MK-0249

• CAT Number: I032376
• CAS Number: 862309-06-6
• Molecular Formula: C23H24F3N3O2
• Molecular Weight: 431.45
• Purity: ≥95%
• Synonyms: 2-methyl-3-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-5-(trifluoromethyl)quinazolin-4-one
• InChI: InChI=1S/C23H24F3N3O2/c1-16-27-20-7-4-6-19(23(24,25)26)21(20)22(30)29(16)17-8-10-18(11-9-17)31-15-5-14-28-12-2-3-13-28/h4,6-11H,2-3,5,12-15H2,1H3
• InChIKey: DDDZBLNULGDPGA-UHFFFAOYSA-N
• SMILES: CC1=NC2=CC=CC(=C2C(=O)N1C3=CC=C(C=C3)OCCCN4CCCC4)C(F)(F)F

MK-0249 (Compound 1) is a potent, selective and orally active histamine H3 receptor antagonist, with an IC50 of 1.7 nM for human H3[1].
MK-0249 (Compound 1) shows very good hepatic clearance values (CLh e 11 mL/min/kg), and is a substrate for rat P-gp but not for human P-gp[1].
MK-0249 displays potent binding affinity to human, rat, and rhesus H3 receptors with Ki values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM, respectively[1]. MK-0249 shows high intrinsic activity[1].
MK-0249 (Compound 1) (0-30 mg/kg; p.o.; once) elevates histamine levels in the rat brain in a dose-dependent manner[1].
MK-0249 (10 mg/kg; p.o.; once) shows markedly higher brain penetrability and a lower plasma Occ90 value in mdr1a (-/-) mice than in mdr1a (+/+) mice[1].
MK-0249 shows rodent brain permeability and is significantly limited by P-gp mediated efflux in rodents, whereas the extent of P-gp mediated efflux in humans should be very small or negligible[1].

Reference

[1]. Nagase T, et al. Synthesis, structure-activity relationships, and biological profiles of a quinazolinone class of histamine H3 receptor inverse agonists. J Med Chem. 2008 Aug 14;51(15):4780-9.
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