122111-03-9 Usage
Product Description
Gemcitabine hydrochloride is a synthetic novel difluoro nucleoside drug that is anti-metabolic and antineoplastic. It is researched and developed by the Eli Lilly and Company and approved to be listed in South Africa, Sweden, the Netherlands, Australia and other countries in 1995. The United States Food and Drug Administration ( referred FDA) approved it as the first-line therapy for the clinical treatment of non-small cell lung cancer and pancreatic cancer. The main manufacturers of gemcitabine hydrochloride in domestic are Jiangsu Stock hausen Pharmaceutical Co., Ltd., and Harbin, Yu Heng Pharmaceutical company.
Gemcitabine hydrochloride, as a pro-drug, is a good substrate for the acidification of deoxygenation of thymine kinase phosphorus in the cell, and under the action of the enzyme, it can be converted into the following metabolites: gemcitabine mono-phosphate (dFdCMP), gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate (dFdCTP), among which the latter two are the active products.
In recent years, new drugs such as gemcitabine, paclitaxel, docetaxel, vinorebine are effective drugs for the treatment of non-small cell lung cancer (abbreviated NSCLC). Compared with traditional chemotherapy drugs, these drugs have the advantages of high curative effect and low toxicity.
Gemcitabine hydrochloride is a new generation of anti-metabolites drug and a type of special medicine for cell cycle, playing a major role in DNA synthesis phase, namely S phase of cells. Under certain conditions, this medicine can prevent progression of cells from G1 phase to S phase, and have a strong anti-cancer activity non-small cell lung cancer(NSCLC). Foreign studies have shown that the efficient of the single treatment for NSCLC with gemcitabine hydrochloride only is about 18%~35%, while combined the treatment with cisplatin the efficiency for NSCLC is 41.7%. In advanced NSCLC, effective rate of carboplatin is 16%, which is similar to cisplatin, but has low toxicity, especially for gastrointestinal reactions, bone marrow suppression and the toxic reaction of kidney and nerve ending. In combination with carboplatin, both of them have mutual coordination and additive effect, and can produce higher curative effects.
Content Determination
According to the efficient chromatography (Chinese Pharmacopoeia Edition 2000 Part two Appendix VD) determination.
Chromatography conditions and system suitability test
Use octadecylsilane bonded silica as a filler and ammonium acetate buffer (ammonium acetate 3.85g, add water 800ml to dissolve and glacial acetic acid to adjust the pH to 5.7, adding water to 1000ml)-methanol (90:10) as mobile phase, detecting the wavelength of 268nm. The theoretical plate number calculated according to the peak of gemcitabine hydrochloride should not be less than 2000 and the resolution between the peaks of gemcitabine hydrochloride and cytosine should be greater than 2.0.
Measurements
Take this product about 25mg, weigh it accurately, and put it into a 25ml volumetric flask, dissolved in water and diluted to the scale. Precisely measure this solution 5ml and put the solution into 50ml volumetric flask, diluted with water to the mark. Shake well and use this solution as the test solution. Precisely measure 20μl injection fluid into chromatography and record the chromatograms; Take another appropriate amount of gemcitabine hydrochloride and dry it to constant weight under the temperature of 105℃, using the processed product as the reference. Operate the reference with the same method mentioned above, and calculate it by peak area on the basis of the external standard method.
The above information is edited by the lookchem of Bai Linlin.
Distinguish
1.Take appropriate amount of gemcitabine hydrochloride, make into solution containing the 10μg per ml by adding water and measure it according to the spectrophotometric method (Chinese Pharmacopoeia Edition 2000 Part 2 Appendix Ⅳ A). It has the maximum absorption at the wavelength of 269nm, and the minimum absorption at the wavelength of 249nm.
2.In the chromatogram recorded in content determination, the retention time of the major peak in the test solution should correspond to that in the reference solution.
3.The infrared absorption spectrum should be consistent with the reference standard spectrum.
