RQ-00203078 Chemical Properties

Boiling point:

602.0±65.0 °C(Predicted)

Density 

1.588±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

insoluble in H2O; ≥18.85 mg/mL in DMSO; ≥27.25 mg/mL in EtOH

form 

solid

pka

3.39±0.10(Predicted)

color 

White to off-white

InChI

InChI=1S/C21H13ClF6N2O5S/c22-17-9-14(20(23,24)25)10-29-18(17)30(11-12-1-5-15(6-2-12)35-21(26,27)28)36(33,34)16-7-3-13(4-8-16)19(31)32/h1-10H,11H2,(H,31,32)

InChIKey

IJGQFZYYEHCCIZ-UHFFFAOYSA-N

SMILES

C(O)(=O)C1=CC=C(S(N(C2=NC=C(C(F)(F)F)C=C2Cl)CC2=CC=C(OC(F)(F)F)C=C2)(=O)=O)C=C1

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

Hazard Classifications

Eye Irrit. 2
Skin Irrit. 2
STOT SE 3

RQ-00203078 Usage And Synthesis

Description

RQ-00203078 is a selective antagonist of transient receptor potential melastatin 8 (TRPM8; IC₅₀s = 8.3 and 5.8 nM in human and rat, respectively), while having little inhibitory action against TRPV1 (IC₅₀ > 30 μM), TRPA1 (IC₅₀ > 10 μM), TRPV4 (IC₅₀ = 10 μM), or TRPM2 channels (IC₅₀ > 10 μM). It attenuates icilin-induced wet-dog shakes in rats (ED₅₀ = 0.65 mg/kg) after oral administration. RQ-00203078 has been shown to reduce HSC3 and HSC4 oral squamous carcinoma cell migration and invasion in vitro. TRPM8, a member of the TRP melastatin subgroup, plays a role in cold hyperalgesia and cold allodynia caused by disease conditions such as chemotherapy-induced peripheral neuropathy, diabetic neuropathy, migraine, and overactive bladder. It is also known to be involved in the tumor progression of certain carcinomas.

Uses

RQ 00203078 is a selective and orally active TRPM8 antagonist.

in vitro

in the menthol-induced calcium influx assay, rq-00203078 is a novel and highly potent trpm8 antagonist with human and rat ic50 values of 8.3 nm and 5.8 nm, respectively. rq-00203078 was highly selective over other trp channels [1].

in vivo

rq-00203078 demonstrated excellent activity in vivo in a dose dependent manner with an ed50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration [1].

IC 50

8.3 and 5.8 nm for htrpm8 and rtrpm8, respectively

storage

Store at +4°C

References

[1] ohmi m, shishido y, inoue t, ando k, fujiuchi a, yamada a, watanabe s, kawamura k. identification of a novel 2-pyridyl-benzensulfonamide derivative, rq-00203078, as a selective and orally active trpm8 antagonist. bioorg med chem lett. 2014 dec 1;24(23):5364-8.