Synthetic salicylihalamides, apicularens and derivatives thereof
AssigneeUt Southwestern Medical Center
InventorsJef Karel De Brabander, Yusheng Wu
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds having improved stability over that of natural benzolactones, and a process for synthesizing these compounds. These compounds exhibit anti-cancer activity and inhibit V-ATPase activity.
Claims36
A composition comprising a compound of formula:
- wherein E is selected from the group consisting of:
- X═O, S, NR2;
- Y═CH2, O, S, NR2;
- Q═O, NH;
- F=ortho, meta, para substituents including halogen, CN, OR2, OC(O)R3, NO2, OSO2R3, NR2R2, NR2C(O)R3, NR2SO2R3, R3;
- R1═H, Me;
- R2═R1, straight chain saturated alkyl, straight chain unsaturated alkyl, branched chain alkyl, branched chain unsaturated alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, CH2aryl, CH2 heteroaryl, CH2 heterocycle, CHR1CHR1, CHR1CHR1heteroaryl, CHR1CHR1heterocycle;
- R3═R2 or CR1═CR1aryl, CR1═CR1heteroaryl, CR1═CR1heterocycle, C≡Caryl, C≡Cheteroaryl, C≡Cheterocycle;
- and Z is a contiguous linker whose presence completes an 11 to 15 membered ring.
A composition comprising a compound of formula:
- wherein E is selected from the group consisting of:
- X=O, S, NR2
- Y=CH2, O, S, NR2
- Q═O, NH
- F=ortho, meta, para substituents including halogen, CN, OR2, OC(O)R3, NO2, OSO2R3, NR2R2, NR2C(O)R3, NR2SO2R3, R3
- R1═H, Me
- R2═R1, straight chain saturated alkyl, straight chain unsaturated alkyl, branched chain alkyl, branched chain unsaturated alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, CH2aryl, CH2heteroaryl, CH2heterocycle, CHR1CHR1aryl, CHR1CHR1heteroaryl, CHR1CHR1heterocycle
- R3═R2 or CR1═CR1aryl, CR1═CR1heteroaryl, CR1═CR1heterocycle, C≡Caryl, C≡Cheteroaryl, C≡Cheterocycle;
- and R4═R1, C(O)R3, SO2R3, R2.
A composition comprising a compound of formula:
- wherein E is selected from the group consisting of:
- X═O, S, NR2
- Y═CH2, O, S, NR2
- Q═O, NH
- F=ortho, meta, para substituents including halogen, CN, OR2, OC(O)R3, NO2, OSO2R3, NR2R2, NR2C(O)R3, NR2SO2R3, R3
- R1═H, Me
- R2═R1, straight chain saturated alkyl, straight chain unsaturated alkyl, branched chain alkyl, branched chain unsaturated alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, CH2aryl, CH2heteroaryl, CH2heterocycle, CHR1CHR1aryl, CHR1CHR1heteroaryl, CHR1CHR1heterocycle
- R3═R2 or CR1═CR1aryl, CR1═CR1heteroaryl, CR1═CR1heterocycle, C≡Caryl, C≡Cheteroaryl, C≡Cheterocycle;
- and R4═R1, C(O)R3, SO2R3, R2.
A composition comprising a compound of formula:
- where F=ortho, meta, para substituents including halogen, CN, OR2, OC(O)R3, NO2, OSO2R3, NR2R2, NR2C(O)R3, NR2SO2R3, R3;
- R1═H, Me;
- R2═R1, straight chain saturated alkyl, straight chain unsaturated alkyl, branched chain alkyl, branched chain unsaturated alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, CH2aryl, CH2 heteroaryl, CH2 heterocycle, CHR1CHR1aryl, CHR1CHR1heteroaryl, CHR1CHR1heterocycle;
- R3═R2 or CR1═CR1aryl, CR1═CR1heteroaryl, CR1═CR1heterocycle, C≡Caryl, C≡Cheteroaryl, C≡Cheterocycle;
- and
- R4═R1, C(O)R3, SO2R3, R2.
A composition comprising a compound of formula:
- where F=ortho, meta, para substituents including halogen, CN, OR2, OC(O)R3, NO2, OSO2R3, NR2R2, NR2C(O)R3, NR2SO2R3, R3;
- R1═H, Me;
- R2═R1, straight chain saturated alkyl, straight chain unsaturated alkyl, branched chain alkyl, branched chain unsaturated alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, CH2aryl, CH2heteroaryl, CH2heterocycle, CHR1CHR1aryl, CHR1CHR1heteroaryl, CHR1CHR1heterocycle;
- R3═R2 or CR1=CR1aryl, CR1═CR1heteroaryl, CR1═CR1heterocycle, C≡Caryl, C≡Cheteroaryl, C≡Cheterocycle;
- and
- R4═R1, C(O)R3, SO2R3, R2.
A composition comprising a compound selected from the group consisting of:
- wherein R=straight chain saturated alkyl or straight chain unsaturated alkyl that is comprised of a chain of 5 to 8 carbons.
A composition comprising a compound of formula:
- wherein R=straight chain saturated alkyl or straight chain unsaturated alkyl that is comprised of a chain of 5 to 8 carbons.
A composition comprising a compoun d of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
- wherein R=Z,Z-hexadienyl;
- Z,E-hexadienyl;
- a straight chain alkyl comprising 5 to 8 carbons (e.g. —(CH2)5Me);
- a straight chain alcohol (e.g. —O(CH2)4Me);
- and a straight chain diol (e.g. —S(CH2)4Me).
A composition comprising a compound of formula:
- where R=Bu;
- Ph.
A composition comprising:
- where R=Z,Z-hexadienyl;
- Z,E-hexadienyl;
- and a straight chain alkyl comprising 5-8 carbons.
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
A composition comprising a compound of formula:
- where R=a straight chain alkyl comprising 5-8 carbons, a straight chain alcohol, a straight chain diol, —CCBu, or —CCph.
A composition comprising a compound is selected from the group consisting of:
- wherein R=straight chain saturated alkyl or straight chain unsaturated alkyl that is comprised of a chain of 5 to 8 carbons.
A composition comprising a compound of formula:
- wherein R=straight chain saturated alkyl or straight chain unsaturated alkyl that is comprised of a chain of 5 to 8 carbons.
A process for preparing a salicylihalamide comprising the steps of
- (a) synthesizing the compounds of formula:
- (b) producing from the compounds of step (a), via an ring-closing metathesis, the compound of formula:
- wherein P=a hydroxyl protecting group.
A process for preparing a salicylihalamide comprising the steps of:
- a) synthesizing a salicylihalamide benzolactone core;
- and
- b) adding a side chain to the salicylihalamide benzolactone core.
A process for preparing an apicularen comprising:
- a) synthesizing a apicularen benzolactone core;
- and
- b) adding a chain to the apicularen benzolactone core.
Dependencies are inferred from the claim text.