盐酸贝凡洛尔(Bevantolol Hydrochloride) - 药物靶点：ADRA1 x Cav2.2 x VMAT2 x β1-adrenergic receptor_在研适应症：心绞痛，高血压_专利_临床

概要

基本信息

药物类型

小分子化药

别名

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

+ [15]

靶点

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

作用机制

ADRA1拮抗剂(肾上腺素能受体α-1家族拮抗剂)、Cav2.2阻滞剂(N-型电压门控性钙通道α-1B亚基阻滞剂)、VMAT2抑制剂(突触囊泡单胺转运体抑制剂)

+ [1]

治疗领域

神经系统疾病心血管疾病

在研适应症

心绞痛高血压

非在研适应症

亨廷顿舞蹈病

原研机构

Nippon Chemiphar Co., Ltd.

在研机构

Nippon Chemiphar Co., Ltd.

非在研机构

SOM Innovation Biotech SA

最高研发阶段批准上市

首次获批日期

日本 (1995-03-31),

高血压

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)

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结构

分子式C20H27NO4

InChIKeyHXLAFSUPPDYFEO-UHFFFAOYSA-N

CAS号59170-23-9

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关联

3

项与盐酸贝凡洛尔相关的临床试验

EUCTR2021-003453-28-DE / Unknown status临床2期

Phase IIb, randomized, double-blind, placebo-controlled study in parallel groups assessing the efficacy and safety of two doses of SOM3355 in patients suffering from Huntington’s Disease with choreic movements.

开始日期2022-09-16

申办/合作机构-

NCT05475483 / Active, not recruiting临床2期

Phase IIb, Randomized, Double-blind, Placebo-controlled Study in Parallel Groups Assessing the Efficacy and Safety of Two Doses of SOM3355 in Patients Suffering From Huntington's Disease With Choreic Movements

Phase IIb, randomized, double-blind, placebo-controlled study in parallel groups assessing the efficacy and safety of two doses of SOM3355 in patients suffering from Huntington's Disease with choreic movements.

开始日期2022-08-02

申办/合作机构

SOM Innovation Biotech SA

NCT03575676 / Completed临床2期

Phase IIa, Double-blind, Randomized, Placebo-controlled Study of the Efficacy and Safety of SOM3355 in Huntington's Disease (HD) Patients With Chorea Movements.

Phase IIa study to evaluate the efficacy and safety of SOM3355 in chorea movements associated with Huntington's disease

开始日期2018-08-08

申办/合作机构

SOM Innovation Biotech SA

100 项与盐酸贝凡洛尔相关的临床结果

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100 项与盐酸贝凡洛尔相关的转化医学

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100 项与盐酸贝凡洛尔相关的专利（医药）

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243

项与盐酸贝凡洛尔相关的文献（医药）

2023-05-01·British Journal of Clinical Pharmacology

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

Article

作者: 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.

2023-01-01·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

作者: 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.

2022-12-25·Sheng li xue bao : [Acta physiologica Sinica]

[β-arrestin2 recruitment by β-adrenergic receptor agonists and antagonists].

Article

作者: Wang, Yi-Ran ; Liu, Xing ; Cheng, De-Qin ; Ma, Lan

A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.

100 项与盐酸贝凡洛尔相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01369	盐酸贝凡洛尔	C07AB06	DB01295

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
心绞痛	中国	Nippon Chemiphar Co., Ltd.	2002-12-11
高血压	日本	Nippon Chemiphar Co., Ltd.	1995-03-31

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
亨廷顿舞蹈病	临床1期	西班牙	SOM Innovation Biotech SA	2018-08-08

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03575676 (GlobeNewswire) 人工标引	临床2期	亨廷顿舞蹈病	32	SOM3355	齋壓鬱鬱餘獵襯範簾繭(鑰淵鹽繭糧襯鏇簾顧艱) = 築衊築壓製積鹽觸艱選膚製壓鬱遞願鹽網蓋遞 (糧憲衊願夢簾壓壓觸簾 )	积极	2021-10-04
				Placebo	-
EUCTR2018-000203-16-ES \| NCT03575676 (Pubmed)	临床2期	亨廷顿舞蹈病	32	SOM3355 100 mg BID	築蓋積積築築齋蓋淵醖(積鹽壓艱齋鑰夢膚築範) = The most frequent adverse events during SOM3355 administration were mild to moderate 糧範獵簾遞淵衊觸鹽壓 (膚顧網顧夢糧衊鹹遞壓 )	-	2022-12-09
				SOM3355 200 mg BID