4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid

• ChemBase ID: 176
• Molecular Formular: C14H19Cl2NO2
• Molecular Mass: 304.21216
• Monoisotopic Mass: 303.07928421
• SMILES: ClCCN(c1ccc(CCCC(=O)O)cc1)CCCl
• Canonical SMILES: ClCCN(c1ccc(cc1)CCCC(=O)O)CCCl
• InChI: InChI=1S/C14H19Cl2NO2/c15-8-10-17(11-9-16)13-6-4-12(5-7-13)2-1-3-14(18)19/h4-7H,1-3,8-11H2,(H,18,19)
• InChIKey: JCKYGMPEJWAADB-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid
• IUPAC Traditional name: chlorambucil
• Brand Name: Ambochlorin; Amboclorin; Ecloril; Elcoril; Leukeran; Leukeran Tablets; Leukersan; Leukoran; Linfolizin; Linfolysin; Pepstatin
• Synonyms: 4-(4-[Bis(2-chloroethyl)amino]phenyl)butyric acid; Chlorambucil; 4-(p-[bis-(2-Chloroethyl)-amino]-phenyl)-butyric acid; 4-[Bis(2-chloroethyl)amino]benzenebutyric acid; Chloraminophen; Chloraminophene; Phenylbutyric Acid Nitrogen Mustard; Chlorobutine; Chlorobutin; Chloroambucil; Chlorbutine; Chlorbutin; Chlocambucil; Chlorambucil

Database IDs

• CAS Number: 305-03-3
• EC Number: 206-162-0
• MDL Number: MFCD00021783
• Beilstein Number: 999011
• PubChem SID: 24278287; 24853850; 46506842; 160963639
• PubChem CID: 2708
• CHEBI ID: 28830
• ATC CODE: L01AA02
• CHEMBL: 515
• Chemspider ID: 2607
• DrugBank ID: DB00291
• KEGG ID: D00266
• Unique Ingredient Identifier: 18D0SL7309
• Wikipedia Title: Chlorambucil
• Medline Plus: a682899

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.4555492
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 2.8512278
• LogD (pH = 7.4): 1.0883248
• Log P: 3.937155
• Molar Refractivity: 79.6828 cm^3
• Polarizability: 30.39351 Å^3
• Polar Surface Area: 40.54 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.81
• LOG S: -3.59
• Solubility (Water): 7.73e-02 g/l

PROPERTIES

Physical Property

• Solubility: 1.24E+004 mg/L
• Melting Point: 64-66°C; 65-70 °C
• Vapor Pressure: 5.7 x 10-8 mm Hg at 25 °C
• Hydrophobicity(logP): 3.9

Safety Information

• Storage Condition: 2-8°C
• RTECS: ES7525000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3; III
• Australian Hazchem: 2X
• Risk Statements: 45-25-36/37/38; R:25-45
• Safety Statements: 53-26-45; S:28-36/37/39-45-53
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• GHS Pictograms: GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H315-H319-H335-H350
• GHS Precautionary statements: P201-P261-P301 + P310-P305 + P351 + P338-P308 + P313
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: Oral
• Excretion: N/A
• Half Life: 1.5 hours
• Metabolism: Hepatic
• Legal Status: Rx-only
• Pregnancy Category: D (US)
• Gene Information: human ... CYP2D6(1565)

Product Information

• Purity: ≥98.0% (T)
• Grade: purum
• Empirical Formula (Hill Notation): C14H19Cl2NO2

DETAILS

MP Biomedicals - 02101346

Alkylating antitumor agent.
Can be covalently coupled to monoclonal anticarcinombryonic antigen.

DrugBank - DB00291

• Drug Groups: approved
• Description: A nitrogen mustard alkylating agent used as antineoplastic agent for the treatment of various malignant and nonmalignant diseases. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
• Indication: For treatment of chronic lymphatic (lymphocytic) leukemia, childhood minimal-change nephrotic syndrome, and malignant lymphomas including lymphosarcoma, giant follicular lymphoma, Hodgkin's disease, non-Hodgkin's lymphomas, and Waldenstr?m’s Macroglobulinemia.
• Pharmacology: Chlorambucil is an antineoplastic in the class of alkylating agents that is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
• Affected Organisms: Humans and other mammals
• Half Life: 1.5 hours
• Protein Binding: 99%
• Elimination: Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.
• References: Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [Pubmed] ; Yang K, Tan J, Wu T: Alkylating agents for Waldenstrom's macroglobulinaemia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006719. [Pubmed] ; Foon KA, Hallek MJ: Changing paradigms in the treatment of chronic lymphocytic leukemia. Leukemia. 2010 Mar;24(3):500-11. Epub 2009 Dec 24. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - C0253

Biochem/physiol Actions
Chlorambucil is an anti-cancer drug that alkylates DNA and induces apoptosis. Death of chronic lymphocytic leukemia cells occurs via a p53-dependent mechanism.

Sigma Aldrich - 23125

Other Notes
Alkylating antitumor agent, can be covalently coupled to monoclonal anticarcinoembryonic antigen1

REFERENCES

• Bernier, L.G., et al., Protides Biol. Fluids , 31 : 787 (1983).
• Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. Pubmed
• Yang K, Tan J, Wu T: Alkylating agents for Waldenstrom's macroglobulinaemia. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006719. Pubmed
• Foon KA, Hallek MJ: Changing paradigms in the treatment of chronic lymphocytic leukemia. Leukemia. 2010 Mar;24(3):500-11. Epub 2009 Dec 24. Pubmed