Segatroxaban(Segatroxaban) - 药物靶点：factor Xa x thrombin_在研适应症：血液透析并发症，静脉血栓栓塞，静脉血栓形成_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

factor Xa x thrombin

作用机制

factor Xa抑制剂(激活型凝血因子X抑制剂)、thrombin抑制剂(激活型凝血因子II抑制剂)

治疗领域

心血管疾病其他疾病

在研适应症

血液透析并发症静脉血栓栓塞静脉血栓形成

非在研适应症-

原研机构

Sanofi

在研机构

北京科莱博医药开发有限责任公司

非在研机构

Sanofi SA

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)临床1期

特殊审评特殊审批 (中国)

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结构

分子式C24H30ClN5O5S2

InChIKeyCYVVCTRDWISRAC-KRWDZBQOSA-N

CAS号1184300-63-7

关联

3

项与 Segatroxaban 相关的临床试验

CTR20240453 / Recruiting临床1期

SAR107375E注射液在肾功能衰竭患者血液透析的动态调整给药方案的安全性、药代动力学和初步药效学研究的Ic期临床试验

主要目的：评估 SAR107375E 注射液在肾功能衰竭患者血液透析的安全性和人体药代动力学（PK）特征；次要目的：探索 SAR107375E 注射液在肾功能衰竭患者血液透析的给药方案；初步探索 SAR107375E 注射液在肾功能衰竭患者血液透析的药效学特征。

开始日期2024-04-06

申办/合作机构

北京科莱博医药开发有限责任公司

CTR20222815 / Completed临床1期

SAR107375E 注射液在中国健康成年受试者的随机双盲、安慰剂对照、多次静脉推注的安全性、耐受性、药代动力学和初步药效学研究的Ⅰb 期临床试验

主要目的：评估中国健康成年受试者多次静脉推注（推注时间约 10min）SAR107375E 注射液的安全耐受性和人体药代动力学（PK）特征；次要目的：评估 SAR107375E 注射液多次静脉推注的药效学评价指标及特征。

开始日期2023-01-03

申办/合作机构

北京科莱博医药开发有限责任公司

CTR20211082 / Completed临床1期

SAR107375E注射液在中国健康成年受试者的随机双盲、安慰剂对照、剂量递增、单次静脉推注的安全性、耐受性、药代动力学和初步药效学研究的Ⅰa期临床试验

主要目的：评估中国健康成年受试者单次静脉推注（推注时间10min） SAR107375E注射液的安全耐受性；评估中国健康成年受试者单次静脉推注（推注时间10min） SAR107375E注射液的人体药代动力学（PK）特征。次要目的：初步探索SAR107375E注射液的药效学评价指标及特征。

开始日期2021-07-09

申办/合作机构

北京科莱博医药开发有限责任公司

100 项与 Segatroxaban 相关的临床结果

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100 项与 Segatroxaban 相关的转化医学

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100 项与 Segatroxaban 相关的专利（医药）

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3

项与 Segatroxaban 相关的文献（医药）

2023-11-02·Expert Opinion on Investigational Drugs

First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa

Article

作者: Chen, Guiying ; Li, Chen ; Li, Yongmei ; Wu, Shuanzhi ; Zhan, Yaoxuan ; Zheng, Sichao ; Wang, Xiaole ; Wang, Tenghua ; Li, Xianbo ; Xiao, Shuangshuang ; Liu, Haiyan ; Li, Jieyun ; Wang, Xuan ; Zhang, Zhixin ; He, Jin ; Liang, Xintong ; Jiang, Hongliang ; Ban, Li ; Zou, Qinwen ; Hu, Zhiqin ; Zheng, Qingshan ; Fang, Yi

BACKGROUNDSAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects.METHODSIn this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.5, 1.5, 3.0, 5.0, 7.5, 10.0, 15.0, or 20.0 mg) of SAR107375E (N = 44) or placebo (N = 16). Plasma and urine concentrations of SAR107375E were measured and used to calculate pharmacokinetic parameters. Coagulation functions were measured and compared with baseline values. Treatment-emergent adverse events were recorded to evaluate safety.RESULTSIn plasma, from the 0.5 to 20.0 mg dose group, t_1/2 is 1.51-4.00 h, C_max is 59.05-1360 ug/L, and AUC_0-t is 25.01-528.45 h*ug/L. And it shows dose proportionality in the 5.0-20.0 mg range. Activated partial thromboplastin time and Ecarin clotting time correlated linearly with drug plasma concentration. No serious adverse events were reported during the study.CONCLUSIONSAR107375E exhibits good safety and tolerability, predictable pharmacokinetics and pharmacodynamics.CLINICAL TRIAL REGISTRATIONwww.chinadrugtrials.org.cn, identifier is CTR20211082.

2013-12-12·Journal of Medicinal Chemistry1区 · 医学

5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor

1区 · 医学

Article

作者: Schreuder, Herman ; Follmann, Markus ; Meneyrol, Jerome ; Bono, Françoise ; Altenburger, Jean-Michel ; Klieber, Sylvie ; Herault, Jean-Pascal ; Bocskei, Zsolt ; Rousseaux, Tristan ; Dol, Frederique ; Alet, Nathalie ; Briot, Christophe ; Sadoun, Freddy ; Barre, Guillaume ; Petit, Frederic ; Herbert, Jean-Marc ; Schaeffer, Paul ; Millet, Laurence ; Wehner, Volkmar ; Lassalle, Gilbert ; Florian, Peter

Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 μM, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene P1 fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with Ki's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 μM) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

Molecules3区 · 化学

Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors

3区 · 化学

ArticleOA

作者: Remková, Anna ; Remko, Milan ; Broer, Ria

The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p) or Grimme’s B97D/6-31++G(d,p) method. The fully optimized conformers of these anticoagulants show a characteristic l-shape structure, and the water had a remarkable effect on the equilibrium geometry. According to the calculated pKa values eribaxaban and letaxaban are in neutral undissociated form at pH 7.4, while fidexaban and tanogitran exist as zwitterionic structures. The lipophilicity of the inhibitors studied lies within a large range of log P between 1 and 4. The dual inhibitor SAR107375 represents an improvement in structural, physicochemical and pharmacokinetic characteristics over tanogitran. At blood pH, SAR107375 predominantly exists in neutral form. In contrast with tanogitran, it is better absorbed and more lipophilic and active after oral application.

100 项与 Segatroxaban 相关的药物交易

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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
血栓形成	临床2期	法国	Sanofi SA	2012-01-30
血液透析并发症	临床1期	中国	北京科莱博医药开发有限责任公司	2024-04-06
静脉血栓栓塞	临床1期	中国	北京科莱博医药开发有限责任公司	2023-01-03
静脉血栓形成	临床1期	中国	北京科莱博医药开发有限责任公司	2021-07-09