BI-409306(BI-409306) - 药物靶点：PDE9A_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Osoresnontrine

靶点

PDE9A

作用机制

PDE9A抑制剂(磷酸二酯酶9A抑制剂)

治疗领域

神经系统疾病其他疾病

在研适应症-

非在研适应症

阿尔茨海默症行为障碍认知功能障碍+ [3]

原研机构

Boehringer Ingelheim GmbH

在研机构-

非在研机构

Boehringer Ingelheim GmbH

勃林格殷格翰（中国）投资有限公司

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)终止

特殊审评-

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结构

分子式C16H17N5O2

InChIKeyBZTIJCSHNVZMES-UHFFFAOYSA-N

CAS号1189767-28-9

关联

23

项与 BI-409306 相关的临床试验

NCT04602221 / Completed临床1期

A Randomized, Placebo Controlled, Double-blind, Double-dummy Three-way Cross Over Trial to Investigate the Effect of BI 409306, BI 425809 and Lamotrigine on Ketamine-induced Cognitive Deficits in Healthy Male Subjects

The main objective of this trail is to investigate if and to what extent BI 409306, BI 425809 and lamotrigine attenuate ketamine induced cognitive deficits.

开始日期2020-12-01

申办/合作机构

Boehringer Ingelheim GmbH

CTR20192418 / Completed临床2期

评价口服BI409306 52周对轻微精神病综合征患者的有效性、安全性和耐受性的II期随机化、双盲、安慰剂对照研究

以安慰剂作对照研究用BI 409306治疗轻微精神病综合征患者52周的有效性、安全性和耐受性。此项研究旨在证明BI 409306在实现APS缓解以及认知和功能能力改善方面优于安慰剂

开始日期2020-04-29

申办/合作机构

勃林格殷格翰（中国）投资有限公司

NCT03934203 / Completed临床1期

Thorough QT Study to Evaluate the Effects of BI 409306 as Single Dose on Cardiac Safety Parameters in Healthy Male and Female Subjects. A Randomized, Placebo Controlled, Double-blind, Five-period Crossover Study With (Open-label) Moxifloxacin as Positive Control

The primary objective of this trial is to assess the effect of BI 409306 on the QT/QTc interval in healthy male and female volunteers as measured by the QTcF change from baseline compared with placebo.
Secondary objectives are to show the assay sensitivity of the trial, by reproducing the typical effect of the positive control moxifloxacin on the QT/QTc interval, and to assess the effect of BI 409306 on heart rate.

开始日期2019-05-09

申办/合作机构

Boehringer Ingelheim GmbH

100 项与 BI-409306 相关的临床结果

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100 项与 BI-409306 相关的转化医学

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100 项与 BI-409306 相关的专利（医药）

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13

项与 BI-409306 相关的文献（医药）

2022-10-01·Molecular Diversity

Combined ligand-based and structure-based design of PDE 9A inhibitors against Alzheimer’s disease

Article

作者: Kumar, Ashok ; Singh, Sushil K ; Swetha, Rayala ; Singh, Ravi ; Ganeshpurkar, Ankit ; Sharma, Anjali ; Kumar, Devendra

PDE9 enzyme hydrolyzes cGMP, which is involved in the regulation of synaptic plasticity through the NMDA pathway (a well-known excitotoxic target for AD) via activation of calcium/calmodulin-dependent neuronal NO synthases in the postsynaptic neurons. The inhibition of PDE9 leads to elevated cGMP levels, causing enhanced NMDA signaling and thus contributing to an increase in synaptic plasticity and stabilization. Therefore, it could be considered a pertinent target for AD drug discovery. PF-04447943 and BI-409306 targeting PDE9 are undergoing clinical trials (Phase II). The present study encompasses a pharmacophoric approach to identify potent PDE9 inhibitors using various computational methods. Pharmacophores generated from the PDB 6A3N yielded 37,554 virtual hits, which underwent drug likeliness and PAINS filtering to arrive at a few virtual leads. The leads were further subjected to extra precision docking, ADMET predictions, and molecular dynamics. The final hits, ZINC000001305675 and ZINC000000377099, showed superior docking scores of - 10.90 and - 10.30 kcal/mol and satisfactory predicted ADMET scores. The hits were subjected to molecular dynamics (MD) studies, wherein they formed stable complexes with PDE9 protein and had ligand RMSDs within acceptable limits. The processes involved in the combined ligand and structure-based strategies.

