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1. 发明申请

WO2011104637A9 CRYSTALLINE FORMS OF THE TRI-MESYLATE SALT OF PERPHENAZINE-GABA AND PROCESS OF PRODUCING THE SAME 审中-公开
标题翻译：石榴酸三苯甲基肼的结晶形式及其生产方法
公开(公告)号：WO2011104637A9
公开(公告)日：2011-09-01
申请号：PCT/IB2011/000915
申请日：2011-02-24
申请人： RAMOT AT TEL-AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , BIOLINERX LTD. , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , SHAUL, Mazal , HALBFINGER, Efrat
发明人： NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , SHAUL, Mazal , HALBFINGER, Efrat
IPC分类号： G06Q10/00
摘要： Novel crystalline form of perphenazine 4-aminobutyrate trimesylate and a process of producing the same are disclosed. The novel crystalline form is characterized by a unique XRPD pattern and a DSC that exhibits an endothermic peak at a relatively high temperature (e.g., higher than 209 °C). Also disclosed are a process of preparing perphenazine 4- aminobutyrate trimesylate by in situ deprotection and salification, in a single-step synthesis, and a highly pure perphenazine 4-aminobutyrate trimesylate obtained thereby. Uses of any of the described perphenazine 4-aminobutyrate trimesylate are also disclosed.
摘要翻译：公开了新型奋乃静4-氨基丁酸三甲磺酸盐的晶型及其制备方法。新型结晶形式的特征在于独特的XRPD图和在相对高的温度（例如高于209℃）下显示吸热峰的DSC。还公开了一步法合成制备奋乃静4-氨基丁酸三甲磺酸酯的原位脱保护和成盐的方法，以及由此得到的高纯度奋乃静4-氨基丁酸三甲磺酸盐。也公开了任何所述奋乃静4-氨基丁酸三甲磺酸盐的用途。

2. 发明申请

WO2008120205A1 NOVEL DERIVATIVES OF PURINIC AND PYRIMIDINIC ANTIVIRAL AGENTS AND USE THEREOF AS POTENT ANTICANCER AGENTS 审中-公开
标题翻译：胭脂红抗菌药物的新型衍生物及其作为抗原剂的用途
公开(公告)号：WO2008120205A1
公开(公告)日：2008-10-09
申请号：PCT/IL2008/000443
申请日：2008-03-30
申请人： RAMOT AT TEL AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , NUDELMAN, Abraham , REPHAELI, Ada
发明人： NUDELMAN, Abraham , REPHAELI, Ada
IPC分类号： C07D473/18
CPC分类号： C07D473/18
摘要： Novel N-acylated, O-acylated and (bis or tris)-N,O-acylated derivatives of purinic and pyrimidinic nucleoside analogs, pharmaceutical compositions containing same, and uses thereof for treating proliferative diseases or disorders are disclosed.
摘要翻译：公开了嘌呤和嘧啶核苷类似物的新型N-酰化，O-酰化和（双或三）-N，O-酰化衍生物，含有它们的药物组合物及其用于治疗增殖性疾病或病症的用途。

3. 发明申请

WO2006131923A2 NOVEL SALTS OF CONJUGATED PSYCHOTROPIC DRUGS AND PROCESSES OF PREPARING SAME 审中-公开
标题翻译：联合心肌麻醉药物的新口服及其制备方法
公开(公告)号：WO2006131923A2
公开(公告)日：2006-12-14
申请号：PCT/IL2006/000666
申请日：2006-06-07
申请人： RAMOT AT TEL AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , BIOLINERX LTD. , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , HALACHMI, Shlomit , BENJAMIN, Eran, J.
发明人： NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , HALACHMI, Shlomit , BENJAMIN, Eran, J.
IPC分类号： A61K47/48 , A61P25/00 , A61P35/00
CPC分类号： C07D279/28 , A61K47/542
摘要： Novel chemical conjugates of a psychotropic drug residue and an amino-containing organic acid residue selected to reduce side effects induced by the psychotropic drug when administered per se, to enhance the therapeutic activity of the psychotropic drug and/or to exert anti-proliferative activity, in which the amino group is in the form of an acid addition salt thereof and which are characterized by high stability are disclosed. Further disclosed are processes for preparing the chemical conjugates and addition salts thereof, pharmaceutical compositions containing the chemical conjugates and methods utilizing the chemical conjugates for treating various medical conditions.
摘要翻译：精神药物残基和含氨基的有机酸残基的新型化学共轭物被选择用于减少由精神药物本身引起的副作用，以增强精神药物的治疗活性和/或发挥抗增殖活性，其中氨基为其酸加成盐的形式，其特征在于高稳定性。进一步公开的是制备化学共轭物及其加成盐的方法，含有化学共轭物的药物组合物和利用化学共轭物治疗各种医学病症的方法。

