159138-80-4

Basic information

• Product Name: CARIPORIDE
• Synonyms: CARIPORIDE;N-(diaminomethylene)-4-isopropyl-3-mesyl-benzamide;N-[bis(azanyl)methylidene]-3-methylsulfonyl-4-propan-2-yl-benzamide;N-(Aminoiminomethyl)-4-(1-methylethyl)-3-(methylsulfonyl)benzamide;BenzaMide,N-(aMinoiMinoMethyl)-4-(1-Methylethyl)-3-(Methylsulfonyl)-;Cariporide (HOE-642)
• CAS NO: 159138-80-4
• Molecular Formula: C₁₂H₁₇N₃O₃S
• Molecular Weight: 283.35
• EINECS: 1592732-453-0
• Product Categories: Inhibitors
• Mol File: 159138-80-4.mol
• Article Data: 2

Chemical Properties

• Melting Point: 90-94° (dec)
• Boiling Point: 542.8 °C at 760 mmHg
• Flash Point: 282.1 °C
• Appearance: /
• Density: 1.34
• Vapor Pressure: 7.62E-12mmHg at 25°C
• Refractive Index: 1.601
• Storage Temp.: 2-8°C
• Solubility: insoluble in H2O; ≥12.05 mg/mL in DMSO; ≥2.675 mg/mL in EtOH with gentle warming and ultrasonic
• CAS DataBase Reference: CARIPORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: CARIPORIDE(159138-80-4)
• EPA Substance Registry System: CARIPORIDE(159138-80-4)

Safety Data

• RTECS: CV2310560
• Hazardous Substances Data: 159138-80-4(Hazardous Substances Data)

Usage

Description

Cariporide, also known as HOE-642, is a pharmaceutical compound that acts as a selective inhibitor of the Na+/H+ exchanger. It is a promising agent for various medical applications due to its ability to improve cellular integrity and prevent damage during cardiac ischemia and reperfusion events.

Uses

Used in Cardiology:
Cariporide is used as a therapeutic agent for the reduction of death and nonfatal myocardial infarction in patients undergoing Coronary Artery Bypass Graft (CABG) surgery. Its Na+/H+ exchange inhibitory properties help in minimizing the damage caused by cardiac ischemia and reperfusion, leading to improved patient outcomes.
Used in High-Risk Ischemic Patients:
Cariporide is also used as a preventive measure for heart attacks in high-risk ischemic patients. By inhibiting the Na+/H+ exchanger, it helps in maintaining cellular integrity and reducing the risk of cardiac events in these patients.
Used in Organ Transplantation:
Cariporide is used as a protective agent during organ transplantation, particularly in non-heart beating donor organs. Its ability to improve cellular integrity following ischemic and reperfusion events helps in reducing the damage to the organs and increasing the success rate of transplantation.

Biological Activity

na–h exchange (nhe) represents an important mechanism for mediating such injury. nhe represents an important mechanism for the development of myocardial ischemic and reperfusion injury and inhibitors have been consistently shown to protect the ischemic and reperfused heart by correcting the ionic imbalance associated with this form of pathological insult. cariporide is a potent nhe inhibitor.

Biochem/physiol Actions

Cariporide is a selective inhibitor of the Na+/H+ exchanger subtype 1 (NHE-1), also known as the Na+/H+ antiporter. Cariporide has shown cardioprotective and antiarrhythmic effects, and has recently been investigated for anticancer activity.

in vitro

cariporide concentration dependently inhibited the amiloride sensitive sodium influx in rabbit erythrocytes, reduced the swelling of human platelets caused by intracellular acidification, and delayed ph recovery in rat cardiomyocytes [1].

in vivo

in anaesthetised rats undergoing coronary artery ligation intravenous and oral pretreatment with cariporide caused a dose dependent reduction or a complete prevention of ventricular premature beats, ventricular fibrillation, and ventricular tachycardia. the compound was well tolerated and neutral to circulatory variables [1].

