Grapiprant
Grundinformationen
- CAS
415903-37-6- Standard-SMILES
CCc1nc2c(C)nc(C)cc2n1-c1ccc(CCNC(=O)NS(=O)(=O)c2ccc(C)cc2)cc1- InChIKey
HZVLFTCYCLXTGV-UHFFFAOYSA-N- Summenformel
- C26H29N5O3S
- Durchschnittliche Molmasse
- 491,6 g/mol
- Monoisotopische Masse
- 491,19911098
Überblick
Grapiprant, also known as AT-001 and CJ-023, is a drug from the piprant class. These molecules were derived from acylsulfonamide and are characterized to be a novel series of para-N-acylaminomethylbenzoic acid known to be prostaglandin receptor antagonists. This type of molecules is currently in development for veterinary patients. This class of drugs was defined in 2013 by the World Health Organization. Grapiprant has been approved in March 2016 by the FDA's Center for Veterinary Medicine as a non-cyclooxygenase inhibiting NSAID for veterinary use.
Namen und Bezeichner
- Bevorzugter Name
- Grapiprant
- IUPAC
- 1-[2-[4-(2-ethyl-4,6-dimethylimidazo[4,5-c]pyridin-1-yl)phenyl]ethyl]-3-(4-methylphenyl)sulfonylurea
- Englischer Name
- Grapiprant
- Summenformel
- C26H29N5O3S
- Molmasse
- 491.61
Namen und Synonyme
Grapiprant415903-37-6CJ-023423CJ 023423CJ-023,423AAT-007MR-10A7CJ-023MR10A7RQ-00000007J9F5ZPH7NB1-[2-[4-(2-ethyl-4,6-dimethylimidazo[4,5-c]pyridin-1-yl)phenyl]ethyl]-3-(4-methylphenyl)sulfonylurea
Weitere Namen anzeigen
N-((4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenethyl)carbamoyl)-4-methylbenzenesulfonamideRQ 7MR 10A7AAT 007CS-1556GrprantGrapironGraprantKoplante
DTXSID60194419Benzenesulfonamide, N-(((2-(4-(2-ethyl-4,6-dimethyl-1H-imidazo(4,5-c)pyridin-1-yl)phenyl)ethyl)amino)carbonyl)-4-methyl-1-(2-(4-(2-ethyl-4,6-dimethylimidazo(4,5-c)pyridin-1-yl)phenyl)ethyl)-3-(4-methylphenyl)sulfonylureagrapiprantumGalliprant3-(2-(4-(2-ethyl-4,6-dimethyl-1H-imidazo(4,5-c)pyridin-1-yl)phenyl)ethyl)-1-(4-methylbenzenesulfonyl)urea3-[2-(4-{2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl}phenyl)ethyl]-1-(4-methylbenzenesulfonyl)ureaRefChem:57297
Datenbank-Bezeichner
- CAS
415903-37-6
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 4,6
- Polarare Oberfläche (TPSA)
- 114 Ų
- H-Brücken-Donoren
- 2
- H-Brücken-Akzeptoren
- 5
- Frei drehbare Bindungen
- 7
- Schwere Atome
- 35
- Formalladung
- 0
- Komplexität
- 802
Experimentelle und physikochemische Eigenschaften
DrugsPharmaceuticals -> Listed in ZINC15
SolubilityInsoluble
Animal Drugs
EMA approved medicines: Veterinary medicine
FDA approved animal drugs -> Active ingredient
Pharmaceuticals -> UK Veterinary Medicines Directorate List
Melting Point>136 ºC (Grapiprant hydrochloride)
Physikochemische Eigenschaften
- Schmelzpunkt
- 151 °C · >151°C (dec.)
- Dichte
- 1.29 · 1.29±0.1 g/cm3(Predicted)
- storage temp.
- -20 °C · Sealed in dry,Store in freezer, under -20°C
- Löslichkeit
- Soluble in DMSO (up to at least 10 mg/ml)
- pka
- 5.19 · 5.19±0.10(Predicted)
- Aggregatzustand
- solid
- Farbe
- Off-white
Sicherheit und Regulatorisches
Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.
GHS-Klassifizierung
GHS Classification
Warning
H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.
Gefahrenhinweise
Hazard Classes and CategoriesAcute Tox. 4 (100%)
Sicherheitsdaten
- wgk
- WGK 3
- Speicherklasse
- 11 - Combustible Solids
- Hazard Classifications
- Acute Tox. 4 Oral
Chemie und Industrie
Pharmakologische Informationen
ATC CodeQM - Musculo-skeletal system
Protein BindingThe serum protein binding of grapiprant was of about 95%. The main protein that binds to grapiprant is albumin.
Pharmacodynamics
Preclinical studies have shown that grapiprant is very effective to reduce acute and chronic pain and inflammation. The effect of grapiprant seems to be dose-dependent and it is comparable to the effect of rofecoxib and piroxicam. The effects of grapiprant have been reported to be effective in the relief from arthritic pain in canine patients.
Mechanism of Action
Grapiprant is an EP4 prostaglandin receptor antagonist and thus the activity of this drug is thought to be completely related to the selective blockade of this receptor. It binds to human and other mammals EP4 prostaglandin receptor with high affinity without interfering with other prostaglandin pathways which are important for a variety of physiological functions. The binding of grapiprant blocks PGE2 binding and hence its biological effect related to the signaling pain and inflammation cascade. Grapiprant has been accepted very greatly in veterinary as its mechanism of action is a targeted approach to pain management by not having any interaction with the production of prostanoids and thus, by not interacting with other prostaglandin receptor pathways.
Biological Half-LifeThe reported elimination half-life in animal studies (horse) is of 5.86 hours.
Metabolism/Metabolites_In vitro_ studies with dog microsomes have reported the identification of four metabolites, an N-deamination metabolite which is the major metabolite in urine and feces, two hydroxylated metabolites and one N-oxidation metabolite.
Absorption, Distribution and Excretion
Studies in animals (horse) have shown the presence of a concentration >0.005 ng/ml in serum 72 hours after initial administration of a dose of 2 mg/kg. It is rapidly absorbed and the reported Cmax in this reports was 31.9 ng/ml in a Tmax of 1.5 hours and AUC of 2000 ng.hr/ml. In the case of bioavailability, grapiprant presents a mean bioavailability of 39%. The bioavailability, time for peak concentration and maximal concentration has been reported to be significantly reduced after food.
Zugehörige Reaktionen
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