1204329-34-9

Usage

Uses

Used in Pharmaceutical Industry:
N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethylbenzoyl]guanidine is used as an inhibitor for sodium-hydrogen exchanger isoform 1 (NHE1) for its role in regulating intracellular pH. This makes it a potential therapeutic agent for conditions where the regulation of intracellular pH is disrupted, such as certain types of cancer or other diseases involving cellular acidification.
The compound's ability to target NHE1 suggests that it could be used in the development of drugs aimed at treating diseases associated with the overactivity or dysregulation of this ion channel. Further research and development would be necessary to determine its full potential and efficacy in various medical applications.

Upstream product

• 1204331-63-4 4-(1-acetylpiperidin-4-yl)-3-(trifluoromethyl)methylbenzoate 
• 161622-14-6 4-bromo-3-(trifluoromethyl)benzoic acid 
• 1204331-50-9 C₂₇H₃₁F₃N₄O₅ 
• 107317-58-8 4-bromo-3-trifluoromethylbenzoic acid methyl ester 
• 1204331-26-9 4-(4-methoxycarbonyl-2-trifluoromethylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 1204331-48-5 4-(4-methoxycarbonyl-2-trifluoromethylphenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 1204331-27-0 4-(4-carboxy-2-trifluoromethylphenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 1393368-47-2 N-(4-piperidin-4-yl-3-trifluoromethylbenzoyl)-N'-(carbobenzyloxy)guanidine hydrochloride 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 375853-82-0 tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate 
• 110-86-1 pyridine 
• 1422252-48-9 1-(4-(2-(trifluoromethyl)phenyl)piperidin-1-yl)ethanone 
• 50-01-1 guanidine hydrochloride 

Downstream Products

• 1422252-46-7 C₁₆H₁₉F₃N₄O₂*ClH 

Relevant academic research and scientific papers

Synthesis of a sodium-hydrogen exchange type 1 inhibitor: An efficient Cu-catalyzed conjugated addition of a Grignard reagent to an acetyl pyridinium salt

A facile and economical five-step process for the synthesis of a sodium-hydrogen exchange type I inhibitor (NHE-1) was developed from readily available starting materials in 43% overall yield. Key transformations included a highly efficient copper-catalyzed conjugate addition of 2- trifluoromethylphenyl Grignard reagents to acetyl pyridinium salts, a facile hydrogenation of 4-aryl dihydropyridines, a regioselective aromatic bromination, an efficient palladium-catalyzed carbonylation of aryl bromides, and a high-yielding acyl guanidine formation. A safe and scalable protocol for preparation of 2-trifluoromethyl phenyl Grignard reagent was developed, and a facile method for controlling the palladium content with N-acetyl-L-cysteine as the scavenger was demonstrated. Process issues in controlling the formation of a key diacylation side product during acyl guanidine formation are also addressed.

Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat

Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl- piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.

PYRROLIDINYL AND PIPERIDINYL COMPOUNDS USEFUL AS NHE-1 INHIBITORS

Disclosed are compounds of formula (I) and compositions of the present invention which are inhibitors of the sodium proton exchanger isoform-1 (NHE-I). Also disclosed are methods of using and making the same.