10315. Belotecan

Nomenclature

CAS number: 256411-32-2
(4S)-4-Ethyl-4-hydroxy-11-[2-[(1-methylethyl)amino]ethyl]-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; (20S)-7-(2-isopropylamino)ethylcamptothecin; 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin; (S)-7-[2-(N-propylamino)ethyl]camptothecin.
C25H27N3O4; mol wt 433.50.
C 69.27%, H 6.28%, N 9.69%, O 14.76%.

Description and references

DNA topoisomerase I inhibitor; semi-synthetic analog of camptothecin, q.v. Prepd (not claimed): C. I. Hong et al., WO 9902530; eidem, US 6310207 (1999, 2001 both to Chong Kun Dang). Improved synthesis: S. K. Ahn et al., J. Heterocycl. Chem. 37, 1141 (2000). Characterization of physicochemical properties: J.-H. Kim et al., Int. J. Pharm. 239, 207 (2002) DOI PubMed. HPLC determn in plasma: J.-Y. Cho et al., J. Chromatogr. B 784, 25 (2003) DOI. Inhibition of topoisomerase I in mammalian tumor cells and human tumor xenografts: L.-H. Lee et al., Arch. Pharmacal Res. 21, 581 (1998). Clinical pharmacology: D. H. Lee et al., Clin. Cancer Res. 13, 6182 (2007) DOI PubMed. Clinical evaluation in small cell lung cancer: D. H. Lee et al., Ann. Oncol. 19, 123 (2008) DOI PubMed.

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 213819-48-8
CKD-602; Camtobell (Chong Kun Dang).
C25H27N3O4.HCl; mol wt 469.96.
C 63.89%, H 6.01%, N 8.94%, O 13.62%, Cl 7.54%.

Properties

Slightly hygroscopic, pale yellow, crystalline powder, mp 267-268° (dec). [α]D +53.49° (c = 0.1 in water). pKa1 2.32±0.05, pKa2 9.15±0.02. Soly at 25° (mg/ml): acetic acid 10.70±0.08; methanol 4.13±0.32; ethanol 1.11±0.10; deionized water 8.22±0.18; acetonitrile 0.057±0.004.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Alkaloids/Natural Products; Camptothecin Derivatives; Topoisomerase I Inhibitor