Remington’s Pharmaceutical Sciences.

Abstract

(m,4H, aromatic) ppm. The spectra of XI1 and XI11 showed a singlet a t 6 3.60 ppm that integrated for 5 protons (aryl CHz and aryl OCH3). Aryl-substituted 5 4 1-Amino-2-phenylethy1)tetrazoles XV-XXI1)-Compounds XV-XX and XXII were prepared by a previously reported method (6). Compound XXI was prepared by modification of a previously reported method (9). A mixture of compound XX (3.0 g, 0.014 mole) in 48% hydrogen bromide (50 ml) was heated at reflux under nitrogen for 4 hr. The mixture was concentrated under reduced pressure. The residue was dissolved in distilled water and the pH was adjusted to 7 with concentrated ammonium hydroxide. After standing a t room temperature for 12 hr, the product was filtered, air dried, and recrystal-lized from N,N-dimethylformamide, 2.2 g (76.6%), mp 290' dec. Table I11 contains physical and chemical data for XV-XXII. Assignments of the common NMR absorption peaks are (10% sodium deuteroxide): 6 2.95-3.10 (m, 2H, aryl CH2), 4.30-4.50 (m, lH, CCH), and 6.70-7.20 (m, 4H, aromatic) ppm. There was an additional absorption peak for XIX and XX at 6 3.40 (s, 3H, aryl OCHj) ppm. Anticancer Screening-The tetrazole analogs of substituted phen-ylalanines were screened for anticancer activity2 using P-388 lymphocytic leukemia cells in mice of either sex. On day zero, mice were inoculated intraperitoneally with 106 leukemic cells. Twenty-four hours later, a test compound was administered intraperitoneally once daily for the first 9 days or in three injections on every 4th day (XVI, XXIII). The test results were recorded on the 30th day. RESULTS AND DISCUSSIONS All compounds were tested for antileukemic activity at doses of 25,50, 100, and 200 mg/kg (some in triplicate). For compounds XVI, XVIII, and XIX, the T/C% was near or greater than 125. For all other compounds, the T/C% was < 125 (all mice died when compounds XX and XXIII were administered at 200 mg/kg). Compounds XVI, XVIII, and XIX were retested a t 400 mg/kg (in duplicate) and exhibited a T/C% < 125. None of the compounds exhibited significant antileukemic activity. Abstract 0 Pilocarpine, isopilocarpine, pilocarpic acid, and isopilocarpic acid can be measured effectively by high-performance liquid chromatography (HPLC). Previous reports have differed on the degree of contamination of commercial pilocarpine preparations with isopilocarpine and pilocarpic acid. This report describes a study of commercial pilo-carpine in which no significant contamination was found. Keyphrases 0 Pilocarpine-analysis of commercial preparations by high-performance liquid chromatography 0 High-performance liquid chromatography-analysis of commercial pilocarpine Ocular agents-pilocarpine, analysis by high-performance liquid chromatography