1.
Chem Pharm Bull (Tokyo)
; 43(3): 501-4, 1995 Mar.
Article
in English
| MEDLINE
| ID: mdl-7774034
ABSTRACT
3'-Amino-2',3'-dideoxycytidine (8) was directly synthesized from 2'-deoxycytidine. 2',3'-Dideoxy-3'-(N-acyl-L-phenylalanylamino)cytidines (acyl = butoxycarbonyl (9a), acetyl (9b), benzoyl (9c), and n-hexanoyl (9d)) were synthesized as chymotrypsin-activated prodrugs of 8. This N-protection was required for activation by chymotrypsin to 8. In vitro, compound 8 showed high cytotoxic activity against P388 cells, but the prodrugs 9a-d were ineffective. In vivo, however, these prodrugs showed much higher activity than 8 in mice bearing P388 cells.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Chymotrypsin/pharmacokinetics , Zalcitabine/analogs & derivatives , Animals , Antineoplastic Agents/pharmacokinetics , Biotransformation , Deoxycytosine Nucleotides/chemical synthesis , Deoxycytosine Nucleotides/pharmacokinetics , Deoxycytosine Nucleotides/pharmacology , Leukemia P388/drug therapy , Mice , Zalcitabine/chemical synthesis , Zalcitabine/pharmacokinetics , Zalcitabine/pharmacology
2.
Phys Rev B Condens Matter
; 38(5): 3189-3198, 1988 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-9946659