New potential immunoenhancing compounds. Synthesis and pharmacological evaluation of new long-chain 2-amido-2-deoxy-D-glucose derivatives.

A series of long-chain fatty acids and the corresponding 2-hydroxy, 2-oxo, 3-hydroxy acid glucosamides were evaluated as immunomodulating compounds. In a preliminary screening, 2-[(2-ethoxycarbonyloxy)tetradecanoylamino]-2-deoxy-D-glucos e (2b) and 2-(3-hydroxydodecanoylamino)-2-deoxy-D-glucose (5a) resulted to be the most effective in enhancing the glucosamine activity. The findings of in vitro-ex vivo tests (unidirectional mixed lymphocyte culture reaction and primary antibody production) and in vivo tests (delayed type hypersensitivity, protection against bacterial or fungal infection and against Sarcoma 180 or Lewis lung carcinoma transplants) were very encouraging and allowed to assume for the two substances a protective activity, presumably through the ability of activating phagocytic and NK cells.

Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins.

A series of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins 1a-h was prepared. Whenever possible, E and Z isomers were isolated, and their relative stabilities and their interconversions were tested. The antibacterial activity was tested against Gram-positive and Gram-negative bacteria. For compound 1c, whose Z and E forms do not interconvert rapidly, the Z form was the more active one. Among the other compounds, for which the E form is the only stable one for practical purposes, compound 1a was the most active. When compared with cefuroxime and cefotaxime, compound 1a showed slightly lower antibacterial activity but good serum level and half-life values.

Chemical modifications in the tetracycline series.

New tetracycline analogs modified at position 5, 6 and 2 were synthetized. The 5-deoxy-5-oxo-derivatives, 2a and 3a, were obtained by DMSO/acetic anhydride oxidation of doxycycline (2) and methacycline (3), respectively; the 6-demethyl-6-hydroxymethyl-6-alpha-hydroxyoxytetracycline (3b) by methacycline oxidation with the KCIO3/OsO4 system and the 6-hydroxyanhydrooxytetracycline (4) treating 3b with periodic acid. The 2-ethoxycarbonyl-2-decarboxamidodoxycycline (2b), was synthesized by treating doxycycline nitrile (2c) with EtOH and anhydrous HCl, 2-thiocarboxamide-2-decarboxamidodoxycycline (2d) by reaction of doxycycline with P2S5 in dioxane and 2-aminomethyl-2-decarboxamidodoxycycline (2e) by RANEY-Nickel reduction of 2d. All the synthetized compounds proved to be almost inactive on agar plates both on Gram-positive and Gram-negative bacteria.

Synthesis and antibacterial activity of some ureido cephalexin and cefadroxil derivatives.

The antibacterial activity of some ureido, acylureido and carbamoylureido derivatives of cephalexin and cefadroxil, prepared in our laboratories, as compared to parent compounds is reported. Only the 7-[D-alpha-(imidazolidin-2-one-1-ylcarbonylamino)-alpha-phenylacetamido]-3-methyl-3-cephem-4-carboxylic acid (IV d) and the 7-[D-alpha-(imidazolidin-2-one-1-ylcarbonylamino)-alpha-p-hydroxyphenylacetamido]-3-methyl-3-cephem-4-carboxylic acid (V c) showed some antibiotic activity. However we found no activity improvement against Pseudomonas strains (contrary to the results obtained in similar penicillin derivatives) and a lower beta-lactamase resistance.