Bropirimine

Bropirimine is an experimental drug with anti-cancer and antiviral properties.^{[citation needed]} It is an orally effective immunomodulator and is being tried in bladder cancers.^[1]

Bropirimine

Clinical data
ATC code	none
Identifiers
IUPAC name 2-amino-5-bromo-6-phenylpyrimidin-4(1H)-one
CAS Number	56741-95-8
ChemSpider	58914
UNII	J57CTF25XJ
ChEMBL	ChEMBL37387
CompTox Dashboard (EPA)	DTXSID5046803
ECHA InfoCard	100.231.001
Chemical and physical data
Formula	C10H8BrN3O
Molar mass	266.098 g·mol−1
3D model (JSmol)	Interactive image
SMILES Br\C2=C(/c1ccccc1)N\C(=N/C2=O)N
InChI 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) Key:CIUUIPMOFZIWIZ-UHFFFAOYSA-N

Synthesis

Bropirimine synthesis:^[2] other syntheses:^[3][4]

For the first step, the dianion from malonic acid half-ester is formed by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the carbanion, which is more nucleophilic (because of the higher charge density). This tricarbonyl compound decarboxylates on acidification to the β-ketoester. Condensation with guanidine leads to the pyrimidone. NBS mediated bromination then gives bropirimine.

References

1. Akaza H, Kotake T, Machida T (August 1998). "Bropirimine, an orally active anticancer agent for superficial bladder cancer". European Urology. 34 (2): 107–10. doi:10.1159/000019693. PMID 9693244. S2CID 46069874.
2. Skulnick HI, Weed SD, Eidson EE, Renis HE, Wierenga W, Stringfellow DA (December 1985). "Pyrimidinones. 1. 2-Amino-5-halo-6-aryl-4(3H)-pyrimidinones. Interferon-inducing antiviral agents". Journal of Medicinal Chemistry. 28 (12): 1864–9. doi:10.1021/jm00150a018. PMID 2999405.
3. Brown TB, Stevens MF (1975). "Triazines and related products. Part XV. 2,4-Diaminopyrimidines and 2-aminopyrimidin-4(3H)-ones bearing 1,2,3-benzotriazinyl groups as potential dihydrofolic reductase inhibitors". Journal of the Chemical Society, Perkin Transactions 1 (11): 1023–8. doi:10.1039/p19750001023. PMID 1170192.
4. Stevens MF, Baig GU, Gate EN, Wheelhouse RT (April 1995). "Structural studies on bioactive compounds. Part 27. Chemistry of the immunomodulatory agent bropirimine". Anti-Cancer Drug Design. 10 (3): 215–26. PMID 7748456.