公开(公告)号：US08765945B2

公开(公告)日：2014-07-01

申请号：US13023140

申请日：2011-02-08

Applicant: Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

Inventor： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Quan Jiang ,  Lei Lu

IPC: C07D237/36

CPC classification number: C07D405/06 ,  C07D249/08 ,  C07D401/04 ,  C07D403/06 ,  C07D471/06

Abstract: Provided herein are processes for synthesizing dihydropyridophthalazinone derivatives, such as for example, 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and its stereoisomers, which are potent poly(ADP-ribose)polymerase (PARP) inhibitors as well as novel synthetic intermediate compounds.

Abstract translation: 本文提供了合成二氢吡啶并二氮杂萘酮衍生物的方法，例如5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基） 9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮及其立体异构体，它们是有效的聚（ADP-核糖）聚合酶（PARP）抑制剂以及新的合成中间体化合物。

公开(公告)号：US08735392B2

公开(公告)日：2014-05-27

申请号：US13277607

申请日：2011-10-20

Applicant: Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Shichun Peng

Inventor： Bing Wang ,  Daniel Chu ,  Yongbo Liu ,  Shichun Peng

IPC: A01N43/58 ,  A61K31/495

CPC classification number: C07D471/06

Abstract: Provided herein are (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, and methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.

Abstract translation: 本文提供的是（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H- - 吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲磺酸盐形式，包括晶型，及其制备方法。 包含（8S，9R）-5-氟-8-（4-氟苯基）-9-（1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢 - 还提供了使用（8S，9R）-5-氟-8-（4-氟苯基）-9（7H） - 酮的方法，使用2-吡啶并[4,3,2- - （1-甲基-1H-1,2,4-三唑-5-基）-8,9-二氢-2H-吡啶并[4,3,2-de]酞嗪-3（7H） - 酮甲苯磺酸盐 治疗疾病或病症，如癌症。

公开(公告)号：US20120314092A1

公开(公告)日：2012-12-13

申请号：US13483771

申请日：2012-05-30

Applicant: Daniel Chu ,  Eli A. Hefner ,  Yann Jouvenot

Inventor： Daniel Chu ,  Eli A. Hefner ,  Yann Jouvenot

IPC: H04N5/225 ,  B01L3/00

CPC classification number: G01N15/1463 ,  G01N2015/1006

Abstract: An automated system captures multiple digital images of a sample, from different viewing areas of the sample. The images are analyzed and a test result may be reported based on the count of cells in all of the digital images. The system may be especially applicable to the testing of samples having low cell concentrations, as the variability between tests may be reduced as compared with a system that bases its test results on only a single image of the sample. The system may count the cells in a first digital image of the sample, and may capture or analyze one or more additional digital images only when it is recognized that additional measurements are needed to ensure adequate accuracy and repeatability of the test.

Abstract translation: 自动化系统从样品的不同观察区域捕获样品的多个数字图像。 分析图像，并且可以基于所有数字图像中的单元的计数来报告测试结果。 该系统可能特别适用于具有低细胞浓度的样品的测试，因为与将其测试结果仅基于样品的单个图​​像的系统相比，可以减少测试之间的可变性。 系统可以对样本的第一数字图像中的单元进行计数，并且可以仅在认识到需要额外的测量以确保测试的足够的精度和可重复性时才捕获或分析一个或多个附加的数字图像。

公开(公告)号：US20110217323A1

公开(公告)日：2011-09-08

申请号：US13108937

申请日：2011-05-16

Applicant: Nicholas VALIANTE ,  Feng Xu ,  Xiaodong Lin ,  Daniel Chu ,  Xiaojing Michael Wang

Inventor： Nicholas VALIANTE ,  Feng Xu ,  Xiaodong Lin ,  Daniel Chu ,  Xiaojing Michael Wang

IPC: A61K39/00 ,  C07D471/04 ,  A61P37/02 ,  A61P37/04 ,  A61P35/00

CPC classification number: C07D471/14 ,  C07D471/04 ,  Y02P20/55

Abstract: The invention provides novel compositions comprising imidazoquinoline compounds. Also provided are methods of administering the compositions in an effective amount to enhance the immune response of a subject. Further provided are novel compositions and methods of administering the compositions in combination with (an) other agent(s).