4. 发明申请

WO1995024189A1 INCREASING FETAL HEMOGLOBIN LEVELS USING CARBOXYLIC ESTERS 审中-公开
标题翻译：使用羧酸酯增加天冬氨酸蛋白酶水平
公开(公告)号：WO1995024189A1
公开(公告)日：1995-09-14
申请号：PCT/US1995002769
申请日：1995-03-06
申请人： REPHAELI, Ada
发明人： NUDELMAN, Abraham , SHAKLAI, Matityahu
IPC分类号： A61K31/265
CPC分类号： A61K31/355 , A61K31/22 , A61K31/23 , A61K31/265 , A61K31/335 , A61K31/365 , Y02A50/411 , Y10S514/815 , Y10S514/895
摘要： This invention relates to novel methods of increasing the level of fetal hemoglobin (HbF) in a subject and methods of treating, preventing or ameliorating beta -globin or other HbF-related disorders by increasing the level of HbF in a subject in need of such treatment comprising administering one or more compounds of the formulae: (I) XCH2-CHX-CHX-C(=O)-O-Z, (II) CH3-CO-CH2-C(=O)-O-Z or (III) CH3-CH2-CO-C(=O)-O-Z, wherein X is H, or one of X only may be OH; Z is -CHR-O-C(=O)R', -CHR-O-C(=O)-O-R', or (IV); R is H, alkyl, aryl, arylalkyl; and R' is alkyl, aminoalkyl, aralkyl, aryl, alkoxy, aralkoxy and aryloxy, in which aryl by itself, and aryl in aralkyl, aralkoxy and aryloxy are each selected from the group consisting of phenyl, naphthyl, furyl, or thienyl, each of which is unsubstituted or substituted by at least one substituent selected from the group consisting of alkyl, alkoxy, or halogen; and pharmaceutically acceptable salts and prodrugs thereof.
摘要翻译：本发明涉及增加受试者胎儿血红蛋白（HbF）水平的新方法以及通过增加需要这种治疗的受试者中HbF水平来治疗，预防或改善β-珠蛋白或其他HbF相关疾病的方法包括施用一种或多种下式的化合物：（I）XCH2-CHX-CHX-C（= O）-OZ，（II）CH3-CO-CH2-C（= O）-OZ或（III）CH3-CH2 -CO-C（= O）-OZ，其中X是H，或者X中的一个可以是OH; Z是-CHR-O-C（= O）R'，-CHR-O-C（= O）-O-R'或（IV）; R是H，烷基，芳基，芳基烷基; 和R'是烷基，氨基烷基，芳烷基，芳基，烷氧基，芳烷氧基和芳氧基，其中芳基本身和芳烷基，芳烷氧基和芳氧基中的芳基各自选自苯基，萘基，呋喃基或噻吩基，各自其中未取代或被至少一个选自烷基，烷氧基或卤素的取代基取代; 及其药学上可接受的盐和前药。

5. 发明申请

WO2008010223A2 GABA CONJUGATES FOR PAIN 审中-公开
标题翻译： GABA联合痛苦
公开(公告)号：WO2008010223A2
公开(公告)日：2008-01-24
申请号：PCT/IL2007/000903
申请日：2007-07-17
申请人： RAMOT AT TEL AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
发明人： NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
IPC分类号： A61K45/06 , A61K47/48 , A61P25/18 , A61P25/28 , A61P25/24 , A61P25/22 , A61P25/16 , A61P25/14 , A61P25/04 , A61P25/30 , A61P25/32 , A61P25/34
CPC分类号： A61K45/06 , A61K47/55
摘要： A novel use of conjugates of psychotropic drugs (e.g., antidepressants or anti-epileptic drugs) and organic acids such as GABA in the treatment of pain is disclosed. A novel GABA conjugate and uses thereof is also disclosed.
摘要翻译：公开了一种在治疗疼痛中使用精神药物（例如抗抑郁药或抗癫痫药物）和有机酸如GABA的缀合物的新用途。还公开了一种新型的GABA缀合物及其用途。

