Polyamine analogues with antitumor activity.
A series of tetraamines derived from 1,8-diaminooctane was prepared and tested as antitumor agents. The reaction of 1,8-diaminooctane with acrylonitrile gave N,N'-bis(cyanoethyl)-1,8-diaminooctane, which was reduced to tetraamine 20. Alkylation of the terminal nitrogen atoms of the tetra-Boc derivative of this compound by methyl or ethyl halide followed by removal of the Boc groups gave the bis(alkyl)polyamines 26a and 26b, respectively. These three compounds exhibit promising antitumor activity in the mouse L1210 leukemia model. Coadministration of a polyamine oxidase inhibitor potentiated the antitumor activity.
Edwards
M L
ML
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Prakash
N J
NJ
Stemerick
D M
DM
Sunkara
S P
SP
Bitonti
A J
AJ
Davis
G F
GF
Dumont
J A
JA
Bey
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011073:Polyamines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D000097667:Polyamine Oxidase
D000970:Antineoplastic Agents; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase