Synthesis of new derivatives of 2,3-dihydro-7-benzo[b]furanol with potential pharmacological activity

A series of 13 new ether-linked derivatives of 2,2-dimethyl-2.3-dihydro-7-benzofuranol have been designed and synthesized. Seven of them were evaluated for anti-HIV potency. They showed a relatively high cytotoxicity and a low anti-HIV- I activity.     

Synthesis and pharmacological activity of some 2,3-dihydro-1,4-benzodioxin and 1,3-benzodioxol derivatives, as cyclic analogs of isoxsuprine

A few analogs of the isoxsuprine drug with the phenoxyethyl group incorporated into the heterocyclic 2,3-dihydro-1,4-benzodioxin or 1,3-benzodioxol ring have been synthesized. Among these compounds, the benzodioxol derivative (I e) has been found to possess hypotensive activity in rats in the same range as isoxsuprine, with no alpha-adrenolytic and central sedative properties. Cardiovascular studies in dogs have shown that (I e) is less potent than isoxsuprine, although its activity is longer-lasting at an equally hypotensive dose.     

Synthesis and pharmacological study of 7-phenyl-1,4-diazepin-5-one and its derivatives]

We studied the synthesis and psychotropic activity of the 7-phenyl-1,4-diazepin-5-one and derivatives. It can be conclude that these products have sedative, myorelaxant and anxiolytic actions. The toxicity study demonstrated that two diazepines are non-toxic at therapeutic dosages but that a third compound is very toxic.     

Antiphlogistic 2,3-dihydro-1H-pyrrolizines. 5. Synthesis of 3-(6,7-diphenyl-2,3-dihydro-1H-pyrrolizin-5-yl)-propionic acid

Antiinflammatory 2,3-Dihydro-1H-pyrrolizines, V: Syntheses of 3-(2,3-Dihydro-6,7-diphenyl-1H-pyrrolizin-5-yl)propionic Acid. Vinylation of DADHP 1 to yield 2 was achieved with dimethyl(methoxymethylene)malonate. The title compound 5 was prepared by hydrogenation of 2 followed by hydrolysis and decarboxylation.     

Synthesis of 4-(2,4-dioxo-5-pyrimidyl)-1,4-dihydropyridine derivatives

Hantzsch synthesis of 5-formyluracil (1), methyl acetoacetate (2) and methyl 3-aminocrotonate (3) gave 2,6-dimethyl-4-(2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3, 5-dicarboxylic acid dimethylester (4a) in 54.6% yield. As the same procedure, 1,3-dimethyl-5-formyl-uracil (6) gave 2,6-dimethyl-4-(1,3-dimethyl-2,4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (7a) in 52.2% yield.4a was methylated to afford7a also in 52% yield.     

Synthesis and cytostatic effect of 2-phenyl-3-alkyl(aryl)-2,3-dihydro-1,3,2(lambda-5)- benzoxazaphosphorine-4-one derivatives]

Preparation of 2,3-dihydro-1,3,2-benzoxazaphosphorin-4-one derivatives and their 2-oxo derivatives is described. Compounds 1 and 12 have anticancer activity.     

Synthesis and evaluation of antileukemic activity of 5-thienyl- or 5-(2-furyl)-2,3-dihydro-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(alkylcarbamates) and derivatives

Treatment of N-(2-furoyl)proline or N-thenoylprolines and N-(2-thenoyl)thiazolidine-4-carboxylic acid with acetic anhydride and dimethyl acetylenedicarboxylate gave 5-substituted derivatives of dimethyl 2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate and derivatives of dimethyl 5-(2-thienyl)pyrrolo[1,2-c]thiazole. Reduction of 2 with lithium aluminum hydride gave the diols 3a, 3b, 3c and 3d. These diols yielded the corresponding diacetates 4 by treatment with acetic anhydride. The bis(methylcarbamates) 5a, 5b, 5c, and 5d and bis(isopropylcarbamates) 6b and 6c are obtained with the appropriate isocyanates. The 1-substituted pyrrolizines were synthesized, the 1-acetoxy compounds 7b and 7c further transformed into 1-hydroxy and 1-oxo analogues. The action of hydrochloric acid on 1-acetoxy derivatives gave 3H-pyrrolizines. Evaluation of antileukemic activity was investigated on the leukemia L1210 in vivo, on several bis(alkylcarbamates). The compounds 5c and 5d show good antileukemic activity comparable with the mitomycin.     

Synthesis and pharmacological activities of some novel 5-chloro-N-(4-(1,5-(disubstituted)-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-2-methoxybenzamide derivatives

A series of substituted pyrazole derivatives were prepared from N1-[4-(cinnamoyl) phenyl]-5-chloro-2-methoxybenzamides 2a–c, which were prepared from N-(4-acetylphenyl)-5-chloro-2-methoxybenzamide as starting material. Treating of compound 2a–c with methylhydrazine or phenylhydrazine afforded the corresponding N-substituted pyrazoline derivatives 3a–c and 4a–c, respectively. The acryloyl derivatives 2a–c were reacted with hydrazine hydrate in dioxane afforded a pyrazoline 5a–c, which was acetylated with acetyl chloride in dioxane to yield the N-acetyl analogue 6a–c. In addition, pyrazoline 5c was reacted with morpholine in the presence of paraformaldehyde to give the corresponding N-substituted pyrazoline derivative 7. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. The pharmacological screening showed that many of these compounds have less toxicity and good anti-inflammatory activities.