Compounds > phenylenediamine mustard
Page last updated: 2024-11-06

phenylenediamine mustard

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Phenylenediamine mustard, also known as chlorambucil, is an alkylating agent used in chemotherapy to treat various types of cancers, including chronic lymphocytic leukemia, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. It is synthesized through a multi-step process involving the reaction of a nitrogen mustard with a phenylenediamine derivative. Chlorambucil exerts its anticancer effects by binding to DNA and inhibiting its replication, leading to cell death. Its ability to target rapidly dividing cancer cells makes it an effective treatment option for a range of malignancies. Research on phenylenediamine mustard continues to explore its efficacy in combination therapies, mechanisms of action, and potential side effects. The compound's importance lies in its contribution to the development of effective cancer therapies, particularly for hematologic malignancies. It is studied to gain a deeper understanding of its mechanism of action, optimize its therapeutic use, and identify potential new therapeutic targets.'

phenylenediamine mustard: RN given refers to parent cpd [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID74946
CHEMBL ID275497
SCHEMBL ID1269424
MeSH IDM0114637

Synonyms (17)

Synonym
n-(p-amino-phenyl)-nitrogen mustard
p-phenylenediamine, n,n-bis(2-chloroethyl)-
n-(p-amino-phenyl)-2,2'-dichlorodiethylamine
phenylenediamine mustard
brn 1641056
n,n-di(2-chloroethyl)-p-phenylenediamine
p-aminophenyl derivative of nitrogen mustard
n,n-bis(2-chloroethyl)-p-phenylenediamine
CHEMBL275497
4-n,4-n-bis(2-chloroethyl)benzene-1,4-diamine
2067-58-5
n,n-bis(2-chloroethyl)benzene-1,4-diamine
SCHEMBL1269424
HWAVIYAFGOQVNJ-UHFFFAOYSA-N
DTXSID00174715
n1,n1-bis(2-chloroethyl)benzene-1,4-diamine
EN300-8830166

Research Excerpts

Compound-Compound Interactions

ExcerptReferenceRelevance
"17-bL in combination with C-Dox."( Regressions and cures of melanoma xenografts following treatment with monoclonal antibody beta-lactamase conjugates in combination with anticancer prodrugs.
Hellström, I; Hellström, KE; Kerr, DE; Schreiber, GJ; Senter, PD; Svensson, HP; Vrudhula, VM, 1995)		0.29

Dosage Studied

ExcerptRelevanceReference
" S-9 activation was required in the Ames test using TA-100, and the dose-response curve, prior to toxicity, appeared biphasic."( A comparison of mutagenic and carcinogenic activities of aniline mustards.
Andrews, AW; Hansch, C; Leo, A; Panthananickal, A; Shimkin, M; Theiss, J, 1981)		0.26
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (35)

