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1. 发明授权

US06949644B2 Methods for the synthesis of substituted purines 失效
标题翻译：合成取代嘌呤的方法
公开(公告)号：US06949644B2
公开(公告)日：2005-09-27
申请号：US10270031
申请日：2002-10-12
申请人： Sheng Ding , Qiang Ding , Nathanael S. Gray , Peter G. Schultz
发明人： Sheng Ding , Qiang Ding , Nathanael S. Gray , Peter G. Schultz
IPC分类号： C07D473/16 , C07D473/18 , C07D473/22 , C07D473/40
CPC分类号： C07D473/16
摘要： The invention provides general methods for preparing 2,9-, 2,6,9-, O6-aryl- and O6-alkyl-substituted purines in a combinatorial and traceless fashion. The methods involve, in some embodiments, Mitsunobu alkylation of 2-fluoro-6-phenylsulfenylpurine at N9 with alcohols in solution, followed by C2-capture of the purine core with a resin-bound amine and subsequent oxidation and displacement of the C6 sulfonyl group with amines and anilines. In one aspect, the present invention provides a method of preparing a 2,6,9-substituded purine compounds of Formula I: the method comprising: a) oxidizing a resin-bound compound of Formula II: to provide a resin-bound compound of Formula III: b) reacting the compound of Formula III with an amine of Formula IV NR3R4 IV, to provide a resin-bound compound of Formula V c) cleaving the resin-bound compound of Formula V from the resin to provide the substituted purine compounds of Formula I.
摘要翻译：本发明提供了一种制备组合中的2,9-，2,6,9-六-O-芳基和O-6 - 烷基取代的嘌呤的一般方法，无痕的时尚。在一些实施方案中，所述方法涉及N9上的2-氟-6-苯基亚磺酰基嘌呤在溶液中的醇的Mitsunobu烷基化，随后用树脂结合的胺C2-捕获嘌呤核心，随后氧化和置换C6磺酰基与胺和苯胺。一方面，本发明提供了制备式I的2,6,9-取向嘌呤化合物的方法：所述方法包括：a）氧化式II的树脂结合化合物：提供与式式III：b）使式III的化合物与式IV的胺反应，其中式“=”在线式“末端=”铅“→NR 3 R” 提供一种树脂结合的式V化合物，c）将含有树脂的化合物切割成来自树脂的式V提供式I的取代的嘌呤化合物。

2. 发明授权

US07176312B2 Kinase inhibitor scaffolds and methods for their preparation 失效
标题翻译：激酶抑制剂支架及其制备方法
公开(公告)号：US07176312B2
公开(公告)日：2007-02-13
申请号：US10270030
申请日：2002-10-12
申请人： Sheng Ding , Qiang Ding , Nathanael S. Gray
发明人： Sheng Ding , Qiang Ding , Nathanael S. Gray
IPC分类号： C07D473/16 , C07D487/04 , C07D239/94 , C07D401/14 , C07D403/12
CPC分类号： C07D239/42 , C07D239/94 , C07D241/20 , C07D241/44 , C07D473/16 , C07D473/18 , C07D473/34
摘要： General methods for the solution phase as well as solid phase synthesis of various substituted heteroaryls has been demonstrated. These substituted heteroaryls can be further elaborated by aromatic substitution with amines at elevated temperature or by anilines, boronic acids and phenols via palladium catalyzed cross-coupling reactions.
摘要翻译：已经证明了溶液相的一般方法以及各种取代的杂芳基的固相合成。这些取代的杂芳基可以通过在升高的温度下用胺进行芳族取代或通过苯胺，硼酸和酚通过钯催化的交叉偶联反应进一步精制。