4.Identification reaction that aqueous solution is chloride. (Chinese Pharmacopoeia Edition 2000 Part two Appendix III)
Adverse reactions and side effects
The effect of bone marrow suppression. Symptoms such as anemia, leucopenia and thrombocytopenia will appear.
Approximately 66% of patients have liver aminotransferase abnormalities, which mostly are mild, non-progressive damage.
About 33% of patients experience nausea and vomiting.
About 50% of patients have the symptoms of mild proteinuria and hematuria. There are some cases of unexplained renal failure.
About 25% of patients have skin rash, 10% patients with itching.
Less than 1% of patients experience bronchial spasms.
Gemcitabine hydrochloride has significant cytotoxic activity on cultured human and mouse tumors, whose antitumor activity is associated with the administration. For example, daily dosing can lead to death of the animal, but the anti-cancer activity is very small; and when giving the drug every 3-4 days at a time, drug dose is non-lethal dose and has good anti-tumor activities on many tumors.
Uses
Different sources of media describe the Uses of 122111-03-9 differently. You can refer to the following data:
1. Suitable for the treatment of inoperable advanced or metastatic pancreatic cancer and the treatment of locally advanced or metastatic non-small cell lung cancer, and the treatment for mid-term and advanced non-small cell lung cancer, non-small cell lung cancer, pancreatic cancer, bladder cancer, breast cancer and other solid tumors.
2. An antineoplastic.
3. An antineoplastic
Description
Gemcitabine is a novel nucleoside analog that was launched in 1995 in the
Netherlands for the treatment of non-small cell lung cancer (nsclc) and in Sweden for
pancreatic cancer. Gemcitabine is a prodrug which is phosphorylated intracellularly by
deoxycytadine kinase to its active forms, the di- and triphosphates which bind to DNA
competitively. This insertion inhibits processes required for DNA synthesis and
metabolism, the essential function for both cell replication and repair. Furthermore,
gemcitabine displays an extraordinary array of self-potentiating mechanisms that
increase the concentration and prolong the retention of its active nucleotides in tumor
cells. The title compound has shown activity against a wide spectrum of human solid
tumors including colon, mammary, breast, bladder cancers. Synergistic activity of
gemcitabine with other anticancer agents such as cisplatin has been reported.
Chemical Properties
White crystalline granular, odorless
Originator
Lilly (U.S.A.)
Definition
ChEBI: A 2'-deoxycytidine hydrochloriode having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine hydrochloride is used in the treatment of various carcinomas, including non-small cell lung cancer, pancreatic ca
cer, bladder cancer and breast cancer.
Brand name
Gemzar (Lilly).
Biological Activity
Deoxycytidine analog that inhibits DNA synthesis. Metabolized to form gemcitabine triphosphate (dFdCTP) and gemcitabine diphosphate (dFdCDP). dFdCTD inhibits ribonucleotide reductase causing a reduction in cellular nucleotides. dFdCTP is incorporated in DNA resulting in DNA strand termination. Displays antitumor activity in vitro and in vivo .
Biochem/physiol Actions
Gemcitabine is a widely used antitumor agents in both clinics and research labs. It is an antineoplastic agent and antimetabolite.
Veterinary Drugs and Treatments
Very limited clinical use and research performed with this drug to
date have demonstrated limited clinical efficacy. However, it potentially
may be useful as a radiosensitizer for non-resectable tumors,
as part of combination protocols, or as a single agent for tumors
not amenable to more accepted therapies. Follow research reports
for the most up-to-date information.
In humans, gemcitabine has shown some efficacy in treating
pancreatic carcinoma, small-cell lung carcinoma, lymphoma, bladder
and other soft tissue carcinomas.
