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A convenient synthesis of a series of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones (IV), which are 7-thioisosteres of 4-amino-3-chloroangelicins, was accomplished via dehydrochlorination and dehydrogenation of the 1,4-cycloadducts obtained by reaction of dichloroketene with N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo-[b]thiophen-4(5H)-ones . Some aspects of the photobiological activity of these thioangelicins were studied; three of them (IV a, e, f) appeared to inhibit DNA synthesis in Ehrlich ascites tumor cells. The most active compound, namely 3-chloro-4-morpholino-7-thioangelicin (IV e), afforded 70% of the antiproliferative effect of 8-MOP, but unlike this reference compound was unable to induce erythema on guinea pig skin. However, compounds (IV a, f) produced a slight erythema, thus suggesting that a relationship between antiproliferative and phototoxic effects does not exist.

A series of title compounds were synthesized starting from heterocyclic alpha-hydroxymethyleneketones and 1,1'-carbonyldiimidazole and tested against gram-positive and gram-negative bacteria, as well as fungi. 7,8-Dihydro-6-(1H-imidazol-1-ylmethylene)-2-phenylquinazolin -5(6H)-one showed a remarkable activity against Candida krusei.

The synthesis of a series of new N,N-disubstituted 4-amino-3-chloroangelicins (4-amino-3-chloro-2H-furo[2,3-h]-1-benzopyran-2-ones) starting from N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]furan-4(5H)-ones is described. Their capacity of inhibiting DNA synthesis in Ehrlich ascites tumor cells by U.V.-A light irradiation as well as their phototoxic activity on guinea-pig skin have been studied and the data computed by probit analysis; the results are discussed in the light of the modifications introduced in the molecular structure.

The synthesis of [(1-phenyl-1H-indazol-4-yl)oxy]acetic acid (IV), (1-phenyl-1H-indazol-4-yl)acetic acid (IX) and (1,5,6,7)tetrahydro-1-phenyl-4H-indazol-4-iminooxy)acetic acid (XIII) starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one (I) is described. These compounds showed a good antiinflammatory activity in rats, and an analgesic activity in mice similar or comparable to that of indomethacin.

The 1,4-cycloaddition of dichloroketene to N,N-disubstituted 6-aminomethylene-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones afforded N,N-disubstituted 4-amino-3,3-dichloro-3,4,10,11-tetrahydro-5H-benzo[5,6]cyclohepta[2,1-b]pyran-2-ones only in the case of full or partial aromatic N-substitution. The relative adducts gave N,N-disubstituted 4-amino-3-chloro-10,11-dihydro-5H-benzo[5,6]cyclohepta[2,1-b]pyran-2-ones by dehydrochlorination. The 1,4-cycloaddition with sulfene occurred readily in the case of both aliphatic and aromatic N-substitution to give N,N-disubstituted 4-amino-3,4,10,11-tetrahydro-5H-benzo[5,6]cyclohepta[1,2-e]-1,2-oxathiin-2,2-dioxides. These compounds, as well as the pyran derivatives, can be considered as linear heterocyclic analogues of the Amitriptyline ring system.

The reaction of N,N-disubstituted open-chain and cyclohexane alpha-aminomethyleneketones (I) and (II) with p-toluenesulfonyl (tosyl) isocyanate gave amino-disubstituted 2-acyl-3-amino-N-tosylpropenamides (III) and/or N,N-(3-amino-1-alkyl-2-propenylidene) and N,N-[2-(aminomethylene)-cyclohexylidene] tosylamides (IV) and (V), the final product being related to the carbon and nitrogen substituents of the enaminone. The evaluation of the hypoglycemic activity concerning some of the above compounds gave no interesting results.

The synthesis of 1-phenyl- and 1-methyl-5-dialkylamino-methyl-1,5,6,7-tetrahydroindazol-4-ones (III) and (IV) by Mannich reaction of the corresponding 1-substituted 1,5,6,7-tetrahydroindazol-4-ones (I) and (II) is described. Some compounds (III) showed a good antiinflammatory and analgesic activity in rats and mice, respectively. Infiltration anesthesia in mice and antiacetylcholine activity in vitro are also reported.