3. 发明申请

US20080214541A1 COMPOSITIONS AND METHODS FOR INDUCING OSTEOGENESIS 审中-公开
标题翻译：用于诱导卵泡发育的组合物和方法
公开(公告)号：US20080214541A1
公开(公告)日：2008-09-04
申请号：US11858827
申请日：2007-09-20
申请人： Xu Wu , Sheng Ding , Nathanael S. Gray
发明人： Xu Wu , Sheng Ding , Nathanael S. Gray
IPC分类号： A61K31/5377 , C07D473/00 , A61K31/52 , C12Q1/02 , C12Q1/68 , C12N5/00 , C07D295/00
CPC分类号： C07D473/16 , C07D473/18 , C07D473/34 , C07D473/40
摘要： The present invention provides compositions and methods for differentiating and transdifferentiating mammalian cells into cells of an osteoblast lineage.
摘要翻译：本发明提供用于将哺乳动物细胞分化和转分化成成骨细胞谱系细胞的组合物和方法。

4. 发明授权

US07253166B2 6-phenyl-7H-pyrrolo[2,3-d]pyrimidine compounds that induce neuronal differentiation in embryonic stem cells 有权
标题翻译： 6-苯基-7H-吡咯并[2,3-d]嘧啶化合物，其诱导胚胎干细胞中的神经元分化
公开(公告)号：US07253166B2
公开(公告)日：2007-08-07
申请号：US10829804
申请日：2004-04-22
申请人： Sheng Ding , Tom Wu , Nathanael S. Gray , Peter Schultz
发明人： Sheng Ding , Tom Wu , Nathanael S. Gray , Peter Schultz
IPC分类号： C07D413/10 , C07D487/04 , A61K31/519 , A61K31/5355 , A61P25/28
CPC分类号： C07D487/04
摘要： The invention provides a novel class of compounds and compositions of Formula I: in which R1, R2 and R3 are defined herein, that are useful in the treatment or prevention of diseases or disorders associated with kinases, particularly GSK-3β, c-Abl, HER-1, HER-2, KDR, Flt-3, c-Raf-1, PDGFR-β, c-Kit, Flt-4, Flt-1, Tek, c-src, CDK1, PDK1, FGFR-1, FGFR-2, Fer, MAP3K13, EPHA7 and c-Met kinases. The invention further relates to the use of the compounds of the invention as potent inducers of neurogenesis in embryonic stem cells.
摘要翻译：本发明提供了一类新颖的式I化合物和组合物，其中R 1，R 2和R 3是本文定义的，可用于治疗或预防与激酶相关的疾病或病症，特别是GSK-3β，c-Abl，HER-1，HER-2，KDR，Flt-3，c-Raf-1，PDGFR-β， Kit，Flt-4，Flt-1，Tek，c-src，CDK1，PDK1，FGFR-1，FGFR-2，Fer，MAP3K13，EPHA7和c-Met激酶。本发明还涉及本发明化合物在胚胎干细胞中作为神经发生的有效诱导剂的用途。

5. 发明授权

US07273864B2 Compositions and methods for inducing osteogenesis 失效
标题翻译：诱导成骨的组合物和方法
公开(公告)号：US07273864B2
公开(公告)日：2007-09-25
申请号：US10687220
申请日：2003-10-15
申请人： Xu Wu , Sheng Ding , Nathanael S. Gray
发明人： Xu Wu , Sheng Ding , Nathanael S. Gray
IPC分类号： C07D473/40 , C07D473/34 , C07D473/18 , A61K31/522 , A61K31/52
CPC分类号： C07D473/16 , C07D473/18 , C07D473/34 , C07D473/40
摘要： The present invention provides compositions and methods for differentiating and transdifferentiating mammalian cells into cells of an osteoblast lineage, using compounds of the following formula: wherein R4 is a functional group including, for example, C1-4alkyl, C3-8cycloalkyl, hydroxyl-C1-4alkyl, aryl-C0-3alkyl, substituted with 0-2 R4a groups, and heterocyclo-C0-2alkyl, optionally substituted with C1-4alkyl; R5 is hydrogen and R6 is a functional group including, for example, halogen, C1-4alkyl, —C(O)—C1-4alkyl, —SO2—N(R2b R2b), halo—C1-4alkyl, —O-aryl and —N(R7 R8), or when R5 and R6 are on adjacent ring atoms they are optionally taken together to form —O—(CH2)1-2—O—; and all pharmaceutically acceptable salts and hydrates thereof.
摘要翻译：本发明提供了使用下式化合物将哺乳动物细胞分化和转分化成成骨细胞谱系细胞的组合物和方法：其中R 4是包括例如C 1 -C 6烷基的官能团， 1-4个碳原子的烷基，C 3-8环烷基，羟基-C 1-4烷基，芳基-C 0-3-3烷基，被0-2个R 4a取代的烷基和任选被C 1-4烷基取代的杂环-C 0-2-2烷基; R 5是氢，R 6是官能团，包括例如卤素，C 1-4烷基，-C（O） -C 1-4烷基，-SO 2 -N（R 2b，R 2b），卤代-C 1-4芳烷基，-O-芳基和-N（R 7 R 8），或当R 5 O >和R 6'在相邻的环原子上，它们任选地一起形成-O-（CH 2）2 - N 2 -O- ; 及其所有药学上可接受的盐和水合物。

