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    • 2. 发明申请
    • PERIPHERICAL TISSUE SAMPLE CONTAINING CELLS EXPRESSING THE 5HTR2C AND/OR ADARS AS MARKERS OF THE ALTERATION OF THE MECHANISM OF THE 5HTR2C MRNA EDITING AND ITS APPLICATIONS
    • 包含表达5HTR2C和/或ADARS的细胞的外周组织样品作为改变5HTR2C MRNA编码机制的标记及其应用
    • WO2008152146A1
    • 2008-12-18
    • PCT/EP2008/057519
    • 2008-06-13
    • BIOCORTECHWEISSMANN, DinahPUJOL, Jean-FrançoisVINCENT, LaurentCAVAREC, LaurentMANN, John
    • WEISSMANN, DinahPUJOL, Jean-FrançoisVINCENT, LaurentCAVAREC, LaurentMANN, John
    • C12Q1/68
    • C12Q1/6883C12Q2600/136C12Q2600/158G01N33/6896G01N33/942
    • The present invention relates to an in vitro method for predicting a pathology related to an alteration of the mechanism of the mRNA editing of ADAR dependent A to I mRNA editing, particularly the serotonin 2C receptor (5HTR2C), in a patient from a peripherical tissue sample containing cells expressing said mRNA, such as the 5HTR2C mRNA, and/or adenosine deaminases acting on RNA (ADARs), such as skin and/or blood tissue sample. The present invention further comprises a method for identifying if an agent is capable of in vivo modifying the editing of the 5HTR2C mRNA in brain tissue or to control the efficiency of a drug intended to prevent or to treat a pathology related to an alteration of the mechanism of the 5HTR2C mRNA editing brain tissue, these methods comprising the implementation of said peripherical tissue markers. In a particular aspect, the present invention relates to such methods wherein the 5HTR2C mRNA editing rate or profile, when it is necessary, is determined by a single strand conformation polymorphism (SSCP) method after amplification by a PCR, preferably by a nested PCR, of the specific mRNA fragment containing the edition sites, making it possible, under given analytical conditions, to obtain the editing rate and/or profile of this edited 5HTR2C mRNA from said peripherical tissue. Finally the invention relates to particular nucleic acid primers implemented in said nested PCR.
    • 本发明涉及一种用于预测来自外周组织样品的患者中ADAR依赖性A至I mRNA编辑的mRNA编辑,特别是5-羟色胺2C受体(5HTR2C)的mRNA编辑的机制的改变的病理学的体外方法 含有表达所述mRNA的细胞,例如5HTR2C mRNA,和/或作用于RNA(ADAR)的腺苷脱氨酶,例如皮肤和/或血液组织样品。 本发明还包括用于鉴定药物是否能够体内修饰脑组织中的5HTR2C mRNA的编辑或控制旨在预防或治疗与机制改变有关的病理学的效力的方法 的5HTR2C mRNA编辑脑组织,这些方法包括实施所述外周组织标记物。 在特定方面,本发明涉及这样的方法,其中当需要时,通过PCR扩增后优选通过巢式PCR,通过单链构象多态性(SSCP)方法确定5HTR2C mRNA编辑速率或分布, 的具有编码位点的特异性mRNA片段,使得在给定的分析条件下可以从所述外周组织获得该编辑的5HTR2C mRNA的编辑率和/或分布。 最后,本发明涉及在所述巢式PCR中实施的特定核酸引物。
    • 4. 发明申请
    • DERIVES DU 14.15-DIHYDRO 20.21-DINOREBURNAMENIN-14-OL, ET LEURS APPLICATIONS
    • 14.15-二氢O O O O O IN IN IN IN IN IN IN IN IN IN IN IN IN IN IN IN OF OF OF OF OF OF OF OF OF OF OF OF OF OF
    • WO2005103047A1
    • 2005-11-03
    • PCT/FR2005/000902
    • 2005-04-14
    • BIOCORTECHCIAPETTI, PaolaDEYON, LaurenceWERMUTH, Camille-GeorgesPUJOL, Jean-FrançoisWEISSMANN, Dinah
    • CIAPETTI, PaolaDEYON, LaurenceWERMUTH, Camille-GeorgesPUJOL, Jean-FrançoisWEISSMANN, Dinah
    • C07D461/00
    • C07D461/00
    • L'invention a pour objet de nouveaux dérivés du 14,15-dihydro 20,21 dinoréburnaméninl4-ol, de formule (I) dans laquelle R représente un radical -AR', dans lequel A représente un hétéroatome et R' représente un groupement choisi dans le groupe constitué par les radicaux alkyles en C 1 -C 6 , alcényles en C 1 -C 6 , alcynyles en C 1 -C 6 , aralkyles; les esters de formule - R 1 -CO-O-R 2 ; les amides de formule -R 3 -CO-NZY dans laquelle Y et Z peuvent former ensemble un radical cycloalkyle ou un radical hétérocyclique, éventuellement substitué par un ou plusieurs radicaux alkyles; un radical choisi dans le groupe constitué par les radicaux alkyles, alcényles ou alcynyles, substitués par au moins une amine de formule -NZY; ou l'un de ses sels pharmaceutiquement acceptables, y compris ses isomères, ses énantiomères, ses diastéréoisomères et leurs mélanges. L'invention a également pour objet l'utilisation de ces nouveaux dérivés pour la préparation d'une composition pharmaceutique, notamment destinée au traitement et/ou la prévention chez l'Homme des dépressions, des troubles du cycle veille-sommeil et des troubles symptomatiques frontaux dans leur composantes cognitives.