Abstract translation: 本发明提供包含咪唑并喹啉化合物的新型组合物。 还提供了以有效量施用组合物以增强受试者的免疫应答的方法。 进一步提供了组合物与（一种或多种）其它试剂组合施用的新组合物和方法。

公开(公告)号：US20100216699A1

公开(公告)日：2010-08-26

申请号：US12697967

申请日：2010-02-01

Applicant: Daniel Chu ,  Tao Ye

Inventor： Daniel Chu ,  Tao Ye

IPC: A61K38/14 ,  C07K9/00 ,  C07K7/64 ,  A61K38/12 ,  A61P31/04

CPC classification number: C07K9/008 ,  A61K38/00 ,  C07K7/06

Abstract: Semi-synthetic glycopeptides having antibacterial activity are described. Also described are processes of preparing such semi-synthetic glycopeptides by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in mild acidic medium to give the amino acid-4 monosaccharide; protection of the amino groups in the molecule; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also included are the process of conversion of the amide group in amino acid-3 on these scaffolds to various acylureas, acylamide, acylsulfonamide, acylsulfonylurea derivatives and aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction procedures. Further provided herein are pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, including bacterial infections.

Abstract translation: 描述了具有抗菌活性的半合成糖肽。 还描述了通过糖肽（化合物A，化合物B，化合物H或化合物C）的化学修饰或通过水解母体糖肽的氨基酸-4的二糖部分制备的单糖制备这种半合成糖肽的方法 温和酸性培养基，得到氨基酸-4单糖; 保护分子中的氨基; 并将这些支架的大环上的酸部分转化为某些取代的酰胺。 还包括在氨基酸-7上通过曼尼希反应方法将这些支架上的氨基酸3中的酰胺基团转化为各种酰基脲，酰基酰胺，酰基磺酰胺，酰基磺酰脲衍生物和氨基甲基化，其中氨基酸-7的取代基含有磺酰胺或酰基磺酰胺基团。 本文进一步提供含有该化合物的药物组合物，以及该化合物用于治疗和/或预防疾病包括细菌感染的方法。

公开(公告)号：US20100105607A1

公开(公告)日：2010-04-29

申请号：US12603435

申请日：2009-10-21

Applicant: Daniel Chu ,  Tao Ye ,  Bing Wang

Inventor： Daniel Chu ,  Tao Ye ,  Bing Wang

IPC: A61K38/08 ,  C07K9/00 ,  A61P31/04

CPC classification number: C07K9/006

Abstract: Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of the a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; conversion of the amide group in amino acid-3 on these scaffolds to various acylamide, acylsulfonamide, acylsulfonylurea derivatives; aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.

Abstract translation: 具体描述了具有抗菌活性的半合成糖肽，特别是本文所述的半合成糖肽通过化学修饰糖肽（化合物A，化合物B，化合物H或化合物C）或通过水解二糖而制备的单糖 在酸性介质中母体糖肽的氨基酸-4部分得到氨基酸-4单糖; 单糖转化为氨基糖衍生物; 在这些支架上的氨基酸4氨基取代的糖部分上的氨基取代基被某些酰基酰化; 这些支架上氨基酸-3中的酰胺基转化为各种酰基酰胺，酰基磺酰胺，酰基磺酰脲衍生物; 通过曼尼希反应在氨基酸-7上氨基甲基化与含有磺酰胺或酰基磺酰胺基团的取代基; 并将这些支架的大环上的酸部分转化为某些取代的酰胺。 还提供了合成化合物的方法，含有该化合物的药物组合物，以及该化合物用于治疗和/或预防疾病，特别是细菌感染的方法。

