[Translation] Phase IIa clinical exploratory study on the efficacy and safety of levoclatamide tablets in the treatment of mild to moderate Alzheimer's disease

初步评价左黄皮酰胺片治疗轻中度阿尔茨海默病的有效性和安全性，分析其量效关系，为后续的临床研究提供剂量依据。

[Translation]

To preliminarily evaluate the efficacy and safety of levoclatamide tablets in the treatment of mild to moderate Alzheimer's disease, analyze its dose-effect relationship, and provide a dosage basis for subsequent clinical studies.

Start Date-

Sponsor / Collaborator

Institute of Materia Medica

[+2]

100 Clinical Results associated with L-clausenamide

100 Translational Medicine associated with L-clausenamide

100 Patents (Medical) associated with L-clausenamide

Literatures (Medical) associated with L-clausenamide

11 Feb 2022·Organic LettersQ1 · CHEMISTRY

Diastereoselective Addition of Prochiral Nucleophilic Alkenes to α-Chiral N-Sulfonyl Imines

Q1 · CHEMISTRY

Article

Author: Fettinger, James ; Houk, K. N. ; Ando, Kaori ; Gutierrez, David A. ; Shaw, Jared T.

The Lewis-acid-promoted addition of prochiral E- and Z-allyl nucleophiles to chiral α-alkoxy N-tosyl imines is described. Alkene geometry is selectively transferred to the newly formed carbon-carbon bond, resulting in stereochemical control of C1, C2, and C3 of the resulting 2-alkoxy-3-N-tosyl-4-alkyl-5-hexene products. A computational analysis to elucidate the high selectivity is also presented. This methodology was employed in the synthesis of two naturally occurring isomers of clausenamide.

01 Oct 2021·ChiralityQ4 · CHEMISTRY

The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate

Q4 · CHEMISTRY

Article

Author: Lin, Hansen ; Rao, Yu ; He, Guantao ; Yan, Yixiao ; Zhu, Senmei ; Su, Jinlong ; Luo, Xuna

AbstractWe synthesized the optically active epineoclausenamide by utilizing chiral reagents, such as R‐α‐methylbenzylamine and S‐α‐methylbenzylamine, for the resolution of the intermediate (trans‐3‐phenyl‐oxiranecarboxylic acid 12), followed by amide exchange, cyclization, and reduction, unlike previously reported methods. The Meerwein–Ponndorf–Verley reduction was used to asymmetrically reduce neoclausenamidone. A plausible reduction mechanism of this method was elucidated. Thereafter, high‐performance liquid chromatography (HPLC) was investigated for the resolution of the epineoclausenamide enantiomers. HPLC was also used to determine the optical purity of these isomers. Two chiral stationary phases (CSPs) for separating the enantiomers were compared. Different mobile phase compositions were tested at 298.15 K. The results showed that the best separation was obtained when the mobile phase was composed of n‐hexane and isopropanol (IPA) (75/25, v/v), the racemate was separated on a Chiralcel OJ‐H column, and the flow rate was 1.0 mL/min at a wavelength of 210 nm and a temperature of 25°C. The enantiomeric ratio (e.r.) values of both the synthetic (−)‐epineoclausenamide and (+)‐epineoclausenamide were 1.3(+):98.7(−) and 99.3(+):0.7(−), respectively. In this study, a new synthetic route was designed with a yield of 12.3–14.1%, and a quick (8 min) effective separation method was obtained. This provides basis for pharmacological research and quality control of clausenamide analogues.

01 Sep 2020·Neurological ResearchQ4 · MEDICINE

(-)-Clausenamide alleviated ER stress and apoptosis induced by OGD/R in primary neuron cultures

Q4 · MEDICINE

Article

Author: Wu, Fei ; Chen, Jing ; Feng, Qizhen ; Cheng, Hongju ; Xue, Jianjun ; Zhang, Rumin

OBJECTIVEThe endoplasmic reticulum stress (ERS) and ERS-related neuronal apoptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. (-)-Clausenamide has been reported to be nootropic and improve learning and memory in amnesia animal models. However, whether (-)-Clau could protect neurons from ischemic injury and the possible mechanism needed further study. The present study aimed to explore the effects of (-)-Clau on primary cortical neurons treated with oxygen-glucose deprivation/reoxygenation (OGD/R).METHODSRat primary cortical neurons were used to set up an injury model of OGD/R which imitated the clinical I/R injury. Cell viability and apoptosis were measured by CCK-8 assay, LDH detection and TUNEL staining, respectively. The activation of GRP78/eIF2α-ATF4-CHOP signaling pathway, one of the three branches of ERS, and cleaved caspase-3, the apoptotic marker, were assessed by western blotting.RESULTSOGD/R induced activation of GRP78/eIF2α-ATF4-CHOP signaling pathway. (-)-Clau significantly attenuated OGD/R-induced decrease in the cellular viability and the activation of GRP78, eIF2α, ATF4 and CHOP. To further confirm the effect of (-)-Clau on OGD/R-induced ERS activation, the ERS inducer Tunicamycin (TM) was applied. TM significantly abolished (-)-Clau's protective effect against ERS and neuronal apoptosis, indicating that the protective effect of (-)-Clau was dependent on inhibiting ERS.CONCLUSIONSThe present work demonstrated for the first time that (-)-Clau could reverse the activation of GRP78/eIF2α-ATF4-CHOP branch, thus inhibited ERS and the subsequent apoptosis induced by OGD/R and promoted cell viability in vitro. (-)-Clau could serve as a promising therapeutic agent in the treatment for ischemic stroke in the future.ABBREVIATIONSATF4: activating transcription factor-4; ATF6: activating transcription factor-6; CHOP: transcriptional induction of CCAAT/enhancer binding protein homologous protein; (-)-Clau: 3-hydroxy-4-phenyl-5a-hydroxybenzylN-methyl-g-lactam; eIF2α: eukaryotic initiation factor 2α; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; GRP78: 78-kDa glucose regulated protein; I/R: ischemia/reperfusion; IRE1: inositol requiring enzyme-1; JNK: c-Jun N-terminal kinase; OGD/R: oxygen-glucose deprivation/reoxygenation; PERK: double-stranded RNA-dependent protein kinase-like ER kinase; TM: Tunicamycin; UPR: unfolded protein response.

100 Deals associated with L-clausenamide

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Cognitive Dysfunction	Phase 2	CN	Institute of Materia Medica	12 Oct 2016
Cognitive Dysfunction	Phase 2	CN	Qingdao Huanghai Pharmaceutical Operation Co. Ltd.	12 Oct 2016
Cognitive Dysfunction	Phase 2	CN	Guangzhou Nuohao Pharmaceutical Technology Co Ltd	12 Oct 2016
Memory Disorders	Phase 2	CN	Qingdao Huanghai Pharmaceutical Operation Co. Ltd.	12 Oct 2016
Memory Disorders	Phase 2	CN	Institute of Materia Medica	12 Oct 2016
Memory Disorders	Phase 2	CN	Guangzhou Nuohao Pharmaceutical Technology Co Ltd	12 Oct 2016
Alzheimer Disease	Phase 2	CN	Fuan Pharmaceutical (Group) Co., Ltd.	-
Alzheimer Disease	Phase 2	CN	Chinese Academy of Medical Sciences	-
Cognitive Dysfunction	Preclinical	CN	Chinese Academy of Medical Sciences	12 Oct 2016
Memory Disorders	Preclinical	CN	Chinese Academy of Medical Sciences	12 Oct 2016

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