BBS-4

• CAT Number: I004087
• CAS Number: 402934-09-2
• Molecular Formula: C22H24N6O3
• Molecular Weight: 420.46
• Purity: ≥95%
• Synonyms: (2R)-N-[2-(1,3-benzodioxol-5-yl)ethyl]-1-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)pyrrolidine-2-carboxamide
• InChI: InChI=1S/C22H24N6O3/c1-15-11-20(26-22(25-15)27-10-8-23-13-27)28-9-2-3-17(28)21(29)24-7-6-16-4-5-18-19(12-16)31-14-30-18/h4-5,8,10-13,17H,2-3,6-7,9,14H2,1H3,(H,24,29)/t17-/m1/s1
• InChIKey: LBCGUKCXRVUULK-QGZVFWFLSA-N
• SMILES: CC1=CC(=NC(=N1)N2C=CN=C2)N3CCCC3C(=O)NCCC4=CC5=C(C=C4)OCO5

BBS-4 is a potent and selective inducible nitric oxide synthase (NOS2) dimerization inhibitor, with an IC50 of 0.49 nM. BBS-4 can protect mice from the cardiovascular dysfunction of sepsis[1].
BBS-4 exhibits ∼300–2000-fold selective for inhibiting iNOS dimerization in cells versus CYP-3A4 (∼150 nM in a microsomal benzyloxyresorufin assay; ∼1 μM in a cell-based testosterone hydroxylase assay)[2].
BBS-4 (10 mg/kg; i.p.; 1 h after endotoxin administration) prevents endotoxin-induced hypotension in mice[1].
BBS-4 (30 mg/kg; i.p.; 1 h after endotoxin administration) prevents endotoxin-induced myocardial dysfunction in mice[1].
BBS-4 (10 mg/kg; i.p.; 1 and 8 h after endotoxin administration) prevents endotoxin-induced impairment of murine hypoxic pulmonary vasoconstriction (HPV)[1].
BBS-4 (10 mg/kg; i.p.; 1 and 8 h after endotoxin administration) does not affect the endotoxin-induced increase in pulmonary NOS2 gene expression, but it (30 mg/kg) prevents cardiac and pulmonary NOS2 protein dimerization and increases plasma nitrate and nitrite (NOx) concentration in mice[1].
BBS-2 (30 mg/kg; s.c. twice daily for 10 d) does not affect agonist-stimulated NOS3-dependent aortic relaxation ex vivo[1].
BBS-4 (10-30 mg/kg; i.p.) does not improve mortality rate in endotoxemic mice[1].

Reference

[1]. Ichinose F, et, al. A selective inducible NOS dimerization inhibitor prevents systemic, cardiac, and pulmonary hemodynamic dysfunction in endotoxemic mice. Am J Physiol Heart Circ Physiol. 2003 Dec; 285(6): H2524-30.
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[2]. https://pubmed.ncbi.nlm.nih.gov/12907425/
 [Content Brief]