吉西他滨盐酸盐, Gemcitabine HCl

Gemcitabine hydrochloride is a chemotherapy drug used to treat various types of cancers, including breast, lung, pancreas, and bladder cancer. It is a nucleoside analogue, meaning that it resembles the building blocks of DNA and RNA. Gemcitabine hydrochloride works by interfering with the production of DNA and RNA in cancer cells, which slows or stops the growth and spread of cancer.

Physical and Chemical Properties:

Gemcitabine hydrochloride is a white to off-white crystalline powder that is freely soluble in water, slightly soluble in methanol, and practically insoluble in ethanol, acetone, and ethyl acetate. Its molecular formula is C9H11F2N3O4·HCl, and its molecular weight is 299.7 g/mol. Gemcitabine hydrochloride has a melting point of 148-149°C.

Synthesis and Characterization:

Gemcitabine hydrochloride can be synthesized by a multistep process starting from 2'-deoxy-2',2'-difluorocytidine. The synthesis involves a reaction between 2'-deoxy-2',2'-difluorocytidine and trimethylsilyl trifluoromethanesulfonate followed by a nucleophilic substitution of 4-nitrobenzyl chloride. The resultant 4-nitro-2'-deoxy-2',2'-difluorocytidine undergoes a reduction reaction to form the final product, gemcitabine hydrochloride.

Analytical Methods:

Various analytical methods have been developed for the analysis of gemcitabine hydrochloride, including high-performance liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and capillary electrophoresis. These methods are used for the quality control of gemcitabine hydrochloride in the pharmaceutical industry.

Biological Properties:

Gemcitabine hydrochloride has been shown to have antitumor activity against a wide range of cancers, including breast, lung, pancreas, and bladder cancer. It works by inhibiting the production of DNA and RNA in cancer cells, which slows or stops the growth and spread of cancer. Gemcitabine hydrochloride has also been shown to enhance the effectiveness of other chemotherapy drugs when used in combination.

Toxicity and Safety in Scientific Experiments:

Gemcitabine hydrochloride is generally well tolerated in patients, but it can cause side effects, including nausea, vomiting, fatigue, and low white blood cell count. In scientific experiments, gemcitabine hydrochloride has been shown to have toxic effects on various organs, including the liver, kidneys, and bone marrow, at high doses.

Applications in Scientific Experiments:

Gemcitabine hydrochloride has a wide range of applications in scientific experiments, including cell culture studies, animal experiments, and clinical trials. It is used to study the mechanisms of cancer growth and to develop new treatments for cancer. Gemcitabine hydrochloride is also used to study drug resistance in cancer cells and to develop more effective chemotherapy regimens.

Current State of Research:

Gemcitabine hydrochloride is currently used as a standard treatment for various types of cancers, but its effectiveness is limited by drug resistance and toxicity. Current research is focused on developing new formulations of gemcitabine hydrochloride that can overcome drug resistance and reduce toxicity. There is also research focused on developing new combinations of gemcitabine hydrochloride with other chemotherapy drugs to enhance its effectiveness.

Potential Implications in Various Fields of Research and Industry:

Gemcitabine hydrochloride has potential implications in various fields of research and industry, including drug development, cancer research, and personalized medicine. It can be used to develop new chemotherapy drugs and to study the mechanisms of cancer growth. Gemcitabine hydrochloride can also be used to develop personalized chemotherapy regimens based on a patient's genetic profile.

Limitations and Future Directions:

The limitations of gemcitabine hydrochloride include drug resistance and toxicity. Future directions of research include developing new formulations of gemcitabine hydrochloride that can overcome drug resistance and reduce toxicity. There is also research focused on developing new combinations of gemcitabine hydrochloride with other chemotherapy drugs to enhance its effectiveness. Other future directions of research include developing new methods for drug delivery and optimizing chemotherapy regimens based on a patient's genetic profile.

Title: Gemcitabine

CAS Registry Number: 95058-81-4

CAS Name: 2’-Deoxy-2‘,2’-difluorocytidine

Additional Names: 1-(2-oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,2-difluororibose; dFdC; dFdCyd

Manufacturers' Codes: LY-188011

Trademarks: Gemzar (Lilly)

Molecular Formula: C9H11F2N3O4

Molecular Weight: 263.20

Percent Composition: C 41.07%, H 4.21%, F 14.44%, N 15.97%, O 24.32%

Literature References: Prepn: L. W. Hertel, GB 2136425; idem, US 4808614 (1984, 1989 both to Lilly); L. W. Hertel et al., J. Org. Chem. 53, 2406 (1988); T. S. Chou et al., Synthesis 1992, 565. Antitumor activity: L. W. Hertel et al., Cancer Res. 50, 4417 (1990). Mode of action study: V. W. T. Ruiz et al., Biochem. Pharmacol. 46, 762 (1993). Clinical pharmacokinetics and toxicity: J. L. Abbruzzese et al., J. Clin. Oncol. 9, 491 (1991). Review of clinical studies: B. Lund et al., Cancer Treat. Rev. 19, 45-55 (1993).

Properties: Crystals from water, pH 8.5. [a]365 +425.36°; [a]D +71.51° (c = 0.96 in methanol). uv max (ethanol): 234, 268 (e 7810, 8560). LD10 i.v. in rats: 200 mg/m2 (Abbruzzese).

Optical Rotation: [a]365 +425.36°; [a]D +71.51°

Absorption maximum: uv max (ethanol): 234, 268 (e 7810, 8560)

Toxicity data: LD10 i.v. in rats: 200 mg/m2 (Abbruzzese)

Derivative Type: Hydrochloride

CAS Registry Number: 122111-03-9

Molecular Formula: C9H11F2N3O4.HCl

Molecular Weight: 299.66

Percent Composition: C 36.07%, H 4.04%, F 12.68%, N 14.02%, O 21.36%, Cl 11.83%

Properties: Crystals from water-acetone, mp 287-292° (dec). [a]D +48°; [a]365 +257.9° (c = 1.0 in deuterated water). uv max (water): 232, 268 nm (e 7960, 9360).

Melting point: mp 287-292° (dec)

Optical Rotation: [a]D +48°; [a]365 +257.9° (c = 1.0 in deuterated water)

Absorption maximum: uv max (water): 232, 268 nm (e 7960, 9360)

Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Antimetabolites; Pyrimidine Analogs.