174275-05-9Relevant academic research and scientific papers
High-affinity inhibitors of dihydrofolate reductase: Antimicrobial and anticancer activities of 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines with small molecular size
Kuyper, Lee F.,Baccanari, David P.,Jones, Michael L.,Hunter, Robert N.,Tansik, Robert L.,Joyner, Suzanne S.,Boytos, Christine M.,Rudolph, Sharon K.,Knick, Vince,Wilson, H. Robert,Caddell, J. Marc,Friedman, Henry S.,Comley, John C. W.,Stables, Jeremy N.
, p. 892 - 903 (2007/10/03)
A series of 7,8-dialkylpyrrolo[3,2-f]quinazolines were prepared as inhibitors of dihydrofolate reductase (DHFR). On the basis of an apparent inverse relationship between compound size and antifungal activity, the compounds were designed to be relatively small and compact. Inhibitor design was aided by a GRID analysis of the three-dimensional structure of Candida albicans DHFR, which suggested that relatively small, branched alkyl groups at the 7- and 8-positions of the pyrroloquinazoline ring system would provide optimal interactions with a hydrophobic region of the protein. The compounds were potent inhibitors of fungal and human DHFR, with K(i) values as low as 7.1 and 0.1 pM, respectively, and were highly active against C. albicans and an array of tumor cell lines. In contrast to known lipophilic inhibitors of DHFR such as trimetrexate and piritrexim, members of this series of pyrroloquinazolines were not susceptible to P-glycoprotein-mediated multidrug resistance and also showed significant distribution into lung and brain tissue. The compounds were active in lung and brain tumor models and displayed in vivo activity against Pneumocystis carinii and C. albicans.
ALCOHOLYSIS OF N,N'-DIARYLSULPHURDIIMIDES
Carpanelli, Corrado,Gaiani, Giovanni,Albini, Adriana
, p. 409 - 414 (2007/10/02)
The reaction of some N,N'-diarylsulphurdiimides, Ar-N=S=N-Ar, with ethanol, in the presence of anhydrous CuCl2, involves the cleavage of the substrate to amine, diethyl sulphite and diethyl ether.In addition to the reactions with this typical primary alcohol, the reactions between 5 (Ar = p-O2N-C6H4) and some secondary and tertiary alcohols, in the presence of the corresponding aluminium alkoxides, were investigated.While the reaction of 2-propanol is quite similar to that with ethanol, a rather different behaviour was observed with cyclohexanol and two tertiary alcohols, since they formed the alkenes which correspond to their formal dehydration products.All attempts to ethanolyse in basic solution led, instead, to the formation of a presumed adduct between 5 and sodium ethoxide.
