2-Methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide

Product Name2-Methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide
CAS883031-03-6
MFC26H28F3N3O2
MW471.51
EINECS
MOL File883031-03-6.mol

Chemical Properties

storage temp.	2-8°C
solubility	DMSO: ≥15mg/mL
form	powder
color	white to tan
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
InChIKey	NCZYSQOTAYFTNM-UHFFFAOYSA-N
SMILES	CC1=C(C(NC2=CC(C(F)(F)F)=CC=C2)=O)C=C(C3=CC=CC=C3)N1CCCN4CCOCC4

Safety Information

Hazard Codes	T
Risk Statements	25-36
Safety Statements	26-45
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Description

HC-067047 (883031-03-6) is a potent reversible and selective TRPV4 blocker. Active at mouse, human and rat TRPV4, IC50= 17, 48 and 133 nM respectively. Also inhibits the endogenous TRPV4-mediated response to 4α-PDH (IC50 = 22 nM). Selective for TRPV4 over TRPV1, TRPV2, TRPV3 and TRPM8 channels.1 Increases functional bladder capacity and reduces micturition frequency in mice and rats with cystitis.1 Inhibits brain edema in middle cerebral artery occlusion mice.2 HC-067047 induces an increase in core body temperature accompanied by increased oxygen consumption in Wistar rats.3Activein vivo.

Uses

HC-067047has been used as a transient receptor potential cation channel subfamily V member 4 (TRPV4)inhibitor:

to study its effects on organoid formation and proliferation in human endometrial tissues
to determine its effects on neuronal survival after intracerebral hemorrhage (ICH)
to study its effects on TRPV4 regulation of angiotensin II receptor type 1 (AT1R) task, phosphorylation and β-arrestin recruitment in choroid plexus

Biochem/physiol Actions

HC-067047 is a potent, selective inhibitor of hTRPV4. The compound inhibits human, rat and mouse TRPV4 with IC50 values of 48, 133 and 17 nM, respectively. HC-067047 does not inhibit other TRPV isoforms at concentrations up to 5 μM. HC-067047 inhibits hERG channel and the menthol receptor TRPM8 with IC50 values of 370 and 780 nM, respectively.

in vivo

HC-067047 (0-50 mg/kg; intraperitoneal injection; for 30 minutes; cyclophosphamide-treated WT and Trpv4^/ mice, and naive WT mice) treatment increases functional bladder capacity and reduces micturition frequency in WT mice with cystitis. HC-067047 do not affect bladder function in Trpv4^/ mice^[1].

Animal Model:	Cyclophosphamide-treated WT and Trpv4^/ mice, and naive WT mice^[1]
Dosage:	0 mg/kg, 1 mg/kg, 10 mg/kg, 50 mg/kg
Administration:	Intraperitoneal injection; for 30 minutes
Result:	Increased functional bladder capacity and reduces micturition frequency in WT mice with cystitis and did not affect bladder function in Trpv4^/ mice.

storage

+4°C

References

[1] WOUTER EVERAERTS. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2010: 19084-19089. DOI:10.1073/pnas.1005333107
[2] PINGHUI JIE. Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice.[J]. Frontiers in Cellular Neuroscience, 2015: 141. DOI:10.3389/fncel.2015.00141
[3] R. C. L. VIZIN. TRPV4 activates autonomic and behavioural warmth-defence responses in Wistar rats[J]. Acta Physiologica, 2015, 214 2: 275-289. DOI:10.1111/apha.12477

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