2461-42-9Relevant articles and documents
Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents
Chang, Qi,Long, Jing,Hu, Liqing,Chen, Zhuo,Li, Qianbin,Hu, Gaoyun
, (2020)
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.
Propranolol Activates the Orphan Nuclear Receptor TLX to Counteract Proliferation and Migration of Glioblastoma Cells
Faudone, Giuseppe,Bischoff-Kont, Iris,Rachor, Lea,Willems, Sabine,Zhubi, Rezart,Kaiser, Astrid,Chaikuad, Apirat,Knapp, Stefan,Fürst, Robert,Heering, Jan,Merk, Daniel
, p. 8727 - 8738 (2021)
The ligand-sensing transcription factor tailless homologue (TLX, NR2E1) is an essential regulator of neuronal stem cell homeostasis with appealing therapeutic potential in neurodegenerative diseases and central nervous system tumors. However, knowledge on TLX ligands is scarce, providing an obstacle to target validation and medicinal chemistry. To discover TLX ligands, we have profiled a drug fragment collection for TLX modulation and identified several structurally diverse agonists and inverse agonists of the nuclear receptor. Propranolol evolved as the strongest TLX agonist and promoted TLX-regulated gene expression in human glioblastoma cells. Structure-activity relationship elucidation of propranolol as a TLX ligand yielded a structurally related negative control compound. In functional cellular experiments, we observed an ability of propranolol to counteract glioblastoma cell proliferation and migration, while the negative control had no effect. Our results provide a collection of TLX modulators as initial chemical tools and set of lead compounds and support therapeutic potential of TLX modulation in glioblastoma.
One pot synthesis of (±)/(S)-atenolol and (±)/(S)-propranolol by employing polymer supported reagent
Damle, Subhash V.,Patil, Prashant N.,Salunkhe, Manikrao M.
, p. 1639 - 1644 (1999)
(±)/(S)-Atenolol and (±)/(S)-propranolol were synthesized by using reaction of (±)/(S)-epichlorohydrin with polymer supported phenoxide anion followed by reaction with isopropylamine.
Relationship of nonspecific antiarrhythmic and negative inotropic activity with physicochemical parameters of propranolol analogues
Rauls,Baker
, p. 81 - 86 (1979)
in an attempt to separate the nonspecific antiarrhythmic activity of propranolol from its negative inotropic effects, analogues containing hydrophilic and lipophylic substituents on the nitrogen and on the naphthyl ring were prepared and tested in an isolated tissue preparation. Though it had been predicted that analogues containing a very hydrophilic group on the nitrogen would have the highest antiarrhythmic/negative inotropic effect ratio, it was found that both effects increased identically when the lipophilicity of either the nitrogen or ring substituent was increased.
Synthetic method of propranolol hydrochloride
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Paragraph 0014; 0019-0020; 0023-0024; 0027-0035; 0038-0040, (2021/09/04)
The invention belongs to the field of medicines, and particularly relates to a synthetic method of propranolol hydrochloride. The preparation method comprises the following steps: by taking epoxy chloropropane and methyl naphthol as raw materials and acetonitrile as a solvent, firstly reacting in tetramethylammonium hydroxide to obtain an intermediate product, then reacting the intermediate product with isopropylamine in the presence of a metal salt Ni/alpha-Al2O3 catalyst to obtain propranolol, and finally salinizing to obtain the propranolol hydrochloride. The method can significantly improve the yield and purity of the propranolol hydrochloride.
