Synthesis of gem-difluoro-avermectin derivatives: potent anthelmintic and anticonvulsant agents

P T Meinke; W L Shoop; B F Michael; T A Blizzard; G R Dawson; M H Fisher; H Mrozik

doi:10.1016/s0960-894x(98)00674-x

Synthesis of gem-difluoro-avermectin derivatives: potent anthelmintic and anticonvulsant agents

Bioorg Med Chem Lett. 1998 Dec 15;8(24):3643-6. doi: 10.1016/s0960-894x(98)00674-x.

Authors

P T Meinke¹, W L Shoop, B F Michael, T A Blizzard, G R Dawson, M H Fisher, H Mrozik

Affiliation

¹ Merck Research Laboratories, Department of Medicinal Chemistry, Rahway, NJ 07065-0900, USA.

PMID: 9934486
DOI: 10.1016/s0960-894x(98)00674-x

Abstract

A series of gem-difluoro-avermectin derivatives was synthesized from the corresponding ketones at positions 4", 4', 13, and 23 using diethylaminosulfur trifluoride (DAST). These fluorinated avermectins exhibit potent antiparasitic activity in a new Haemonchus contortus larval assay and are equipotent to ivermectin. In addition, 23-gem-difluoro-ivermectin displays useful anticonvulsant activity in mouse models.

MeSH terms

Animals
Anthelmintics / chemical synthesis*
Anthelmintics / therapeutic use
Anticonvulsants / chemical synthesis*
Anticonvulsants / therapeutic use
Epilepsy / drug therapy
Ivermectin / analogs & derivatives*
Ivermectin / chemical synthesis
Ivermectin / chemistry
Ivermectin / therapeutic use
Mice
Molecular Structure

Substances

Anthelmintics
Anticonvulsants
Ivermectin
avermectin