Inhibition of HIV-1 replication using oligocarbamate derivatives
AssigneeUniversity of Medicine and Dentistry of New Jersey
InventorsTariq M. Rana, Ikramul Huq
Life of this patent
Estimating the term…
Abstract
Tat-inhibitory oligocarbamate derivatives of the formula I ##STR1## and analogs thereof, and the biologically and pharmaceutically acceptable salts thereof exhibit advantageous properties, including specific binding to TAR RNA with high affinities, and stability of the resultant oligocarbamate-RNA complexes to proteolytic digestion. Site-specific photocrosslinking experiments using a photoactive analog (4-thio-uracil) containing TAR RNA indicate that these oligocarbamates interact with RNA in the major groove. These oligocarbamates are thus capable of competing with the TAR RNA-binding domain of Tat protein and thus are useful as a therapeutic agents in the treatment of AIDS.
Claims21
An oligocarbamate derivative of the formula ##STR8## wherein R.sup.1 is a p-hydroxybenzyl or benzyl group;
- R.sup.2 is hydrogen or methyl;
- R.sup.3 is guanidinopropyl;
- R.sup.4 is aminobutyl or guanidino propyl;
- and
- R.sup.5 is amidomethyl or amidoethyl;
- and analogs thereof, and the biologically and pharmaceutically acceptable salts thereof.
A pharmaceutical composition comprising an oligocarbamate of the formula ##STR9## wherein R.sup.1 is a p-hydroxybenzyl or benzyl group;
- R.sup.2 is hydrogen or methyl;
- R.sup.3 is guanidinopropyl;
- R.sup.4 is aminobutyl or guanidino propyl;
- and
- R.sup.5 is amidomethyl or amidoethyl;
- or an analog thereof, or a biologically and pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier therefor.
A method of inhibiting HIV-1 replication which comprises administration of an oligocarbamate of the formula ##STR10## wherein R.sup.1 is a p-hydroxybenzyl or benzyl group;
- R.sup.2 is hydrogen or methyl;
- R.sup.3 is guanidinopropyl;
- R.sup.4 is aminobutyl or guanidino propyl;
- and
- R.sup.5 is amidomethyl or amidoethyl;
- or an analog thereof, or a biologically
- and pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.