环胞苷, Cyclocytidine

2,2'-Anhydrocytidine

2,2'-Anhydrocytidine is a cytosine analogue that has been shown to have anticancer activity against solid tumours in mice. The mechanism of action of 2,2'-Anhydrocytidine is not fully understood, but it may be due to its ability to bind to fatty acids and tubule cells in the liver. This compound also induces the production of epidermal growth factor (EGF) and has been shown to inhibit the phase transition temperature of nuclear DNA. It can be used as a model system for hydrogen bonding interactions and chemical stability. 2,2'-Anhydrocytidine can also be used for tissue culture experiments or as a reaction solution in vivo.

Ancitabine is a cytarabine congener prodrug with antineoplastic activity. Upon administration, ancitabine is slowly hydrolyzed into cytarabine, which is converted to the active triphosphate form and competes with deoxycytidine triphosphate 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. This agent also inhibits DNA and RNA polymerases, resulting in a decrease in cell growth. 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 is an organic heterotricyclic compound resulting from the formal condensation of the oxo group of cytidine to the 2' position with loss of water to give the corresponding cyclic ether. A prodrug, it is metabolised to the antineoplastic agent cytarabine, so is used to maintain a more constant antineoplastic action. It has a role as a prodrug, an antimetabolite and an antineoplastic agent. It is an organic heterotricyclic compound and a diol. It is a conjugate base of 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)

Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Pyrimidine Analogs.