Gemcitabine

Base Information

• Chemical Name: Gemcitabine
• CAS No.: 95058-81-4
• Deprecated CAS: 1239668-67-7
• Molecular Formula: C9H11F2N3O4
• Molecular Weight: 263.201
• Hs Code.: 29349990
• European Community (EC) Number: 619-100-6
• UNII: B76N6SBZ8R
• DSSTox Substance ID: DTXSID3040487
• Nikkaji Number: J357.909C
• Wikipedia: Gemcitabine
• Wikidata: Q414143
• NCI Thesaurus Code: C66876
• RXCUI: 12574
• Pharos Ligand ID: UQUPNFUQA8KX
• Metabolomics Workbench ID: 42796
• ChEMBL ID: CHEMBL888
• Mol file: 95058-81-4.mol

Synonyms:188011, LY;2' Deoxy 2' Difluorocytidine;2' Deoxy 2',2'' Difluorocytidine 5' O Monophosphate;2',2'-DFDC;2',2'-difluoro-2'-deoxycytidine;2',2'-difluorodeoxycytidine;2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate;2'-deoxy-2'-difluorocytidine;dFdCyd;gemcitabine;gemcitabine hydrochloride;gemcitabine, (alpha-D-threo-pentofuranosyl)-isomer;gemcitabine, (beta-D-threo-pentafuranosyl)-isomer;gemcitabine, (D-threo-pentafuranosyl)-isomer;gemicitabine;Gemzar;Hydrochloride, Gemcitabine;LY 188011;LY-188011

Chemical Property of Gemcitabine

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 168.64 °C
• Refractive Index: 1.652
• Boiling Point: 482.7 °C at 760 mmHg
• PKA: 11.65±0.70(Predicted)
• Flash Point: 245.7 °C
• PSA: 110.60000
• Density: 1.84 g/cm³
• LogP: -0.70740
• Storage Temp.: Keep in dark place,Sealed in dry,Store in freezer, under -20°C
• Solubility.: Methanol (Slightly), Water (Slightly, Heated)
• XLogP3: -1.5
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 263.07176216
• Heavy Atom Count: 18
• Complexity: 426

Purity/Quality:

99.0%, ^*data from raw suppliers

Gemcitabine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,Xi
• Hazard Codes: Xn,Xi
• Statements: 21-36/38-46-62-63
• Safety Statements: 25-26-36/37-53

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=CN(C(=O)N=C1N)C2C(C(C(O2)CO)O)(F)F
• Isomeric SMILES: C1=CN(C(=O)N=C1N)[C@H]2C([C@@H]([C@H](O2)CO)O)(F)F
• Recent ClinicalTrials: Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
• Recent EU Clinical Trials: Phase 2 Study of Preoperative Gemcitabine Plus Cisplatin with Durvalumab (MEDI4736) and Tremelimumab in intrahepatic cholangiocarcinoma (NeoTreme)
• Recent NIPH Clinical Trials: Multicenter Phase II Study of AHCC (Functional Food) to Explore Improvement in Treatment Outcome in Patients with Unresectable Pancreatic Cancer
• Description: Gemcitabine (2’,2’-difluorodeoxycytidine; dFdCyd) is a novel deoxycytidine analogue with both structural and metabolic similarities to cytarabine. It has a broad spectrum of antitumor activity in preclinical murine leukemia and solid tumor models. This drug requires intracellular phosphorylation that results in the accumulation of difluorodeoxycytidine triphosphate (dFdCTP). The dFdCTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, which in turn inhibits DNA synthesis and terminates DNA chain elongation. In addition, this drug reduces intracellular deoxynucleoside triphosphate pools, presumably through the inhibition of ribonucleotide reductase. Gemcitabine is used alone or with other treatments/medications to treat certain types of cancer (including breast cancer, non-small cell lung cancer, ovarian cancer, pancreatic cancer, bladder cancer, bone cancer, Ewing’s sarcoma, mesenchymal chondrosarcoma osteosarcoma, dedifferentiated chondrosarcoma, head and neck cancers-cancer of the nasopharynx, hepatobiliary cancers including gallbladder cancer, Hodgkin lymphoma, kidney cancer, malignant pleural mesothelioma, non Hodgkin lymphoma, non-melanoma skin cancer – dermatofibrosarcoma protuberans (DFSP), occult primary, small cell lung cancer, soft tissue sarcoma, testicular cancer, thymic malignancies, uterine malignancies). It is a chemotherapy drug that works by slowing or stopping the growth of cancer cells. One commercial product of gemcitabine is Gemzar, which is supplied in a sterile form for intravenous use only. Gemcitabine is an anticancer nucleoside analog that inhibits the growth of HL-60 promyelocytic leukemia cells with an LC50 value of 40 nM. It inhibits the growth of MX-1 mammary, CX-1, HC-1, GC3, and VRC5 colon, LX-1, Calu-6, and NCI-H460 lung, and HS766T, PaCa-2, PANC-1, and BxPC-3 pancreatic cancer tumors in mouse xenograft models (45-93% inhibition). Gemcitabine is a prodrug that is metabolized to a diphosphate and triphosphate form in cells. The triphosphate form is incorporated into DNA which induces masked chain termination and cell death. By specifically inhibiting growth arrest and DNA damage inducible protein 45 a (Gadd45a), a key mediator of active DNA demethylation, gemcitabine, at concentrations ranging from 34 to 134 nM, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay. Gemcitabine also has broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC50 = ~1.5 nM) and inhibits the progression of murine AIDS in vivo at a dose of 1-2 mg/kg per day.
• Uses: Gemcitabine is used for breast cancer treatment. First-line treatment for locally advanced pancreatic cancer. 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 a
• Indications: Gemcitabine (Gemzar), an antimetabolite, undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes with DNA synthesis and repair. It is the single most active agent for the treatment of metastatic pancreatic cancer, and it is used as a first-line treatment for both pancreatic and small cell lung cancer. It is administered by intravenous infusion. The dose-limiting toxicity is bone marrow suppression.
• Clinical Use: Antineoplastic agent: Palliative treatment, or first-line treatment with cisplatin, of locally advanced or metastatic non-small cell lung cancer Pancreatic, ovarian and breast cancer Bladder cancer in combination with cisplatin
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Technology Process of Gemcitabine

