1. Compounds 2 and 3 (2,3,6-trisubstituted clonidine-like 2-(phenylimino)imidazolidines) and clonidine were studied for their hypotensive activity in pentobarbital-anesthetized normotensive rats and chloralose-anesthetized cats. Upon intravenous administration to rats, compound 2 was approximately 3 times more potent than clonidine in decreasing mean arterial pressure, while compound 3 had comparable activity. Via vertebral artery infusion in cats, compound 2 was also ~3 times more effective than clonidine, and compound 3 was less active. The results show that introducing a third meta substituent in 2,6-disubstituted analogs does not hamper hypotensive activity, and compound 2 is the most effective clonidine-like imidazolidine reported so far, possibly due to better lipophilicity. 2,3,6-trisubstituted derivatives show potential for pronounced hypotensive activity following systemic administration and need further exploration of phenyl ring substituents. 2. Based on the hypothesis that hybrid antibiotics derived from chloramphenicol (la) and sparsomycin (1c) could inhibit ribosomal peptide synthesis, sparsophenicol (lb) was synthesized by coupling chloramphenicol base with a mixed anhydride of (E)-1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidineacrylic acid. Sparsophenicol is a strong inhibitor of N-acetyl-L-phenylalanylpuromycin formation from the N-acetyl-L-phenylalanyl tRNA-70s Escherichia coli ribosome-poly(U) complex and puromycin, competitively at lower concentrations and uncompetitively at higher concentrations. It lacks antimicrobial activity (minimal inhibitory concentrations >100 mg/mL for E. coli) and in vitro antitumor activity (no inhibition of murine leukemia L1210 cells), likely due to poor microbial and cell membrane penetration. Sparsophenicol exhibits properties distinctive from both chloramphenicol and sparsomycin. 3. A new series of non-μ opioid analgesics (benzeneacetamide amines) that do not have morphine-like behavioral effects or narcotic antagonist activity is reported. The prototype compound 9 (pyrrolidine benzeneacetamide) has analgesic activity in mice (tail-flick ED50 = 16 mg/kg orally), which is antagonized by the opioid antagonist naloxone, indicating opioid activity. It lacks μ receptor-related behaviors (e.g., Straub tail, arched back) but is structurally similar to potent μ agonists. Extensive biological evaluation suggests it is a highly selective agonist for the κ opioid receptor, which may be a useful tool for delineating the functions of κ receptors. The benzeneacetamide amines may prove to be useful analgesics lacking many of the undesirable properties of morphine and benzomorphans.