Delving into the Latest Updates on Bevantolol Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(±)-bevantolol, 1-((2-(3,4-dimethoxyphenyl)ethyl)amino)-3-(3-methylphenoxy)-2-propanol, 1-(3,4-dimethoxyphenethylamino)-3-(m-tolyloxy)-2-propanol

+ [17]

Target

ADRA1 x Cav2.2 x VMAT2 x β1-adrenergic receptor

Mechanism

ADRA1 antagonists(Adrenergic receptor alpha-1 antagonists), Cav2.2 blockers(Voltage-gated N-type calcium channel alpha-1B subunit blockers), VMAT2 inhibitors(Synaptic vesicular amine transporter inhibitors)

+ [1]

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesCongenital Disorders+ [1]

Active Indication

HypertensionHuntington Disease

Inactive Indication-

Originator Organization

Nippon Chemiphar Co., Ltd.

Active Organization

SOM Innovation Biotech SA

Nippon Chemiphar Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (31 Mar 1995),

Hypertension

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC20H27NO4

InChIKeyHXLAFSUPPDYFEO-UHFFFAOYSA-N

CAS Registry59170-23-9

View All Structures (2)

OBJECTIVEBreast cancer is a global health concern, with millions of cases reported annually worldwide, making it the most common cancer among women. In India, the incidence of breast cancer has been steadily rising, reflecting a growing public health challenge and hence in the development of new drug moieties. Toxicity analysis of such novel drug candidates play a critical role in drug development, ensuring the safety and efficacy of potential therapeutics. Animal models, especially mice and zebrafish in the recent days, have been extensively used for toxicity evaluation owing to their physiological and genetic similarities to humans. This study was hence conducted with an aim to assess the toxicity using animal models, particularly mice and zebrafish.METHODSIn this study, 3-(2-(3,4-dimethoxyphenyl)-2-oxoethylidene)indolin-2-one (RAJI) - a chemically synthesised novel drug, was assessed for its toxicological potential in both zebrafish and mice models highlighting its survival, hatching, locomotor, neuromotor, behavioural abnormalities in zebrafish model and haematological and biochemical abnormalities in mice model.RESULTSThe results obtained emphasise that no significant damages were seen in both zebrafish (survival, hatching, locomotor, neuromotor, behavioural abnormalities) and mice (body weight, haematological and biochemical abnormalities) models when administered in low doses.CONCLUSIONAll results obtained signifies that RAJI poses no harmful effects in the model organisms until administered in higher concentrations, thereby emphasising the fact that RAJI is a safe drug.

01 May 2023·British Journal of Clinical Pharmacology

A proof‐of‐concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease

Article

Author: Huertas, Oscar ; Ferré, Aileen ; McAllister, Kevin ; Scart‐Grès, Catherine ; Reig, Núria ; Gamez, Josep ; Kulisevsky, Jaime ; Muñoz, Esteban ; Calopa, Matilde ; Insa, Raúl

AimsThe study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a β1‐adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD).MethodsA randomized, placebo‐controlled proof‐of‐concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6‐week periods each. Patients received placebo and SOM3355 at 100 and 200 mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period.ResultsThe primary endpoint was met in 57.1% of the patients. Improvements ≥3, ≥4, ≥5 and ≥6 points vs. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed‐model analysis found a significant improvement in the total maximal chorea score of −1.14 (95% confidence interval, −2.11 to −0.16; P = .0224) with 200 mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7–1.9‐fold was recorded (P < .005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate.ConclusionWithin the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well‐tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug.EudraCT number: 2018–000203‐16 and ClinicalTrials.gov Identifier: NCT03575676.

01 Jan 2023·Anti-Cancer Agents in Medicinal Chemistry

Design, Synthesis, Docking Studies, Enzyme Inhibitory and Antiplatelet Aggregation Activities of New 1,3-Diphenyl-3-(Phenylthio)Propan-1-One Derivatives as Selective COX-2 Inhibitors

Article

Author: Zarghi, Afshin ; Bayanati, Maryam ; Daraei, Bahram

Background:Cancer is the second leading cause of death worldwide after heart disease. A vast number of studies indicated that selective cyclooxygenase-2 (COX-2) inhibitors could be chemopreventive against different types of cancer because the expression of COX-2 is increased. Therefore, to develop new therapeutics for cancer, the design and synthesis of new COX-2 inhibitors with few side effects seem attractive as anti-cancer agents.Objective:Some of the well-known drugs that have been widely used for some time have been removed from the market due to the cardiac side effects they cause, so there is a need to introduce a scaffold that can inhibit COX-2 with high potency and low side effects. This study aimed to introduce a new COX-2 inhibitor structure.Methods:A new series of β-aryl-β-mercapto ketones possessing a methylsulfonyl pharmacophore was synthesized and evaluated as selective COX-2 inhibitors. In-vitro COX-1 and COX-2 inhibition effects of these compounds were evaluated, and molecular modeling was examined. Also, the antiplatelet aggregation activity of the synthesized compounds was tested.Results:In-vitro COX-1 and COX-2 inhibition assays indicated that almost all newly synthesized compounds showed selectivity for COX-2 with IC50 values in the 0.07-0.22 μM range and COX-2 selectivity indexes in the 170 to 703.7 range. Among the tested compounds 1-(4-(methylsulfonyl)phenyl)-3-phenyl-3-(phenylthio)propan-1-one (4a), 3-(3,4- dimethoxyphenyl)-1-(4-(methylsulfonyl)phenyl)-3-(phenylthio)propan-1-one (4g) and 3-(4-fluorophenyl)-1-(4-(methyl sulfonyl)phenyl)-3-(phenylthio)propan-1-one (4h) were the most potent COX-2 inhibitors and 3-(3,4- dimethoxyphenyl)-1-(4-(methylsulfonyl)phenyl)-3-(phenylthio)propan-1-one had the highest selectivity index for COX-2 enzyme inhibitory activity. The Anti-platelet aggregation activity results indicated that the compound 1-(4- (methylsulfonyl)phenyl)-3-(phenylthio)-3-(p-tolyl)propan-1-one (4b) possesses the strong anti-platelet activity. Our molecular modeling studies also indicated that the methylsulfonyl pharmacophore group is placed into the adjunct pocket in the COX-2 active site and forms hydrogen bond interactions with NH of Arg513 and NH of His90.Conclusion:In brief, all designed and synthesized compounds showed moderate to good COX-2 inhibitory effects and showed good anti-platelet activity. Therefore, these compounds have the potential for further research into developing anti-cancer agents.

100 Deals associated with Bevantolol Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D01369	Bevantolol Hydrochloride	C07AB06	DB01295

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypertension	JP	Nippon Chemiphar Co., Ltd.	31 Mar 1995

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Huntington Disease	Phase 2	ES	SOM Innovation Biotech SA	08 Aug 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EUCTR2018-000203-16-ES \| NCT03575676 (Pubmed)	Phase 2	Huntington Disease	32	SOM3355 100 mg BID	idofincvrx(kzcfmyejru) = The most frequent adverse events during SOM3355 administration were mild to moderate whofzvuqxk (zqwqxgpdfj )	-	09 Dec 2022
				SOM3355 200 mg BID
NCT03575676 (GlobeNewswire) Manual	Phase 2	Huntington Disease	32	SOM3355	esdqpmwdha(cpuqogzxot) = zsuxacghst mvskqiimwm (ijsuwtfcpz )	Positive	04 Oct 2021
				Placebo	-