Halogenated tetracyclic compounds
AssigneeKing Saud University
InventorsUsama Sayed Eisa Karama, Mujeeb Abdullah Saeed Sultan, Abdulrahman Ibrahim Almansour, Kamal Eldin Hussein El Tahir, Yasser Abbas Elnakady, Talal Abdul Aziz Mohaya
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Abstract
The anti-cancer compounds are represented by Formula I: wherein R1 and R2 are either both hydrogen or both halogen, and if R1 and R2 are both hydrogen, R3 and R4 are both halogen, otherwise both R3 and R4 are hydrogen; wherein R5 is CHO or NHCH3; and wherein n is 0 to 3; provided that n is 0 only when R5 is CHO, or a pharmaceutically acceptable salt or isomer thereof.
Claims10
An anti-cancer compound having the formula:
- wherein R1 and R2 are either both hydrogen or both halogen, and if R1 and R2 are both hydrogen, R3 and R4 are both halogen, otherwise both R3 and R4 are hydrogen;
- wherein R5 is CHO or NHCH3;
- and
- wherein n is 0 to 3;
- provided that n is 0 only when R5 is CHO,
- or a pharmaceutically acceptable salt thereof.
A method of preparing an anti-cancer compound, comprising the steps of:
- (a) reducing 1,8-dihaloanthraquinone with zinc powder in aqueous ammonia, followed by acidic treatment to provide 1,8-dihaloanthracene;
- (b) performing a Diels-Alder [4+2] cycloaddition reaction of the 1,8-dihaloanthracene and acrolein at room temperature in the presence of boron trifluoride etherate to obtain a mixture of the intermediate compounds 1,8-dihalo-9,10-dihydro-9,10-ethanoanthracene-11-carbaldehyde and 4,5-dihalo-9,10-dihydro-9,10-ethanoanthracene 11-carbaldehyde;
- (c) separating the mixture of carbaldehydes by column chromatography;
- (d) converting the 4,5-dihalo-9,10-dihydro-9,10-ethanoanthracene 11-carbaldehyde into Z-ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propenoate and E-ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propenoate by Wittig homologation using (carbethoxymethylene)triphenylphosphorane;
- (e) hydrogenating Z-ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propenoate and E-ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propenoate at room temperature in methanol in the presence of palladium catalyst under hydrogen to obtain ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propanoate;
- (f) reducing ethyl 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propanoate with DIBAL at room temperature to obtain 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propan-1-ol;
- (g) oxidizing 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propan-1-ol using PCC at room temperature in dichloromethane to obtain 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propanal;
- and
- (h) aminating the 3-(1,8-dihalo-9,10-dihydro-9,10-ethanoanthracen-11-yl)propanal by direct reductive amination to obtain the anti-cancer compound of the formula
Dependencies are inferred from the claim text.