95093-96-2

Usage

Uses

Used in Organic Synthesis:
(R)-(-)-4-(2,3-Epoxypropoxy)carbazole is used as a key intermediate in organic synthesis for the development of novel chemical compounds and materials. Its epoxy and propoxy functional groups provide a platform for further chemical reactions, making it a valuable building block in the creation of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (R)-(-)-4-(2,3-Epoxypropoxy)carbazole is utilized as a precursor for the synthesis of various drug candidates. Its unique structure allows for the design of molecules with specific biological activities, targeting a range of therapeutic areas, including but not limited to cardiovascular, neurological, and oncological applications.
Used in Agrochemical Industry:
(R)-(-)-4-(2,3-Epoxypropoxy)carbazole also finds application in the agrochemical sector, where it serves as a starting material for the synthesis of new pesticides and plant growth regulators. Its chemical properties enable the development of compounds with enhanced efficacy and selectivity, contributing to more sustainable agricultural practices.
Used in Specialty Chemicals:
(R)-(-)-4-(2,3-Epoxypropoxy)carbazole is employed in the production of specialty chemicals, such as dyes, pigments, and polymers. Its ability to undergo various chemical transformations allows for the creation of innovative materials with unique properties, catering to the needs of diverse industries, including textiles, coatings, and plastics.

Upstream product

• 52602-39-8 9H-carbazol-4-ol 
• 3132-64-7 1,2-Epoxy-3-bromopropane 
• 106-89-8 epichlorohydrin 
• 152333-94-3 glycidyl nosylate 
• 50-59-9 cefaloridine 
• 67-68-5 dimethyl sulfoxide 
• 67800-62-8 (S)-oxirane-2-methyl methanesulfonate 
• 115314-14-2 (2s)-(+)-glycidyl 3-nitrobenzenesulfonate 
• 51594-55-9 (R)-(-)-epichlorohydrin 
• 591-20-8 3-Bromophenol 
• 67843-74-7 (S)-epichlorohydrin 
• 1253792-50-5 2'-bromo-[1,1'-biphenyl]-2-ol 
• 583-53-9 2,3-dibromobenzene 
• 89466-08-0 2-hydroxyphenyl boronic acid 

Downstream Products

• 85135-33-7 4-(2,3-epoxypropoxy)-1-iodocarbazole 
• 890017-26-2 9-methyl-4-(oxiran-2-ylmethoxy)-9H-carbazole 
• 1198090-71-9 4-(oxiran-2-ylmethoxy)-9-(oxiran-2-ylmethyl)-9H-carbazole 
• 391901-59-0 (2 S)-1-[(4-Aminophenethyl)amino]-3-(9 H-carbazol-4-yloxy)-2-propanol 
• 391901-60-3 tert-butyl 4-aminophenethyl[(2 S)-3-(9 H-carbazol-4-yloxy)-2-hydroxypropyl]carbamate 
• 392690-75-4 (+)-(S)-1-bromo-4-(oxiran-2-ylmethoxy)carbazole 
• 78859-34-4 NSC 305336 
• 146574-43-8 1-[3-hydroxycarbazolyl-⁽⁴⁾-oxy]-3-[2-(2-methoxyphenoxy)ethylamino]propanol-⁽²⁾ 
• 1187921-93-2 1-(9H-carbazol-4-yloxy)-3-chloropropan-2-ol 

Relevant academic research and scientific papers

Fine-tuning hydroxylamines as single-nitrogen sources for Pd(0)-catalyzed diamination of o-bromo(or chloro)-biaryls

Transition metal-catalyzed diamination by hydroxylamines is a common approach for making three-membered aziridines, while its use for building the larger N-heterocycles is still underdeveloped. Herein, we report an efficient Pd(0)-catalyzed inter-molecular [4+1] annulation of o-bromo(or chloro)-biaryls with bifunctional secondary hydroxylamines for the one-step assembly of synthetically useful carbazoles. Noteworthily, a linchpin for this domino reaction was the judicious selection of both the amino-sources and Pd(0)-catalysts for enabling the prerequisite oxidative addition of aryl halides to Pd(0)-species in the presence of hydroxylamines with a labile N-O bond. [Figure not available: see fulltext.].

Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents

Malignant melanoma (MM) presents as the highest morbidity and mortality type in skin cancer. Herein, inspired by the previously reported anti-melanoma effect of propranolol, a widely applied β adrenergic receptor antagonist as cardiovascular drug, we set out to exploit its potential as anti-melanoma therapy based on the drug repurposing strategy. Structural optimization of propranolol yielded 5m, which exhibits dramatically improved potency on human melanoma cell growth (1.98–3.70 μM), compared to propranolol (59.5–75.8 μM). Further investigation demonstrated that 5m could inhibit colony formation of melanoma cell line (completely abolished at 2 μM for 5m, partially inhibited at 50 μM for propranolol), induce cell apoptosis and cell cycle arrest in the G2/M phase (both observed at 1 μM). Preliminary mechanism study indicated that 5m could disrupt the cellular microtubule network, which suggested tubulin as a potential target. Docking study provided a structural insight into the interaction between 5m and tubulin. In summary, our study presents a drug repurposing case that redirects a cardiovascular agent to an anti-melanoma agent.

Hybridization of β-Adrenergic Agonists and Antagonists Confers G Protein Bias

Starting from the β-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no β-arrestin-2 recruitment at both β1- and β2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and β-arrestin recruitment of the hybrid (S)-22, the full agonist epinephrine, and the β2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.

