[CAS NO. 913064-47-8] ELN-441958
PRODUCTS SPECIFICATIONS [913064-47-8]
DESCRIPTION [913064-47-8]
Overview
| MDL | MFCD27665467 |
|---|---|
| Molecular Weight | 501.02 |
| Molecular Formula | C29H29ClN4O2 |
| SMILES | ClC1=C2C(CN(C3=CC=CC(C(N4CCC5(CCN(C6=CC=NC=C6)CC5)CC4)=O)=C3)C2=O)=CC=C1 |
Summary
ELN-441958 is a potent, neutral, competitive and selective bradykinin B 1 receptor antagonist with a K i of 0.26 nM against native human bradykinin B 1 receptor. ELN-441958 has high oral bioavailability, and has low CNS exposure in the mouse [1] .
IC50 & Target
K i : 0.26 nM (native human bradykinin B 1 receptor) [1]
In Vitro
ELN-441958 is selective for primate over rodent B
1
receptors with a rank order potency (K
B
, nanomolar) of human (0.12 ± 0.02) ~ rhesus monkey (0.24 ± 0.01) > rat (1.5 ± 0.4) > mouse (14 ± 4)
[1]
.
ELN-441958 has good permeability and metabolic stability
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ELN-441958 (1-10 mg/kg; s.c.; once) dose-dependently reduces carrageenan-induced thermal hyperalgesia in a rhesus monkey tail-withdrawal model
[1]
.
ELN-441958 (0-10 mg/kg; i.v. or p.o.) exhibits a favorable pharmacokinetic profile in the rat and rhesus monkey
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Adult male and female rhesus monkeys [1] |
| Dosage: | 1, 3, or 10 mg/kg |
| Administration: | Subcutaneous injection, 30 min before carrageenan injection |
| Result: | Increased the tail-withdrawal latencies in a dose-dependent manner. |
| Animal Model: | Rhesus monkeys or Sprague-Dawley rats [1] |
| Dosage: | 2.5 or 10 mg/kg for rats, 1 mg/kg or 5 mg/kg for rhesus monkeys |
| Administration: | Intravenous injection (2.5 mg/kg and 1 mg/kg) or oral administration (10 mg/kg and 5 mg/kg) (Pharmacokinetic Analysis) |
| Result: |
In rats: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg, approximately four times total body water) and a moderate clearance (0.96 L/h/kg, approximately 24% of hepatic blood flow). The terminal plasma half-life of this compound in rats was 1.7 h. When dosed orally, the concentrations increased to a maximum of 1.2 g/mL at 2 h after dosing. The oral availability was 57%.
In rhesus monkeys: When dosed intravenously, showed a moderate volume of distribution (2.7 L/kg) and a moderate clearance (0.49 L/h/kg, approximately 32% of hepatic blood flow). The terminal plasma half-life was 3.9 h. When dosed orally, the concentrations increased to a maximum of 3.6 g/mL at 3.3 h after dosing. The calculated oral bioavailability was greater than 100%. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 199.59 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9959 mL | 9.9796 mL | 19.9593 mL |
| 5 mM | 0.3992 mL | 1.9959 mL | 3.9919 mL |
| 10 mM | 0.1996 mL | 0.9980 mL | 1.9959 mL |