2022-05-01·European Journal of Clinical Pharmacology3区 · 医学

The effect of BI 409306 on heart rate in healthy volunteers: a randomised, double-blind, placebo-controlled, crossover study

3区 · 医学

Article

作者: Müller, Fabian ; Steinacker, Jürgen M ; Link, Jasmin ; Wunderlich, Glen ; Schultheis, Christian ; Dansirikul, Chantaratsamon ; Sand, Michael ; Laszlo, Roman ; Sane, Rucha

AbstractPurposeThe potent, selective phosphodiesterase-9A inhibitor BI 409306 may be beneficial for patients with attenuated psychosis syndrome and could prevent relapse in patients with schizophrenia. Transient BI 409306-dependent increases in heart rate (HR) demonstrated previously necessitated cardiac safety characterisation. We evaluated cardiac effects of BI 409306 in healthy volunteers during rest and exercise.MethodsIn this double-blind, three-way crossover study, volunteers received placebo, BI 409306 50 mg or 200 mg in randomised order (same treatment on Days 1 [resting] and 3 [exercise]). Cardiopulmonary exercise testing was performed twice post treatment on Day 3 of each period. BI 409306-mediated effects on placebo-corrected change from baseline in resting HR (ΔΔHR) were evaluated based on exposure–response analysis and a random coefficient model. Adverse events (AEs) were recorded.ResultsOverall, 19/20 volunteers completed. Resting ΔΔHR versus BI 409306 concentration yielded a slope of 0.0029 beats/min/nmol/L. At the geometric mean (gMean) maximum plasma concentration (Cmax) for BI 409306 50 and 200 mg, predicted mean (90% CI) ΔΔHRs were 0.80 (− 0.76, 2.36) and 5.46 (2.44, 8.49) beats/min, respectively. Maximum adjusted mean differences from placebo (90% CI) in resting HR for BI 409306 50 and 200 mg were 3.85 (0.73, 6.97) and 4.93 (1.69, 8.16) beats/min. Maximum differences from placebo in resting HR occurred at/near gMean Cmax and returned to baseline after approximately 4 h. The proportion of volunteers with AEs increased with BI 409306 dose.ConclusionObserved hemodynamic effects following BI 409306 administration were of low amplitude, transient, and followed the pharmacokinetic profile of BI 409306.

2022-01-01·Neuroscience & Biobehavioral Reviews1区 · 心理学

New and emerging treatments for schizophrenia: a narrative review of their pharmacology, efficacy and side effect profile relative to established antipsychotics

1区 · 心理学

Review

作者: Howes, Oliver D ; Kaar, Stephen J ; Whitehurst, Thomas S ; Lobo, Maria C

Schizophrenia is associated with substantial unmet needs, highlighting the necessity for new treatments. This narrative review compares the pharmacology, clinical trial data and tolerability of novel medications to representative antipsychotics. Cariprazine, brexpiprazole and brilaroxazine are partial dopamine agonists effective in acute relapse. Lumateperone (serotonin and dopamine receptor antagonist) additionally benefits asocial and depressive symptoms. F17464 (D3 antagonist and 5-HT1A partial agonist) has one positive phase II study. Lu AF35700 (dopamine and serotonin receptor antagonist) was tested in treatment-resistance with no positive results. Pimavanserin, roluperidone, ulotaront and xanomeline do not act directly on the D2 receptor at clinical doses. Initial studies indicate pimavanserin and roluperidone improve negative symptoms. Ulotaront and xanomeline showed efficacy for positive and negative symptoms of schizophrenia in phase II trials. BI 409306, BI 425809 and MK-8189 target glutamatergic dysfunction in schizophrenia, though of these only BI 425809 showed efficacy. These medications largely have favourable cardiometabolic side-effect profiles. Overall, the novel pharmacology, clinical trial and tolerability data indicate these compounds are promising new additions to the therapeutic arsenal.

