Analogues and derivatives of cephalotaxine and methods for making and using the compounds
AssigneeOregon State University
InventorsChristopher M. Beaudry, Xuan Ju
Life of this patent
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Abstract
Disclosed herein are embodiments of a compound having a Formula I or a salt, solvate, N-oxide, prodrug, diastereomer or enantiomer thereof. Also disclosed are derivative compounds made from the compound of Formula I. Certain derivative compounds have a Formula V-2, or a salt, solvate, N-oxide, prodrug, diastereomer or enantiomer thereof. Also disclosed are method for making and using the disclosed compounds. Certain disclosed embodiments are useful for treating and/or preventing certain diseases and/or disorders, including proliferation diseases, such as leukemia.
Claims24
A compound having a formula
- or a salt, solvate, N-oxide, diastereomer or enantiomer thereof, wherein:
- x is from 0 to 4;
- each R1 independently is hydroxyl, halogen, aliphatic, alkoxy, haloalkyl, amino, protected amino, carboxylic ester, or two R1s, together with the atoms to which they are attached, form an aryl or heterocyclyl;
- each of R2, R3, R4 and R5 independently is H, halogen, aliphatic, hydroxyalkyl, protected hydroxyalkyl, aryl, heteroaryl, hydroxyl, protected hydroxyl, haloalkyl, amino, protected amino, carboxylic ester, or two of R2, R3, R4 and R5 that are attached to the same carbon together form ═O or ═S;
- and
- each of Q1 and Q2 independently is aliphatic.
A method for making a compound of Formula I, comprising:
- i) treating a protected hydroxyl ketone of formula A-1 with a haloacetate ester of formula A-2 to form a compound of formula A-3
- ii) treating the compound of formula A-3 with a protected amino compound of formula A-4 to form a compound of formula A-5
- iii) converting the OPG moiety of A-5 to a leaving group in a compound of formula A-6
- and
- iv) cyclizing A-6 to form the compound of Formula I,
- or a salt, solvate, N-oxide, prodrug, diastereomer or enantiomer thereof, wherein:
- each PG independently is a protecting group;
- LG is a leaving group;
- each X1 independently is a halogen;
- x is from 0 to 4;
- RA is alkyl;
- if present, each R1 independently is hydroxyl, halogen, aliphatic, alkoxy, haloalkyl, amino, protected amino, carboxylic ester, or two R1s, together with the atoms to which they are attached, form an aryl or heterocyclyl;
- each of R2, R3, R4 and R5 independently is H, halogen, aliphatic, hydroxyalkyl, protected hydroxyalkyl, aryl, heteroaryl, hydroxyl, protected hydroxyl, haloalkyl, amino, protected amino, carboxylic ester, or two of R2, R3, R4 and R5 that are attached to the same carbon together form ═O or ═S;
- and
- each of Q1 and Q2 independently is aliphatic.
A method, comprising:
- treating a compound of Formula I
- or a salt, solvate, N-oxide, diastereomer or enantiomer thereof, with an oxidizing agent to form a racemic compound of Formula II
- or a salt, solvate, or N-oxide thereof, wherein:
- x is from 0 to 4;
- if present, each R1 independently is hydroxyl, halogen, aliphatic, alkoxy, haloalkyl, amino, protected amino, carboxylic ester, or two R1s, together with the atoms to which they are attached, form an aryl or heterocyclyl;
- each of R2, R3, R4 and R5 independently is H, halogen, aliphatic, hydroxyalkyl, protected hydroxyalkyl, aryl, heteroaryl, hydroxyl, protected hydroxyl, haloalkyl, amino, protected amino, carboxylic ester, or two of R2, R3, R4 and R5 that are attached to the same carbon together form ═O or ═S;
- and
- each of Q1 and Q2 independently is aliphatic.
Dependencies are inferred from the claim text.