6. 发明申请

WO2003026563A3 CONJUGATED ANTI-PSYCHOTIC DRUGS AND USES THEREOF 审中-公开
公开(公告)号：WO2003026563A3
公开(公告)日：2003-04-03
申请号：PCT/IL2002/000795
申请日：2002-09-29
申请人： RAMOT AT TEL AVIV UNIVERSITY LTD. , BAR ILAN UNIVERSITY , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
发明人： NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
IPC分类号： A61P25/18
摘要： Novel chemical conjugates of anti-psychotic drugs and organic acids, uses thereof in the treatment of psychotic and/or proliferative disorders and diseases and as chemosensitizing agents, and their syntheses are disclosed. The organic acids are selected to reduce side effects induced by the anti-psychotic drugs and/or to exert an anti-proliferative activity.

7. 发明申请

WO2012127466A1 5-AMINOLEVULINIC ACID DERIVATIVES, METHODS FOR THEIR PREPARATION AND USES THEREOF 审中-公开
标题翻译： 5-氨基酸衍生物，其制备方法及其用途
公开(公告)号：WO2012127466A1
公开(公告)日：2012-09-27
申请号：PCT/IL2012/000127
申请日：2012-03-22
申请人： BAR ILAN UNIVERSITY , RAMOT AT TEL AVIV UNIVERSITY LTD. , REPHAELI, Ada , TARASENKO, Nataly , MALIK, Zvi , NUDELMAN, Abraham , BERKOVITCH-LURIA, Gili , DORON, Dvir
发明人： REPHAELI, Ada , TARASENKO, Nataly , MALIK, Zvi , NUDELMAN, Abraham , BERKOVITCH-LURIA, Gili , DORON, Dvir
IPC分类号： A61K31/221
CPC分类号： A61K31/221 , A61K31/197 , A61K31/225 , A61K41/0061 , A61K45/06 , A61K47/48023 , A61K47/481 , A61K47/54 , A61K47/55 , A61K2300/00 , A61N5/062 , C07C229/22
摘要： The present invention provides drug conjugates comprising 5-aminolevulinic acid (ALA), an aldehyde and a carboxylic acid that may function as a histone deacetylase inhibitor (HDACI). These conjugates may serve as co-drugs which release a plurality of active species in vivo. The novel drug conjugates may be used, for the treatment or prevention of cancer in PDT-dependent and/or PDT-independent (nonPDT) treatments, as well as for cosmetic uses. In addition the present invention provides novel uses for both the novel and known compounds. According to some embodiments, the present invention provides drug conjugates (co-drugs) comprising (i) ALA, (ii) an aldehyde and (iii) a carboxylic acid that may function as a histone deacetylase inhibitor (HDACO for the treatment of anemia and/or for the induction of erythropoiesis.
摘要翻译：本发明提供了包含5-氨基乙酰丙酸（ALA），醛和可用作组蛋白脱乙酰酶抑制剂（HDACI）的羧酸的药物偶联物。这些缀合物可以作为在体内释放多种活性物质的共同药物。可以使用新的药物缀合物，用于治疗或预防PDT依赖和/或不依赖于PDT的（nonPDT）治疗中的癌症，以及用于化妆品用途。此外，本发明提供新颖和已知化合物的新用途。根据一些实施方案，本发明提供了药物偶联物（共药物），其包含（i）ALA，（ii）醛和（iii）可用作组蛋白脱乙酰酶抑制剂（HDACO用于治疗贫血和 /或用于诱导红细胞生成。

