4902. Imatinib

Nomenclature

CAS number: 152459-95-5
4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide; N-[5-[4-(4-methylpiperazinomethyl)benzoylamido]-2-methylphenyl]-4-(3-pyridyl)-2-pyrimidineamine.
C29H31N7O; mol wt 493.60.
C 70.57%, H 6.33%, N 19.86%, O 3.24%.

Description and references

Tyrosine kinase inhibitor; highly specific for BCR-ABL, the enzyme associated with chronic myelogenous leukemia (CML) and certain forms of acute lymphoblastic leukemia (ALL). Also shown to inhibit the transmembrane receptor KIT and platelet-derived growth factor (PDGF) receptors. Prepn: J. Zimmermann, EP 564409; idem, US 5521184 (1993, 1996 both to Ciba-Geigy); idem et al., Bioorg. Med. Chem. Lett. 7, 187 (1997). Structural mechanism of ABL specificity: T. Schindler et al., Science 289, 1938 (2000). Activity vs KIT and PDGF receptor kinases: E. Buchdunger et al., J. Pharmacol. Exp. Ther. 295, 139 (2000). Clinical trial in CML: H. Kantarjian et al., N. Engl. J. Med. 346, 645 (2002); in gastrointestinal stromal tumors related to KIT: G. D. Demetri et al., ibid. 347, 472 (2002). Review of clinical experience: D. G. Savage, K. H. Antman, ibid. 346, 683-693 (2002); and pharmacology: V. K. Pindolia et al., Pharmacotherapy 22, 1249-1265 (2002); and development of therapeutic target: B. J. Druker, Adv. Cancer Res. 91, 1-30 (2004).

Chemical structure

Properties

mp 211-213°. pKa1 8.07; pKa2 3.73; pKa3 2.56; pKa4 1.52.

Derivative

Methanesulfonate.

Nomenclature

CAS number: 220127-57-1
STI-571; CGP-57148B; Gleevec (Novartis); Glivec (Novartis).
C29H31N7O.CH3SO3H; mol wt 589.71.
C 61.10%, H 5.98%, N 16.63%, O 10.85%, S 5.44%.

Description and references

Prepn of crystalline form: J. Zimmermann et al., WO 9903854 (1999 to Novartis).

Properties

Occurs in 2 crystalline modifications. α-form, begins to melt at 226°; β-form, mp 217°. Lipophilic at pH 7.4. Soly in water: >100 g/l (pH 4.2); 49 mg/l (pH 7.4).

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Tyrosine Kinase Inhibitors