AZD-5672

Product NameAZD-5672
CAS780750-65-4
MFC32H38F2N2O5S2
MW632.78
EINECS
MOL File780750-65-4.mol

Chemical Properties

Boiling point	800.4±65.0 °C(Predicted)
Density	1.33±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
form	Solid
pka	8.54±0.20(Predicted)
color	White to light brown

Usage And Synthesis

Uses

AZD-5672 is an orally active, potent, and selective CCR5 antagonist (IC50=0.32 nM). AZD-5672 shows moderate activity against the hERG ion channel (binding IC50=7.3 μM). AZD5672 is a substrate of human P-gp, and inhibits P-gp-mediated digoxin transport (IC50=32 μM). AZD-5672 can be used for the research of rheumatoid arthritis[1][2][3].

in vivo

In vivo pharmaeokineties data for AZD-5672 (compound 1)^[1]

Species	CI^a (mL/min/kg)	V_ss^a (L/kg)	t_1/2^a (h)	F^b (%)
Rat	28	5.3	2.6	38
Dog	18	5.7	3.9	86

^a AZD-5672 dosed 1-2 mg/kg i.v.
^b AZD-5672 dosed 2-5 mg/kg p.o.

IC 50

CCR5: 0.32 nM (IC₅₀); hERG: 7.3 μM (IC₅₀); hP-gp: 32 μM (IC₅₀)

References

[1] Cumming JG, et al. Balancing hERG affinity and absorption in the discovery of AZD5672, an orally active CCR5 antagonist for the treatment of rheumatoid arthritis. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1655-9. DOI:10.1016/j.bmcl.2011.12.117
[2] Elsby R, et al. The utility of in vitro data in making accurate predictions of human P-glycoprotein-mediated drug-drug interactions: a case study for AZD5672. Drug Metab Dispos. 2011 Feb;39(2):275-82. DOI:10.1124/dmd.110.035881
[3] Gerlag DM, et al. Preclinical and clinical investigation of a CCR5 antagonist, AZD5672, in patients with rheumatoid arthritis receiving methotrexate. Arthritis Rheum. 2010 Nov;62(11):3154-60. DOI:10.1002/art.27652