6. 发明申请

US20070191380A1 KINASE INHIBITOR SCAFFOLDS AND METHODS FOR THEIR PREPARATION 审中-公开
标题翻译：激酶抑制剂及其制备方法
公开(公告)号：US20070191380A1
公开(公告)日：2007-08-16
申请号：US11673976
申请日：2007-02-12
申请人： Sheng Ding , Qiang Ding , Nathanael Gray
发明人： Sheng Ding , Qiang Ding , Nathanael Gray
IPC分类号： A61K31/522 , A61K31/52 , A61K31/4965 , A61K31/498 , A61K31/517 , C07D473/12 , C07D473/10 , C07D239/94 , C07D239/32
CPC分类号： C07D239/42 , C07D239/94 , C07D241/20 , C07D241/44 , C07D473/16 , C07D473/18 , C07D473/34
摘要： General methods for the solution phase as well as solid phase synthesis of various substituted heteroaryls has been demonstrated. These substituted heteroaryls can be further elaborated by aromatic substitution with amines at elevated temperature or by anilines, boronic acids and phenols via palladium catalyzed cross-coupling reactions.
摘要翻译：已经证明了溶液相的一般方法以及各种取代的杂芳基的固相合成。这些取代的杂芳基可以通过在升高的温度下用胺进行芳族取代或通过苯胺，硼酸和酚通过钯催化的交叉偶联反应进一步精制。

7. 发明申请

US20060009642A1 Methods for the synthesis of substituted purines 审中-公开
标题翻译：合成取代嘌呤的方法
公开(公告)号：US20060009642A1
公开(公告)日：2006-01-12
申请号：US11223429
申请日：2005-09-09
申请人： Sheng Ding , Qiang Ding , Nathanael Gray , Peter Schultz
发明人： Sheng Ding , Qiang Ding , Nathanael Gray , Peter Schultz
IPC分类号： C07D473/24 , C07D473/16
CPC分类号： C07D473/16 , C07D473/06 , C07D473/18
摘要： The invention provides general methods for preparing 2,9-, 2,6,9-, O6-aryl- and O6-alkyl-substituted purines in a combinatorial and traceless fashion. The methods involve, in some embodiments, Mitsunobu alkylation of 2-fluoro-6-phenylsulfenylpurine at N9 with alcohols in solution, followed by C2-capture of the purine core with a resin-bound amine and subsequent oxidation and displacement of the C6 sulfonyl group with amines and anilines.
摘要翻译：本发明提供了一种制备组合中的2,9-，2,6,9-六-O-芳基和O-6 - 烷基取代的嘌呤的一般方法，无痕的时尚。在一些实施方案中，所述方法涉及N9上的2-氟-6-苯基亚磺酰基嘌呤在溶液中的醇的Mitsunobu烷基化，随后用树脂结合的胺C2-捕获嘌呤核心，随后氧化和置换C6磺酰基与胺和苯胺。

