4-Amino-substituted derivatives of pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine and their preparation, pharmaceutical composistion and use antitumor and antileukemic agents

4-\u200bAmino-\u200bsubstituted pyrazolo[3,\u200b4-\u200bd]\u200bpyrimidine and pyrrolo[2,\u200b3-\u200bd]\u200bpyrimidine derivs., particularly I [X = CH or N; R = H, alkylthio, aminoalkylthio; R1 = NH-\u200bcyclopropyl, NHPr, NHBu, NEt2, NHCH2CH2OEt, pyrrolidin-\u200b1-\u200byl, piperidin-\u200b1-\u200byl, morpholin-\u200b4-\u200byl, NH-\u200bcyclohexyl, hexahydroazepin-\u200b1-\u200byl, NHCH2Ph, NHCH2CH2Ph (others unclaimed)\u200b; R2 = H, C6H4R3; R3 = H, halo, alkyl; R4 = CH2CH(R5)\u200bC6H4R3 or CH:CHC6H4R3; R5 = Cl, Br, OH]\u200b, are described. I are inhibitors of cell proliferation in A431, 8701-\u200bBC, and leukemia cell lines, and are thus potential antitumor and antileukemic agents. Approx. 50 compds. I were tested in bioassays, and preparatory data for most of the compds. is given. For instance, Et 5-\u200bamino-\u200b1-\u200b(2-\u200bhydroxy-\u200b2-\u200bphenylethyl)\u200b-\u200b1H-\u200bpyrazole-\u200b4-\u200bcarboxylate was thioacylated with benzoyl isothiocyanate (93\u200b%)\u200b, cyclized with aq. NaOH (80\u200b%)\u200b, S-\u200bmethylated with MeI (72\u200b%)\u200b, and chlorinated at both the ring and sidechain with POCl3 and DMF (Vilsmeier complex) (65\u200b%)\u200b, to give the chloride intermediate II. Reaction of II with PhCH2NH2 in PhMe at room temp. for 24 h gave 81\u200b% invention compd. III. This compd. inhibited Src phosphorylation with almost the same efficacy as PP2. In regard to antiproliferative activity toward A431 cells, 11 compds. including III had IC50 values comparable to or better than PP2. Compds. I showed no cytotoxicity toward tested cell lines at 10 nM to 10 \u3bcM when evaluated by trypan blue exclusion