(2R)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid

• ChemBase ID: 532
• Molecular Formular: C20H23N7O7
• Molecular Mass: 473.43932
• Monoisotopic Mass: 473.16589611
• SMILES: O=c1nc([nH]c2NCC(N(c12)C=O)CNc1ccc(cc1)C(=O)N[C@H](CCC(=O)O)C(=O)O)N
• Canonical SMILES: O=CN1C(CNc2ccc(cc2)C(=O)N[C@@H](C(=O)O)CCC(=O)O)CNc2c1c(=O)nc([nH]2)N
• InChI: InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/t12?,13-/m1/s1
• InChIKey: VVIAGPKUTFNRDU-ZGTCLIOFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R)-2-[(4-{[(2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
• IUPAC Traditional name: leucovorin
• Brand Name: Calcium citrovorum factor; Citrovorum factor; Folinic acid-SF; Leucal; Wellcovorin
• Synonyms: Folinic acid; Folinic acid calcium salt; Folinic acid calcium salt USP27; L-leucovorin; Leucovorin calcium; Leucovorin folinic acid; Calcium folinate; Leucovorin

Database IDs

• CAS Number: 1492-18-8
• PubChem SID: 46505436; 160963995
• PubChem CID: 54575

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.0870106
• H Acceptors: 12
• H Donor: 7
• LogD (pH = 5.5): -6.242469
• LogD (pH = 7.4): -8.894597
• Log P: -3.8975205
• Molar Refractivity: 126.462 cm^3
• Polarizability: 43.311886 Å^3
• Polar Surface Area: 215.55 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: -1.06
• LOG S: -3.2
• Solubility (Water): 3.00e-01 g/l

PROPERTIES

Physical Property

• Solubility: Complete
• Hydrophobicity(logP): -3.2

DETAILS

DrugBank - DB00650

• Drug Groups: approved
• Description: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [PubChem]
• Indication: For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
• Pharmacology: Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Leucovorin is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Leucovorin has also been used to enhance the activity of fluorouracil.
• Toxicity: LD₅₀>8000 mg/kg (orally in rats). Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic and intestinal mucosal, the main metabolite being the active 5-methyltetrahydrofolate. Leucovorin is readily converted to another reduced folate, 5,10-methylenetetrahydrofolate, which acts to stabilize the binding of fluorodeoxyridylic acid to thymidylate synthase and thereby enhances the inhibition of this enzyme.
• Absorption: Following oral administration, leucovorin is rapidly absorbed. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg.
• Half Life: 6.2 hours
• Protein Binding: ~15%
• References: Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. Pubmed