Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids
AssigneeEli Lilly and Company
InventorsGeorge J. Cullinan, Koert Gerzon
Life of this patent
Estimating the term…
Abstract
Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids are useful as anti viral and anti-neoplastic agents or as intermediates in the preparation of such agents.
Claims23
A compound of the formula ##STR11## wherein R is NH.sub.2, NH--NH.sub.2, N(CH.sub.3).sub.2, N.sub.3, NH--CH.sub.2 --Y wherein Y is H, CN, CHO, CH(O--C.sub.1 -C.sub.3 -alkyl).sub.2, NH--C.sub.2 --C.sub.6 -alkyl-X, NH--C.sub.2 -C.sub.6 -alkyl-(OH).sub.1-3, NH--(CH.sub.2).sub.n --OAc, NH--(CH.sub.2).sub.n --OCH.sub.3, n is 2 or 3, X is SY', NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, NHAc, CN, H, phenyl, or COOH, Y' is H, or C.sub.1 -C.sub.3 -alkyl and Ac is C.sub.1 -C.sub.17 -alkyl-CO or C.sub.2 -C.sub.7 -alkenyl-CO, pyrrolidinyl or NH--C.sub.3 -C.sub.8 -cycloalkyl;
- R' is H, OH, O--(C.sub.1 -C.sub.3)-alkanoyl or O-chloro-(C.sub.1 -C.sub.3)-alkanoyl, R" is hydrogen, methyl or formyl, one of R''' and R'''' is hydrogen or hydroxyl and the other is ethyl, and R.sup.v and R.sup.vl are hydrogen or hydroxyl, with the proviso that, when either R''' or R'''' is hydrogen, R.sup.v and R.sup.vl must also be hydrogen and pharmaceutically-acceptable salts thereof.
A compound of the formula ##STR12## wherein R is NH.sub.2, NH-NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, pyrrolidinyl, NH-alk-X, NH--(C.sub.3 -C.sub.8)-cycloalk, NH-alk-Am, NH-alk-(OH).sub.1-3, or N.sub.3 ;
- wherein alk is (C.sub.2 -C.sub.6) alkyl, Am is NH.sub.2, NHCH.sub.3 or N(CH.sub.3).sub.2 and X is hydrogen, cyano or phenyl;
- wherein R' is H, OH, O--(C.sub.1 -C.sub.3)-alkanoyl or O-chloro-(C.sub.1 -C.sub.3)-alkanoyl;
- wherein R" is hydrogen, methyl or formyl;
- and wherein one of R''' and R'''' is hydrogen or hydroxyl and the other is ethyl, and R.sup.v and R.sup.vl are H or OH with the proviso that, if one of R''' or R'''' is hydrogen, R.sup.v and R.sup.vl must also be hydrogen and pharmaceutically-acceptable salts thereof.
A compound of the formula ##STR13## wherein R is NH.sub.2, NH--NH.sub.2, N(CH.sub.3).sub.2, NH-alk-X, NH(C.sub.3 -C.sub.8)-cycloalk, NH-alk-Am, NH-alk-(OH).sub.1-3, or N.sub.3 ;
- wherein alk is (C.sub.1 -C.sub.6) alkyl, Am is NH.sub.2, NHCH.sub.3 or N(CH.sub.3).sub.2 and X is hydrogen, cyano, or phenyl, wherein R' is OH, O--(C.sub.1 -C.sub.3)-alkanoyl or O-chloro-(C.sub.1 -C.sub.3)-alkanoyl;
- wherein R" is hydrogen, methyl, formyl or (C.sub.1 -C.sub.3)-alkanoyl;
- and wherein one of R''' and R'''' is hydroxyl and the other is ethyl and pharmaceutically-acceptable salts thereof.
A compound of the formula ##STR14## wherein R is NH.sub.2 ;
- NH--C.sub.1 -C.sub.3 -alkyl or NH--NH.sub.2,
- R' is OH, O--C.sub.1 -C.sub.3 alkanoyl or O-Chloro-C.sub.1 -C.sub.3 alkanoyl and
- R" is H, methyl or formyl and pharmaceutically-acceptable salts thereof.
A compound of the formula ##STR15## wherein R is CH.sub.2 --CH.dbd.CH.sub.2, CH.sub.2 --C.tbd.CH, or ##STR16## wherein m is 0 or 1;
- R' is H, OH, O--(C.sub.1 -C.sub.3)-alkanoyl or O-chloro-(C.sub.1 -C.sub.3)-alkanoyl, R" is hydrogen, (C.sub.1 -C.sub.3)-alkyl or formyl, one of R''' and R'''' is hydrogen or hydroxyl and the other is ethyl, and R.sup.v and R.sup.vl are hydrogen or hydroxyl, with the proviso that, when either R''' or R'''' is hydrogen, R.sup.v and R.sup.vl must also be hydrogen and pharmaceutically-acceptable salts thereof.
A compound of the formula
- Q--NH--(CH.sub.2).sub.p --S--S(CH.sub.2).sub.p --NH--Q
- wherein p is 2 or 3 and Q is ##STR17## wherein R' is H, OH, O--(C.sub.1 -C.sub.3)-alkanoyl or O-chloro-(C.sub.1 -C.sub.3)-alkanoyl, R" is hydrogen, (C.sub.1 -C.sub.3)-alkyl or formyl, one of R''' and R'''' is hydrogen or hydroxyl and the other is ethyl, and R.sup.v and R.sup.vl are hydrogen or hydroxyl, with the proviso that, when either R''' or R'''' is hydrogen, R.sup.v and R.sup.vl must also be hydrogen and pharmaceutically-acceptable salts thereof.
Dependencies are inferred from the claim text.