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Usage

Uses

Used in Oncology:
Chlorambucil is used as an anticancer agent for the treatment of specific types of cancer, such as lymphoma, leukemia, and ovarian cancer. Its alkylating properties allow it to form covalent bonds with DNA, causing DNA damage and preventing the replication of cancer cells, which ultimately results in their death.
Used in Oral Medication:
Chlorambucil is administered as an oral medication, typically taken once a day, providing a convenient and accessible treatment option for patients with cancer. This mode of administration helps in maintaining a consistent level of the drug in the bloodstream, ensuring its effectiveness in combating cancer cells.
Used in Bone Marrow Suppression Management:
Although chlorambucil is known to cause side effects such as nausea, vomiting, and suppression of bone marrow function, its use in cancer treatment is carefully managed by medical professionals to minimize these adverse effects. The drug's benefits in treating cancer often outweigh the potential side effects, making it an important treatment option for many patients.
Used in Secondary Cancer Prevention:
Chlorambucil is associated with an increased risk of developing secondary cancers. However, its use in cancer treatment is carefully evaluated by healthcare providers to ensure that the benefits of its anticancer properties outweigh the potential risks. Patients receiving chlorambucil are closely monitored to detect and manage any secondary cancers that may arise.

Upstream product

• 305-03-3 chlorambucil 
• 20637-09-6 methyl 4-(4-aminophenyl)butanoate 

Downstream Products

• 34677-78-6 4-phenyl>butyric acid 

Relevant academic research and scientific papers

Preparation method of chlorambucil derivative

The invention discloses a preparation method of a chlorambucil derivative. The method comprises the steps that 4-(4-aminophenyl)butanoic acid methyl ester serves as the starting material, and the chlorambucil derivative is synthesized through six-step reactions. The optimal preparation steps and reaction conditions are screened out by means of a large number of experiments, the whole process is reasonable in design and high in operability, and purification is convenient. According to the prepared chlorambucil derivative, the purity can reach 99% or above, and the total yield can reach 50% or above. The prepared chlorambucil derivative can be widely applied to experiments for comprehensively analyzing pharmacology, pharmacologic metabolism, toxicology and the like of chlorambucil.

Reactions of N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil) with 2′-deoxyguanosine

N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) was allowed to react in the presence of 2′-deoxyguanosine (16 mM) at physiological pH (cacodylic acid, 50% base), and the reactions were followed by HPLC/MS/MS techniques. Although the predominant reaction observed was chlorambucil hydrolysis, ca. 24% of 1 reacted with different heteroatoms of the nucleoside. As expected, the principal site of 2′-deoxyguanosine alkylation was N7. Alkylation of N7 caused spontaneous depurination, and N-(7-guaninylethyl)-N-hydroxyethyl-p-aminophenylbutyric acid (5) and the corresponding N7,N7-bis-adduct (6) were the major stable dGuo derivatives. Also several other adducts were detected and tentatively identified by means of MS/MS and UV. From them, the O6-, N1-, N2-, and O5′-derivatives can be biologically significant. Our results shed new light on DNA modifications caused by chlorambucil, which is an important chemotherapeutic drug and a known carcinogen.

Mechanism and reactivity of chlorambucil and chlorambucil-spermidine conjugate

The mechanism and kinetics of hydrolysis of chlorambucil and chlorambucil-spermidine conjugate in aqueous buffered solutions have been compared.In the absence of added chloride ion the reactions are shown to be first-order in the nitrogen mustard and independent of the nucleophile concentration.In the presence of high concentrations of sodium chloride the reaction is reversible and is subject to a significant common-ion effect.The rates of hydrolysis of both compounds are independent of pH in the range 8 to 3.5, and both rates begin to drop rapidly below pH 3.5 which corresponds to the pKas of the aryl amine groups.The relative rates of alkylation of a range nucleophiles by chlorambucil have been deduced from the isokinetic points, and have shown that the phosphate dianion, imidazole base and particularly thiolates are all capable of competing with water for the aziridinium ion at comparatively low concentrations.The rates of reaction of chlorambucil and chlorambucil-spermidine conjugate have been shown to be sensitive to the medium, and, in particular, there is a large micellar inhibition of the hydrolysis of chlorambucil (60-fold reduction in rate) in the presence of hexadecyltrimethylammonium chloride that is not seen for the conjugate.These data are all accounted for in terms of a rate limiting formation of the aziridinium ion intermediate in each case.No evidence for any other mechanistic pathways was found.