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更新于：2025-05-10
Ocinaplon
奥西普隆
更新于：2025-05-10
概要
基本信息
药物类型 小分子化药 |
别名 Ocinaplon (USAN/INN)、CL 273547、CL-273547 + [1] |
作用方式 调节剂 |
作用机制 GABAA receptor调节剂(γ-氨基丁酸 A 受体调节剂) |
治疗领域 |
在研适应症- |
非在研适应症 |
原研机构 |
在研机构- |
最高研发阶段终止临床3期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C17H11N5O |
InChIKeyOQJFBUOFGHPMSR-UHFFFAOYSA-N |
CAS号96604-21-6 |
关联
100 项与 奥西普隆 相关的临床结果
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100 项与 奥西普隆 相关的转化医学
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100 项与 奥西普隆 相关的专利（医药）
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30
项与 奥西普隆 相关的文献（医药）2024-12-01·PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Nonsedating anxiolytics
Review
作者: Smith, Jodi L ; Lippa, Arnold ; Smith, Jodi L. ; Cerne, Rok ; Chrzanowska, Aleksandra
Anxiety disorders are the most prevalent psychiatric pathology with substantial cost to society, but the existing treatments are often inadequate. This has rekindled the interest in the GABAA-receptor (GABAAR) positive allosteric modulator (PAM) compounds, which have a long history in treatment of anxiety beginning with diazepam, chlordiazepoxide, and alprazolam. While the GABAAR PAMs possess remarkable anxiolytic efficacy, they have fallen out of favor due to a host of adverse effects including sedation, motor impairment, addictive potential and tolerance development. A substantial effort was thus devoted to the design of GABAAR PAMs as anxiolytics with reduced sedative liabilities. Several non-benzodiazepine (BZD) GABAAPAMs progressed to clinical trials (bretazenil, abecarnil, alpidem, and ocinaplon) with alpidem obtaining regulatory approval as anxiolytic, but later withdrawn from market due to hepatotoxicity. Advances in molecular biology gave birth to a host of subtype selective GABAAR-PAMs which suffered from signs of sedation and motor impairment and only three compounds progressed to proof-of-concept studies (TPA-023, AZD7325 and PF-06372865). TPA-023 was terminated due to toxicity in preclinical species while AZD7325 and PF-06372865 did not achieve efficacy endpoints in patients. We highlight a new compound, KRM-II-81, that is an imidazodiazepine selective for GABAAR containing α2/3 and β3 proteins. In preclinical studies KRM-II-81 produced anxiolytic-like effects but with minimal sedation, respiratory depression, and abuse liability. Thus, KRM-II-81 is a newly discovered, non- BZD anxiolytic compound, which targets a selective population of GABAAR for improved therapeutic gain and reduced side effects.
2022-11-01·Medicinal Chemistry4区 · 医学
New Route to the Synthesis of Novel Pyrazolo[1,5-a]pyrimidines and
Evaluation of their Antimicrobial Activity as RNA Polymerase Inhibitors
4区 · 医学
Article
作者: Elgemeie, Galal H. ; Abdallah, Amira E. M.
Aims::
The current study aimed to synthesize novel pyrazolo[1,5-a]pyrimidines based on 5-
aminopyrazoles 3, evaluate their antimicrobial activity, and study the minimum inhibitory concentration (MIC)
for the most active compounds. In addition, molecular docking studies and RNA polymerase inhibitory activity
were determined.
Background::
Starting with our previously reported 5-aminopyrazoles 3, a number of novel pyrazolo[1,5-
a]pyrimidines were synthesized. Due to the similarity of pyrazolopyrimidine derivatives with the purine systems,
pyrazolopyrimidines are important in many different biological applications, most notably as anti-tumor, antibacterial,
and hepatitis C virus inhibitors. The pharmaceutical applications of the pyrazolopyrimidine derivatives
were explained in several approved drugs like Indiplon, Zaloplan, and Ocinaplon.
Objective::
To prepare a novel antimicrobial agent, namely pyrazolo[1,5-a]pyrimidine, reveal their structures
using different spectral data, the minimum inhibitory concentration (MIC) for the most active compounds was
evaluated, and both the molecular docking and the RNA polymerase inhibitory activity were determined.
