Patent GB-1123601-A (GB)
Title: New derivatives of trans-4a-acylaminodecalin
Inventor: EDWARDS PHILIP NEIL
IPC: C07D277/30
Filed: 1965-03-12
Abstract: Novel trans-4a-acylaminodecalin derivatives of the general formula <FORM:1123601/C2/1> (wherein R1 represents H or an alkyl or alkenyl radical and R2 represents an unsubstituted alkyl radical of at least 2 carbon atoms; a cycloalkyl radical optionally substituted by an aryl radical; or an alkyl radical bearing one or more substituents selected from halogen atoms, alkoxy and alkenyl radicals, and aryl, aryloxy, arylthio, arylamino, heterocyclyl, heterocyclyloxy and heterocyclythio radicals themselves optionally bearing one or more halogen, alkyl, alkoxy, aryloxy, acyl, hydroxy or nitro substituents, or R1 and R2 jointly form an alkylene radical, and wherein the decalin ring may optionally carry one or more halogen or OH substituents) are prepared as follows:  (a) (when R1=H and the decalin ring is not further substituted) by reacting a carbonium ion of the formula <FORM:1123601/C2/2> with a cyano compound R2CN in the presence of a strong acid; (b) (when R1 is an alkyl or alkenyl radical) by reacting the corresponding compound in which R1 is H with an alkylating or alkenylating agent R1X (wherein X is a halogen atom, an alkane- or arene-sulphonyloxy radical or a sulphate radical); (e) (when R2 is a radical -CH2R4, where R4 is an alkoxy radical or an optionally substituted aryloxy, arylthio, arylamino, heterocyclyl, heterocyclyloxy or heterocyclythio radical as defined above) by reacting a compound of the formula <FORM:1123601/C2/3> (wherein Y is a halogen atom, an alkane- or arene-sulphonyloxy radical or a sulphate radical and the decalin ring may be further substituted as indicated above) with a compound R4H; (d) (in all cases where R1 and R2 are not joined together to form an alkylene radical) by acylation of the corresponding compounds containing H in place of -COR2, by means of an acylating agent derived from an acid R2COOH.  The carbonium ion in process (a) may be formed by treating a - or b -decalol, D 1,8a- or D 4a ,8a-octalin or 2 - hydroxycyclohexanespirocyclopentane with a strong acid.  4 - Hydroxy - 2 - n - propylpyrimidin - 5 -ylacetic acid is prepared by heating diethyl 2-formylsuccinate with butyramidine hydrochloride in a solution of sodium in ethanol and hydrolysing the resulting ethyl-4-hydroxy-2-n-propylpyrimidin-5-ylacetate.  1b  - Hydroxy - 4ab - trans - decalylamine hydrochloride is prepared by shaking 1b ,11-epoxy - 4ab  - ethylideneamino - trans - decalin with hot aqueous caustic soda, isolating the resulting base and treating it with ethereal HCl solution.ALSO:Pharmaceutical compositions, useful for treating viral diseases, comprise, in association with a pharmaceutically acceptable diluent or carrier, one or more trans-4a-acylaminodecalin derivatives of the general formula:- <FORM:1123601/A5-A6/1> (wherein R1 represents H or an alkyl or alkenyl radical and R2 represents an unsubstituted alkyl radical of at least 2 carbon atoms; a cycloalkyl radical optionally substituted by an aryl radical; or an alkyl radical bearing one or more substituents selected from halogen atoms, alkoxy and alkenyl radicals, and aryl, aryloxy, arylthio, arylamino, heterocyclyl, heterocyclyloxy and heterocyclylthio radicals themselves optionally bearing one or more halogen, alkyl, alkoxy, aryloxy, acyl, hydroxy or nitro substituents, or R1 and R2 jointly form an alkylene radical, and wherein the decalin ring may optionally carry one or more halogen or hydroxy substituents), with or without one or more known antiviral agents, e.g. 1-adamantanamine hydrochloride.