IC 50

0.05, 3 and 1000 μm for nhe1, nhe3 and nhe2, respectively

InChI:InChI=1/C12H17N3O3S/c1-7(2)9-5-4-8(11(16)15-12(13)14)6-10(9)19(3,17)18/h4-7H,1-3H3,(H4,13,14,15,16)

Synthetic route

3-Methylsulfonyl-4-i-propylbenzoyl Chloride (167764-63-8) + guanidine hydrochloride (50-01-1) → cariporide (159138-80-4)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 30 - 40℃; for 4h;

2-Isopropyl-5-carboxybenzenesulfinic acid (159139-34-1) → cariporide (159138-80-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / water; N,N-dimethyl-formamide / 3 h / 60 °C 2: thionyl chloride / toluene / 1 h / Heating / reflux 3: sodium hydroxide / tetrahydrofuran; water / 4 h / 30 - 40 °C View Scheme

4-Isopropylbenzoic acid (536-66-3) → cariporide (159138-80-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: chlorosulfonic acid / 3 h / 95 °C 2: sodium hydroxide; sodium sulfite / water / 60 °C / pH 9 - 10 3: sodium hydroxide / water; N,N-dimethyl-formamide / 3 h / 60 °C 4: thionyl chloride / toluene / 1 h / Heating / reflux 5: sodium hydroxide / tetrahydrofuran; water / 4 h / 30 - 40 °C View Scheme

3-Methanesulfonyl-4-iso-propylbenzoic Acid (159139-35-2) → cariporide (159138-80-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / toluene / 1 h / Heating / reflux 2: sodium hydroxide / tetrahydrofuran; water / 4 h / 30 - 40 °C View Scheme

3-(chlorosulfonyl)-4-isopropylbenzoic acid (59815-29-1) → cariporide (159138-80-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide; sodium sulfite / water / 60 °C / pH 9 - 10 2: sodium hydroxide / water; N,N-dimethyl-formamide / 3 h / 60 °C 3: thionyl chloride / toluene / 1 h / Heating / reflux 4: sodium hydroxide / tetrahydrofuran; water / 4 h / 30 - 40 °C View Scheme

cariporide (159138-80-4) → bis(3-methylsulfonyl-4-i-propylbenzoyl)guanidine

Conditions	Yield
With potassium carbonate; sodium chloride In hydrogenchloride; diethyl ether; water; N,N-dimethyl-formamide

methanesulfonic acid (75-75-2) + cariporide (159138-80-4) → (4-isopropyl-3-methanesulfonylbenzoyl)guanidine methanesulfonate

Upstream product

• 59815-29-1 3-(chlorosulfonyl)-4-isopropylbenzoic acid 
• 159139-35-2 3-Methanesulfonyl-4-iso-propylbenzoic Acid 
• 536-66-3 p-isopropylbenzoic acid 
• 159139-34-1 2-Isopropyl-5-carboxybenzenesulfinic acid 
• 167764-63-8 3-Methylsulfonyl-4-i-propylbenzoyl Chloride 
• 50-01-1 guanidine hydrochloride 
• 154117-61-0 methyl 3-methylsulfonyl-4-bromobenzoate 
• 113-00-8 guanidine nitrate 
• 176107-23-6 4-Isopropyl-3-methanesulfonyl-benzoic acid methyl ester 

Downstream Products

• 159138-81-5 HOE₆₄₂ 

Relevant articles and documents

COMPOUNDS FORTREATMENT OF CARDIOVASCULAR DISEASES

Pharmaceutical compositions containing sodium-hydrogen exchanger type 1 (NHE-1) inhibitors in combination with Ca 2+ overload inhibitors, and the use of such combination inhibitors to treat, for example, cardiovascular disease, such as ischemia, particularly, perioperative myocardial ischemic injury in mammals, including humans, are disclosed.