We describe here a new and efficient method for synthesis of N-(3-phenyl[2.2.1]bicyclohept-2-yl)-N-ethylamine hydrochloride (Fencamfamine), based on the reduction of trans-5-nitro-6-phenylbicyclo[2.2.1]hept-2-ene with Raney alloy mixed with aqueous NaOH and tetrahydrofuran followed by N-alkylation of the resulting product with 95% ethanol in the presence of skeletal nickel.

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Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60.

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We have investigated the potential use of a solid-phase synthesis of novel 6-(arylmethyl)-5-methylisocytosine derivatives based on the immobilization of the corresponding 2-thiothymine on a Merrifield resin, oxidation of the immobilized form to the sulfone, and aminolysis of the latter under mild conditions. Isocytosine derivatives are characterized by a number of practically useful properties amongst which a prominent place is occupied by the antiviral activity of specific members of this series which contain specific hydrocarbon radicals at atoms C-5 and C-6 of the pyrimidine ring and also at the exocyclic nitrogen atom [1]. The corresponding 2-N-unsubstituted and disubstituted derivatives [1, 2] can be readily prepared via condensation of the corresponding guanidine derivatives with 3-oxoesters in a basic medium. At the same time the synthesis of 2-N-monosubstituted members of this series unavoidably leads to the formation of a difficult to separate mixture of condensation products [3]. In this connection the preparation of the corresponding derivatives broadly involves the use of indirect methods based on the aminolysis of the corresponding S-alkylated 2-thiouracil derivatives [1,2,[4][5][6]. This process generally occurs under rigid conditions and demands the use of a cosolvent [2, 4-6]. The absence of the latter usually leads to a lower yield of the target isocytosine derivatives and to difficulties in their separation and purification [1].In this connection we have studied the use of a solid-phase synthetic strategy which is well established in the chemistry of peptides [7] in order to prepare the corresponding isocytosine derivatives. It should be noted that a solid-phase synthesis has already been successfully used in the chemistry of pyrimidine derivatives [3,8].The choice of starting materials and target products in the synthesis was carried out on the basis of a previously established structure -antiviral activity in this series of compounds [1].We have used a Merrifield resin as solid carrier which contained 1-1.3 milliequivalents of chloromethyl groups per gram and 1% of divinylbenzene cross-links. Reaction of this resin with the sodium salts of the corresponding 2-thiothymines 1a-c in anhydrous DMF medium caused the heterocyclic compound to be attached to the resin through the sulfur atom. The sulfides obtained 2a-c were oxidized by m-chloro-perbenzoic acid [8,9] to the corresponding sulfones 3a-c and then treated with excess amine in anhydrous THF