Methods::
A number of different pyrazolopyrimidines namely 2-(phenylamino)-6,11-dihydrobenzo[g]pyrazolo
[1,5-a]quinazoline-3-carboxamides (5a-c), (E)-5,7-dimethyl-2-(phenylamino)-6-(phenyldiazenyl)pyrazolo-[1,5-
a]pyrimidine-3-carboxamides (7a-c), 7-amino-2-(phenylamino) pyrazolo[1,5-a]pyrimidine-3-carboxamides (11af),
7-amino-2-(phenylamino)-5-(2-thienyl)pyrazolo[1,5-a]pyrimidine-3-carboxamides (14-f) and ethyl 7-amino-3-
carbamoyl-2-(phenylamino)-5-(4-pyridyl)pyrazolo[1,5-a]pyrimidine-6-carboxylate derivatives (14g-i) were synthesized
through the reaction of 5-aminopyrazoles 3 with a variety of chemical reagents. On the other hand, the
evaluation of the antimicrobial activity for all the prepared compounds was screened through different strains as
Gram-positive bacteria, such as staphylococcus aureus and Streptococcus mutans, and Gram-negative bacteria,
such as Escherichia coli, Pseudomonas aeruginosa, and klebsiella. The antifungal activity was determined by
Candids Albicans fungal strain, and the MIC of the most active compounds was measured. The molecular docking
was recorded, and the RNA polymerase inhibitory activity was estimated for the high docking score compounds.
Results::
Compounds 5a, 5b, 5c, 7a, 7b, 7c, 11d, 14b, and 14h were the most active compounds against some of
the bacterial and fungal tested strains. MIC was determined for the most active tested compounds. As an antimicrobial
agent, compound 7b was the most potent, with a high docking score and RNA polymerase inhibitory
activity (IC50= 0.213 μg/ml) compared to Rifampicin (IC50= 0.244 μg/ml). The reactivity of the latter compound
was attributed to the presence of 4-Br-C6H4 moiety. The results demonstrated that docking studies on the most
active compounds in the RNA polymerase active site were consistent with in vitro assays.
Conclusion::
The resultant novel bioactive pyrazolo[1,5-a]pyrimidine derivatives were synthesized based on 5-
aminopyrazole derivatives 3. The current study evaluated the antimicrobial activity for all the prepared compounds,
followed by the determination of the MIC for the most potent active compounds. The molecular docking
study was performed, and it was appropriate with the in vitro activity. The RNA polymerase inhibitory activity
was assessed for the most active antimicrobial compounds with a high docking score (7b, 7c, 14a, 14b, 14e, 14i).
Compound 7b was the most potent compound inhibiting RNA polymerase enzyme compared to the reference
drug Rifampicin.
Other::
The novel prepared heterocyclic systems are extremely important in a variety of domains, especially biological
and pharmacological ones.
2019-02-01·Lancet (London, England)1区 · 医学
Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis
1区 · 医学
Review
作者: Cheng, Zhihang ; Nazareth, Irwin ; Bondaronek, Paulina ; Liu, Yifeng ; Slee, April ; Freemantle, Nick
BACKGROUND:
Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices.
METHODS:
A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106.
FINDINGS:
Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias.
INTERPRETATION:
To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy.
FUNDING:
No funding was received for this research.
1
项与 奥西普隆 相关的新闻（医药）2025-02-11
·漫游药化
本综述概述了用于制备许多现代六元杂环化合物的最常见的合成路线。所报道的例子是基于顶级零售药物分子，结合了来自科学期刊和更广泛的专利文献的合成信息。希望本汇编结合先前发表的关于五元环的综述，为对药物、合成和制备化学感兴趣的个人形成一个全面的基础和参考来源。
The subsections are:
1. Pyridines and quinolines
2. Dihydropyridines and piperidines
3. Pyrimidines and quinazolines
4. Pyrazines and piperazines
5. Pyridazines and perhydropyridazines
6. Triazines and polyazacyclic systems
之前，我们回顾了市面上最畅销的含五元环杂环药物的最常见合成路线，这让我们能够分析药物化学家在过去30年是如何应对挑战的。这项工作不仅是对各种化学转化的概述，也让我们可以判断是否和在何种程度上新的想法和概念已经收获，以提高成功率和加快药物的开发时间。在这篇新的综述文章中，我们希望对目前含有六元杂环的药物的合成路线进行补充汇编。我们相信，芳香族和非芳香族六元结构的结合将提供一个全面的概述，对任何学生、学者或未来对应用化学合成感兴趣的药物化学家都有价值。
clarinex的合成：
rosiglitazone的合成路线一：
rosiglitazone的合成路线二：
pioglitazone的合成：
etoricoxib的合成路线一：
etoricoxib的合成路线二：
moxifloacin的合成：
clevidipine的三条合成路线：
tiagabine的合成：
solifenacin的合成：
carmegliptin HCl salt的合成：
raltegravir的合成：
imatinib的合成路线一：
imatinib的合成路线二：
erlotinib的合成路线一：
erlotinib的合成路线二：
lapatinib的合成：
varenicline的合成：
bortezomib的合成：
cilazapril的合成：
imiquimod的合成路线一：
imiquimod的合成路线二：
abacavir的合成：
ocinaplon的合成：
sidenafil的合成路线一：
sidenafil的合成路线二：
vardenafil的合成：
参考文献：Beilstein J. Org. Chem. 2013, 9,2265–2319.
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 焦虑症 | 临床3期 | 美国 | - | - |
| 焦虑症 | 临床3期 | - | - | |
| 焦虑症 | 临床3期 | - | - |
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