8. 发明申请

WO2011070579A1 METHODS OF IMPROVING COGNITIVE FUNCTIONS 审中-公开
标题翻译：改进认知功能的方法
公开(公告)号：WO2011070579A1
公开(公告)日：2011-06-16
申请号：PCT/IL2010/001041
申请日：2010-12-09
申请人： BIOLINERX LTD. , BAR-ILAN UNIVERSITY , RAMOT AT TEL-AVIV UNIVERSITY LTD. , GEFFEN, Yona , SAVITSKY, Kinneret , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
发明人： GEFFEN, Yona , SAVITSKY, Kinneret , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham
IPC分类号： A61K31/5415 , C07D417/06
CPC分类号： C07D279/26 , A61K31/5415
摘要： Conjugates comprising a first moiety having GABA agonist activity and a second moiety having CNS activity being covalently linked to the first moiety, for use in improving a cognitive function, and in preventing onset or inhibiting progression of a cognitive impairment or dysfunction are disclosed. Methods utilizing these conjugates and articles of manufacture comprising these conjugates are also disclosed.
摘要翻译：公开了包含具有GABA激动剂活性的第一部分和具有与第一部分共价连接的CNS活性的第二部分，用于改善认知功能以及预防认知障碍或功能障碍发作或抑制进展的缀合物。还公开了利用这些缀合物和包含这些缀合物的制品的方法。

9. 发明申请

WO2012038963A1 AN ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME 审中-公开
标题翻译：一种硝酸加成盐和其制备方法
公开(公告)号：WO2012038963A1
公开(公告)日：2012-03-29
申请号：PCT/IL2011/000752
申请日：2011-09-22
申请人： RAMOT AT TEL-AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , BIOLINERX LTD. , NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , SHAUL, Mazal , HALBFINGER, Efrat
发明人： NUDELMAN, Abraham , REPHAELI, Ada , GIL-AD, Irit , WEIZMAN, Abraham , SHAUL, Mazal , HALBFINGER, Efrat
IPC分类号： C07C233/02
CPC分类号： C07C57/15 , C07B2200/13 , C07C51/412 , C07C231/02 , C07C231/12 , C07C237/06 , C07C2603/32
摘要： An acid addition salt of a nortriptyline-GABA conjugate, a novel crystalline form of a fumaric acid addition salt of a nortriptyline-GABA conjugate, and processes of preparing the forgoing are disclosed. Uses of the above-indicated forms of a nortriptyline-GABA conjugate in the treatment of CNS disorders, and in the treatment of pain in particular, are also disclosed. Further disclosed in a large-scale process of preparing a nortriptyline-GABA conjugate.
摘要翻译：公开了去甲替林-GABA缀合物的酸加成盐，去甲替林-GABA缀合物的富马酸加成盐的新结晶形式及其制备方法。还公开了上述形式的去甲替林-GABA缀合物在治疗CNS障碍中的用途，特别是用于治疗疼痛。在制备去甲替林-GABA缀合物的大规模方法中进一步公开。

10. 发明申请

WO2005120577A2 NOVEL DERIVATIVES OF CHEMOTHERAPEUTIC AGENTS AND USES THEREOF 审中-公开
标题翻译：化学药剂的新型衍生物及其用途
公开(公告)号：WO2005120577A2
公开(公告)日：2005-12-22
申请号：PCT/IL2005/000614
申请日：2005-06-09
申请人： RAMOT AT TEL AVIV UNIVERSITY LTD. , BAR-ILAN UNIVERSITY , NUDELMAN, Abraham , REPHAELI, Ada
发明人： NUDELMAN, Abraham , REPHAELI, Ada
IPC分类号： A61K47/48
CPC分类号： C07D473/38 , A61K31/45 , A61K31/454 , A61K31/506 , A61K31/513 , A61K31/522 , A61K47/54 , A61K47/542 , A61K47/545 , C07D239/54 , C07D239/553 , C07D401/04 , C07D405/04 , C07D473/24
摘要： Novel conjugates of chemotherapeutic agents, which are designed so as to release formaldehyde or analogs thereof upon cleavage, processes of preparing same, pharmaceutical compositions containing same and methods utilizing same for treating medical conditions such as cancer, immune-mediated diseases, viral infections and diseases, bacterial infections and diseases, fungal infections and diseases, protozal infections and diseases and more, and particularly for treating such conditions which are characterized by drug resistance are provided.
摘要翻译：化学治疗剂的新缀合物，其设计用于在切割时释放甲醛或其类似物，其制备方法，含有其的药物组合物和利用其的方法用于治疗医学病症如癌症，免疫介导的疾病，病毒感染和疾病，细菌感染和疾病，真菌感染和疾病，原虫感染和疾病等，并且特别是用于治疗特征为耐药性的病症。

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