cas 51997-51-4, 4-Epoxypropanoxycarbazole | Articles data

Articles about 51997-51-4Total 27 be found

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Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives
Subtype-selective α1-adrenoceptor (AR) antagonists display optimum therapeutic efficacies for the treatment of benign prostatic hyperplasia (BPH). In this study, we designed and synthesized novel carbazole-arylpiperazines derivatives (1 and 2) on the basis of the proposed pharmacophore model for α1-AR antagonists. Structural properties were investigated using single-crystal X-ray diffraction analysis. Comparison of crystal structures with ligand-based pharmacophore models revealed that the two agents may possess antagonistic effects on α1Dsubtype. Tissue functional assay in vitro showed that compound 2 exerted strong antagonistic activity on α1B-AR (pA27.13) with a poor selectivity for α1Aand α1Dsubtypes. Compound 1 exhibited enhanced antagonistic effect on α1Dsubtype (pA27.06) and excellent selectivity for α1Dover α1B(α1D/α1Bratio?=?79.4). To illustrate the relationship between antagonistic activity and chemical structure, molecular docking studies were performed using the homology models of α1receptors. Binding mechanism indicated that small hydrophobic substituents attached to the arylpiperazine moiety were essential for rational design of α1D-selective antagonists.
Xu, Wei,Huang, Junjun,Shao, Binhao,Xu, Xingjie,Jiang, Renwang,Yuan, Mu
p. 5565 - 5572
(2016)
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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.
Zhang, Xiao,Wang, Ying,Wang, Sheng-nan,Chen, Qiu-he,Tu, Ya-lin,Yang, Xiao-hong,Chen, Jing-kao,Yan, Jin-wu,Pi, Rong-biao,Wang, Yan
p. 777 - 784
(2018)
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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.].
Bai, Jiaxing,Ding, Pin,Han, Lingbo,Liu, Jingjing,Luan, Xinjun
(2022/03/19)

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.
Chang, Qi,Long, Jing,Hu, Liqing,Chen, Zhuo,Li, Qianbin,Hu, Gaoyun
(2020/04/09)

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.
O'Reilly, Molly,Kirkwood, Nerissa K.,Kenyon, Emma J.,Huckvale, Rosemary,Cantillon, Daire M.,Waddell, Simon J.,Ward, Simon E.,Richardson, Guy P.,Kros, Corné J.,Derudas, Marco
p. 5312 - 5329
(2019/06/07)

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.
Xu, Yao,Chen, Shujun,Cao, Ying,Zhou, Pingzheng,Chen, Zhipeng,Cheng, Kui
p. 253 - 266
(2018/05/29)

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.
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Paragraph 0019; 0020

(2017/08/29)

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.
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Paragraph 0011; 0044; 0045; 0046; 0053; 0054

(2017/02/02)

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.
Malig, Thomas,Xiao, Zhichao,Chen, S.R. Wayne,Back, Thomas G.
p. 149 - 153
(2015/12/18)

Design and synthesis of 3-(3-((9 H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2-phenylquinazolin-4(3 H)-one derivatives to induce ACE inhibitory activity
In an attempt to develop a new class of cardiovascular drugs, a series of novel carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these compounds exhibited activity as significant ACE inhibitors and three compounds (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render support to the experimental results, a series of quinazolinone derivatives were docked into active site of ACE and identified the probable binding modes compared to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR) among the best docked conformers of most potent compounds in a series of compounds. The most potent 9b, 9c, 9e compounds shared common active site with the Lisinopril binding site and retained the key active site residue interactions. The obtained results from pharmacological and molecular modeling studies can be utilized for further optimization of identified hits for selective inhibition of ACE.
Venkatesh, Ramineni,Kasaboina, Suresh,Gaikwad, Hanmant K.,Janardhan, Sridhara,Bantu, Rajashaker,Nagarapu, Lingaiah,Sastry, G. Narahari,Banerjee, Sanjay K.
p. 22 - 29
(2015/04/22)