Assay IDTitleYearJournalArticle
AID67765Inhibitory activity against EMT6 murine cell line2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID1130929Antitumor activity against mouse B16 cells allografted in BDF mouse assessed as increase in life span at 1 mg/kg, ip administered for 9 days relative to untreated control1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Structure-activity relationship of aniline mustards acting against B-16 melanoma in mice.
AID231700Ratio between WiDr and WiDr-NTRneo was determined2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID231692Ratio between SKOV3 and SKOV3-NTR neo was determined2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID408372Selectivity ratio of IC50 for taxol-resistant human CCRF-CEM cells to IC50 for human CCRF-CEM cells2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID101151Cytotoxicity was evaluated against LS174T-stCPG2(Q)3-expressing cell clone1998Journal of medicinal chemistry, Dec-17, Volume: 41, Issue:26
Self-immolative nitrogen mustard prodrugs for suicide gene therapy.
AID28203Solubility in alpha-MEM culture medium; not determined2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID123958Compound was evaluated for low level mutagenicity1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
A comparison of mutagenic and carcinogenic activities of aniline mustards.
AID408352Cytotoxicity against vinblastine-resistant human CCRF-CEM cells after 72 hrs by XTT assay2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID408373Selectivity ratio of IC50 for vinblastine-resistant human CCRF-CEM cells to IC50 for human CCRF-CEM cells2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID231698Ratio between V79 and V79-NTRpuro was determined2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID124081Compound was evaluated for mutagenicity after threshold range1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
A comparison of mutagenic and carcinogenic activities of aniline mustards.
AID67762Cytotoxicity on EMT6 cells growth (reduce cell number by 50%).1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID1132032Stability of the compound in acetone assessed as hydrolysis at 66 degC after 30 mins1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Structure-activity relationships in antitumor aniline mustards.
AID215471Cytotoxicity on UV4 cells growth (reduce cell number by 50%).1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID231468Ratio between EMT6 and EMT6-NTRpuro was determined2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID200277Inhibitory activity was determined against SKOV3 cell line in human2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID408350Cytotoxicity against human CCRF-CEM cells after 72 hrs by XTT assay2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID408353Cytotoxicity against human MX1 cells after 72 hrs by SRB assay2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID215470The compound concentration to reduce plating efficiency of UV4 cells to 10% controls under aerobic conditions of 20% oxygen1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID408351Cytotoxicity against taxol-resistant human CCRF-CEM cells after 72 hrs by XTT assay2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID102183Inhibitory concentration was evaluated against colorectal tumar cell line LoVo1996Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5
New mustard prodrugs for antibody-directed enzyme prodrug therapy: alternatives to the amide link.
AID200281Cytotoxicity on SKOV3 cells growth (reduce cell number by 50%).1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID216594Inhibitory activity was determined against WiDr cell line in human2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID23577Kinetic parameter (half-life) was evaluated1998Journal of medicinal chemistry, Dec-17, Volume: 41, Issue:26
Self-immolative nitrogen mustard prodrugs for suicide gene therapy.
AID1132021Toxicity in rat allografted with rat Walker 256 cells1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Structure-activity relationships in antitumor aniline mustards.
AID124078Compound was evaluated for Carcinogenicity to produce 0.5 tumors per mouse (B.5)1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
A comparison of mutagenic and carcinogenic activities of aniline mustards.
AID1130920Antitumor activity against mouse B16 cells allografted in ip dosed BDF mouse assessed as 25% increase in life span administered for 9 days1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Structure-activity relationship of aniline mustards acting against B-16 melanoma in mice.
AID215469Compound concentration to reduce plating efficiency of UV4 cells to 10% controls under aerobic conditions of 20% oxygen to that under aerobic conditions of nitrogen1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID216750Inhibitory activity was determined against V79 cell line in chinese hamster2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy.
AID123956Compound was evaluated for Carcinogenicity based on concentration necessary to produce one tumor per mouse (Strain A)1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
A comparison of mutagenic and carcinogenic activities of aniline mustards.
AID1132020Antitumor activity against rat Walker 256 cells allografted in rat1978Journal of medicinal chemistry, Jan, Volume: 21, Issue:1
Structure-activity relationships in antitumor aniline mustards.
AID9829Cytotoxicity on AA8 cell growth (reduce cell number by 50%).1999Journal of medicinal chemistry, Feb-11, Volume: 42, Issue:3
N-Substituted 2-(2,6-dinitrophenylamino)propanamides: novel prodrugs that release a primary amine via nitroreduction and intramolecular cyclization.
AID408354Cytotoxicity against human HCT116 cells after 72 hrs by SRB assay2008Bioorganic & medicinal chemistry, May-15, Volume: 16, Issue:10
Synthesis and biological activity of stable and potent antitumor agents, aniline nitrogen mustards linked to 9-anilinoacridines via a urea linkage.
AID151790Cytotoxic concentration in vitro in well-oxygenated mammalian cells1994Journal of medicinal chemistry, Feb-04, Volume: 37, Issue:3
Relationships between structure and kinetics of cyclization of 2-aminoaryl amides: potential prodrugs of cyclization-activated aromatic mustards.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (12)

TimeframeStudies, This Drug (%)All Drugs %
pre-19904 (33.33)18.7374
1990's5 (41.67)18.2507
2000's3 (25.00)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.62

