N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives with heterocyclic substitutions as potent and broad spectrum anticoccidial agents.

Diaryl-(4-piperidinyl)-pyrrole derivatives bearing cyclic amine substituents have been synthesized and evaluated as anticoccidial agents. Improvements in potency of Et-PKG inhibition, such as azetidine derivative 3a, and broad spectrum anticoccidial activities in feed, such as morpholine derivative 8c, have been achieved.

Isolation, structure, and coccidiostat activity of coccidiostatin A.

Coccidiosis is one of the more common and costly diseases in poultry that is caused by various Eimeria species. In our quest to discover coccidiostats from natural products, we discovered a microbial fermentation extract that exhibited in vivo anticoccidial activity. Fractionation of this extract led to the discovery of two potent antiprotozoals, emecorrugatin A (1) and coccidiostatin A (2).

Hydroxylated N-alkyl-4-piperidinyl-2,3-diarylpyrrole derivatives as potent broad-spectrum anticoccidial agents.

Diaryl-(4-piperidinyl)-pyrrole derivatives bearing hydroxylated N-alkyl substituents have been synthesized and evaluated as anticoccidial agents. High potency in Et-PKG inhibition and broad-spectrum anticoccidial activities have been observed on compounds, such as 4b and 5h, which are fully efficacious in vivo at 50 ppm in feed.

Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal alpha-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities.

Apicidins are a class of cyclic tetrapeptides that do not contain the classical electrophilic alpha-keto epoxide yet are potent (nM) inhibitors of histone deacetylase and antiprotozoal agents. These compounds showed broad-spectrum activities against the apicomplexan family of protozoa including Plasmodium sp (malarial parasite), Toxoplasma gondii, Cryptosporidium sp., and Eimeria sp.

Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target.

The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (Compound 1) inhibits the growth of Eimeria spp. both in vitro and in vivo. The molecular target of Compound 1 was identified as cGMP-dependent protein kinase (PKG) using a tritiated analogue to purify a approximately 120-kDa protein from lysates of Eimeria tenella.