4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one

• ChemBase ID: 324
• Molecular Formular: C9H11F2N3O4
• Molecular Mass: 263.1981464
• Monoisotopic Mass: 263.07176229
• SMILES: FC1(F)[C@H](O)[C@H](O[C@H]1n1ccc(nc1=O)N)CO
• Canonical SMILES: OC[C@H]1O[C@H](C([C@@H]1O)(F)F)n1ccc(nc1=O)N
• InChI: InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
• InChIKey: SDUQYLNIPVEERB-QPPQHZFASA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
• IUPAC Traditional name: gemcitabine
• Brand Name: DDFC; DFDC; GEO; Gemcin; Gemcitabina [INN-Spanish]; Gemcitabine HCl; Gemcitabine hydrochloride; Gemcitabinum [INN-Latin]; Gemtro; Gemzar
• Synonyms: Gemcitabine; Gemzar

Database IDs

• CAS Number: 95058-81-4
• MDL Number: MFCD00869720
• PubChem SID: 46506425; 160963787
• PubChem CID: 60750

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.51707
• H Acceptors: 6
• H Donor: 3
• LogD (pH = 5.5): -1.4665402
• LogD (pH = 7.4): -1.4665728
• Log P: -1.4665396
• Molar Refractivity: 53.2503 cm^3
• Polarizability: 20.563793 Å^3
• Polar Surface Area: 108.38 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.14
• LOG S: -1.07
• Solubility (Water): 2.23e+01 g/l

PROPERTIES

Physical Property

• Solubility: Soluble
• Hydrophobicity(logP): -1.4

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• TSCA Listed: false

Product Information

• Purity: 95+%
• Salt Data: Free Base

DETAILS

DrugBank - DB00441

• Drug Groups: approved
• Description: Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar? by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").; Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.
• Indication: For the first-line treatment of patients with metastatic breast cancer, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer and as first-line treatment for patients with adenocarcinoma of the pancreas.
• Pharmacology: Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand.
• Toxicity: Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD₅₀=500 mg/kg (orally in mice and rats)
• Affected Organisms: Humans and other mammals
• Biotransformation: Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).
• Absorption: 100%
• Half Life: Short infusions ranged from 32 to 94 minutes, and the value for long infusions vary from 245 to 638 minutes, depending on age and gender.
• Protein Binding: Plasma protein binding is negligible (<10%)
• Distribution: * 50 L/m^2 [infusions lasting <70 minutes]; * 370 L/m^2 [long infusions]
• Clearance: * 92.2 L/hr/m2 [Men 29 yrs]; * 75.7 L/hr/m2 [Men 45 yrs]; * 55.1 L/hr/m2 [Men 65 yrs]; * 40.7 L/hr/m2 [Men 79 yrs]; * 69.4 L/hr/m2 [Women 29 yrs]; * 57 L/hr/m2 [Women 45 yrs]; * 41.5 L/hr/m2 [Women 65 yrs]; * 30.7 L/hr/m2 [Women 79 yrs]
• References: [Link]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1714

Research Area: Cancer
Biological Activity:
Gemcitabine(Gemzar) belongs to the group of medicines called antimetabolites. It is used alone or in combination with other medicines to treat cancer of the breast, ovary, pancreas, and lung. Gemcitabine interferes with the growth of cancer cells, which are eventually destroyed. [1, 2]

REFERENCES

• Link
• http://www.mayoclinic.com/health/drug-information/DR601499