Sparsentan (RE-021) Property

Melting point:

148 °C(Solv: isopropanol (67-63-0); water (7732-18-5))

Boiling point:

744.4±70.0 °C(Predicted)

Density 

1.28±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO: soluble

form 

A crystalline solid

pka

7.06±0.50(Predicted)

color 

White to off-white

InChI

InChI=1S/C32H40N4O5S/c1-5-7-14-29-33-32(17-10-11-18-32)31(37)36(29)20-24-15-16-26(25(19-24)21-40-6-2)27-12-8-9-13-28(27)42(38,39)35-30-22(3)23(4)41-34-30/h8-9,12-13,15-16,19H,5-7,10-11,14,17-18,20-21H2,1-4H3,(H,34,35)

InChIKey

WRFHGDPIDHPWIQ-UHFFFAOYSA-N

SMILES

C1(C2=CC=C(CN3C(=O)C4(CCCC4)N=C3CCCC)C=C2COCC)=CC=CC=C1S(NC1C(C)=C(C)ON=1)(=O)=O

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

Sparsentan (RE-021) Chemical Properties,Usage,Production

Description

Sparsentan (PS-433540, RE-021, DARA) is a dual endothelin type A receptor(ETA) and angiotensin II type 1 receptor antagonist.

Uses

RE 201 is used an Endothelin A receptor antagonist used in the treatment of hypertension.

Definition

Sparsentan (RE-021) is a selective dual-acting receptor antagonist with affinity for endothelin (A type) and angiotensin II receptors (Type 1). Sparsentan combines the active moieties of the selective AT1 receptor antagonist irbesartan and a selective ETA receptor antagonist.

Biological Activity

Sparsentan (RE-021) is a highly potent dual angiotensin II and endothelin A receptor antagonist with Kis of 0.8 and 9.3 nM, respectively.

Side effects

Common side effects of Sparsentan include swelling of the hands, legs, ankles and feet; dizziness; and low red blood cells (anaemia).
Serious side effects of Sparsentan include hives; difficulty breathing; swelling of the face, lips, tongue, or throat; nausea; vomiting; stomach pain (upper right side); tiredness; loss of appetite; yellowing of the skin or eyes (jaundice); dark urine; fever; itching; severe birth defects low blood pressure; dizziness; lightheadedness; fainting; muscle cramps; dry skin; shortness of breath; trouble sleeping; frequent urination; little or no urination; abnormal blood test results (increased potassium); unusual weight gain and swelling of the ankles or legs.

in vitro

Sparsentan dose dependently antagonizes the angiotensin II-induced pressor response with an ED50 value of 0.8 μmol/kg iv and 3.6 μmol/kg po. Sparsentan also shows efficacious and long acting in the big ET-1-induced pressor model. Sparsentan causes a significant lowering of blood pressure at the lowest dose tested (10 μmol/kg/day) in spontaneously hypertensive rats. Sparsentan shows good oral bioavailability in rats, dogs, and monkeys, averaging 40%, 86%, and 21% F, respectively. At 100 μmol/kg/day, Sparsentan reduces the blood pressure from 170 to less than 100 mmHg during the course of the drug’s pharmacokinetic duration. Sparsentan at 100 μmol/kg/day essentially converts the spontaneously hypertensive rats into normotensive rats during the course of its pharmacokinetic duration.