安西他滨盐酸盐, Ancitabine Hydrochloride

2,2'-Anhydrocytidine HCl

2,2'-Anhydrocytidine HCl is a compound that is used in biochemical research. It is synthesized from 2-amino-6-chloro-9H-purin-9-one by reacting with potassium dichromate and sodium carbonate. This molecule has been shown to have the ability to inhibit the growth of tubule cells in hyperproliferative disease. 2,2'-Anhydrocytidine HCl can also be used as a probe for nuclear DNA due to its sensitivity to hydrogen bonding interactions. The melting point of this compound has been observed to be 125°C. This chemical has been shown to have pharmacokinetic properties and a phase transition temperature of about 126°C.

Cyclocytidine is a prodrug form of cytarabine that is hydrolyzed to cytarabine in vivo. It inhibits the growth of L5178Y leukemia cells in vitro (IC50 = 0.041 µg/ml) and inhibits DNA synthesis by inhibiting thymidine incorporation into DNA (IC50 = 110 µg/ml). It increases lifespan in an L1210 mouse model of leukemia when administered at doses ranging from 3 to 1,000 mg/kg per day. Cyclocytidine transiently increases blood pressure in dogs, cats, and rats when administered at doses ranging from 5 to 100 mg/kg and induces postural hypotension in dogs, an effect that can be blocked by the α-adrenergic receptor antagonist phentolamine.

Ancitabine Hydrochloride is the hydrochloride salt of a cytarabine congener prodrug with antineoplastic activity. Upon administration, ancitabine is slowly hydrolyzed into cytarabine. Subsequently, cytarabine is converted to the triphosphate form within the cell and then competes with cytidine for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. Cytarabine agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Compared to cytarabine, a more prolonged, consistent cytarabine-mediated therapeutic effect may be achieved with ancitabine because of the slow hydrolytic conversion of ancitabine to cytarabine.

Ancitabine hydrochloride is a hydrochloride salt resulting from the reaction of equimolar amounts of ancitabine and hydrogen chloride. It has a role as an antimetabolite and an antineoplastic agent. It contains an ancitabine(1+).

Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.

Title: Ancitabine

CAS Registry Number: 31698-14-3

CAS Name: [2R-(2a,3b,3ab,9ab)]-2,3,3a,9a-Tetrahydro-3-hydroxy-6-imino-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidine-2-methanol

Additional Names: 2,2'-anhydro-(1b-D-arabinofuranosyl)cytosine; 2,2'-O-cyclocytidine; O2,2'-cyclocytidine; ancytabine; anhydroara C

Molecular Formula: C9H11N3O4

Molecular Weight: 225.20

Percent Composition: C 48.00%, H 4.92%, N 18.66%, O 28.42%

Literature References: A cytostatic agent and intermediate in the synthesis of cytarabine, q.v. Prepn of the hydrochloride: E. R. Walwick et al., Proc. Chem. Soc. London 1959, 84; T. Y. Shen, W. V. Ruyle, US 3463850 (1969 to Merck & Co.); E. K. Hamamura et al., J. Med. Chem. 19, 654 (1976). General pharmacological properties: H. Hirayama et al., Oyo Yakuri 6, 1259 (1972), C.A. 79, 49175f (1973). Metabolism: D. H. W. Ho, Drug Metab. Dispos. 1, 752 (1973). Biochemical study: idem, Biochem. Pharmacol. 23, 1235 (1974). Pharmacokinetic study: H. S. Chen, J. F. Gross, Cancer Chemother. Pharmacol. 2, 85 (1979). Clinical studies: J. Z. Finklestein et al., Cancer Treat. Rep. 63, 1331 (1979); T. Miale et al., ibid. 1913. Toxicity studies: K. Sugihara et al., Oyo Yakuri 8, 1469 (1974); H. Hirayama et al., ibid. 1693, C.A. 83, 71766, 37747 (1975). HPLC study: V. Reichelova et al., J. Chromatogr. 588, 147 (1991).

 Derivative Type: Hydrochloride

CAS Registry Number: 10212-25-6

Manufacturers' Codes: NSC-145668

Trademarks: Cyclo-C (Kohjin)

Molecular Formula: C9H11N3O4.HCl

Molecular Weight: 261.66

Percent Composition: C 41.31%, H 4.62%, N 16.06%, O 24.46%, Cl 13.55%

Properties: Cryst, mp 248-250° (dec). [a]D23 -21.8° (c = 2.0 in water). uv max (pH 1-7): 262, 231 nm (e 10600, 9400).

Melting point: mp 248-250° (dec)

Optical Rotation: [a]D23 -21.8° (c = 2.0 in water)

Absorption maximum: uv max (pH 1-7): 262, 231 nm (e 10600, 9400)