Dihydrofuran azetidine derivatives as antiparasitic agents

摘要

This invention recites dihydrofuran substituted azetidine derivatives of Formula (1) stereoisomers thereof, veterinarily acceptable salts thereof, compositions thereof, and their use as a parasiticide in mammals and birds. The substituents A, R1a, R1b, R1c, R2, R3, R4, R6, and n are as described herein.;

主权项

1. A compound of Formula (1) wherein
A is phenyl, naphthyl, or heteroaryl where said heteroaryl contains 1 to 4 heteroatoms each independently selected from N, O and S;R1a, R1b, and R1c are each independently hydrogen, halo, hydroxyl, cyano, nitro, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C0-C3alkylC3-C6 cycloalkyl, C1-C6haloalkoxy, —C(O)NH2, —SF5, or —S(O)pR;R2 is halo, cyano, C1-C6alkyl, C1-C6haloalkyl, nitro, hydroxyl, —C(O)NRaRb, C2-C6alkenyl, C2-C6alkynyl, —S(O)pR, or —OR;R3 is hydrogen, halo, hydroxyl, cyano, C1-C6alkyl, C1-C6haloalkyl, C0-C3alkylC3-C6cycloalkyl, —C(O)NH2, nitro, —SC(O)R, —C(O)NRaRb, C0-C3alkylNRaR4, —NRaNRbR4, —NRaORb, —ONRaRb, N3, —NHR4, —OR, or —S(O)pR;R4 is hydrogen, C1-C6alkyl, C0-C6alkylC3-C6cycloalkyl, —C(O)R5, —C(S)R5, —C(O)NRaR5, —C(O)C(O)NRaR5, —S(O)pRc, —S(O)2NRaR5, —C(NR7)R5, —C(NR7)NRaR5, C0-C6alkylphenyl, C0-C6alkylheteroaryl, or C0-C6alkylheterocycle;R5 is hydrogen, C1-C6alkyl, C2-C6alkenyl, C0-C6alkylC3-C6cycloalkyl, C0-C6alkylphenyl, C0-C6alkylheteroaryl, or C0-C6alkyl heterocycle;R6 is cyano, C1-C6haloalkyl, —C(O)NRaRb, C2-C6alkenyl, C2-C6alkynyl, C2-C6haloalkenyl, or C2-C6haloalkynyl;R7 is hydrogen, C1-C6alkyl, hydroxyl, cyano, nitro, —S(O)pRc, or C1-C6alkoxy;R is C1-C6alkyl or C3-C6cycloalkyl each optionally substituted by at least one halo;Ra is hydrogen, C1-C6alkyl, or C0-C3alkylC3-C6cycloalkyl; wherein the alkyl and alkylcycloalkyl is optionally substituted by cyano or at least one halo substituent;Rb is hydrogen, C1-C6alkyl, C3-C6cycloalkyl, C0-C3alkylphenyl, C0-C3alkylheteroaryl, or C0-C3alkylheterocycle, each optionally substituted, where chemically possible, with at least one substituent selected from hydroxyl, cyano, halo, or —S(O)pR;Rc is C1-C6alkyl, C1-C6haloalkyl, C1-C6haloalkylC3-C6cycloalkyl, C0-C3alkylC3-C6cycloalkyl, C0-C3alkylphenyl, C0-C3alkylheteroaryl, or C0-C3alkylheterocycle each optionally substituted with at least one substituent selected from cyano, halo, hydroxyl, oxo, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6haloalkyl, —S(O)pR, —SH, —S(O)pNRaRb, —NRaRb, —NRaC(O)Rb, —SC(O)Rb, —SCN, or —C(O)NRaRb;each of R4 and R5 C1-C6alkyl or C0-C6alkylC3-C6cycloalkyl can be optionally and independently substituted by at least one substituent selected from C1-C6alkyl, C1-C6hydroxyalkyl, cyano, halo, hydroxyl, oxo, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6haloalkyl, —S(O)pRc, —SH, —S(O)pNRaRb, —NRaRb, —NRaC(O)Rb, —SC(O)Rb, —SCN, or —C(O)NRaRb; andwherein R4 and R5 C0-C6alkylphenyl, C0-C6alkylheteroaryl, or C0-C6alkylheterocycle moiety can be further optionally substituted with at least one substituent selected from C1-C6alkyl, C1-C6hydroxyalkyl, cyano, halo, oxo, ═S, ═NR7, hydroxyl, C1-C6alkoxy, C1-C6alkyl, C1-C6haloalkyl, —SH, —S(O)pR, and C1-C6haloalkoxy;n is the integer 0, 1, or 2, and when n is 2, each R2 may be identical or different from each other; andp is the integer 0, 1, or 2; stereoisomers thereof, and pharmaceutically or veterinarily acceptable salts thereof.