is shown in formula (d):


wherein R1is —CN, —CF3, —COCH3or —CH2NH2, and R2is —OCF3, —CF3, —CN, —SOCF3, —SOCH3, —SOCH2CH3, —SOPh, —SOCH2Ph, —SOC6H13,


R6is —Cl or —CF3; R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9;

or,

when Z1and Z2are both C, R6is disubstituents at the 3-position and the 6-position, or at the 3-position and the 4-position, or at the 4-position and the 5-position, or at the 5-position and the 6-position of the benzene ring, and R3is hydrogen, the general formula of the compound is shown in formula (e):


wherein R1is —CN, and R2is —SOCF3; R6is —Cl or —CF3; R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9; and R4and R5are not hydrogen at the same time.

Preferably, R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein R7is hydrogen, halogen, hydroxyl, C1-4alkyl, C1-4haloalkyl, C1-4alkenyl, C1-4haloalkenyl, amino or substituted amino.

Preferably, when the compound is shown in the formula (a) or the formula (b), and any one of R4and R5is hydrogen, R1is —CN, and R2is —SOCF3or —OCF3; or R1is —CF3, and R2is —SOCF3;

or, when neither R4nor R5is hydrogen, R1is —CN or —CF3; and R2is —SOCF3, —SOCH2CH3, —OCF3, —CF3, —CN or halogen.

Preferably, when the compound is shown in the formula (c), R3is —CH3, —Ac or —CH2CH2Cl, R2is —SOCF3, R1is —CN, and both R4and R5are —CO2Me;

or, when R3is hydrogen, R2is —SOCF3, and R1is —COCH3or —CH2NH2, R4and R5are independently —CO2Me or —CO2CH2Me;

or, when R3is hydrogen, and R2is —OCF3or —SOCF3, R1is —CN or —CF3, R4and R5are each independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9.

Preferably, when the compound is shown in the formula (d), R3is hydrogen, and R2is —CN, —CF3, —SOPh, —SOCH2Ph, —SOC6H13,


R1is —CN, and R4and R5are independently —CO2Me or —CO2CH2Me;

or, when R3is hydrogen, R2is —SOCF3, and R1is —COCH3or —CH2NH2, R4and R5are independently —CO2Me or —CO2CH2Me;

or, when R3is hydrogen, and R2is —OCF3or —SOCF3, R1is —CN or —CF3, R4and R5are independently hydrogen, halogen, —CN, —COR7, —CO2R7, —CH2COR7, —CH2COOR7, amino, alkyl, heteroalkyl, aryl or heteroaryl; wherein the amino, the alkyl, the aryl or the heteroaryl is unsubstituted or substituted with one or more substituents R9.

Preferably, when the compound is shown in the formula (e), R6is 3-Cl and 6-CF3, 3-Cl and 4-CF3, 4-Cl and 5-CF3, or 5-Cl and 6-CF3on the benzene ring; and R4and R5are each independently —CO2Me, —CH2CO2Me, —CO2Et, —CH2CO2Et, —CH2CO2CH2CF3or —CH2CO2CH2CHF2.

An agricultural composition includes:

(a) 0.001 to 99.99% by weight of the compound above, or the optical isomer, the cis and trans isomers or the agromedically acceptable salt thereof, or a combination thereof; and

(b) an agromedically acceptable carrier and/or excipient.

A method of using the agricultural composition according to the present invention in preparing an insecticide for killing or preventing agroforestry pests, sanitary insect pests and pests harmful to animal health.

A specific method of using is that the insecticide is directly applied to the pests or places contacted by the pests (for example, plants suffering from or probably suffering from pest damages, soil or environment therearound).

Compared with the prior art, the present invention has the following beneficial effects.

The present invention discloses the fused heterocyclic compounds with a new structure and the pyrazole-ring-containing fused heterocyclic compound. The fused heterocyclic compound and the pyrazole-ring-containing fused heterocyclic compound, and the optical isomer, cis and trans isomers or the agromedically acceptable salt thereof have high killing activity on agroforestry pests and sanitary insect pests and the like, and the compound according to the present invention has a delayed effect on pests such asSolenopsis invictaand the like, which enables the pests to carry the compound to a nest, thereby having a better killing effect on the wholeSolenopsis invictanest and a queenSolenopsis invicta. The compound according to the present invention has a good application prospect in pest control. The compound according to the present invention has lower toxicity to environmental organisms such as bees,Bombyx moriL. and the like, thus having a good application prospect.

