Clinical data | |
---|---|
ATC code |
|
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.236.552 |
Chemical and physical data | |
Formula | C32H31F2N3O2 |
Molar mass | 527.61 g/mol g·mol−1 |
3D model (JSmol) | |
| |
| |
(what is this?) (verify) |
Zosuquidar is an experimental antineoplastic drug currently under development. It is now in Phase 3 clinical trials in the United States. It inhibits P-glycoproteins. Other drugs with this mechanism include tariquidar and laniquidar. P-glycoproteins are trans-membrane proteins that pump foreign substances out of cells in an ATP dependent fashion. Cancers overexpressing P-glycoproteins are able to pump out therapeutic molecules before they are able to reach their target, effectively making the cancer multi-drug resistant. Zosuquidar inhibits P-glycoproteins, inhibiting the efflux pump and restoring sensitivity to chemotherapeutic agents.
Chemistry
Reaction of dibenzosuberone (1) with the difluorocarbene from chlorodifluoroacetate (2) affords the cyclopropyl adduct (3). Reduction of the ketone with borohydride proceeds to afford the derivative wherein the fused cyclpropyl and alcohol are on the same side of the seven-membered ring (4). The carbinol is then converted to the halide with thionyl chloride apparently with retention of configuration (5). Displacement with piperazine monoformamide (6) leads to the alkylated product in which the groups are now anti. Hydrolysis of the formamide grouping then affords secondary amine (7). In a convergent sequence, 5-hydroxyquinoline (8) is allowed to react with the tosyl derivative of chiral glycidol (9), thus affording the final product in good yield.[1]
References
- ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1016/0960-894X(95)00426-T, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with
|doi=10.1016/0960-894X(95)00426-T
instead.