    • 本发明涉及具有式(I)的14,15-二氢20,21二辛烷亚胺-14-醇的新衍生物,其中R表示一个自由基-AR',其中A表示杂原子,R'表示选自 该基团包括C1-C6的烷基,C1-C6的烯基,C1-C6的炔基,芳烷基; 具有式-R1-CO-O-R2的酯; 具有式-R3-CO-NZY的酰胺,其中Y和Z一起可以形成任选被一个或多个烷基取代的环烷基或杂环基; 选自由至少一个具有式-NZY的胺取代的烷基,烯基或炔基的基团; 或其药学上可接受的盐之一,包括其异构体,对映体和非对映异构体及其混合物。 本发明还涉及所述新型衍生物用于制备药物组合物的用途,该药物组合物特别用于治疗和/或预防人类中认知成分中的抑郁症,睡眠/觉醒周期障碍和症状性正面疾病。
    • 9. 发明公开
    • DERIVES DU 14.15-DIHYDRO 20.21-DINOREBURNAMENIN-14-OL, ET LEURS APPLICATIONS
    • DERIVES DU 14.15-DIHYDRO 20.21-DINOREBURNAMENIN-14-OL,ET LEURS应用
    • EP1737856A1
    • 2007-01-03
    • EP05757149.9
    • 2005-04-14
    • Biocortech
    • CIAPETTI, PaolaDEYON, LaurenceWERMUTH, Camille-GeorgesPUJOL, Jean-FrançoisWEISSMANN, Dinah
    • C07D461/00A61K31/437A61P25/24A61P25/18
    • C07D461/00
    • The invention relates to novel derivatives of 14,15-dihydro 20,21 dinoreburnamenin-14-ol, having formula (I), in which R represents a radical -AR', wherein A represents a heteroatom and R' represents a group selected from the group comprising alkyl radicals at C1-C6, alkenyls at C1-C6, alkynyls at C1-C6, aralkyls; esters having formula -R1-CO-O-R2; amides having formula -R3-CO-NZY, wherein Y and Z together can form a cycloalkyl radical or a heterocyclic radical, optionally substituted by one or more alkyl radicals; a radical selected from the group comprising alkyl radicals, alkenyls or alkynyls, substituted by at least one amine having formula -NZY; or one of the pharmaceutically-acceptable salts thereof, including the isomers, enantiomers and diastereoisomers thereof and mixtures of same. The invention also relates to the use of said novel derivatives for the preparation of a pharmaceutical composition which is intended, in particular, for the treatment and/or prevention of depression, sleep/wake cycle disorders and symptomatic frontal disorders in cognitive components among humans.
    • 本发明涉及具有式(I)的新颖的14,15-二氢20,21 ore铃啉-14-醇的衍生物,其中R表示基团-AR',其中A表示杂原子且R'表示选自 该基团包含C1-C6烷基,C1-C6烯基,C1-C6炔基,芳烷基; 具有式-R1-CO-O-R2的酯; 具有式-R3-CO-NZY的酰胺,其中Y和Z一起可以形成任选被一个或多个烷基取代的环烷基或杂环基团; 选自包含烷基,烯基或炔基的基团,其被至少一种具有式-NZY的胺取代; 或其药学上可接受的盐之一,包括其异构体,对映异构体和非对映异构体及其混合物。 本发明还涉及所述新衍生物在制备药物组合物中的用途,所述药物组合物特别旨在用于治疗和/或预防人类认知成分中的抑郁症,睡眠/觉醒周期障碍和症状性前额障碍。