8. 发明授权

US10421798B2 Factor VIII compositions and methods of making and using same 有权
公开(公告)号：US10421798B2
公开(公告)日：2019-09-24
申请号：US14379192
申请日：2012-07-11
申请人： Volker Schellenberger , Pei-Yun Chang , Fatbardha Varfaj , Sheng Ding , Joshua Silverman , Chia-wei Wang , Benjamin Spink , Willem P. Stemmer , Volker Schellenberger , Nathan Geething , John Kulman , Tongyao Liu , Garabet G. Toby , Haiyan Jiang , Robert Peters , Deping Wang , Baisong Mei
发明人： Volker Schellenberger , Pei-Yun Chang , Fatbardha Varfaj , Sheng Ding , Joshua Silverman , Chia-wei Wang , Benjamin Spink , Willem P. Stemmer , Nathan Geething , John Kulman , Tongyao Liu , Garabet G. Toby , Haiyan Jiang , Robert Peters , Deping Wang , Baisong Mei
IPC分类号： C07K14/755 , A61K38/00
摘要： The present invention relates to compositions comprising factor VIII coagulation factors linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in treatment of factor VIII-related diseases, disorders, and conditions.

9. 发明授权

US09376664B2 Reprogramming of cells to a new fate 有权
标题翻译：将细胞重新编程到新的命运
公开(公告)号：US09376664B2
公开(公告)日：2016-06-28
申请号：US13704214
申请日：2011-06-14
申请人： Jem A. Efe , Janghwan Kim , Saiyong Zhu , Simon Hilcove , Sheng Ding
发明人： Jem A. Efe , Janghwan Kim , Saiyong Zhu , Simon Hilcove , Sheng Ding
IPC分类号： C12N15/85 , C12N5/071 , C12N5/077 , C12N5/079 , C12N5/0793 , C12N5/0797
CPC分类号： C12N5/0676 , A61K35/30 , A61K35/33 , A61K35/34 , A61K35/39 , C12N5/0602 , C12N5/0603 , C12N5/0607 , C12N5/0618 , C12N5/0619 , C12N5/0623 , C12N5/0657 , C12N5/0678 , C12N15/85 , C12N2501/01 , C12N2501/155 , C12N2501/235 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/605 , C12N2501/606 , C12N2501/727 , C12N2506/02 , C12N2506/08 , C12N2506/1307 , C12N2510/00
摘要： Methods and compositions for transdifferentiation of an animal cell from (i) a first pluripotent cell fate to a second nonpluripotent cell fate or (ii) from a non-pluripotent mesodermal, endodermal, or ectodermal cell fate to a different non-pluripotent mesodermal, endodermal, or ectodermal cell fate.
摘要翻译：用于将动物细胞转分化为（i）第一多能细胞命运到第二非多能细胞命运的方法和组合物，或（ii）从非多能中胚层，内胚层或外胚层细胞命运到不同的非多能中胚层，内胚层，或外胚层细胞命运。

10. 发明授权

US09005968B2 Induction of pluripotent cells 有权
标题翻译：诱导多能细胞
公开(公告)号：US09005968B2
公开(公告)日：2015-04-14
申请号：US13500373
申请日：2010-10-15
申请人： Tongxiang Lin , Sheng Ding
发明人： Tongxiang Lin , Sheng Ding
IPC分类号： C12N5/00 , C12N5/074
CPC分类号： C12N5/0696 , C12N2501/065 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/606 , C12N2501/727 , C12N2501/999 , C12N2506/094 , C12N2506/1307 , C12N2506/28 , C12N2510/00
摘要： The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.
摘要翻译：用于产生人诱导多能干细胞（iPSCs）的重编程方法的缓慢动力学和低效率对其在生物医学应用中的实用性施加了主要限制。在这里，我们描述了一种化学方法，在治疗后7天内显着改善（> 200倍）来自人成纤维细胞的iPSC生成的效率。这将为重新编程人体细胞提供更安全，更有效，非病毒的方法的基础。

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