ChemInform Abstract: Cyclopentenylcytosine. A Carbocyclic Nucleoside with Antitumor and Antiviral Properties.

Abstract

ChemInform Abstract Coupling of the cyclopentenylamine (I) with the isocyanate (II) yields the intermediate (III) which undergoes cyclization, forming the protected uracil (IVa). Sulfuration of (IVa) to give (IVb) is accomplished with Lawesson's reagent. Treatment of the mercaptouracil (IVb) with ammonia (V) produces the protected cyclopentenylcytosine (VI). Removal of the protective groups gives the compound (VIII) which shows significant antitumor activity in vivo and antiviral properties in vitro.

Cyclopentenyl cytosine: Interspecies predictions based on rodent plasma and urine kinetics

“…Cyclopentenyl cytosine [1-(3-hydroxymethyl-4,5 -dihydroxy-2-cyclopenten-1 -yl)cytosine; NSC 375575; CPE-C], a pyrimidine analogue of cytidine with a molecular weight of 239, recently synthesized by Lim et al [I], is currently being studied by the National Cancer Institute as a potential antitumor agent [2][3][4]. One known mechanism of its antitumor and host toxic action is its metabolic conversion to CPE-C triphosphate which inhibits CTP synthetase, a rate limiting enzyme step in de novo pyrimidine synthesis [5,6].…”

“…Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of CPE-C (Km --196 ~M) and CPE-C triphosphate is the major intracellular metabolite [6]. CPE-C triphosphate, but not the mono or diphosphate, inhibits bovine CTP synthetase with an IC50 of 6 #M. CPE-C is reported not to be a substrate for pyrimidine deaminase nor pyrimidine phosphorylase [1,4].…”