Synthesis and biological activity of anthelmintic thiadiazoles using an AF-2 receptor binding assay

B H Lee; F E Dutton; M F Clothier; J W Bowman; J P Davis; S S Johnson; E M Thomas; M R Zantello; E W Zinser; J C McGuire; D P Thompson; T G Geary

doi:10.1016/s0960-894x(99)00267-x

Synthesis and biological activity of anthelmintic thiadiazoles using an AF-2 receptor binding assay

Bioorg Med Chem Lett. 1999 Jun 21;9(12):1727-32. doi: 10.1016/s0960-894x(99)00267-x.

Authors

B H Lee¹, F E Dutton, M F Clothier, J W Bowman, J P Davis, S S Johnson, E M Thomas, M R Zantello, E W Zinser, J C McGuire, D P Thompson, T G Geary

Affiliation

¹ Animal Health Discovery Research, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49001, USA.

PMID: 10397509
DOI: 10.1016/s0960-894x(99)00267-x

Abstract

Following our discovery of the strong binding of thiadiazole 1 to the AF-2 neuropeptide receptor of gastrointestinal nematodes (e.g., Ascaris suum), we prepared two series of analogs. Only the series containing the thiadiazole ring had potencies comparable to that of compound 1. Analog 50 exhibited an apparent potency in the AF-2 binding assay 300 times that of compound 1.

MeSH terms

Animals
Anthelmintics / chemical synthesis*
Anthelmintics / chemistry
Anthelmintics / pharmacology
Ascaris suum
Caenorhabditis elegans / drug effects
Caenorhabditis elegans / physiology
Helminth Proteins / drug effects
Helminth Proteins / metabolism*
Neuropeptides / drug effects
Neuropeptides / metabolism*
Structure-Activity Relationship
Thiadiazoles / chemical synthesis*
Thiadiazoles / chemistry
Thiadiazoles / pharmacology

Substances

Anthelmintics
Helminth Proteins
Neuropeptides
Thiadiazoles
AF2 neuropeptide