5091. Irinotecan

Nomenclature

CAS number: 97682-44-5
[1,4′-Bipiperidine]-1′-carboxylic acid (4S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinolin-9-yl ester; 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin; (+)-7-ethyl-10-hydroxycamptothecine 10-[1,4′-bipiperidine]-1′-carboxylate; (+)-(4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyloxy]-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione.
C33H38N4O6; mol wt 586.68.
C 67.56%, H 6.53%, N 9.55%, O 16.36%.

Description and references

DNA topoisomerase I inhibitor. Semisynthetic derivative of camptothecin, q.v.; de-esterified in vivo to the active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). Prepn: JP Kokai 85 19790; T. Miyasaka et al., US 4604463 (1985, 1986 both to Yakult Honsha); S. Sawada et al., Chem. Pharm. Bull. 39, 1446 (1991). Antitumor activity and toxicity data: T. Kunimoto et al., Cancer Res. 47, 5944 (1987). Mechanism of action study: Y. Kawato et al., ibid. 51, 4187 (1991). Clinical trial in colorectal cancer: J. Y. Douillard et al., Lancet 355, 1041 (2000). Review of pharmacology and clinical experience: N. Masuda et al., Crit. Rev. Oncol. Hematol. 24, 3-26 (1996); S. O'Reilly, E. K. Rowinsky, ibid. 47-70; of clinical toxicity: K. Seiter, Expert Opin. Drug Saf. 4, 45-53 (2005); of clinial trials in colorectal cancer: C. Fuchs et al., Cancer Treat. Rev. 32, 491-503 (2006).

Chemical structure

Properties

Pale yellow powder, mp 222-223°.

Derivative

Hydrochloride trihydrate.

Nomenclature

CAS number: 136572-09-3; 100286-90-6 (hydrochloride)
CPT-11; DQ-2805; Campto (Sanofi-Aventis); Camptosar (Pharmacia & Upjohn).
C33H38N4O6.HCl.3H2O; mol wt 677.18.
C 58.53%, H 6.70%, N 8.27%, O 21.26%, Cl 5.24%.

Properties

Slightly pale yellow needles or crystalline powder from water, mp 256.5°. [α]D20 +67.7° (c = 1 in water). uv max (ethanol): 221, 254, 359, 372 nm (ε 53800, 36600, 26200, 25300). Slightly sol in water and organic solvents. pH of 2% aqueous soln = 4. LD50 in mice (mg/kg): 177.5 i.p.; 765.3 orally (Kunimoto).

Therapeutic Category

Antineoplastic.

Keywords

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