An efficient improved synthesis of carvedilol, via 2-(2-methoxyphenoxy)ethyl 4-methylbenzenesulfonate intermediate
A facile synthesis of Carvedilol via a key 2-(2-methoxyphenoxy) ethyl 4-methylbenzenesulfonate intermediate is described and this approach avoids the formation of bis side product (impurity-B) due to weak basic conditions and also operationally suitable for industrial application.
Tatendra Reddy,Suneel Kumar,Omprakash,Dubey
p. 1615 - 1618
(2015/02/02)

A facile synthesis of carvedilol via β-amino alcohol intermediate
A facile synthesis of Carvedilol via a key β-amino alcohol intermediate is described and this approach avoids the formation of bis side product (impurity B).
Tatendra Reddy,Suneel Kumar,Omprakash,Dubey
p. 251 - 254
(2013/09/24)

Convenient synthesis of Carvedilol utilizing 3-(9H-carbazol-4-yloxy)-1- chloropropan-2-yl phenyl carbonate as a key intermediate
Convenient synthesis of pharmaceutically important moiety Carvedilol, 1 (β-adrenergic blocking agent) has been reported utilizing 3-(9H-carbazol-4-yloxy)-1-chloropropan-2-yl phenyl carbonate 8 as a key intermediate. The synthetic scheme involves the reaction of intermediate 8 with 2-(2-methoxy phenoxy)- ethanamine 5 by using N,N-Dimethyl-4-aminopyridine (DMAP) in N,N-dimethylformamide (DMF) which yield 3-(2-(2- methoxyphenoxy)ethyl)-5- ((9H-carbazol-4-yloxy)methyl)oxazolidin- 2-one 7 via 1-(9H-carbazol-4-yloxy)-3- chloropropan-2-yl 2- (2-methoxyphenoxy)ethylcarbamate 6. The resulted compound 7 has further been converted to the required Carvedilol and this approach could be useful for the preparation of many β-amino alcohols without formation of Impurity B.
Kumar, B. Anand,Ashrafuddin,Rajesh,Parveen, Sadhika,Madhusudhan
scheme or table
p. 780 - 784
(2012/06/30)

Synthesis and characterization of potential impurities of carvedilol, an antihypertensive drug
Carvedilol (Coreg) is a nonselective -adrenergic blocking agent with vasodilating activity. It is used for the treatment of congestive heart failure and hypertension. During the bulk synthesis of carvedilol, we have observed six impurities: Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V, and Imp-VI. The present work describes the synthesis and characterization of these impurities. Copyright
Rao, Somisetti Narender,Sitaramaiah, Devarasetty,Srimannarayana, Kema,Rao, Challa Nageswar,Rao, Peddi Srinivasa,Babu, K. Sudhakar
experimental part
p. 85 - 93
(2011/03/19)

A facile synthesis of carvedilol, β-adrenergic blocking agent, via a key 5-substituted-.-oxazolidinone intermediate
A facile synthesis of Carvedilol via a key 5-substituted-.-oxazolidinone intermediate is described and this approach avoids the formation of bis side product (impurity B). This approach could be useful for the preparation of many β-amino alcohols without formation of bis impurity.
Madhusudhan,Kumar, B. Anand,Chintamani,Rao, M. Narasimha,Udaykiran,Suresh,Kumar, V. Kiran,Mukkanti
experimental part
p. 606 - 610
(2010/12/25)

Synthesis and cytotoxicity evaluation of 1-[3-(9H-carbazol-4-yloxy)-2- hydroxypropyl]-3-aryl-1H-pyrazole-5-carboxylic acid derivatives
Several novel molecules, 1-(3′-(9H-carbazol-4-yloxy)-2′- hydroxypropyl)-3-aryl-1H-pyrazole-5-carboxylic acid derivatives 3a-g were synthesized and screened to evaluate their cytotoxicity against cancer cells in vitro. The compounds 3a-g has been prepared by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 4-oxiranylmethoxy-9H-carbazole in moderate to excellent yields. The cytotoxicity of synthesized compounds was evaluated by a SRB (sulforhodamine B) assay against cancer cell such as SK-N-SH human neuroblastoma (NB), human A549 lung carcinoma, human breast cancer MCF-7 cell lines. The results showed that seven compounds can suppress SK-N-SH tumor cancer cell growth. Among them, compound 3d was the most effective small molecule in inhibiting SK-N-SH cell growth.
Nagarapu, Lingaiah,Gaikwad, Hanmant K.,Sarikonda, Kartheeka,Mateti, Jhansi,Bantu, Rajashaker,Raghu,Manda, Krishna Madhuri,Kalvendi, Shasi Vardhan
experimental part
p. 4720 - 4725
(2010/11/16)

