Hz). l,4,6-Triphenylpyridinium-2-carboxylate (11). 2-(Ethoxycarbonyl)-1,4,6-triphenylpyridinium tetrailuoroborate (8a; 5 g, 10.7 mmol) was stirred at 25 °C as a suspension in aqueous NaOH (0.5 N, 25 mL, 12.5 mmol) for 24 h. The white solid was filtered off and washed with water (500 mL) and ether (50 mL) to give the betaine as microcrystals: 3.2 g (85%); mp 150 °C dec (satisfactory analysis not obtained due to decomposition on attempted recrystallization); IR (CHBr3) 1650 (s), 1618 (s) cm"1; NMR (CDC13/TFA) 7.S-7.9 (m, 15 ), 8.10 (d, 1 H, J = 2 Hz), 8.38 (d, 1 H, J = 2 Hz).1,2,4-Triphenylpyridinium iodide (13) was obtained by refluxing 1,4,6-triphenylpyridinium-2-carboxylate (11) (2 g, 5.7 mmol) with aqueous HI (65%, 1.20 g, 6.1 mmol) in THF (50 mL)for 4 h to yield yellow crystals (washed with ether). Recrystallization from absolute EtOH gave yellow needles: 2.1 g (85%); mp 273-274 °C; IR (CHBr3) 1630 cm"1; NMR (CDC13/TFA) 7.6-7.9 (m, 15 ), 8.

Magnetic microsphere-methoxtrexate (MM-MTX) conjugates prepared by several different methods were analyzed for their suitability for in vivo use. MM-MTX were prepared by the following methods: (A) reaction of MTX with poly(ethylene glycol) 1500 (PEG) to form a poly(ethylene glycol)-methotrexate conjugate (PEGMTX) which was then added to a ferrous/ferric ion salt solution to give MM-MTX I; (B) reaction of ferrous/ferric ion salts with PEG to give a ferromagnetic polymer complex which was then coupled with MTX to give MM-MTX II; (C) MM-MTX IIIA were prepared by reacting MTX with amino-terminated magnetic microspheres, commercially available, in the presence of 1-ethyl-3,3-bis(methylamino)propylcarbodiimide (EDCI); (D) reaction of aminohexanol with di-tert-butyl dicarbonate to form an [N-(tert-butoxycarbonyl)amino]hexanol (t-Boc-AH), which was then coupled with MTX in the presence of 1,3-dicyclohexylcarbodiimide and 4-pyrrolidinopyridine to give a t-Boc-AH-MTX conjugate, which was then saturated with hydrogen chloride to give an aminohexanol-methotrexate (AH-MTX) conjugate. MM-MTX IIIB were then prepared by reacting AH-MTX with carboxyl-terminated magnetic microspheres, commercially available, in the presence of EDCI and 4-(dimethylamino)pyridine. The identity of MTX conjugates was confirmed using ultraviolet, infrared, and nuclear magnetic resonance spectroscopy. Drug content of the magnetic microsphere-methotrexate conjugates as determined by HPLC was 0.45% (w/w), 4.0% (w/w), and 6.3% (w/w) MTX for MM-MTX I, MM-MTX II, and MM-MTX IIIB, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In view of the antitumor activity reported for 7,8-dimethylbenzo[b]azepine-2,5-dione, new isosteric thieno[2,3-b]-azepin-4-ones have been prepared by a Dieckmann ring closure reaction. Substituted 2-amino-3-carbethoxythiophenes were tosylated, or benzoylated, and the corresponding sodium salt was alkylated with ethyl 4-bromobutyrate. The resulting product was cyclized in the presence of sodium hydride, and the azepinones were detosylated with 40% sulfuric acid-acetic acid solution. Preliminary biological data do not indicate any siginificant antineoplastic activity.

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Twenty-three substituted 3,4-dihydro-4-oxoquinazolines or 3,4-dihydro-4-oxoazaquinazolines have been synthesized utilizing 2-amino-3-cyano-4,5-dimethylfuran and methyl acrylate as precursors for synthesis of the required substituted anthranilates. Six additional azaquinazolones were synthesized from 2-aminonicotinic or 3-aminopicolinic acid for comparison studies. All compounds were evaluated in mice with the maximal electroshock (MES) seizure and pentylenetetrazol (sc Met) seizure threshold tests for potential anticonvulsant activity and in the rotorod test to evaluate neurotoxicity. Nine of the twenty-nine compounds in the series demonstrated anticonvulsant action. The azaquinazolones were found to possess the most significant activity.