JNJ-17203212 - CAS 821768-06-3
Catalog number: 821768-06-3
Category: Inhibitor
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Molecular Formula:
C17H15F6N5O
Molecular Weight:
419.32
COA:
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Targets:
TRP Channel
Description:
JNJ-17203212 is a novel, reversible, and selective TRPV1 antagonist which could not inhibit related TRP channels. Its IC50 values are 65 nM and 102 nM for human TRPV1 and rat TRPV1. It could reduce sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. It inhibits capsaicin- and H+-induced channel activation, which pIC50 values are 6.32 and 7.23 respectively. It exhibits antitussive and analgesic activity in vivo.
Purity:
>99 %
Appearance:
Solid powder
Synonyms:
JNJ-17203212; JNJ 17203212; JNJ17203212. 4-[3-(Trifluoromethyl)-2-pyridinyl]-N-[5-(trifluoromethyl)-2-pyridinyl]-1-piperazinecarboxamide;1-PiperazinecarboxaMide, 4-[3-(trifluoroMethyl)-2-pyridinyl]-N-[5-(trifluoroMethyl)-2-pyridinyl]-;N1-(3-Trifluoromethylpyrid-2-yl)-N4-(4-trifluoromethylpyrid-2-yl)carbamoylpiperazine
Solubility:
10 mM in DMSO
Storage:
-20°C Freezer
MSDS:
Inquire
Application:
JNJ-17203212 could reduce sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. It inhibits capsaicin- and H+-induced channel activation. It exhibits antitussive and analgesic activity in vivo.
Quality Standard:
In-house standard
Shelf Life:
2 month in rt, long time
Quantity:
Milligrams-Grams
Boiling Point:
551.3±50.0 °C | Condition: Press: 760 Torr
Density:
1.472±0.06 g/cm3 | Condition: Temp: 20 °C Press: 760 Torr
InChIKey:
JFRYYGVYCWYIDQ-UHFFFAOYSA-N
InChI:
InChI=1S/C17H15F6N5O/c18-16(19,20)11-3-4-13(25-10-11)26-15(29)28-8-6-27(7-9-28)14-12(17(21,22)23)2-1-5-24-14/h1-5,10H,6-9H2,(H,25,26,29)
Canonical SMILES:
C1CN(CCN1C2=C(C=CC=N2)C(F)(F)F)C(=O)NC3=NC=C(C=C3)C(F)(F)F
1.Pharmacology and antitussive efficacy of 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs.
Bhattacharya A;Scott BP;Nasser N;Ao H;Maher MP;Dubin AE;Swanson DM;Shankley NP;Wickenden AD;Chaplan SR J Pharmacol Exp Ther. 2007 Nov;323(2):665-74. Epub 2007 Aug 9.
Transient receptor potential vanilloid 1 (TRPV1) plays an integral role in modulating the cough reflex, and it is an attractive antitussive drug target. The purpose of this study was to characterize a TRPV1 antagonist, 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), against the guinea pig TRPV1 receptor in vitro followed by a proof-of-principle study in an acid-induced model of cough. The affinity of JNJ17203212 for the recombinant guinea pig TRPV1 receptor was estimated by radioligand binding, and it was functionally characterized by antagonism of low-pH and capsaicin-induced activation of the ion channel (fluorometric imaging plate reader and electrophysiology). The nature of antagonism was further tested against the native channel in isolated guinea pig tracheal rings. Following pharmacokinetic characterization of JNJ17203212 in guinea pigs, pharmacodynamic and efficacy studies were undertaken to establish the antitussive efficacy of the TRPV1 antagonist. The pK(i) of JNJ17203212 for recombinant guinea pig TRPV1 was 7.14 +/- 0.06. JNJ17203212 inhibited both pH (pIC(50) of 7.23 +/- 0.05) and capsaicin (pIC(50) of 6.
2.Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents.
Hofmann ME;Andresen MC PLoS One. 2017 Mar 30;12(3):e0174915. doi: 10.1371/journal.pone.0174915. eCollection 2017.
The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release-spontaneous, evoked, and asynchronous release-at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 μM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction-a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC.
3.Two TRPV1 receptor antagonists are effective in two different experimental models of migraine.
Meents JE;Hoffmann J;Chaplan SR;Neeb L;Schuh-Hofer S;Wickenden A;Reuter U J Headache Pain. 2015;16:57. doi: 10.1186/s10194-015-0539-z. Epub 2015 Jun 24.
BACKGROUND: ;The capsaicin and heat responsive ion channel TRPV1 is expressed on trigeminal nociceptive neurons and has been implicated in the pathophysiology of migraine attacks. Here we investigate the efficacy of two TRPV1 channel antagonists in blocking trigeminal activation using two in vivo models of migraine.;METHODS: ;Male Sprague-Dawley rats were used to study the effects of the TRPV1 antagonists JNJ-38893777 and JNJ-17203212 on trigeminal activation. Expression of the immediate early gene c-fos was measured following intracisternal application of inflammatory soup. In a second model, CGRP release into the external jugular vein was determined following injection of capsaicin into the carotid artery.;RESULTS: ;Inflammatory up-regulation of c-fos in the trigeminal brain stem complex was dose-dependently and significantly reduced by both TRPV1 antagonists. Capsaicin-induced CGRP release was attenuated by JNJ-38893777 only in higher dosage. JNJ-17203212 was effective in all doses and fully abolished CGRP release in a time and dose-dependent manner.;CONCLUSION: ;Our results describe two TRPV1 antagonists that are effective in two in vivo models of migraine. These results suggest that TRPV1 may play a role in the pathophysiological mechanisms, which are relevant to migraine.
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CAS 821768-06-3 JNJ-17203212

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