A vHTS approach for the identification of β-adrenoceptor ligands
Using a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, a set of intriguing β-adrenoceptor ligands was identified, optimization of which resulted in a selective and potent human β2-AR antagonist.
Tasler, Stefan,Baumgartner, Roland,Aschenbrenner, Andrea,Ammendola, Astrid,Wolf, Kristina,Wieber, Tanja,Schachtner, Josef,Blisse, Marcus,Quotschalla, Udo,Ney, Peter
scheme or table
p. 3399 - 3404
(2010/08/06)

A PROCESS FOR THE PREPARATION OF CARVEDILOL
The present invention provides a more simplified, cost effective, commercially feasible process for the preparation of Carvedilol (I) comprising a step of reacting 4-hydroxy oarbazole (II) with epichlorohydrin and directly isolating the intermediate 4-(2,3- epoxypropoxy) carbazole (III) which on purification followed by reaction with 2-(2- methoxyphenoxy) ethylamine (IV) yields crude Carvedilol (I). The crude Carvedilol (I) is converted to pure product either through solvent crystallization (without salt formation) or through salt formation followed by salt cleavage and solvent crystallization resulting in highly pure (i.e. ICH grade) Carvedilol.
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Page/Page column 10

(2010/11/30)

NOVEL HETEROCYCLIC COMPOUNDS AS PSTAT3/IL-6 INHIBITORS
The present invention relates to novel heterocyclic compounds of the general formula (I), as IL-6 inhibitors, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their hydrates, their solvates, their pharmaceutically acceptable salts and compositions, their metabolites and prodrugs thereof. The present invention more particularly provides novel heterocyclic compounds of the general formula (I). Also included is a method for treatment of cancer, cancer cachexia and inflammatory diseases including immunological diseases, particularly those mediated by cytokines such as IL-6, through pSTAT3 inhibition, in a mammal comprising administering an effective amount of a compound of formula (I) as described above.
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Page/Page column 20

(2010/11/27)

Novel heterocyclic compounds as pSTAT3/IL-6 inhibitors
The present invention relates to novel heterocyclic compounds of the general formula (I), as IL-6 inhibitors, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their hydrates, their solvates, their pharmaceutically acceptable salts and compositions, their metabolites and prodrugs thereof. The present invention more particularly provides novel heterocyclic compounds of the general formula (I). Also included is a method for treatment of cancer, cancer cachexia and inflammatory diseases including immunological diseases, particularly those mediated by cytokines such as IL-6, through pSTAT3 inhibition, in a mammal comprising administering an effective amount of a compound of formula (I) as described above.
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Page/Page column 9-10

(2010/11/27)

A NOVEL PROCESS FOR THE PREPARATION OF 1-(9H-CARBAZOL-4-YLOXY)-3-[[2-(-METHOXYPHENOXY)-ETHYL] AMINO]-PROPAN-2-OL
The present invention discloses a novel process for preparation of carvedilol by using eco friendly solvents to obtain the said carvedilol in high purity. The said process comprises, reacting 4-hydroxy carbazole of formula (IV) with epichlorhydrin in presence of an organic solvent and a base at temperatures between 10°C - 30°C; further reacting the resultant 4-(2,3-epoxypropoxy)- carbazole of formula (II) with a salt of 2-(2-methoxyphenoxy) ethylamine of formula (III), preferably hydrochloride salt in presence of a base and a hydroxylic solvent at temperatures between 30°C - 90°C.
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Page/Page column 10

(2010/02/14)