Design, Synthesis, and Biological Evaluation of a New Series of Carvedilol Derivatives That Protect Sensory Hair Cells from Aminoglycoside-Induced Damage by Blocking the Mechanoelectrical Transducer Channel

Aminoglycosides (AGs) are broad-spectrum antibiotics used for the treatment of serious bacterial infections but have use-limiting side effects including irreversible hearing loss. Here, we assessed the otoprotective profile of carvedilol in mouse cochlear cultures and in vivo zebrafish assays and investigated its mechanism of protection which, we found, may be mediated by a block of the hair cell's mechanoelectrical transducer (MET) channel, the major entry route for the AGs. To understand the full otoprotective potential of carvedilol, a series of 18 analogues were prepared and evaluated for their effect against AG-induced damage as well as their affinity for the MET channel. One derivative was found to confer greater protection than carvedilol itself in cochlear cultures and also to bind more tightly to the MET channel. At higher concentrations, both carvedilol and this derivative were toxic in cochlear cultures but not in zebrafish, suggesting a good therapeutic window under in vivo conditions.

Discovery of a novel multifunctional carbazole–aminoquinoline dimer for Alzheimer's disease: copper selective chelation, anti-amyloid aggregation, and neuroprotection

A novel multifunctional carbazole–aminoquinoline dimer PZ001 was designed, synthesized, and evaluated. The results indicated that PZ001 possessed selective copper chelation, and inhibited copper-induced Aβ1–42 aggregation. Furthermore, PZ001 exerted powerful neuroprotection against glutamate-induced HT22 cell death. These results suggest that PZ001 may be a promising multifunctional anti-AD compound.

Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents

Toll-like receptor 4 (TLR4) initiates innate immune response to release inflammatory cytokines and has been pathologically linked to variety of inflammatory diseases. Recently, we found that Carvedilol, as the classic anti-heart failure and anti-inflammatory clinic drug, could inhibit the TLR4 signaling in the TLR4 overexpressed cells. Herein, we have designed and synthesized a small library of novel Carvedilol derivatives and investigated their potential inhibitory activity. The results indicate that the most potent compound 8a (SMU-XY3) could effectively inhibited TLR4 protein and the LPS triggered alkaline phosphatase signaling in HEK-Blue hTLR4 cells. It down regulated the nitric oxide (NO) in both RAW264.7 cells and BV-2 microglial cells, in addition to blocking the TNF-α signaling in ex-vivo human peripheral blood mononuclear cells (PBMC). More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and other inflammatory diseases.

8-aminoquinoline-hydroxyl carbazole heterozygote and preparation method and pharmaceutical composition thereof

The invention relates to synthesis of a series of 8-aminoquinoline-hydroxyl carbazole heterozygote. According to the 8-aminoquinoline-hydroxyl carbazole heterozygote, copper ion can be selectively chelated, and a good nerve cell protection effect can be realized. Therefore, the 8-aminoquinoline-hydroxyl carbazole heterozygote can serve as candidate compound of AD treating medicine development.

Synthesis of Glycoborine, Glybomine A and B, the Phytoalexin Carbalexin A and the β-Adrenoreceptor Antagonists Carazolol and Carvedilol

We describe a regioselective synthesis of 4- or 5-substituted carbazoles by oxidative cyclisation of meta-oxygen-substituted N-phenylanilines. Using the regiodirecting effect of a pivaloyloxy group, we prepared 4-hydroxycarbazole, a precursor for the enantiospecific synthesis of the β-adrenoreceptor antagonists (?)-(S)-carazolol (5) and (?)-(S)-carvedilol (6). Regioselective palladium(II)-catalysed cyclisation of different diarylamines led to total synthesis of glycoborine (7) and the first total syntheses of the phytoalexin carbalexin A (8), glybomine A (9) and glybomine B (10). For glybomine B (10), a 5-hydroxycarbazole was converted into the corresponding triflate and utilized for introduction of a prenyl substituent.

Preparation method of carvedilol phosphate hemihydrate

The invention provides a preparation method of carvedilol phosphate hemihydrates. The preparation method comprises the following steps: carrying out mixing reaction on a compound with a structure as shown in a formula (II) and 2-(2-methoxy phenoxy) ethylamine to obtain reaction liquid containing a compound with the structure as shown in a formula (III); directly adding phosphoric acid in the reaction liquid obtained in the step (1) so that 2-(2-methoxy phenoxy) ethylamine phosphate and filtrate can be obtained; adding phosphoric acid in the filtrate obtained in the step (2) to obtain the carvedilol phosphate hemihydrates. The reaction liquid obtained in the step (1) is not required to be treated, the phosphoric acid is added in the same reaction system in two steps, excessive 2-(2-methoxy phenoxy) ethylamine is recycled and can be continued to be used for reaction, and furthermore, the purity and the yield of the prepared carvedilol phosphate hemihydrates as a target product are quite high. In addition, preparation of the compound with the structure as shown in the formula (II) and the carvedilol phosphate hemihydrate as the target product is realized through a one-pot method, and a synthesis method is simple.

Suppression of store overload-induced calcium release by hydroxylated metabolites of carvedilol

Carvedilol is a drug widely used in the treatment of heart failure and associated cardiac arrhythmias. A unique action of carvedilol is its suppression of store overload-induced calcium release (SOICR) through the cardiac ryanodine receptor (RyR2), which can trigger ventricular arrhythmias. Since the effects of carvedilol metabolites on SOICR have not yet been investigated, three carvedilol metabolites hydroxylated at the 3-, 4′ and 5′-positions were synthesized and assayed for SOICR inhibition in mutant HEK 293 cells expressing the RyR2 mutant R4496C. This cell line is especially prone to SOICR and calcium release through the defective RyR2 channel was measured with a calcium-sensitive fluorescent dye. These results revealed that the 3- and 4′-hydroxy derivatives are slightly more effective than carvedilol in suppressing SOICR, while the 5′-analog proved slightly less active. Metabolic deactivation of carvedilol via these hydroxylation pathways is therefore insignificant.