Rolapitant (SCH619734) hydrochloride 是一种高效选择性和具有口服活性的神经激肽 1 (NK1) 受体拮抗剂，Ki值为 0.66 nM。Rolapitant hydrochloride 不与 CYP3A4 产生互作。Rolapitant hydrochloride 在雪貂呕吐模型中显示出强效的中枢介导的止吐活性。

Rolapitant (SCH619734) hydrochloride is a potent, selective, long-acting and orally active neurokinin 1 (NK1) receptor antagonist with a K i of 0.66 nM. Rolapitant hydrochloride does not interact with CYP3A4. Rolapitant hydrochloride shows potent centrally-mediated anti-emetic activity in both acute and delayed ferret emesis models [1] [2].

In vitro studies indicate that rolapitant has a high affinity for the human NK1 receptor of 0.66 nM and high selectivity over the human NK2 and NK3 subtypes of >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].

Rolapitant (0.03-1 mg/kg for PO, 0.3-1 mg/kg for IV; single dosage) reverses 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 ID 90 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. Clinical efficacy of anti-emetics is highly correlated with efficacy in the ferret emesis model, suggesting rolapitant is a viable clinical candidate for this indication.

858102-79-1

C25H27ClF6N2O2

536.94

Rolapitant HCl;罗拉匹坦盐酸盐

DMSO:10 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years