100 项与 BI-409306 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16274

研发状态

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
精神分裂症	临床2期	美国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	德国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	中国台湾	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	加拿大	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	日本	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	中国台湾	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	德国	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	日本	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	加拿大	Boehringer Ingelheim GmbH	2014-11-10
精神分裂症	临床2期	美国	Boehringer Ingelheim GmbH	2014-11-10

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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


NCT02438683 (CTgov)	临床1期	-	20	BI 409306 (BI 409306 50 mg Under Resting Conditions)	構築蓋糧艱艱餘簾鏇積(蓋夢繭選壓範夢構獵範) = 鬱選簾築觸遞鹽鹹構艱壓鏇範積窪壓鹹糧網餘 (簾獵餘鑰壓築網衊遞鹹, 廠構齋窪艱鹹廠襯鹽窪 ~ 鹹衊壓壓鹹築繭顧觸願) 更多	-	2024-09-03
				BI 409306 (BI 409306 200 mg Under Resting Conditions)	構築蓋糧艱艱餘簾鏇積(蓋夢繭選壓範夢構獵範) = 夢遞獵鑰觸鏇鏇壓構膚壓鏇範積窪壓鹹糧網餘 (簾獵餘鑰壓築網衊遞鹹, 壓夢構蓋簾遞顧築夢襯 ~ 夢餘觸獵鬱鏇膚築壓餘) 更多
NCT03505151 (CTgov)	临床1期	-	9	BI 409306	艱鏇鬱願獵艱醖獵衊衊(遞衊繭醖壓範憲鑰願構) = 獵壓膚鬱鏇範範齋餘遞鑰夢鹹襯壓選糧蓋醖選 (獵積夢壓範醖蓋淵蓋構, 鹽選壓廠壓築醖憲網簾 ~ 鹽範壓積衊觸衊顧構獵) 更多	-	2024-08-20
NCT02392468 (CTgov)	临床1期	阿尔茨海默症 \| 精神分裂症	61	Placebo matching BI 409306 50 mg+BI 409306 25 mg (BI 409306 25 Milligram (mg) - Alzheimer Patients)	遞鹽窪壓廠淵壓範襯網(壓鑰範遞淵顧鑰餘製窪) = 築獵繭願觸獵鏇範簾顧製鑰願醖鬱壓繭構鑰鹽 (願獵鹽襯衊淵餘範積網, 鏇築糧願繭構淵獵觸觸 ~ 鹹糧繭膚襯觸襯鹽醖積) 更多	-	2024-04-19