公开(公告)号：US07632918B2

公开(公告)日：2009-12-15

申请号：US11361852

申请日：2006-02-24

Applicant: Daniel Chu ,  Maria N. Preobrazhenskaya ,  Svetlana S. Printsevskaya ,  Eugenia N. Olsufyeva

Inventor： Daniel Chu ,  Maria N. Preobrazhenskaya ,  Svetlana S. Printsevskaya ,  Eugenia N. Olsufyeva

IPC: A61K38/14

CPC classification number: A61K38/14 ,  C07K9/008

Abstract: Semi-synthetic glycopeptides having antibacterial activity are based on modifications of the eremomycin, A82846B, vancomycin, teicoplanin, and A-40,926 scaffolds, in particular, acylation of the sugar moieties on these scaffolds with certain acyl groups; and/or conversion of an acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides; or having a combination of an alkylation modification of the amino substituent on the amino-substituted sugar moiety on these scaffolds with certain alkyl groups or acylation modification of the amino substituent on the amino-substituted sugar moiety on this scaffold with certain alkyl groups, and conversion of the acid moiety on the macrocyclic ring of this scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.

Abstract translation: 具有抗菌活性的半合成糖肽基于依依霉素，A82846B，万古霉素，替考拉宁和A-40,926支架的修饰，特别是在具有某些酰基的这些支架上糖部分的酰化; 和/或将这些支架的大环上的酸部分转化为某些取代的酰胺; 或具有这些支架上的氨基取代的糖部分上的氨基取代基的烷基化修饰与某些烷基的组合或在该支架上的某些烷基上的氨基取代的糖部分上的氨基取代基的酰化修饰和转化 的该支架的大环上的酸部分与某些取代的酰胺。 还提供了合成化合物的方法，含有该化合物的药物组合物，以及该化合物用于治疗和/或预防疾病，特别是细菌感染的方法。

公开(公告)号：US20090197863A1

公开(公告)日：2009-08-06

申请号：US12355692

申请日：2009-01-16

Applicant: Daniel Chu ,  Bing Wang

Inventor： Daniel Chu ,  Bing Wang

IPC: A61K31/422 ,  C07D263/54 ,  A61K31/423 ,  A61K31/496 ,  C07D413/02 ,  A61P35/00

CPC classification number: C07D263/57 ,  C07D413/04 ,  C07D413/10 ,  C07D455/02 ,  C07D487/04 ,  C07D487/08

Abstract: A compound having the structure set forth in Formula (I) or Formula (II): wherein the variables Y, R1, R2, R3, and R4 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.

Abstract translation: 具有式（I）或式（II）所示结构的化合物：其中变量Y，R1，R2，R3和R4如本文所定义。 本文提供了聚（ADP-核糖）聚合酶活性的抑制剂。 本文还描述了包含本文所述的至少一种化合物和本文所述的化合物或药物组合物用于治疗通过抑制PARP活性而改善的疾病，病症和病症的药物组合物。

