Conformationally restricted polyamines
AssigneeWisconsin Alumni Research Foundation
InventorsBenjamin J. Frydman, Laurence J. Marton, Vendohar K. Reddy, Aldonia L. Valasinas, Donald T. Witiak
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Abstract
Compounds of Formula I: E-NH-D-NH-B-A-B-NH-D-NH-E (I) wherein A is C.sub.2 -C.sub.6 alkene, C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, or cycloaryl; B is independently a single bond, C.sub.1 -C.sub.6 alkyl alkenyl; D is independently C.sub.1 -C.sub.6 alkyl or alkenyl, or C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, or cycloaryl; and E is independently H, C.sub.1 -C.sub.6 alkyl or alkenyl; and pharmaceutically-suitable salts thereof; a synthetic method therefor, pharmaceutical dosage forms containing one of more of these compounds, and use of these compounds in the treatment of neoplastic cell growth, are disclosed.
Claims24
Compounds of Formula I:
- E-NH-D-NH-B-A-B-NH-D-NH-E (I)
- wherein A is selected from the group consisting of cis-C.sub.2 -C.sub.6 alkene and C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, and cycloaryl;
- B is independently selected from the group consisting of a single bond and C.sub.1 -C.sub.6 alkyl and alkenyl;
- D is independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl and alkenyl, and C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, and cycloaryl;
- E is independently selected from the group consisting of C.sub.2 -C.sub.6 alkyl and alkenyl;
- and pharmaceutically-suitable salts thereof.
A method of synthesizing compounds of Formula I
- E-NH-D-NH-B-A-B-NH-D-NH-E (I)
- wherein A is selected from the group consisting of C.sub.2 -C.sub.6 alkene and C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, and cycloaryl;
- B is independently selected from the group consisting of a single bond and C.sub.1 -C.sub.6 alkyl and alkenyl;
- D is independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl and alkenyl, and C.sub.3 -C.sub.6 cycloalkyl, cycloalkenyl, and cycloaryl;
- E is independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl and alkenyl;
- comprising:
- (a) reacting a compound of Formula II
- HO-B-A-B-OH (II)
- with a protecting reagent to yield a compound of Formula III
- PROT-O-B-A-B-O-PROT (III)
- wherein PROT is a protecting group;
- and then
- (b) reacting the Formula III compound from step (a) with a compound of Formula IV
- E-N(PROT)-D-NH-PROT (IV)
- to yield a compound of Formula V
- E-N(PROT)-D-N(PROT)-B-A-B-N(PROT)-D-N(PROT)-E (V)
- and then
- (c) deprotecting the Formula V compound to yield a compound of Formula I.
Dependencies are inferred from the claim text.