FXIa-IN-9 (compound 3f) 是一种有效的的FXIa选择性抑制剂。FXIa-IN-9 可与 FXIa 结合并形成氢键 (human FXIaKi: 0.17 nM，rabbit FXIaK< sub>i: 0.5 nM）。FXIa-IN-9 还具有抗凝活性，可用于心房颤动、中风、心肌梗塞、深静脉血栓、肺栓塞等血栓栓塞性疾病的研究。

FXIa-IN-9 (compound 3f) is a potent and selective FXIa inhibitor. FXIa-IN-9 can bind with FXIa and form hydrogen bond (human FXIa K i : 0.17 nM, rabbit FXIa K i : 0.5 nM). FXIa-IN-9 also has anticoagulant activity, and can be used in the research of thromboembolic diseases such as atrial fibrillation, stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism [1].

FXIa-IN-9 has anticoagulant activity, with EC 1.5x values of 1.31 μM (human plasma aPTT) and 1.39 μM (rabbit plasma aPTT), respectively [1]. FXIa-IN-9 (10 μM, 5-15 min) is highly selective for FXIa against other human serine protease, except for plasma kallikrein (IC 50 : 0.023 μM) [1]. FXIa-IN-9 shows the plasma protein binding ranges from 80.8 to 95.6%, and pharmacological profile is as follows [1]. property/assay value equilibrium solubility (pH 1.2; pH 6.8) 81.0 μM; 171.6 μM PPB % (mouse/rat/dog/human) 91.2/91.6/80.8/95.6 hERG inhibition (IC 50 ) >10 μM S9 aldehyde oxidase (AO) T 1/2 >180 min hLM trapping assay no GSH and CN adducts AMES genotoxicity test negative in vitro micronucleus test negative

FXIa-IN-9 (marginal ear intravenous injection, 1.7-10 mg/kg, dosing at 20 min prior to and 40 min during the AV shunt) achieves more than 50% thrombus reduction in the rabbit arteriovenous (AV) shunt thrombosis model [1]. FXIa-IN-9 (i.v. or p.o., 1-10 mpk ) shows low clearance in rat and dog and moderate clearance in the monkey as well as good oral bioavailability [1]. Animal Model: Rabbit AV shunt thrombosis model [1] Dosage: 1.7 mg/kg bolus + 2.0 mg/kg/h infusion, or 8.5 mg/kg bolus + 10 mg/kg/h infusion. Administration: Intravenous dosing via the marginal ear vein 20 min prior to and 40 min during the AV shunt Result: Showed 36.5% (1.7 mg/kg bolus + 2.0 mg/kg/h infusion) and 62.2% (8.5 mg/kg bolus + 10 mg/kg/h infusion) inhibitions in thrombus weight, respectively. Animal Model: Rat, dog, monkey (pharmacokinetic assay) [1] Dosage: 1 mpk, 2 mpk (i.v.); 5 mpk, 10 mpk (p.o.) Administration: Intravenous injection, oral administration. Result: Pharmacokinetic profile of FXIa-IN-9 in kinds of species. animal species clearance (mL/min/kg) T 1/2 (h) Vd ss (L/kg) F% AUC (iv) (μM h) AUC (po) (μM h) Dose iv/po (mpk) rat 10.7 1.4 0.8 36.4 5.5 10.0 2/10 dog 7.9 2.0 1.5 80.5 3.7 14.7 1/5 monkey 25.6 1.0 1.5 43.0 1.1 2.5 1/5

C23H18Cl2F3N9O2

580.35

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years