PROCESS FOR THE PREPARATION OF CARVEDILOL
A process for the preparation of carvedilol of formula (I) (I) either in enantiomeric substantially pure form, or as an enantiomeric mixture, optionally as a pharmaceutically acceptable salt thereof, which process comprises reacting 2,3-eopxypropoxy carbazole of formula (II) (II) or the R or S enantiomer thereof, with N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) (V) to yield benzyl carvedilol of formula (VI) (VI) which is debenzylated by catalytic hydrogenation to yield carvedilol of formula (I), either in enantiomeric substantially pure form, or as an enantiomeric mixture, and if desired reacting the thus formed carvedilol of formula (I) with an inorganic or organic acid to yield a pharmaceutically acceptable salt thereof, and/or, if desired, separating the enantiomers. The above process is characterised in that reaction of said 2,3-epoxypropoxy carbazole of formula (II) with said N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) is carried out in water as the reaction medium. The present invention further provides carvedilol of formula (I) prepared by a process as described above, and pharmaceutical compositions containing the same and therapeutic uses thereof.
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Page/Page column 14-15

(2008/06/13)

COMPOUNDS WITH COMBINED CALCIUM CHANNEL BLOCKER AND β-ADRENERGIC ANTAGONIST OR PARTIAL AGONIST ACTIVITIES FOR TREATMENT OF HEART DISEASE
The present invention provides compounds possessing inhibitory activity against β-adrenergic receptors and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds, methods of preparing such compounds, and methods of using such compounds for regulating calcium homeostasis, for treating a disease, disorder or condition in which disregulation of calcium homeostasis is implicated, and for treating hypertension, cardiovascular disease, congestive heart failure, myocardial ischemia, cardiomyopathies, stroke or epilepsy.
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Page/Page column 60-61

(2008/06/13)

PROCESS FOR THE PREPARATION OF CARVEDILOL FORM-II
The present invention provides a cost-effective, industrially feasible process for the manufacture of crystalline Carvedilol Form-II using novel Carvedilol salts comprising a step of reacting 4-(2,3-epoxy propoxy) carbazole (II) with 2-(2-methoxy phenoxy) ethyl amine (III) followed by acidification with mineral acid in presence of an organic solvent to yield acid addition salts, treatment of the said salts with base(s) in presence of organic solvent(s), water and isolation from the organic solvent(s) followed by crystallization from ethyl acetate.
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Page 6

(2008/06/13)

Process for preparing heterocyclic indene analogs
A process for the preparation heterocyclic indene analogs, especially with the preparation of 4-hydroxycarbazole or N-protected 4-hydroxycarbazole, involves cyclocarbonylation followed by saponification. This process avoids high temperatures and high catalyst loadings.
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(2008/06/13)

New series of aryloxypropanolamines with both human β3-adrenoceptor agonistic activity and free radical scavenging properties
A series of 13 novel hybrid molecules designed to possess both free radical scavenging activity and to stimulate the β3-adrenoceptors in order to improve antidiabetic effect and to restore insulin sensitivity was synthesized and evaluated. Compounds were of quinolyl-, isoquinolyl-, pyridoindolyl- or carbazolyloxypropanolamine structure with a terminal amino group of benzopyranolyl-, di-tert-butylphenolyl- or methoxyindolyl-type. Some of the products possessed both the expected activities.
Aubriot, Silvere,Nicolle, Edwige,Lattier, Mireille,Morel, Cecile,Cao, Wenhong,Daniel, Kiefer W.,Collins, Sheila,Leclerc, Gerard,Faure, Patrice
p. 209 - 212
(2007/10/03)

Process for the preparation of optically-active carbazole derivatives, new R- and S-carbazole derivatives and pharmaceutical compositions containing these compounds
A process for the preparation of S- or R-carbazole derivatives of the general formula: STR1 in which R is an unsubstituted or substituted amino radical and pharmacologically acceptable salts, by either reacting R-(-)-epichlorohydrin (for the S-carbazole derivative); or reacting an S-epoxide derivative of the general formula: STR2 in which R1 is the residue of a substituted sulphonic acid derivative (for the R-carbazole derivative); with 4-hydroxycarbazole and then with ammonia or a substituted amine of the general formula RH, and recovering the compound or converting it to a pharmacologically acceptable salt. The new R-(+)- and S(-)-carbazole derivatives provided by the inventive process have unexpected beta blocking and vasodilatory properties and are useful in pharmaceutical compositions. R-(+)-carbazole derivatives are also useful for the treatment of glaucoma.
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(2008/06/13)