References
1) Mini et al. (2006), Cellular Pharmacology of Gemcitabine; Ann. Oncol. 17 v7
2) Heinemann et al. (1995), Gemcitabine: a modulator of intracellular nucleotide and deoxynucleotide metabolism; Semin. Oncol. 22 11
3) Heinemann et al. (1992), Cellular elimination of 2′,2′-difluorodeoxycytidine 5’triphosphate: a mechanism of self-potentiation; Cancer Res. 52 533
4) Pourquier et al. (2002), Gemcitabine (2′,2′-difluoro-2′-deoxycytidine), an antimetabolite that poisons topoisomerase I; Clin.Cancer Res. 8 2499
Check Digit Verification of cas no
The CAS Registry Mumber 122111-03-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,2,1,1 and 1 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 122111-03:
(8*1)+(7*2)+(6*2)+(5*1)+(4*1)+(3*1)+(2*0)+(1*3)=49
49 % 10 = 9
So 122111-03-9 is a valid CAS Registry Number.
InChI:InChI=1/C9H11F2N3O4.ClH/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);1H
122111-03-9Relevant articles and documents
Synthesis and in vitro cytotoxic activity on human anaplastic thyroid cancer cells of lipoamino acid conjugates of gemcitabine
Pignatello, Rosario,Vicari, Luisa,Pistara, Venerando,Musumeci, Teresa,Gulisano, Massimo,Puglisi, Giovanni
, p. 294 - 302 (2010)
Lipophilic derivatives of the antitumor drug gemcitabine (GEM) with the potential for improving drug loading in lipid-based colloidal carriers, like liposomes or lipid nanoparticles, are described. GEM free base was conjugated to lipoamino acids bearing an alkyl side chain of different length, by either a carbodiimide-assisted or an ethylchloroformiate-assisted coupling reaction, to obtain N4-acyl GEM derivatives. These compounds retained the same in vitro cell growth inhibitory activity of the parent drug against two lines of human anaplastic thyroid cancer cells. Stability studies suggested that the observed activity was due mainly to intact derivatives and not to released GEM. Accordingly, these amphiphilic derivatives can be proposed in a further step for the encapsulation in liposomes or lipid nanocarriers, to achieve as a final goal an improvement of the pharmacokinetics and therapeutic activity of GEM.
Drug delivery devices with drug-permeable component and methods
-
, (2019/05/26)
Implantable drug delivery devices include a housing having a closed drug reservoir lumen bounded by a first wall structure and a hydrophilic second wall structure, and a drug contained in the drug reservoir lumen, wherein the first wall structure is impermeable to the drug and the second wall structure is permeable to the drug. Methods of providing controlled release of drug to a patient include deploying a drug delivery device in the patient releasing a drug from the drug reservoir lumen via diffusion through the second wall structure.
Preparation method of cytidine
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Paragraph 0123-0128, (2019/12/10)
The invention provides a preparation method of cytidine 1, which comprises the following steps: (1) carrying out a condensation reaction on a compound 6 and a compound 7 in the presence of stannic chloride to generate a compound 8; (2) removing an alpha-isomer and other reaction impurities in the compound 8 to obtain the beta-isomer compound 8; and (3) carrying out a deprotection reaction on the beta-isomer compound 8 in the presence of an alcohol solvent, and then carrying out a salt forming reaction with hydrochloric acid to obtain a compound 1. The nucleoside compound 8 can be obtained withhigh beta-stereoselectivity starting from a cheap raw material 7 with a mixed anomeric carbon configuration, especially the raw material 7a, and a slightly excessive basic group 6, especially the basic group 6a; the trace alpha-compound 8 isomer impurities can be removed from the nucleoside compound 8 through a simple pulping method; and subsequently, deprotection and salifying reactions for beta-compound 8 have high yield, so that the method can reduce the production cost of the compound 1.
Industrial preparation process for key intermediate sulfonated saccharide of Gemcitabine
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Paragraph 0061; 0062; 0063; 0064, (2017/08/28)
The invention relates to a preparation method for a compound represented by a formula (I) shown in the description, i.e., a key intermediate sulfonated saccharide of Gemcitabine. The final product is prepared through subjecting a compound represented by a formula (II) shown in the description to sodium borohydride reduction, hydroxyl protection and resolution. The method is simple in process, high in yield and high in product purity and has no need of harsh reaction conditions, thereby being very suitable for industrial production.