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.62 (24.57)
Research Supply Index2.71 (2.92)
Research Growth Index4.33 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.62)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other14 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
carbamates
[no description available]		2.0110amino-acid anion
chlorambucil
Chlorambucil: A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. 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). chlorambucil : A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.		2.3620aromatic amine;
monocarboxylic acid;
nitrogen mustard;
organochlorine compound;
tertiary amino compound		alkylating agent;
antineoplastic agent;
carcinogenic agent;
drug allergen;
immunosuppressive agent
sarkolysin
[no description available]		2.3620monocarboxylic acid
isoxazoles
Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.. isoxazole : A monocyclic heteroarene with a structure consisting of a 5-membered ring containing three carbon atoms and an oxygen and nitrogen atom adjacent to each other. It is the parent of the class of isoxazoles.. isoxazoles : Oxazoles in which the N and O atoms are adjacent.		1.9610isoxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
oxazoles
Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.. 1,3-oxazole : A five-membered monocyclic heteroarene that is an analogue of cyclopentadiene with O in place of CH2 at position 1 and N in place of CH at position 3.. oxazole : An azole based on a five-membered heterocyclic aromatic skeleton containing one N and one O atom.		1.96101,3-oxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
chlornaphazin
chlornaphazin: structure		1.9510naphthalenes
aniline mustard
Aniline Mustard: Alkylating anti-neoplastic agent.		2.6530
vinblastine
[no description available]		2.0410
4-n-bis(2-chloroethyl)aminobenzoic acid
4-N-bis(2-chloroethyl)aminobenzoic acid: structure given in first source		2.3720
phenacid
phenacid: RN given refers to parent cpd; structure		2.3720
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		2.0410taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
cephalosporin c
cephalosporin C: RN given refers to parent cpd; structure in Merck, 9th ed, #1937. cephalosporin C : A cephalosporin antibiotic carrying a 3-acetoxymethyl substituent and a 6-oxo-N(6)-L-lysino group at position 7.		1.9810cephalosporinfungal metabolite
hydroxyaniline mustard
hydroxyaniline mustard: structure; RN given refers to parent cpd		2.8840
tretazicar
tretazicar: minor descriptor (75-84); on-line & Index Medicus search AZIRIDINES (75-84)		2.0110
4-((2-chloroethyl) (2-mesyloxyethyl)amino)benzoic acid
4-((2-chloroethyl) (2-mesyloxyethyl)amino)benzoic acid: structure given in first source		2.420
4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid
4-((2-chloroethyl)(2-mesyloxyethyl)amino)benzoylglutamic acid: structure in first source		1.9910
4-n-bis(2-chloroethyl)aminobenzoylglutamic acid
4-N-bis(2-chloroethyl)aminobenzoylglutamic acid: structure given in first source		1.9910
acivicin
[no description available]		6.9610isoxazoles;
non-proteinogenic L-alpha-amino acid;
organochlorine compound		antileishmanial agent;
antimetabolite;
antimicrobial agent;
antineoplastic agent;
EC 2.3.2.2 (gamma-glutamyltransferase) inhibitor;
glutamine antagonist;
metabolite
melphalan
Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.. melphalan : A phenylalanine derivative comprising L-phenylalanine having [bis(2-chloroethyl)amino group at the 4-position on the phenyl ring.		2.0410L-phenylalanine derivative;
nitrogen mustard;
non-proteinogenic L-alpha-amino acid;
organochlorine compound		alkylating agent;
antineoplastic agent;
carcinogenic agent;
drug allergen;
immunosuppressive agent
bo-0742
BO-0742: a derivative of AHMA and N-mustard, has selective toxicity to drug sensitive and drug resistant leukemia cells and solid tumors		2.0410
ConditionIndicatedRelationship StrengthStudiesTrials
Malignant Melanoma
[description not available]		02.6630
Experimental Neoplasms
[description not available]		02.6630
Melanoma
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)		02.6630
Carcinoma 256, Walker
A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)		01.9510
Leukemia L 1210
[description not available]		01.9510
Experimental Leukemia
[description not available]		01.9510
Adenoma, Basal Cell
[description not available]		01.9610
Cancer of Lung
[description not available]		01.9610
Adenoma
A benign epithelial tumor with a glandular organization.		01.9610
Lung Neoplasms
Tumors or cancer of the LUNG.		01.9610
Colorectal Cancer
[description not available]		02.420
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		02.420
Cell Transformation, Neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.		01.9610
Cancer of Ovary
[description not available]		01.9610
Ovarian Neoplasms
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.		01.9610