80693-26-1Relevant academic research and scientific papers
Prodrugs of 6-mercaptopurine and 6-mercaptopurine ribosides and therapeutic compositions and methods employing them
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, (2008/06/13)
Novel, transient prodrug forms of biologically active agents containing mercapto groups have (i) the structural formula (I): STR1 wherein X is O, S, or NR5 ; R1 S is the residue of any biologically active agent R1 SH; R2 is selected from the group consisting of straight or branched chain alkyl having from 1 to 20 carbon atoms; aryl having from 6 to 10 carbon atoms; cycloalkyl having from 3 to 8 carbon atoms; alkenyl having from 2 to 20 carbon atoms; cycloalkenyl having from 4 to 8 carbon atoms; alkynyl having from 2 to 20 carbon atoms; aralkyl, alkaryl, aralkenyl, aralkynyl, alkenylaryl, alkynylaryl, loweralkanoyloxyalkyl, carboxyalkyl, and lower alkanoyloxyalkyl wherein alkyl, aryl, alkenyl and alkynyl are as defined above; saturated or unsaturated monoheterocyclic or polyheterocyclic, or fused heterocyclic, either directly bonded to the carbonyl function or linked thereto via an alkylene bridge, containing from 1 to 3 of any one or more of the heteroatoms N, S or O in each heterocyclic ring thereof and each such ring being from 3- to 8- membered; and mono- or polysubstituted derivatives of the above, each of said substituents being selected from the group consisting of lower akyl, lower alkoxy, lower acyl, lower acyloxy, halo, haloloweralkyl, cyano, carbethoxy, loweralkylthio, amino, nitro, loweralkylamino, diloweralkylamino, carboxyl, carbamyl, loweralkylcarbamyl, diloweralkylcarbamyl and STR2 wherein R4 is hydrogen or alkyl having from 1 to 10 carbons; R3 is hydrogen, R2, lower acyl, cyano, haloloweralkyl, carbamyl, loweralkylcarbamyl, diloweralkylcarbamyl, --CH2 ONO2 and --CH2 OCOR2 ; R5 is hydrogen or lower alkyl; and further wherein R2 and R3 may be taken together to form a cyclizing moiety selected from the group consisting of STR3 with the proviso that when R1 S is the residue of a sulfur containing amino acid, then X cannot be NR5 ; (ii) the structural formula (I) wherein STR4 is the residue of any naturally occurring protein amino acid, the residue of any N-substituted naturally occurring amino acid, which N-substituent is lower alkyl or any amino acid protective group cleavable via hydrogenolysis or hydrolysis, or the residue of an N,N-lower dialkyl of C4 -C7 cycloalkylamino acid; and (iii) the non-toxic, pharmaceutically acceptable salts thereof.
