858102-79-1
858102-79-1 structure
- Name: Rolapitant hydrochloride
- Chemical Name: Rolapitant Hydrochloride
- CAS Number: 858102-79-1
- Molecular Formula: C25H27ClF6N2O2
- Molecular Weight: 536.93700
- Catalog: Signaling Pathways GPCR/G Protein Neurokinin Receptor
- Create Date: 2018-09-18 09:04:45
- Modify Date: 2024-01-24 18:42:33
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Rolapitant (SCH619734) hydrochloride is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a Ki of 0.66 nM. Rolapitant hydrochloride does not interact with CYP3A4. Rolapitant hydrochloride shows potent anti-emetic activity in a ferret emesis model[1][2].
| Name | Rolapitant Hydrochloride |
|---|---|
| Synonyms |
Rolapitant HCl
Sch 619734 1,7-Diazaspiro[4.5]decan-2-one, 8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-, hydrochloride (1:1), (5S,8S)- 1,7-Diazaspiro[4.5]decan-2-one, 8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-, monohydrochloride, (5S,8S)- |
| Description | Rolapitant (SCH619734) hydrochloride is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a Ki of 0.66 nM. Rolapitant hydrochloride does not interact with CYP3A4. Rolapitant hydrochloride shows potent anti-emetic activity in a ferret emesis model[1][2]. |
|---|---|
| Related Catalog | |
| Target |
human NK1:0.66 (Ki) gerbil NK1:0.13 (Ki) guinea pig NK1:0.72 (Ki) monkey NK1:2.5 (Ki) rabbit NK1:31.7 (Ki) rat NK1:78.6 (Ki) mouse NK1:60.4 (Ki) |
| In Vitro | Rolapitant has high selectivity over the human NK2 and NK3 subtypes of more than 1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over rat, mouse and rabbit[1]. Rolapitant (1-1000 nM) inhibits the GR-73632 (an NK1 receptor agonist)-induced calcium efflux with a concentration-dependent and competitive manner in CHO cells expressing the human NK1 receptor[1]. |
| In Vivo | Rolapitant (0.03-1 mg/kg for PO, 0.3-1 mg/kg for IV; single dosage) attenuates the GR-73632-induced foot-tapping response in Mongolian Gerbils[1]. Rolapitant (0.03-1 mg/kg; PO; single dosage; observed for 72 h) blocks acute emesis induced by both apomorphine and cisplatin in ferrets[1]. Animal Model: Female Mongolian Gerbils (30-60 g; anesthetized by inhalation of an oxygen:isofluorane mixture after 4 h PO or immediately after IV, then injected with 5 μl of 3 pmol solution of GR-73632 via ICV)[1] Dosage: 0.03, 0.1, 0.3 and 1 mg/kg for PO, 0.3 and 1 mg/kg for IV Administration: PO or IV, single dosage Result: Attenuated dose-dependently the GR-73632-induced foot-tapping response when administered PO 4 h before testing, with an ID90 of 0.3 mg/kg, and the inhibition in foot tapping for at least 24 h. Blocked dose-dependently the foot tapping induced by GR-73632 when administered IV, with complete blockade observed at 1 mg/kg. Animal Model: Ferrets (treated with subcutaneous administration of 0.125 mg/kg apomorphine or intraperitoneal administration of 10 mg/kg cisplatin)[1] Dosage: 0.03, 0.1, 0.3 and 1 mg/kg Administration: PO; single dosage; observed for 72 h Result: Blocked dose-dependently acute emesis induced by both apomorphine and cisplatin in ferrets. Produced a robust decrease in retches and vomits in ferrets that was maintained throughout the 72 h observation period. |
| References |
| Molecular Formula | C25H27ClF6N2O2 |
|---|---|
| Molecular Weight | 536.93700 |
| Exact Mass | 536.16700 |
| PSA | 50.36000 |
| LogP | 7.18910 |