79481-83-7

Usage

InChI:InChI=1/C15H21Cl2NO2/c1-20-15(19)4-2-3-13-5-7-14(8-6-13)18(11-9-16)12-10-17/h5-8H,2-4,9-12H2,1H3

Upstream product

• 130198-76-4 methyl 3-<4-phenyl>butyrate 
• 305-03-3 chlorambucil 
• 67-56-1 methanol 
• 18414-58-9 diphenylmethylsilanecarboxylic acid 
• 124-41-4 sodium methylate 
• 5473-15-4 4-(4-acetamidophenyl)-4-oxobutanoic acid 
• 103-84-4 Acetanilid 
• 62-53-3 aniline 
• 205759-94-0 methyl 4-(p-aminophenyl)butyrate 
• 15118-60-2 4-(4-aminophenyl)butyric Acid 
• 17981-81-6 chlorambucil chloride 
• 20637-02-9 methyl 4-(4-nitrophenyl)butanoate 
• 20637-09-6 methyl 4-(4-aminophenyl)butanoate 

Downstream Products

• 305-03-3 chlorambucil 
• 1452855-76-3 4-(4-(bis(2-(4-hydroxyphenoxy)ethyl)amino)phenyl)butanoic acid 
• 1452855-75-2 methyl 4-(4-(bis(2-(4-hydroxyphenoxy)ethyl)amino)phenyl)butanoate 
• 1026679-23-1 N,N-bis(2-chloroethyl)-4-(4-hydroxybutyl)aniline 
• 130031-42-4 Acridin-9-yl-(3-{4-[bis-(2-chloro-ethyl)-amino]-phenyl}-propyl)-amine 
• 90393-37-6 N,N-bis(2-chloroethyl)-4-(3-isocyanatopropyl)phenylamine 
• 129787-13-9 3-[4-[N,N-bis(2-chloroethyl)amino]-phenyl]-propylamine 
• 269402-54-2 N/[3-(dimethylamino)propyl]-4-{4-[bis(2-chloroethyl)amino]phenyl}-butyramide 
• 17981-81-6 chlorambucil chloride 

Relevant academic research and scientific papers

Nickel-Mediated Alkoxycarbonylation for Complete Carbon Isotope Replacement

Many commercial drugs, as well as upcoming pharmaceutically active compounds in the pipeline, display aliphatic carboxylic acids or derivatives thereof as key structural entities. Synthetic methods for rapidly accessing isotopologues of such compounds are highly relevant for undertaking critical pharmacological studies. In this paper, we disclose a direct synthetic route allowing for full carbon isotope replacement via a nickel-mediated alkoxycarbonylation. Employing a nickelII pincer complex ([(N2N)Ni-Cl]) in combination with carbon-13 labeled CO, alkyl iodide, sodium methoxide, photocatalyst, and blue LED light, it was possible to generate the corresponding isotopically labeled aliphatic carboxylates in good yields. Furthermore, the developed methodology was applied to the carbon isotope substitution of several pharmaceutically active compounds, whereby complete carbon-13 labeling was successfully accomplished. It was initially proposed that the carboxylation step would proceed via the in situ formation of a nickellacarboxylate, generated by CO insertion into the Ni-alkoxide bond. However, preliminary mechanistic investigations suggest an alternative pathway involving attack of an open shell species generated from the alkyl halide to a metal ligated CO to generate an acyl NiIII species. Subsequent reductive elimination involving the alkoxide eventually leads to carboxylate formation. An excess of the alkoxide was essential for obtaining a high yield of the product. In general, the presented methodology provides a simple and convenient setup for the synthesis and carbon isotope labeling of aliphatic carboxylates, while providing new insights about the reactivity of the N2N nickel pincer complex applied.

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs

Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A ser

SULFONAMIDE, SULFAMATE AND SULFAMIDE DERIVATIVES OF ANTI-CANCER AGENTS

The present invention is directed to compounds having formula (I): A-L-R1, wherein A is an anticancer agent comprising at least one group selected from the group comprising OH, NH and NH2 and L is a direct bond or L is a linker and R

A process for synthesizing phenylbutyric acid nitrogen mustard antineoplastic agent

The invention relates to a synthesis process of an antineoplastic drug chlorambucil. The synthesis process comprises the following steps: (1) amino protection reaction; (2) acylation reaction; (3) reduction reaction; (4) carboxyl protection reaction; (5) substitution reaction; (6) chlorination reaction; and (7) deprotection reaction. According to the synthesis process, the amino group is protected by use of acetic anhydride, and then acylation, reduction, carboxyl protection, substitution, chlorination and aqueous hydrochloric acid solution hydrolysis are performed to obtain the chlorambucil. The synthesis process of the antineoplastic drug chlorambucil has the characteristics of low cost, mild reaction conditions, low toxicity, convenience in process operation, and suitability for industrial production.

ROS-Activated Compounds as Selective Anti-Cancer Therapeutics

Provided are compounds according to the following Formula I: The Formula I compounds are activated in the presence of reactive oxygen species (ROS) and are therefore selective anti-cancer therapeutics for cancers associated with elevated ROS. Also provided are methods and pharmaceutical compositions for treating cancers associated with increased ROS.

Synthesis and pharmacokinetic profile of a quaternary ammonium derivative of chlorambucil, a potential anticancer drug for the chemotherapy of chondrosarcoma

As a part of our targeting program based on the affinity of the quaternary ammonium moiety for cartilage, our objective was to develop more selective anticancer drugs towards chondrosarcoma that would concentrate in this malignant cartilaginous tissue and so improve the therapeutic index through a reduction of side effects. For this purpose we have synthesized and labeled with 14C a quaternary ammonium (QA) derivative of chlorambucil. Biological studies performed in rats showed that [14C]-CQA and [ 14C]-chlorambucil exhibited different pharmacokinetic profiles. The blood elimination of [14C]-CQA was faster than that of parent compound. [14C]-CQA was principally excreted by the fecal way. However, until 15 min after administration, levels of radioactivity were measured in cartilaginous tissues of rats given [14C]-CQA which was not the case for the rats which had received [14C]-chlorambucil. Although rates of radioactivity were quantified only during 15 min, these results prove that the functionalization of chlorambucil by a quaternary ammonium group allows the molecule to be carried selectively to cartilaginous tissues.

DNA-Directed Alkylating Agents. 3. Structure-Activity Relationships for Acridine-Linked Aniline Mustards: Consequences of Varying the Length of the Linker Chain

Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability.The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons.Relationships were sought between chain length and biological properties.Within eachseries, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue.The in vivo antitumor activities of the compounds dependend to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive.However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not.Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.