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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 1 (1983), S. 103-115 
    ISSN: 1573-0646
    Keywords: diarylamidines ; diarylimidazolines ; murine leukemia L1210 ; DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benzimidazole. Several of these compounds were found to inhibit L1210 cell proliferation with an ID50 (50% inhibitory dose) of 1 μg/ml or lower. Structure-function analysis revealed that the antitumor cell activity of the diarylamidines depended on the planarity of the molecule, the presence of amidino- (or, preferably, imidazolino-) groups on both aryl moieties, the nature of the bridge connecting the two aryl moieties (preferably no bridge at all, phenoxy or ethene) and, finally, the nature of the aryl moieties (preferably, benzofuran or benzo[b]thiophene). Hence, compound 20 (6-(2-imidazolin-2-yl)-2-[4-(2-imidazolin-2-yl)phenyl] benzo[b]thiophene) emerged as the most potent inhibitor of L1210 cell growth (ID50: 0.21 μg/ml). Its inhibitory potency was similar to that of the well-known trypanocidal drug ethidium bromide (compound 98). For all diarylamidine derivatives taken together, some correlation (r = 0.612) was noted between the log ID50 for L1210 cell proliferation and the log ID50 for L1210 cell DNA synthesis (as monitored by [methyl 3H]dThd incorporation). These findings suggest that the inhibitory effects of the diarylamidines on L1210 cell proliferation may at least partially reside in an inhibition of DNA synthesis. Compound 41 (2,2′-vinylenedi-1-benzofuran-5-carboxamidine), that exhibited a potent antitumor activity in vitro (ID50: 1.5 μg/ml), was further evaluated for its antitumor efficacy in vivo and found to increase the median survival time of L1210 cell-inoculated BDF1 mice up to 204%, if administered at a dose of 200 mg/kg.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1982 (1982), S. 1836-1869 
    ISSN: 0170-2041
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Syntheses of Biscationic, Trypanocidal 1-Benzofuran Compounds2-Phenyl-1-benzofurans with the substituents Br, NO2, CN, and -NH2, -NH-C(=NH)-NH2, -C(=NH)-NH2, -C=N-CH2-CH2-NH in 4′,5-position were synthesized.  -  For arylated formamidine derivatives [Ar-N=CH-N(CH3)2] a simple new preparation was found by reacting amine hydrochlorides with dimethylformamide in the presence of cyanamide.  -  Based on 5- or 6-cyano-1-benzofuran-2-carboxylates a series of α,ω-bis(1-benzofuran-2-yl) derivatives with cyano-, amidino-, or imidazolinyl groups in 5- or 6-position was prepared.
    Notes: 2-Phenyl-1-benzofurane mit den Substituenten Br, NO2 sowie CN und -NH2, -NH-C(=NH)-NH2, -C(=NH)-NH2 sowie -C=N-CH2-CH2-NH in 4′,5-Stellung wurden synthetisiert.  -  Für arylierte Formamidin-Derivate [Ar-N=CH-(CH3)2] fand sich in der Umsetzung von Aminhydrochloriden mit Dimethylformamid in Gegenwart von Cyanamid ein einfaches, neues Herstellungsverfahren.  -  Auf der Basis von 5- oder 6-Cyan-1-benzofuran-2-carbonsäureester konnte eine Serie von α,ω-Bis(1-benzofuran-2-yl)-Derivaten mit Cyan- oder Amidino- oder Imidazolinyl-Gruppen in 5- oder 6-Stellung dargestellt werden.
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 1984 (1984), S. 409-425 
    ISSN: 0170-2041
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Syntheses of Antimicrobial Biscationic 2-(Phenoxyphenyl)indoles and -1-benzofuransTen 2-(phenoxyphenyl)indoles and four 2-(phenoxyphenyl)-1-benzofurans with terminal amidinium or imidazolinium groups were synthesized in respect to growth inhibiting properties.
    Notes: Zehn 2-(phenoxyphenyl)indole und vier 2-(Phenoxyphenyl)-1-benzofurane mit endständigen Amidinium- oder Imidazolinium-Gruppen wurden im Hinblick auf wachstumshemmende Eigenschaften synthetisiert.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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