SB-705498 Struktur

SB-705498

Bezeichnung:SB-705498

CAS-Nr501951-42-4

Englisch Name:SB-705498

CBNumberCB22628383

SummenformelC17H16BrF3N4O

Molgewicht429.23

MOL-Datei501951-42-4.mol

SB-705498 physikalisch-chemischer Eigenschaften

Siedepunkt	506.9±50.0 °C(Predicted)
Dichte	1.59
storage temp.	-20°C
Löslichkeit	Soluble in DMSO (>25 mg/ml)
pka	13.00±0.20(Predicted)
Aggregatzustand	solid
Farbe	White
Stabilität	Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Gefahreninformationscode (GHS)

SB-705498 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
The transient receptor potential vanilloid type 1 (TRPV1) receptor is a nonselective cation channel gated by noxious heat, protons, and capsaicin . SB-705498 is an orally bioavailable, competitive antagonist of the capsaicin-mediated activation of TRPV1 receptors (pK_is = 7.6, 7.5, and 7.3 for human, rat, and guinea pig, respectively). It has been shown to induce rapid, reversible inhibition of capsaicin (IC₅₀ = 3 nM)-, acid (pH 5.3)-, or heat (50°C; IC₅₀ = 6 nM)-mediated activation of human TRPV1 (at -70 mV).
in vitro
using a ca2+-based fluorometric imaging plate reader (flipr) assay, sb-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the human trpv1 receptor (pki = 7.6) with activity at rat (pki = 7.5) and guinea pig (pki = 7.3) orthologs. sb-705498 caused rapid and reversible inhibition of the capsaicin (ic50 = 3 nm)-, acid (ph 5.3)-, or heat (50°c; ic50 = 6 nm)-mediated activation of human trpv1 (at =70 mv) [1].
in vivo
having initially demonstrated that sb-705498 showed good overall in vitro efficacy and oral bioavailability in rat, the in vivo activity of sb-705498 was investigated in the capsaicin-induced secondary hyperalgesia model9 in the rat. this model demonstrates the compound’s antagonist activity in vivo against the specific trpv1 agonist capsaicin. as an early indicator of potential pharmacodynamic activity, sb-705498 showed excellent activity at 10 and 30 mg/kg po with good reversal of allodynia. furthermore, sb-705498 was also shown to give 80% reversal of allodynia in the guinea pig fca model at 10 mg/kg po [2].
target
hTRPV1
Einzelnachweise
Rami et al. (2006), ?Discovery of SB-705498: a potent and orally bioavailable TRPV1 antagonist suitable for clinical development; Bioorg. Med. Chem. Lett., 16 3287 Gunthorpe et al. (2007), Characterization of SB-705498, a Potent and Selective Vanilloid Receptor-1 (VR1/TRPV1) Antagonist That Inhibits the Capsaicin-, Acid-, and Heat-Mediated Activation of the Receptor; J. Pharmacol. Exp. Ther., 321 1183

SB-705498 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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