BROPIRIMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H8BrN3O
Molecular Weight	266.094
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(C2=CC=CC=C2)=C(Br)C(=O)N1

InChI

InChIKey=CIUUIPMOFZIWIZ-UHFFFAOYSA-N

InChI=1S/C10H8BrN3O/c11-7-8(6-4-2-1-3-5-6)13-10(12)14-9(7)15/h1-5H,(H3,12,13,14,15)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9076483
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16301114 | https://www.ncbi.nlm.nih.gov/pubmed/9020948 | https://www.ncbi.nlm.nih.gov/pubmed/26399683

Bropirimine, an immunostimulating agent, and toll-like receptor (TLR7) agonist, with anti-cancer and antiviral properties. Bropirimine may be used in experimental autoimmune encephalomyelitis (EAE) and bladder cancer research. Bropirimine is an immunostimulating agent. The compound induces production of α and β interferons and enhances NK cell function. Bropirimine has antiproliferative effects in cancer cell lines and tumor growth in in vivo models.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Toll-like receptor 7 13 Target ID: CHEMBL5936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26399683	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Bladder cancer 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16301114	Primary	Phase II 1147	Unknown Approved Use Unknown
Renal cell carcinoma 33 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9020948	Primary	Phase II 1147	Unknown Approved Use Unknown
malignant lymphoma 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9020948	Primary	Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
1 g 3 times / day multiple, oral Highest studied dose Dose: 1 g, 3 times / day Route: oral Route: multiple Dose: 1 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8693647/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8693647/	Disc. AE: Pruritic rash, Nausea... AEs leading to discontinuation/dose reduction: Pruritic rash (4.2%) Nausea (4.2%) Vomiting (4.2%) Bone pain (grade 3, 4.2%) Elevated liver enzyme levels (4.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/8693647/
1 g 3 times / day multiple, oral Highest studied dose Dose: 1 g, 3 times / day Route: oral Route: multiple Dose: 1 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9495702/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9495702/	Disc. AE: Neutropenia, Lymphocytopenia... Other AEs: Lymphocytopenia, Hyperglycemia... AEs leading to discontinuation/dose reduction: Neutropenia (grade 3, 1.2%) Lymphocytopenia (grade 4, 2.3%) Thrombocytopenia (grade 4, 1.2%) Bilirubin increased (grade 4, 1.2%) Hyperglycemia (grade 4, 1.2%) Hyperglycemia (grade 4, 1.2%) Other AEs: Lymphocytopenia (grade 3, 20.9%) Hyperglycemia (grade 3, 3.5%) Aspartate aminotransferase increase (grade 3, 5.8%) AST increased (grade 3, 7%) Sources: https://pubmed.ncbi.nlm.nih.gov/9495702/
750 mg 3 times / day multiple, oral Studied dose Dose: 750 mg, 3 times / day Route: oral Route: multiple Dose: 750 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9693244/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/9693244/	Other AEs: Palpitations, Arthralgia... Other AEs: Palpitations (grade 3, 5.9%) Arthralgia (grade 3, 5.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/9693244/

AEs

PubMed

Title	Date	PubMed
Toll-like receptors: role in dermatological disease.	2010	20847936
The expression and functions of toll-like receptors in atherosclerosis.	2010	20652007
Intravesical hyperthermia and mitomycin-C for carcinoma in situ of the urinary bladder: experience of the European Synergo working party.	2009-06	19234857
Current state of immunotherapy for bladder cancer.	2004-12	15606331
Current and new strategies in immunotherapy for superficial bladder cancer.	2004-09	15351555
Superficial bladder cancer therapy.	2004-06-28	15349563
Characterization of bropirimine O-glucuronidation in human liver microsomes.	2003-10	14555337
Recognition of pathogen-associated molecular patterns by TLR family.	2003-01-22	12527213
In vitro antitumor activity of bropirimine against urinary bladder tumor cells.	2002-08-10	12168852
A phase II clinical trial of oral bropirimine in combination with intravesical bacillus Calmette-Guérin for carcinoma in situ of the bladder: a Southwest Oncology Group Study.	2002-03-26	16301114
The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder.	2001-03	11176460
Immunotherapy for bladder cancer.	2001-02	12084297
Lack of interaction between bropirimine and 5-fluorouracil on human dihydropyrimidine dehydrogenase.	2001-01	11334264
Antiviral and immunomodulating inhibitors of experimentally-induced Punta Toro virus infections.	1994-10	7847873
Protection from carcinogen-induced murine bladder carcinoma by interferons and an oral interferon-inducing pyrimidinone, bropirimine.	1990-02-15	2297754
Pyrimidinones. 1. 2-Amino-5-halo-6-aryl-4(3H)-pyrimidinones. Interferon-inducing antiviral agents.	1985-12	2999405
Antiviral and other bioactivities of pyrimidinones.	1985	2428070
5-substituted 2-amino-6-phenyl-4(3H)-pyrimidinones. Antiviral- and interferon-inducing agents.	1980-03	7365739

Patents

Sample Use Guides

In Vivo Use Guide

Initially, daily dosage was 4.5 grams in three divided doses of 1.5 gram every two hours. A dose reduction to 3.0 gm. per day was made after recognition of possible cardiac toxicity in other studies that were ongoing simultaneously. Bropirimine was taken for 12 consecutive weeks

Route of Administration: Oral

In Vitro Use Guide

Bone marrow cells (BMCs) were collected from femora and tibiae of 6-week-old male C57BL/6 mice, and cultured for 6 h in alphaMEM containing 10% fetal bovine serum (FBS) in Petri dishes. Mouse BMCs (1 x 105 cells/well) and mouse osteoblastic UAMS- 32 cells were co-cultured in 96-well plates for 4 days in aMEM supplemented with 10% FBS in the absence or presence of 1alpha,25(OH)2D3 (10 nmol/L), and various concentrations of bropirimine. Medium was replaced with fresh containing the same supplemental agents on day 3. As described above, TRAP activity staining was employed to evaluate osteoclast differentiation.

Name

Type

Language

BROPIRIMINE

Official Name

English

U-54,461

Preferred Name

English

bropirimine [INN]

Common Name

English

BROPIRIMINE [MI]

Common Name

English

U-54461

Code

English

BROPIRIMINE [JAN]

Common Name

English

NSC-149027

Code

English

BROPIRIMINE [MART.]

Common Name

English

BROPIRIMINE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2139