No abstract

L-692,585 is a 2-hydroxypropyl derivative of L-692,429, both novel non-peptidyl growth hormone (GH) secretagogues. The effects of single and repeated intravenous administration of L-692,585 on serum or plasma GH and other hormones in beagles were evaluated. In a balanced 8-dog dose-ranging study, compared to the saline control with a mean (+/- S.E.M.) after-dose serum GH peak of 6.1 +/- 1.3 ng/ml, L-692,585 significantly increased (P < 0.05) peak GH concentrations 4.3-fold (32.5 +/- 7.0 ng/ml) at a dose of 0.005 mg/kg, 7-fold (49.4 +/- 10.6 ng/ml) at a dose of 0.02 mg/kg, and 21-fold (134.3 +/- 29.0 ng/ml) at a dose of 0.10 mg/kg. Total GH release, expressed as area under the curve, showed a similar dose-dependent increase. Peak GH levels were recorded at 5 or 15 min after dosing with the levels returning to near baseline by 90 min. Serum cortisol levels were increased above saline control levels in a dose-dependent manner; however, the increases were modest compared to the GH increases. Based on peak responses and total GH release, L-692,585 was 10- to 20-fold and 2- to 2.5-fold more potent than L-692,429 and the growth hormone releasing peptide, GHRP-6, respectively. When L-692,585 was administered once daily for 14 consecutive days at 0, 0.01 or 0.10 mg/kg to each of 6 dogs, peak plasma GH levels and total GH release on days 1, 8 and 15 significantly increased in a dose-dependent manner, and no desensitization was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

4-Chlorobenzaldehyde 1-(4-chlorophenyl)-4(1H)-pyridinylidene hydrazone fluorusulfonate (4) was found to have excellent anticoccidial activity in chickens. The synthesis and biological evaluation of related analogues are presented. Presumably 4 shares a common mechanism of action with robenidine (25) since it was not active on a robenidine tolerant strain of E. tenella. Structural comparisons of the two molecules are presented.

A 11e1v application of the \Vittig reaction to the preparation of olefins of low molecular weight which allows selective labelling in the vinyl or allyl positions with isotopes of hydrogen and carbon has been developed. Using the modification of the Wittig reaction introduced by E. J. Corey, in which a solution of the methylsulfinyl carbanion in dimethyl sulfoxide serves as the base, a series of olefins from Cz to Cs were synthesized. The synthesis \\,as applied to the preparation of the following labelled compounds: 5-methylene-14C-bicyclo[2.2.1]hept-2-e~ie; propene-1-l"C; 1-butene-1-14C; propene-1-dl; 2-methylpropene-1,l-d!; 2-methyl-d3-propene-3,3,3-d3; 2-methyl-2-butene-4,4,4-d3; 2-methyl-d3-2-butei1e-l,l,l-d3; methylene-d2-cyclohexane.