10363. Laromustine

Nomenclature

CAS number: 173424-77-6
1-(2-Chloroethyl)-2-[(methylamino)carbonyl]-2-(methylsulfonyl)hydrazide methanesulfonic acid; 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine; VNP-40101M; 101M; Cloretazine (Vion).
C6H14ClN3O5S2; mol wt 307.78.
C 23.41%, H 4.58%, Cl 11.52%, N 13.65%, O 25.99%, S 20.84%.

Description and references

DNA alkylating and crosslinking agent. Bifunctional sulfonylhydrazine prodrug that generates a chloroethylating species, VPN-4090CE, and methyl isocyanate, q.v., a carbamoylating agent. Prepn: A. Sartorelli et al., WO 9702029; eidem, US 5637619 (both 1997 to Yale); K. Shyam et al., J. Med. Chem. 39, 796 (1996) DOI PubMed. Analytical methods and formulation: G. Krishna et al., AAPS PharmSciTech 2 (3), 39-47 (2001) DOI. LC-ESI-MS/MS determn in plasma: F. Bai et al., J. Chromatogr. B 853, 97 (2007) DOI. Mechanism of action: K. Ishiguro et al., Mol. Cancer Ther. 5, 969 (2006) DOI PubMed; P. G. Penketh et al., Leuk. Res. 32, 1546 (2008) DOI PubMed. Clinical evaluation in recurrent glioblastoma multiforme: M. A. Badruddoja et al., Neuro Oncol. 9, 70 (2007) DOI PubMed; in acute myeloid leukemia: F. Giles et al., J. Clin. Oncol. 25, 25 (2007) DOI PubMed.

Chemical structure

Properties

Crystals from ethanol, mp 146-147.5°. Soly (mg/ml): water 0.66, propylene glycol 1.4, polyethylene glycol 300 16.8, ethyl alcohol 1.4.

Derivative

VPN-4090CE.

Nomenclature

CAS number: 127792-84-1
2-(2-chloroethyl)-2-(methylsulfonyl)hydrazide methanesulfonic acid; 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine; 90CE.
C4H11ClN2O4S2; mol wt 250.72.
C 19.16%, H 4.42%, Cl 14.14%, N 11.17%, O 25.53%, S 25.58%.

Description and references

Prepn: K. Shyam et al., J. Med. Chem. 33, 2259 (1990).

Properties

Light yellow solid from ethanol, mp 138-139°.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Alkylating Agents