Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.

Wound bursting strength analysis, combined with techniques aimed at elucidating changes at the molecular level, provides a useful tool for the study of factors that impair healing and potential treatments for resulting healing deficits.

A gram-negative bacterium isolated from activated sludge was able to utilize up to 25 mM phosphonoacetate as the sole carbon and phosphorus source, with simultaneous excretion of virtually equimolar levels of phosphate. 2-Aminoethylphosphonate was similarly utilized with equivalent growth rates and cellular yields, while 3aminopropyl-, 4-aminobutyl-, methyl-, ethyl-, and phenylphosphonates served only as phosphorus sources.

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A series of 5-(piperidinylethyloxy)quinoline 5-hydroxytryptamine(1D) (5-HT(1D)) receptor antagonists have been discovered from elaboration of the series of dual 5-hydroxytryptamine(1)-selective serotonin reuptake inhibitors (5HT(1)-SSRIs) reported previously. This is the first report of highly potent, selective antagonists for the 5-HT(1D) receptor, which represents an extremely useful set of pharmacological tools for further understanding the roles of the 5-HT(1) receptor subtypes.

A series of analogues of the larvicide tenuazonic acid [3‐acetyl‐5‐(l‐methylpropyl)‐pyrrolidine‐2,4‐dione] was prepared in an attempt to increase its activity and breadth of spectrum. Substitution brought about some changes in specificity, the greatest improvement being obtained with chlorophenyl substituents.

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