公开(公告)号：USRE39836E1

公开(公告)日：2007-09-11

申请号：US11182038

申请日：2005-07-13

Applicant: Daniel Chu ,  Gary Ashley

Inventor： Daniel Chu ,  Gary Ashley

IPC: A61K31/70 ,  C07H17/08

CPC classification number: C07H17/08 ,  Y02P20/55

Abstract: Compounds of the formula wherein Ra is H; substituted or unsubstituted alkyl (1-10C); substituted or unsubstituted alkenyl (2-10C); substituted or unsubstituted alkynyl (2-10C); substituted or unsubstituted aryl (4-14C); substituted or unsubstituted arylalkyl (5-20C); or ORa is replaced by H; Rb is H or halogen; Rc is H or a protecting group; Rd is methyl, unsubstituted alkyl (3-10C); substituted alkyl (1-10C); substituted or unsubstituted alkynyl (2-10C); substituted or unsubstituted aryl (4-14C); substituted or unsubstituted arylalkyl (5-20C); substituted or unsubstituted arylalkenyl (5-20C); substituted or unsubstituted arylalkynyl (5-20C); substituted or unsubstituted amidoarylalkyl (5-20C); substituted or unsubstituted amidoarylalkenyl (5-20C); or substituted or unsubstituted amidoarylalkynyl (5-20C); Re is H or a protecting group; L is methylene or carbonyl; T is —O—, —N(R)—, —N(OR)—, —N(NHCOR)—, —N(N═CHR)—, or —N(NHR)— wherein R is H or Ra as defined above, with the proviso that when L is methylene, T is —O—; one of Z and Y is H and the other is OH, protected OH, or amino, mono- or dialkylamino, protected amino, or an amino heterocycle or Z and Y together are ═O, ═NOH or a derivatized oxime; including any pharmaceutically acceptable salts thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof, are antimicrobial agents.

Abstract translation: 下式的化合物其中R a a为H; 取代或未取代的烷基（1-10C）; 取代或未取代的烯基（2-10C）; 取代或未取代的炔基（2-10C）; 取代或未取代的芳基（4-14C）; 取代或未取代的芳基烷基（5-20​​℃）; 或OR被替换为H; R b是H或卤素; R c是H或保护基; R d是甲基，未取代的烷基（3-10C）; 取代的烷基（1-10C）; 取代或未取代的炔基（2-10C）; 取代或未取代的芳基（4-14C）; 取代或未取代的芳基烷基（5-20​​℃）; 取代或未取代的芳基烯基（5-20​​℃）; 取代或未取代的芳基炔基（5-20​​℃）; 取代或未取代的酰氨基芳基烷基（5-20​​℃）; 取代或未取代的酰氨基芳基烯基（5-20​​℃）; 或取代或未取代的酰氨基芳基炔基（5-20​​℃）; R e是H或保护基; L是亚甲基或羰基; T是-O - ， - N（R） - ， - N（OR） - ， - N（NHCOR） - ， - N（N-CHR） - 或-N（NHR） 如上所定义，条件是当L是亚甲基时，T是-O-; Z和Y之一是H，另一个是OH，保护的OH或氨基，单或二烷基氨基，保护的氨基或氨基杂环，或Z和Y一起是-O，-NOH或衍生化的肟; 包括其任何药学上可接受的盐和其立体异构体形式及其立体异构形式的混合物均为抗微生物剂。

公开(公告)号：US20070202018A1

公开(公告)日：2007-08-30

申请号：US11361411

申请日：2006-02-24

Applicant: Daniel Chu ,  Paul Patt ,  Jeffry Ceremony

Inventor： Daniel Chu ,  Paul Patt ,  Jeffry Ceremony

IPC: B01L9/00

CPC classification number: G01N35/028 ,  B01L9/523 ,  B01L2200/025 ,  B01L2300/0829

Abstract: A platform that supports a sample plate such as a microtiter plate, a multi-well plate of any size, or a glass slide with sample spots distributed over its surface, and presents the plate for assay detection by a movable scanning head that has a field depth on the millimeter scale is leveled or otherwise adjusted in a planar orientation by an apparatus that includes a rocker plate, position sensors, and motorized risers arranged on the apparatus to provide the rocker plate with tilting capability along either or both or two orthogonal axes.

Abstract translation: 支撑样品板的平台，例如微量滴定板，任何尺寸的多孔板或具有分布在其表面上的样品斑点的玻片，并且通过具有场的可移动扫描头呈现用于测定检测的板 通过包括设置在设备上的摇臂板，位置传感器和电动立管的装置，平面定位或以其它方式调整深度，以使摇杆具有沿着一个或两个或两个正交轴线的倾斜能力。