Synthesis and evaluation of antitumor activity of 1-[N, N-bis(2-chloroethyl) sulfamoylphenyl]-3,3-dialkyltriazenes.

Twenty-two 1-p-sulfamoylphenyl-3,3-dialkyltriazenes, 1-p-dialkylsulfamoylphenyl-3,3-dialkyltriazenes, and 1-p-[N,N-bis(2-chloroethyl) sulfamoylphenyl] -3,3-dialkyltriazenes were synthesized from their corresponding amines. Six of the compounds tested were devoid of antitumor activity.     

Synthesis and antioxidant activity of 1-(4-fluorophenyl)-1-alkyl-2-phenyl-3-morpholinopropan-1-ol hydrochlorides

Reactions of 4-fluorophenyl-β-morpholinopropiophenones with various Grignard reagents in anhydrous ether produced new tertiary aminoalcohols, 1-(4-fluorophenyl)-1-alkyl-2-phenyl-3-morpholinopropan-1-ols, that can be regarded as trihexyphenidyl (cyclodol) analogs. The antioxidant properties of the synthesized compounds were studied using a photochemiluminescence analytical method. It is established that the synthesized compounds exhibit antioxidant activity, the intensity of which depends on the length of the alkyl chain in the para-position of the benzene ring.     

Synthesis and antibacterial activity of 3-(2-arylvinylen)-2-isoxazolines

3-[2-(5-Nitro-2-furyl)vinylen]-2-isoxazoline (VIII) and 3-nitro-, 3-amino- and 3-acylaminostyryl-2-isoxazolines have been synthesized and tested for antibacterial activity. Compound (VIII) showed potent antibacterial activity in vitro against several strains of S. aureus and E. coli (two to eight times more active than furazolidone). None of the styryl derivatives exhibited significant activity.     

Synthesis and pharmacological activity of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides

Aminomethylation of substituted acetophenones with paraformaldehyde and piperidine hydrochloride yielded 4-substituted β-piperidinopropiophenones. Interaction of compounds I with the Grignard reagents in ether yielded 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanols. The anti-inflammatory, analgesic, antipyretic, central m-cholinoblocking, and peripheral n-cholinoblocking actions of 1-(4-substituted phenyl)-1-alkyl(aryl)-3-piperidinopropanol hydrochlorides were studied. The study compounds were found to have marked central m-cholinoblocking and peripheral n-cholinoblocking activities. Only 1-(4-methoxyphenyl)-1-cyclohexyl-3-piperidinopropanol hydrochloride had anti-inflammatory activity.     

Synthesis and pharmacological effect of substituted phenyl-4-(2-chloroethyl)tetrahydro-1,4-oxazine hydrochlorides

Substituted phenyl-4-(2-chloroethyl)tetrahydro-1,4-oxazine hydrochlorides were prepared by treating the corresponding amino alcohols with thionyl chloride. Since these compounds are considered to be monofunctional 2-haloalkylamine type agents, they were tested for possible alpha-adrenergic blocking activity using the rat anococcygeus muscle. The pharmacological action of this series of compounds is discussed.     

3-(4-哌嗪-1-苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑盐酸盐的合成及抗菌活性

为了研究水溶性稠杂环化合物的合成方法及抗菌活性，本研究采用3-(4-氯苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑(2a～n)在相转移催化剂TBAI作用下与哌嗪发生亲核取代，再与盐酸成盐制备了3-(4-哌嗪-1-苯基)-6-取代-s-三唑［3,4-b］［1,3,4］噻二唑盐酸盐(3a～n)。用试管二倍稀释法研究了新化合物的体外抗菌活性。结果表明，合成的28个新化合物极性碱性哌嗪基的引入可提高化合物的抗菌活性。该类稠杂环化合物的结构有待进一步优化。     

Synthesis and antibacterial activity of 1-(3-hydroxy-2-naphthoyl)-4-substituted thiosemicarbazides

1-(3-Hydroxy-2-naphthoyl)-4-substituted thiosemicarbazides were obtained by the addition of 3-hydroxy-2-naphthoic acid hydrazide to various isothiocyanates. The structures of the synthesized compounds were confirmed using UV and 1H-NMR spectral methods together with elemental analysis.     

Synthesis of 1-substituted 3-aryl-5-aryl(hetaryl)-2-pyrazolines and study of their antitumor activity

Three series of novel 1,3,5-trisubstituted 2-pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. The in vitro antitumor activity of the obtained compounds was determined at the National Cancer Institute (NCI). The 5-(benzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (9a) is the most prominent of the compounds due to its remarkable activity toward leukemia (RPMI-8226), renal cancer (UO-31) and prostate cancer (DU-145) cell lines with GI(50) values of 1.88, 1.91 and 1.94 μM, respectively.     

Urinary metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea

Urinary metabolites of ring 14C-labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (Methyl CCNU) from rats have been isolated and characterized by high-performance liquid chromatography and mass spectrometry. About 44% of the cyclohexyl moiety of CCNU was excreted in 24 hr and included approximately 10% of the excreted dose as free amines and 40% as conjugates that could be converted to amines by hydrolysis. Amine composition of free base plus hydrolyzable conjugates was 55% hydroxycyclohexylamines (3-trans, 3-cis, 4-cis, and 4-trans) and 30% cyclohexylamine. This strongly supports previous studies which indicated that CCNU is largely hydroxylated in vivo as well as in vitro. Rats pretreated with phenobarbital excreted high relative amounts of cis-4-hydroxy derivatives (41%), again showing a high degree of correlation between in vitro and in vivo results. Treatment of urine with beta-glucuronidase gave no apparent increase in free amines. However, sulfatase was about 25% as effective as alkaline hydrolysis for releasing free amines from whole urine. Major urinary metabolites were found to have m.w. of about 629, 413, 329, and 243 and represented 55%, 20%, 20%, and 5% of total excreted 14C, respectively. It was concluded that the higher m.w. metabolites may be conjugates of peptides possibly derived from active site-directed inactivation of specific enzymes. Previous work has shown that enzymes such as chymotrypsin and glutathione reductase are inhibited by isocyanates in this manner. Hydroxylated metabolites of Methyl CCNU had a pattern similar to that of CCNU. The major free (12%) and conjugated amine (54%) metabolites of Methyl CCNU in the urine in decreasing order of quantity present were cis-3-hydroxy-trans-4-methylcyclohexylamine, trans-4-methylcyclohexylamine, trans-4-hydroxymethylcyclohexylamine, and trans-3-hydroxy-trans-4-methyl-cyclohexylamine.