Quantitative structure-activity relationships for 2-[(phenylmethyl)sulfonyl]pyridine 1-oxide herbicides.

Phenyl-substituted analogues of 2-[(phenylmethyl)sulfonyl]pyridine 1-oxide preemergent herbicides were examined in order to determine quantitative relationships between structure and activity against the following three weed species: switch grass (Panicum virgatum L.), barnyard grass (Echinochloa crusgalli L. Beauv.), and green foxtail (Setaria viridis L. Beauv.). Analogues were chosen to provide maximum parameter orthogonality. Regression analysis yielded structure-activity relationships wherein the most significant substituent parameters associated with herbicidal activity were found to be the partition coefficient (pi), the molar refractivity (MR), and two indicator variables, Z (denoting the presence of an alpha-methyl group) and H (denoting an ortho substituent capable of hydrogen bonding). For green foxtail, the structure-activity relationship was found to be: -log ED50 = 0.43 pi -0.052MR + 0.50H + 0.24Z + 0.61, where ED50 is expressed in moles per acre. The regression equations were found to explain 79-93% of the bioactivity for the three weed species studied. It was further shown that these equations represent the best possible correlations within the limitations of the biological data.

Synthesis and antibacterial and anticancer evaluations of alpha-methylene-gamma-butyrolactones.

Nine new alpha-methylene-gamma-butyrolactones were synthesized by the Reformatsky condensation of ethyl alpha-bromomethylacrylate with ketones, aldehydes, and an epoxide. A unique spirobutyrolactone class was prepared by reaction of the zinc alkyl derivative and N-methylisatins. The compounds were evaluated against L-1210 and P-388 leukemia and the 9KB carcinoma of the nasopharynx. They also were screened in a microbiocidal and an antifungal assay. The spiro methylene lactone of 5-iodo-N-methylisatin displayed activity in the P-388, 9KB, and antifungal screens.

Antilipidemic activity of 4-oxo-functionalized ethyl 6-chlorochroman-2-carboxylate analogs and a related tricyclic lactone in three rat models.

The synthesis of ethyl cis-6-chloro-4-hydroxychroman-2-carboxylate (IV) and 6-chloro-4-hydroxy-chroman-2-carboxylic acid lactone (V) are reported. The antilipidemic properties of these compounds in 3 rat models were compared to the activity obtained for the previously synthesized related analogs ethyl 6-chlorochroman-2-carboxylate (II), ethyl 6-chlorochromanone-2-carboxylate (III) and clofibrate (I). The biologically most interesting analog, ethyl 6-chlorochroman-2-carboyxlate (II) like clofibrate (I), was an effective antitriglyceridemic and anticholesterolemic agent in Triton WR-1339 hyperlipidemic rats, sucrose-fed hyperlipidemic rats and chow-fed normolipemic rats. Ethyl 6-chlorochromanone-2-carboxylate (III) was found to be active after 7 days of administration to sucrose-fed rats. In sucrose-fed, male Sprague-Dawley rats, the comparative effects of these analogs on various hepatic drug parameters also were carried out. Consistent with previous findings, results obtained with these compounds provide evidence showing that changes in hepatic HMG-CoA reductase activity bear no relationship to serum cholesterol lowering in the sucrose-fed model.

3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities.

The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series.