Introduction：Basic information about CAS 659730-32-2|AMG-517, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | AMG-517 |
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| CAS Number | 659730-32-2 | Molecular Weight | 430.403 |
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| Density | 1.5±0.1 g/cm3 | Boiling Point | / |
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| Molecular Formula | C20H13F3N4O2S | Melting Point | 227ºC |
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| MSDS | / | Flash Point | / |
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Names
| Name | N-[4-[6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl]oxy-1,3-benzothiazol-2-yl]acetamide |
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| Synonym | More Synonyms |
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AMG-517 BiologicalActivity
| Description | AMG 517 is a potent and selective vanilloid receptor-1 (TRPV1) antagonist with an IC50 of 0.5 nM. |
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| Related Catalog | Signaling Pathways >>Membrane Transporter/Ion Channel >>TRP ChannelResearch Areas >>Neurological Disease |
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| Target | IC50: 0.5 nM (TRPV1)[1] |
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| In Vitro | AMG 517 retains potency in the capsaicin- and acid-mediated assays with IC50 values of 0.9 and 0.5 nM[1]. AMG 517 inhibits capsaicin, pH 5, and heat-induced45Ca2+ uptake into cells expressing TRPV1 with IC50 values of 1 to 2 nM. AMG 517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG 517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 ± 0.2 nM. AMG 517 is a competitive antagonist of both rat and human TRPV1 with dissociation constant (Kb) values of 4.2 and 6.2 nM, respectively[2]. |
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| In Vivo | AMG 517 is shown to be effective in a rodent “on-target” biochemical challenge model (capsaicin-induced flinch, ED50=0.33 mg/kg p.o.) and is antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED=0.83 mg/kg, p.o.)[1].The minimally effective dose is 0.3 mg/kg for AMG 517 and the corresponding plasma concentration is 90 ng/mL. Oral administration of AMG 517 reverses established thermal hyperalgesia in a dose-dependent manner at 21 h after CFA injection. AMG 517 causes transient hyperthermia in rodents, dogs, and monkeys. AMG 517 induces hyperthermia in a steep dose-dependent manner, with 0.3, 1, and 3 mg/kg associated with 0.5, 0.6, and 1.6°C increases in body temperature, respectively. Body temperatures of rats treated with all doses of AMG 517 return to baseline within 10 to 20 h[2]. |
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| Animal Admin | Rats: After multiple days of full habituation to the testing equipment and paradigm, CFA-induced thermal hyperalgesia is evaluated by measuring paw withdrawal latencies in male Sprague-Dawley rats. Twenty-one hours after CFA injection (50 μL of 0.1%), animals are dosed (p.o.) with AMG 517 or AMG8163 at a dose range of 0.001 to 30 mg/kg in a volume of 5 mL/kg. Two hours after drug dosing (23 h after CFA injection), paw withdrawal latencies are measured using modified Hargreaves hot boxes by investigators fully blinded to treatment conditions[2]. |
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| References | [1]. Doherty EM, et al. Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate. J Med Chem. 2007 Jul 26;50(15):3515-27. [2]. Gavva NR, et al. Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade. J Pharmacol Exp Ther. 2007 Oct;323(1):128-37. |
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Chemical & Physical Properties
| Density | 1.5±0.1 g/cm3 |
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| Melting Point | 227ºC |
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| Molecular Formula | C20H13F3N4O2S |
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| Molecular Weight | 430.403 |
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| Exact Mass | 430.071136 |
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| PSA | 108.73000 |
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| LogP | 5.41 |
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| Index of Refraction | 1.645 |
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| InChIKey | YUTIXVXZQIQWGY-UHFFFAOYSA-N |
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| SMILES | CC(=O)Nc1nc2c(Oc3cc(-c4ccc(C(F)(F)F)cc4)ncn3)cccc2s1 |
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| Storage condition | -20℃ |
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Synonyms
| BD-0082 |
| N-(4-(6-(4-(trifluoromethyl)phenyl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide |
| UNII-172V4FBZ75 |
| N-[4-({6-[4-(trifluoromethyl)phenyl]pyrimidin-4-yl}oxy)-1,3-benzothiazol-2-yl]acetamide |
| Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl]- |
| N-[4-({6-[4-(Trifluoromethyl)phenyl]-4-pyrimidinyl}oxy)-1,3-benzothiazol-2-yl]acetamide |
| N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl]-acetamide |
| AMG-517 |
| N-(4-(6-(4-trifluoromethylphenyl)pyrimidin-4-yloxy)benzothiazol-2-yl)acetamide |
| N-(4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl)-acetamide |
| AMG517 |
| AMG 517 |
