Patent GB-1321316-A (GB)
Title: Nitrofuryl-thienopyrimidines
IPC: C07D495/04
Filed: 1970-11-25
Abstract: 1321316 Nitrofuran derivatives DR KARL THOMAE GmbH 25 Nov 1970 [26 Nov 1969 16 Oct 1970 (3)] 56146/70 Heading C2C Novel compounds of Formula I (wherein R represents a free amino group; a lower aliphatic acylamino group containing 2 to 5 carbon atoms which may, if desired, be substituted by one or two chlorine atoms; a straight or branched monoalkylamino group containing from 1 to 5 carbon atoms; an allylamino group; a cyclohexylamino group which may, if desired, be substituted in the cyclohexyl radical by a hydroxy group; a dialkylamino group with each alkyl radical containing from 1 to 4 carbon atoms; a straight or branched hydroxyalkylamino group containing from 1 to 6 carbon atoms and from 1 to 5 hydroxyl groups which may, if desired, be substituted at its nitrogen atom by an alkyl group containing from 1 to 4 carbon atoms and/or in its alkylene radical by a phenyl group; a straight or branched di- (hydroxyalkyl)-amino group with each alkyl radical containing from 1 to 5 carbon atoms; an alkoxyalkylamino or di-(alkoxyalkyl)-amino group with 1 to 2 carbon atoms in the alkoxy radical (s) and 1 to 3 carbon atoms in the alkylene radical(s); a free or N,N-dialkylated amino alkylamino group with 1 to 3 carbon atoms in the alkylene radical and any alkyl radicals present which may, if desired, be substituted by a hydroxy group in the alkylene radical; an N-acetylaminoalkyleneamino group with 2 or 3 carbon atoms in the alkylene group; an anilino group the nucleus of which may, if desired, be mono-substituted by a chlorine atom or a methyl, methoxy or hydroxy group; an N- methylanilino group; a phenylalkylamino group with 1 or 2 carbon atoms in the alkylene radical; or a saturated, 5- or 6-membered, monocyclic, heterocyclic ring containing a nitrogen atom and linked via the latter to the thieno [3,2-d] pyrimidine ring, the said ring, if desired, including an oxygen or sulphur atom or a further nitrogen atoms and/or being substituted by an alkyl or hydroxy group, the said ring in the case of a further nitrogen atom being present, if desired, being substituted at the further nitrogen atom by a hydroxyethyl, formyl or carbethoxy group, and the said ring in the ease of a sulphur atom being present, if desired, including the said sulphur atom in oxidized form; and R 1  represents a hydrogen atom or a methyl group) and acid addition salts thereof with inorganic and organic acids, are prepared (a) when R is other than optionally chlorosubstituted acylamino, by reacting a compound of Formula II (in which Z is halogen, mercapto or alkylthio) with an amine of formula R-H, or (b) when R is other than anilino, phenylalkylamino, N- methylanilino, or hydroxyalkylamino substituted in the alkylene moiety by phenyl, by reacting a compound of Formula III with a nitrating agent, or (c) by reacting a compound of Formula IV with a salt of nitrous acid, or (d) by reacting a compound of Formula V with nitric acid or a salt of nitric acid, or (e) when R represents or includes an acylamino group, by reacting a compound of Formula I in which R represents or includes a free amino group, with an appropriate acylating agent. In reactions (b) and (d) any free amino or hydroxy groups present in the starting materials are first protected by the introduction of protective groups and, if necessary, these protective groups are removed after the reaction.  Compounds of Formula II, are prepared (a) for compounds in which Z is SH or SAlkyl, by reacting a corresponding 2-(5-nitro-2-furyl)-4- halo-thieno[3,2-d]pyrimidine with thiourea and optionally alkylating the mercapto compound formed, or (b) for compounds in which Z is halogen, by reacting a 5-nitrofuran-2-iminocarboxylate with a 3-amino-thiophene-2-carboxylate and subsequently halogenating the resulting 2-(5-nitro-2-furyl)-4-hydroxy-thieno- [3,2-d]-pyrimidine. Compounds of Formulae III and V are prepared similarly using furan-2- iminocarboxylate or 5-alkoxycarbonylfuran-2- iminocarboxylate starting materials, and halogenating the resulting 2-[(2-furyl) or (5-alkoxycarbonyl - 2 -furyl)] - 4 - hydroxy - thieno[3,2 d ]- pyrimidine to form the corresponding halo compound, reacting this with an amine RH and, when necessary, hydrolysing the products. Compounds of Formula IV are prepared by brominating compounds of Formula III. Methyl 5 - methoxycarbonyl - furan - 2 - iminocarboxylate is prepared by reacting 5-methoxycarbonyl-furan-2-nitrile with methanol and HCl. Pharmaceutical compositions having antibacterial, antifungal and antitrichomonal activity, for oral or vaginal administration, comprise a compound of Formula I or a physiologically compatible acid addition salt thereof together with a pharmaceutical carrier.