895155-87-0

Usage

Uses

Used in Pharmaceutical Research:
[1-(2-Hydroxyethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone is used as a compound of interest for pharmaceutical research due to the presence of the indole ring, which is a common structural feature in many biologically active compounds.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, [1-(2-Hydroxyethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone is used as a potential starting material for the development of new drugs, given its unique chemical structure and the potential for interaction with biological targets.

Upstream product

• 24303-61-5 2,2,3,3-tetramethylcyclopropanecarbonyl chloride 
• 15641-58-4 2,2,3,3-tetramethylcyclopropane-1-carboxylic acid 
• 895152-66-6 (1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone 

Relevant academic research and scientific papers

Development of high-affinity fluorinated ligands for cannabinoid subtype 2 receptor, and in vitro evaluation of a radioactive tracer for imaging

The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CB2R) expression. Therefore our work aimed to design and synthesize a radiotracer for the detection of CB2R expression by positron emission tomography (PET) allowing an early diagnosis of neurodegenerative diseases. For the development of such a PET tracer, N-alkyl-substituted indole-3-yl-tetramethylcyclopropylketones served as lead structures due to their high CB2R potency and selectivity, allowing radiolabeling on the N-alkyl chain. To this end, eight novel fluorinated N-alkyl-indole-3-yl-tetramethylcyclopropylketones were synthesized, investigated in radioligand binding studies, and structure-activity relationships were evaluated. The most promising candidate was (1-(4-fluoropropyl)-1H-indole-3-yl)(2,2,3,3-tetramethyl-cyclopropyl)methanone (Ki: 7.88 nM at the CB2R, 3430 nM at cannabinoid subtype 1 receptor (CB1R)). A precursor was synthesized, radiofluorinated with no-carrier-added [18F]F? by nucleophilic substitution of a tosyl group, and the resulting PET ligand was purified, all being performed on a fully automated synthesis module. The tracer was produced in 34 ± 6% radiochemical yield within 2 h and with molar activities of up to 1500 GBq/μmol. A first preclinical evaluation was carried out including determination of logP, metabolic stability by liver microsomes, and autoradiography. The novel PET tracer for imaging CB2R showed promising results warranting subsequent clinical evaluation.

Indol-3-ylcycloalkyl ketones: Effects of N1 substituted indole side chain variations on CB2 cannabinoid receptor activity

Several 3-acylindoles with high affinity for the CB2 cannabinoid receptor and selectivity over the CB1 receptor have been prepared. A variety of 3-acyl substituents were investigated, and the tetramethylcyclopropyl group was found to lead to high affinity CB2 agonists (5, 16). Substitution at the N1-indole position was then examined. A series of aminoalkylindoles was prepared and several substituted aminoethyl derivatives were active (23-27, 5) at the CB2 receptor.Astudy of N1 nonaromatic side chain variants provided potent agonists at the CB2 receptor (16, 35-41, 44-47, 49-54, and 57-58). Several polar side chains (alcohols, oxazolidinone) were well-tolerated for CB2 receptor activity (41, 50), while others (amide, acid) led to weaker or inactive compounds (55 and 56). N1 aromatic side chains also afforded several high affinity CB2 receptor agonists (61, 63, 65, and 69) but were generally less potent in an in vitro CB2 functional assay than were nonaromatic side chain analogues.

3-CYCLOALKYLCARBONYL INDOLES AS CANNABINOID RECEPTOR LIGANDS

The present invention provides novel compounds of Formula (I), which are CB2 selective ligands useful for the treatment of pain.