There total 72 articles about Gemcitabine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

(2R,3R,5R)-5-(4-amino-2-oxopyrimidine-1(2H)-yl)-4,4-difluoro-2-((3-fluorobenzoyloxy)methyl)tetrahydrofuran-3-yl 3-fluorobenzoate (942288-40-6) → gemcitabine (95058-81-4,103882-85-5)

Guidance literature:

With ammonia; water; at 20 ℃; for 3h;

Reference yield: 82.7%

(2'-deoxy-2',2'-difluorocytidine)-3',5'-dibenzoate (134790-39-9,1268237-46-2) → gemcitabine (95058-81-4,103882-85-5)

Guidance literature:

With ammonium hydroxide; In methanol; at 20 ℃; for 3h;

Reference yield: 76.9%

1-(2'-deoxy-2',2'-difluoro-5-benzoyl-3-(4-phenyl)benzoyl-β-D-arabinofuranosyl)-4-aminopyrimidine-2-one (896109-84-5) → gemcitabine (95058-81-4,103882-85-5)

Guidance literature:

With ammonia; In methanol; at 20 ℃; for 12h; Product distribution / selectivity;

upstream raw materials:

bis(trimethylsilyl)-N-acetylcytosine

3,5-bis-O-(tert-butyldimethylsilyl)-1-O-(methanesulfonyl)-2-deoxy-2,2-difluororibose

1-[2'-deoxy-2',2'-difluoro-3',5'-bis(tert-butyldiphenylsilyloxy)-ribofuranosyl]-cytosine

1-(2'-deoxy-2',2'-difluoro-5-benzoyl-3-(4-phenyl)benzoyl-β-D-arabinofuranosyl)-4-aminopyrimidine-2-one

Downstream raw materials:

gemcitabine hydrochloride

C₂₃H₂₈F₂N₄O₇

araU

benzyl ((S)-(((2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate

Refernces

• 1、 Matsushita, Katsunori,Okuda, Takumi,Mori, Shohei,Konno, Masamitsu,Eguchi, Hidetoshi,Asai, Ayumu,Koseki, Jun,Iwagami, Yoshifumi,Yamada, Daisaku,Akita, Hirofumi,Asaoka, Tadafumi,Noda, Takehiro,Kawamoto, Koichi,Gotoh, Kunihito,Kobayashi, Shogo,Kasahara, Yuuya,Morihiro, Kunihiko,Satoh, Taroh,Doki, Yuichiro,Mori, Masaki,Ishii, Hideshi,Obika, Satoshi. "A Hydrogen Peroxide Activatable Gemcitabine Prodrug for the Selective Treatment of Pancreatic Ductal Adenocarcinoma". . p. 1384 - 1391. Retrieved 2019/07/12.
• 2、 -. "Fluoro-nucleoside and synthesis method thereof". Paragraph 0038; 0043; 0048; 0053; 0058. . Retrieved 2018/03/26.