NCI172112

• CAT Number: I013345
• CAS Number: 56605-16-4
• Molecular Formula: C14H23Cl2N3O2
• Molecular Weight: 336.26
• Purity: ≥95%
• Synonyms: 3-[2-[bis(2-chloroethyl)amino]ethyl]-1,3-diazaspiro[4.5]decane-2,4-dione
• InChI: InChI=1S/C14H23Cl2N3O2/c15-6-8-18(9-7-16)10-11-19-12(20)14(17-13(19)21)4-2-1-3-5-14/h1-11H2,(H,17,21)
• InChIKey: QNKJFXARIMSDBR-UHFFFAOYSA-N
• SMILES: C1CCC2(CC1)C(=O)N(C(=O)N2)CCN(CCCl)CCCl

NCI172112 is a classical bifunctional alkylating agent synthesized in an effort to develop antitumor agents effective against CNS tumors.
NCI172112 (Spirohydantoin mustard, SHM) might serve as a carrier to cross the blood brain barrier[1]. The cumulative excretion of radioactivity in the urine and faeces of rats after administration of [2-chloroethyl-U-14C]NCI172112 or [hydantoin-4-14C]NCI172112 ( 3.13 mg/kg. i.v.) is measured. Four hours after dosing, a significantly (P<0.005) greater amount of radioactivity has been excreted in the urine of rats treated with [hydantoin-14C]NCI172112 than with [ethyl-14C]NCI172112. However, by 24 h, approx.50% of dose is recovered in the urine with both labelled materials. Clearance of radioactivity in the faeces is slow, but, as for the renal excretion, is significantly greater for the hydantoin-14C moiety. No radioactivity is found in the expired air of a rat receiving a single dosing of [hydantoin-14C]NCI172112 and less than 1% is measured after administration of [ethyl-14C]NCI172112. Renal clearance of radioactivity is similar 4 h after administration of [14C]NCI172112 to rats with biliary cannulas, with 14.1±2.9 and 17.5±2.1% of the ethyl-14C and 34.5±2.5 and 33.1±6.3%, of the hydantoin-14C dose appearing in the urine after dosing with 3.13 and 6.25 mg/kg, respectively. A difference in the 4 h urinary excretion of the two labels also is observed in dogs given [14C]NCI172112 (1 mg/kg, i.v.). The percentages of hydantoin-14C and ethyl-14C eliminated are 29.4±2.7% and 17.2±3.5%, respectively (P<0.05)[2].

Reference

[1]. Brown TD, et al. A phase I trial of spirohydantoin mustard (NSC 172112) in patients with advanced cancer. J Clin Oncol. 1986 Aug;4(8):1270-6.
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[2]. Plowman J, et al. The disposition of spirohydantoin mustard (NSC 172112) in rats and dogs. Xenobiotica. 1979 Jun;9(6):379-91.
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