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TC-N 1752

Names

[ CAS No. ]:
1211866-85-1

[ Name ]:
TC-N 1752

[Synonym ]:
Cyclohexanamine,N-(2-methyl-2-propenylidene)-,(E)
N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide
N-(2-methyl-2-propen-1-ylidene)cyclohexylamine
Cyclohexanamine,N-(2-methyl-2-propenylidene)

Biological Activity

[Description]:

TC-N 1752 is a potent and orally active inhibitor of Nav1.7, with IC50s of 0.17 μM, 0.3 μM, 0.4 μM, 1.1 μM and 2.2 μM at hNav1.7, hNav1.3, hNav1.4, hNaV1.5 and rNav1.8, respectively. TC-N 1752 also inhibits tetrodotoxin-sensitive sodium channels. TC-N 1752 shows analgesic efficacy in the Formalin model of pain[1][2][3].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel
Research Areas >> Neurological Disease

[Target]

hNav1.7:0.17 μM (IC50)

hNav1.3:0.3 μM (IC50)

hNav1.4:0.4 μM (IC50)

hNav1.5:1.1 μM (IC50)

hNav1.8:0.1 μM (IC50)


[In Vitro]

TC-N 1752 (compound 52) state-dependently inhibits Nav1.7, with IC50 of 170 nM on channels that are 20% inactivated and IC50 of 3.6 μM on fully noninactivated channels[1]. TC-N 1752 inhibits hNav1.7, hNav1.8, hNav1.9, rNav1.9, and mNav1.9 with IC50s of 0.2, 0.1, 1.6, 0.5 and 1.4 μM, respectively[2].

[In Vivo]

TC-N 1752 (compound 52) (3-30 mg/kg; p.o.) dose-dependently shows analgesic effect in the Formalin model[1]. TC-N 1752 (3-30 mg/kg; p.o.) decreases thermal hyperalgesia produced by inflammation[3]. TC-N 1752 (5 mg/mL; 500 μL; i.v.) attenuates complete Freund’s adjuvant (CFA)-induced sensitization of C-fiber nociceptors[3]. Animal Model: Rats were injected intraplantar with Formalin[1] Dosage: 3, 10, 20, 30 mg/kg Administration: Administered p.o. 120 min prior to Formalin Result: Showed analgesic efficacy starting at the dose of 3 mg/kg, with full efficacy at 20 mg/kg dose.

[References]

[1]. Bregman H, et, al. Identification of a potent, state-dependent inhibitor of Nav1.7 with oral efficacy in the formalin model of persistent pain. J Med Chem. 2011 Jul 14;54(13):4427-45.

[2]. Lin Z, et, al. Biophysical and Pharmacological Characterization of Nav1.9 Voltage Dependent Sodium Channels Stably Expressed in HEK-293 Cells. PLoS One. 2016 Aug 24;11(8):e0161450.

[3]. Matson DJ, et, al. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain. PLoS One. 2015 Sep 17;10(9):e0138140.

Chemical & Physical Properties

[ Density]:
1.37±0.1 g/cm3(Predicted)

[ Molecular Formula ]:
C25H27F3N6O3

[ Molecular Weight ]:
516.52

[ Exact Mass ]:
516.21000

[ PSA ]:
108.22000

[ LogP ]:
5.10260

[ Storage condition ]:
2-8°C

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds