The synthesis of a series of halogenated 1-benzylindazole-3-carboxylic acids and related derivatives is described. These compounds were studied for their effect on testicular weight and on the inhibition of spermatogenesis. Many of the derivatives, but in particular 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (11), 1-(2,4-dibromobenzyl)-1H-indazole-3-carboxylic acid (13), 1-(4-chloro-2-methylbenzyl)-1H-indazole-3-carboxylic acid (27), and their glycerol esters, showed potent antispermatogenic activity.

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A Practical Regioselective Synthesis of ω-Functionalized, Long-Chain 2,3-Dialkylindoles.-In connection with a research on antithrombotic drugs large-scale laboratory preparations are needed for (I) and (II) starting from inexpensive materials. Several routes, described in the literature, are compared. The method of choice, being versatile and of general applicability for indoles of this type, is shown for the example of ( II). The procedure can be scaled up if iPr2O is used instead of Et2O in conversions of type (V) → (VII) and gives (I) in an amount sufficient for its pharmacological and toxilogical evaluation. -(ARCARI, M.; AVETA, R.; BRANDT, A.; CEC-CHETELLI, L.; CORSI, G. B.; DI RELLA, M.; Gazz. Chim. Ital. 121 (1991) 11, 499-504; Lab. Ric. Ist.

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 KCIO3/0s04 system and the 6-hydroxyanhydrooxytetracycline (4) treating 3b with periodic acid.The 2-ethoxycarbonyl-2-decarboxamidodoxycycline (2b), was synthetized by treating doxycycline nitrile (2c) with EtOH and anhydrous HCI, 2-thiocarboxamide-2-decarboxamidodoxycycline (2d) by reaction of doxycycline with P2Sg 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.Tetracycline antibiotics continue also today to play an important role in human and veterinary medicine and in animal nutrition.The greatest success in the development of new active tetracycline has been up to now obtained by modifications at the position 6. The position 5 also seems not very critical for antimicrobial activity influencing mainly the pharmacokinetics properties1.2).During a research program aimed at finding new and possibly clinically useful tetracycline derivatives, our synthetic efforts followed mainly two routes: on one side we took up the synthesis of some new derivatives (compounds 2a, 3a, 3b, 4) modified at position 5 and 6 starting from the easily available, acid stable doxycycline (2) and methacycline (3) and, on the other side, we paid also our attention to modifications at position 2.From structure-activity relationships studies it is in fact shown that only a carbonyl substituent at position 2 and not the whole carboxamide group is essential for maintenance of activity: the nitrile (1a)3) has no activity but derivatives bearing at the 2 positions an aldehyde (1b)4), aldimine (1c)5) or acetyl (1d)6) group retain a certain degree of antimicrobial activity.It seemed therefore interesting'), in order to define the role of the C-2 carboxamidic group, to synthetize new C-2 derivatives, namely the 2-ethoxycarbonyl (2b), the 2-thiocarboxamide (2d), the 2-aminomethyl (2e) and the 2-N-methylaminomethyl doxycycline.