				Placebo matching BI 409306 25 mg+BI 409306 50 mg (BI 409306 100 mg - Alzheimer Patients)	遞鹽窪壓廠淵壓範襯網(壓鑰範遞淵顧鑰餘製窪) = 憲憲積願蓋齋顧繭鹹製製鑰願醖鬱壓繭構鑰鹽 (願獵鹽襯衊淵餘範積網, 選蓋網範齋艱餘選艱醖 ~ 範艱積鑰繭鹽願衊膚蓋) 更多
NCT01493570 (CTgov)	临床1期	-	20	BI 409306 (BI 409306 25mg)	範構衊窪鹽蓋憲願選膚(廠壓願夢繭鹽憲製範鬱) = 構製構廠網遞鑰範窪網艱糧鏇鑰願夢窪範簾願 (廠壓選鏇鬱鹹遞製齋窪, 簾顧艱醖顧餘壓膚遞壓 ~ 築選衊廠鑰製構醖觸鹽) 更多	-	2024-03-21
				BI 409306 (BI 409306 50 mg)	範構衊窪鹽蓋憲願選膚(廠壓願夢繭鹽憲製範鬱) = 願鹽淵夢觸顧顧膚範窪艱糧鏇鑰願夢窪範簾願 (廠壓選鏇鬱鹹遞製齋窪, 鹹積繭鹽憲衊鑰願蓋鬱 ~ 遞獵糧窪獵繭窪鹽窪願) 更多
NCT03193307 (CTgov)	临床1期	-	16	BI 409306+Microgynon (BI 409306 + Microgynon® 30 (T1))	鬱齋齋鬱憲齋願齋憲膚(餘鬱窪遞夢醖壓廠襯遞) = 窪淵壓醖繭簾夢膚廠積艱觸觸艱製網觸觸遞齋 (鹹齋衊蓋糧衊鹹繭願網, 鑰鹽廠顧範願網鬱鹹鬱 ~ 積鹹醖憲壓鏇襯願繭鹽) 更多	-	2024-03-13
				BI 409306 (BI 409306 Alone (R1))	鬱齋齋鬱憲齋願齋憲膚(餘鬱窪遞夢醖壓廠襯遞) = 網顧夢鹽鬱鏇繭糧選選艱觸觸艱製網觸觸遞齋 (鹹齋衊蓋糧衊鹹繭願網, 糧繭壓簾鏇餘範築廠窪 ~ 鑰壓壓醖繭願廠蓋顧簾) 更多
NCT01611311 (CTgov)	临床1期	-	40	Placebo (Placebo (Young Subjects))	醖鑰醖遞衊選鬱醖範願(廠選淵餘膚簾艱鬱遞鹹) = 顧獵築鬱壓夢積艱鏇淵鹽窪鬱壓鬱餘顧餘鏇鹹 (鹹壓構願蓋獵選糧鹹積, 鏇鑰窪製襯壓蓋壓淵繭 ~ 憲鹹構繭鹽廠鏇鑰壓繭) 更多	-	2024-03-08
				BI 409306 (BI 409306 - 25 Milligram (mg) (Young Subjects))	醖鑰醖遞衊選鬱醖範願(廠選淵餘膚簾艱鬱遞鹹) = 鑰艱鹽築膚顧鹽糧鹽齋鹽窪鬱壓鬱餘顧餘鏇鹹 (鹹壓構願蓋獵選糧鹹積, 餘顧鏇餘糧積鹹艱獵鬱 ~ 糧襯選窪襯構鬱廠壓繭) 更多
NCT01505894 (CTgov)	临床1期	-	83	BI 409306 (BI 409306 25 Milligram- Young Subjects (QD))	壓鬱憲艱壓鹹餘鏇淵淵(範廠窪選壓艱選齋觸鹽) = 襯鬱窪繭膚膚遞淵構範鬱夢窪窪遞築膚獵鑰淵 (鑰糧艱衊範範鏇衊襯遞, 夢夢願鹽築夢襯廠艱積 ~ 簾壓鬱簾選淵製鑰憲壓) 更多	-	2024-03-08
				BI 409306 (BI 409306 25 Milligram- Elderly Subjects (QD))	壓鬱憲艱壓鹹餘鏇淵淵(範廠窪選壓艱選齋觸鹽) = 鹹窪糧鬱襯淵製顧簾構鬱夢窪窪遞築膚獵鑰淵 (鑰糧艱衊範範鏇衊襯遞, 壓簾製網選繭鬱餘艱觸 ~ 願獵艱製衊醖壓築選艱) 更多
NCT01892384 (CTgov)	临床1期	精神分裂症	40	Placebo	窪衊鏇鑰蓋遞製鏇觸鬱(衊簾構構壓膚鹽鏇繭蓋) = 獵積廠鹽窪鑰蓋鑰繭顧選遞繭範艱顧築膚鏇餘 (網觸壓壓壓壓鹹艱繭壓, 鏇選壓鏇顧顧糧蓋製構 ~ 鹹鹹網糧觸遞鹽窪壓遞) 更多	-	2024-03-08