RTI-7470-44

• CAT Number: I043383
• CAS Number: 825658-63-7
• Molecular Formula: C19H11ClF3N5OS
• Molecular Weight: 449.84
• Purity: ≥95%
• Synonyms: 2-[6-(4-chlorophenyl)-3-cyano-4-(trifluoromethyl)pyridin-2-yl]sulfanyl-N-pyrimidin-2-ylacetamide
• InChI: InChI=1S/C19H11ClF3N5OS/c20-12-4-2-11(3-5-12)15-8-14(19(21,22)23)13(9-24)17(27-15)30-10-16(29)28-18-25-6-1-7-26-18/h1-8H,10H2,(H,25,26,28,29)
• InChIKey: WHNQNKYKDSLDKM-UHFFFAOYSA-N
• SMILES: C1=CN=C(N=C1)NC(=O)CSC2=C(C(=CC(=N2)C3=CC=C(C=C3)Cl)C(F)(F)F)C#N

RTI-7470-44 is a potent, selective and blood-brain barrier (BBB) penetrant human trace amine-associated receptor subtype 1 (hTAAR1) antagonist with an IC50 value of 8.4 nM and a Ki value of 0.3 nM. RTI-7470-44 has moderate metabolic stability, and a favorable preliminary off-target profile. RTI-7470-44 can increase the spontaneous firing rate of mouse ventral tegmental area (VTA) dopaminergic neurons. RTI-7470-44 can be used for researching schizophrenia, agent addiction, and Parkinson’s disease (PD)[1].
RTI-7470-44 (10 μM) shows little to no off-target activity with the exception of the benzylpiperazine (BZP) rat brain site and human sigma 2 with inhibition of 75 and 90%, respectively; has a moderate affinity for the BZP rat brain site (Ki=1 μM) and a very weak affinity for human sigma 2 (Ki=8.4 μM)[1].
RTI-7470-44 (40 μM) significantly increases the firing rate of dopaminergic neurons in VTA slices from DAT-IRES-Cre; td-Tomato mice, and reverses the inhibitory effect of RO5166017 (a TAAR1 agonist)[1].
RTI-7470-44 (10 μM) has decent stability in human liver microsomes, less stable in mouse liver microsomes and very poor stability in rat liver microsomes[1].
Stability of RTI-7470-44 in Human, Rat, and Mouse Liver Microsomes[1].

species
half-life (min)
clearance, CLINT (mL/min/mg)

Human
83.9
14.9

Rat
9.11
274

Mouse
65.8
63.5

Reference

[1]. Decker AM, et al. Identification of a Potent Human Trace Amine-Associated Receptor 1 Antagonist. ACS Chem Neurosci. 2022 Apr 6;13(7):1082-1095.
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