NAFTOPIDIL MONOHYDROCHLORIDE DIHYDRATE AND USE THEREOF FOR PREPARATION OF NAFTOPIDIL
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Paragraph 0024-0025, (2021/07/27)
PROBLEM TO BE SOLVED: To provide an intermediate that is useful for the preparation of naftopidil (Naftopidil, (2RS)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(naphthalene-1-yloxy)propan-2-ol), and a method for preparing naftopidil using the same. SOLUTION: By freeing naftopidil monohydrochloride dihydrate, naftopidil can be obtained in high yield and high purity. In particular, a purity of 99.99% can be achieved without repeating purification operation such as recrystallization multiple times. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2021,JPOandINPIT
Facile microwave-assisted synthesis and antitubercular evaluation of novel aziridine derivatives
Sarojini, Perumal,Jeyachandran, Malaichamy,Sriram, Dharmarajan,Ranganathan, Palraj,Gandhimathi
, (2021/02/26)
Novel 2-(aryloxymethyl)aziridines and 2-((3-aryl-1-phenylallyloxy)methyl)aziridine derivatives were prepared via ring-opening reaction of epoxides. The synthesized derivatives were characterized by using elemental analysis (EA), FT-IR, 13C NMR, and 1H NMR. The in vitro antitubercular activities of the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB H37Rv) strain using MTT-MABA assay. All the aziridine derivatives exhibited improved persuasive antitubercular activity against MTB H37Rv in comparison with standard drugs. Among the tested compounds, 2-(naphthalene-1-yloxy) methyl aziridine (5b), 2-(naphthalene-2-yloxy)methylaziridine (5c), 2-(m-tolyloxymethyl)aziridine (5e), 2-(3-(4-methoxyphenyl)-1-phenylalloxy)methylaziridine (12b) and 2-(3-(2-chlorophenyl)-1-phenylallyloxy)methylaziridine (12c) revealed promising activity against MTB H37Rv. Specifically, compound 5b and 12 b showed three-times more active (MIC = 0.5 μg/mL) than the standard drugs ethambutol (MIC = 1.56 μg/mL) and ciprofloxacin (MIC = 1.56 μg/mL).
Synthesis and application of Cu(II) immobilized MCM-41 based solid Lewis acid catalyst for aminolysis reaction under solvent-free condition
Chaudhary, Garima,Gupta, Neha,Singh, Amit Pratap
, (2021/07/22)
In this paper, a Cu(II) immobilized periodic mesoporous organosilica (PMOs) was synthesized and used as a reusable solid Lewis acid catalyst for the aminolysis of epoxides under solvent-free conditions. An amide-based ligand, L-propylsilyl (1) having a specific binding pocket was prepared and fabricated on mesoporous MCM-41 to produce mesoporous organosilica L-propylsilyl@MCM-41 (2). Further, it has been utilized for anchoring Cu(II) ions under controlled reaction conditions to yield solid Lewis acid catalyst Cu(II)-L-propylsilyl@MCM-41 (3). The synthesized catalyst 3 exhibits significantly higher catalytic activity for aminolysis compared to hitherto known solid Lewis acid catalysts. An extensive range of β-amino alcohols with high regio and stereoselectivity were prepared by using catalyst 3. The catalyst was recovered easily and reused eight times without any loss in its catalytic activity. Furthermore, the synthesis of clinically significant propranolol (β-blocker) from α- naphthyl glycidyl ether was attained successfully using catalyst 3 in a very decent yield.
Synthetic method of propranolol hydrochloride (by machine translation)
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Paragraph 0026-0029, (2020/06/30)
To the method, methylnaphthol and epichlorohydrin are subjected to etherification reaction under the action of an alkali condition and a phase transfer catalyst to obtain the key intermediate 3 - (1 - naphthyloxy) -1, 2 - epoxypropane, and then refined to obtain the propranolol hydrochloride crude product which has the advantages of short synthetic route, simple operation and suitableness for industrial production 99.8%. (by machine translation)
Identification of HUHS190, a human naftopidil metabolite, as a novel anti-bladder cancer drug
Fukuhara, Hiroshi,Gotoh, Akinobu,Kino, Yukari,Kurioka, Rina,Mabuchi, Miyuki,Matsunaga, Wataru,Nakao, Syuhei,Shimizu, Tadashi,Tanaka, Akito,Yamaguchi, Keiko,Yamamoto, Momoka
, (2019/11/29)
We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig. 3). Both of 1 and 2 showed broad-spectrum anti-cancer activities in vitro, for example, 1 and 2 showed inhibitory activity IC50 = 21.1 μM and 17.2 μM for DU145, human prostate cancer cells, respectively, and IC50 = 18.5 μM and 10.5 μM for T24 cells, human bladder cancer cells. In this study, we estimated anticancer effects of 2 in a bladder cancer model after intravesical administration similar to clinical cases. A single intravesical administration of 2 exhibited the most potent inhibitory activities among the clinical drugs for bladder cancers, BCG and Pirarubicin, without obvious side effects and toxicity (Fig. 4). Thus, HUHS190 (2) can be effective for patients after post-TURBT therapy of bladder cancer without side effects, unlike the currently available clinical drugs.
