JNJ-41443532

• CAT Number: I007443
• CAS Number: 1228650-83-6
• Molecular Formula: C22H25F3N4O3S
• Molecular Weight: 482.52
• Purity: ≥95%
• Synonyms: N-[2-[[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide
• InChI: InChI=1S/C22H25F3N4O3S/c23-22(24,25)15-3-1-2-14(8-15)20(31)27-10-19(30)28-16-11-29(12-16)17-4-6-21(32,7-5-17)18-9-26-13-33-18/h1-3,8-9,13,16-17,32H,4-7,10-12H2,(H,27,31)(H,28,30)
• InChIKey: CFKBNYUHQSQBSX-UHFFFAOYSA-N
• SMILES: C1CC(CCC1N2CC(C2)NC(=O)CNC(=O)C3=CC(=CC=C3)C(F)(F)F)(C4=CN=CS4)O

JNJ-41443532 (CCR2 antagonist 5) is a selective, orally active hCCR2 inhibitor with good binding affinity (IC50=37 nM) and potent functional antagonism (chemotaxis IC50=30 nM). JNJ-41443532 displays a Ki of 9.6 µM for mCCR2 binding. JNJ-41443532 can be used in the research of inflammatory disease[1].
JNJ-41443532 (compound 8d) dose-dependently inhibits the influx of leukocytes, monocytes/macrophages and T-lymphocytes into the peritoneal cavity with an ED50 of 3 mg/kg p.o. bid in a thioglycollate-induced peritonitis (TG) model[1].
JNJ-41443532 has good CV safety profile. It does not induce dose-dependent or notable effects on most cardiohemodynamic, functional respiratory and electrophysiological parameters up to 10 mg/kg (i.v.) with plasma level at 70 µM in an anesthetized dog[1].
JNJ-41443532 has amendable oral bioavailability in dogs and primates. Pharmacokinetic parameters (p.o.)[1]:

Species
Dose(mg/kg)
Cmax(ng/mL)
AUClast(h*ng/mL)
Oral bioavailability(%)

dogs
6.7
1617
5887
70.2

non-human primates
7.2
740
3061
25.4

mice
10
74
204
19

rats
10
100
416
15.3

Reference

[1]. Zhang X, et al. Discovery of a 4-Azetidinyl-1-thiazoyl-cyclohexane CCR2 Antagonist as a Development Candidate. ACS Med Chem Lett. 2012 Oct 8;3(12):1039-44.
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