公开(公告)号：US20080188651A1

公开(公告)日：2008-08-07

申请号：US12006364

申请日：2008-01-02

申请人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

发明人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

IPC分类号： C07D225/02 ,  C07D313/04 ,  C07C59/10

CPC分类号： C07C33/02 ,  C07B2200/07 ,  C07C59/10 ,  C07C59/42 ,  C07C69/732 ,  C07C69/734 ,  C07D309/10 ,  C07D309/30 ,  C07D313/00 ,  C07D319/06 ,  C07D407/06 ,  C07F7/1804 ,  Y02P20/55

摘要： Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3), —CH═CH—, —CH═C(CH3), or —C≡C—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

公开(公告)号：US07321046B2

公开(公告)日：2008-01-22

申请号：US11139949

申请日：2005-05-27

申请人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

发明人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

IPC分类号： C07D313/04 ,  C07D313/16

CPC分类号： C07C33/02 ,  C07B2200/07 ,  C07C59/10 ,  C07C59/42 ,  C07C69/732 ,  C07C69/734 ,  C07D309/10 ,  C07D309/30 ,  C07D313/00 ,  C07D319/06 ,  C07D407/06 ,  C07F7/1804 ,  Y02P20/55

摘要： Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

公开(公告)号：US09127016B2

公开(公告)日：2015-09-08

申请号：US13256584

申请日：2010-03-19

申请人： Billy W. Day ,  Waikok Michael Tsang ,  Vasiliy N. Korotchenko

发明人： Billy W. Day ,  Waikok Michael Tsang ,  Vasiliy N. Korotchenko

IPC分类号： C07C211/00 ,  A01N33/02 ,  C07D495/04

CPC分类号： C07C225/20 ,  A61K31/135 ,  C07C211/42 ,  C07D495/04

摘要： Compounds that stimulate fibroblast growth factor production, and thus cell growth are provided. Also provided are compositions comprising the compounds and methods of using the compounds. The compounds can be used to treat wounds, to expand cell populations, such as hematopoietic cells, or to grow tissue in vitro, among other uses.

摘要翻译： 提供了刺激成纤维细胞生长因子生成，从而促进细胞生长的化合物。 还提供了包含该化合物的组合物和使用该化合物的方法。 这些化合物可以用于治疗伤口，扩大细胞群体，如造血细胞，或者在体外培养组织以及其他用途。

公开(公告)号：US07815894B2

公开(公告)日：2010-10-19

申请号：US10854894

申请日：2004-05-27

申请人： Jay W. Pettegrew ,  Richard J. McClure ,  Kanagasabai Panchalingam ,  Billy W. Day

发明人： Jay W. Pettegrew ,  Richard J. McClure ,  Kanagasabai Panchalingam ,  Billy W. Day

IPC分类号： A61K51/00 ,  A61M36/14

CPC分类号： G01N33/6896 ,  A61K49/10 ,  A61K51/0406 ,  G01N2800/2821

摘要： Compounds, compositions and methods for the diagnosis of Alzheimer's disease. Synthesized Glycerophosphocholine (GPC) may be used as a diagnostic aid to measure progression of Alzheimer's disease. GPC is a membrane phospholipid metabolite that is capable of binding specifically to the β-turn of beta amyloid (Aβ) peptide. Compounds including non-radioactive, paramagnetic, and radioactive derivatives of GPC are presented. These compounds possess similar binding properties to original GPC molecules and are useful in medical magnetic resonance imaging and/or positron emission tomography applications. By employing these radiological techniques in conjunction with the compositions of the present invention, the diagnosis and assessment of the progression of Alzheimer's disease may be achieved.

摘要翻译： 用于诊断阿尔茨海默病的化合物，组合物和方法。 合成的甘油磷酸胆碱（GPC）可用作诊断阿尔茨海默氏病进展的诊断辅助。 GPC是一种能够特异性结合β-淀粉样蛋白（A＆bgr））肽的膜磷脂代谢产物。 提出了包括GPC的非放射性，顺磁性和放射性衍生物的化合物。 这些化合物具有与原始GPC分子相似的结合特性，并且可用于医学磁共振成像和/或正电子发射断层摄影应用。 通过结合本发明的组合物使用这些放射技术，可以实现阿尔茨海默病进展的诊断和评估。

公开(公告)号：US06673937B2

公开(公告)日：2004-01-06

申请号：US09910195

申请日：2001-07-19

申请人： John S. Lazo ,  Peter Wipf ,  Billy W. Day

发明人： John S. Lazo ,  Peter Wipf ,  Billy W. Day

IPC分类号： C07D40500

CPC分类号： C07D317/72 ,  A61K31/357 ,  A61K31/426 ,  C07D319/08 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D493/10

摘要： Oxidative cyclization of bis-naphthyl ethers allows concise total syntheses of palmarumycin CP1 and deoxypreussomerin A in 8-9 steps and 15-35% overall yield from 5-hydroxy-8-methoxy-1-tetralone. A small library of palmarumycin analogs was created. Biological evaluation of these naphthoquinone spiroketals against MCF-7 and MDA-MB-231 human breast cancer cells revealed several low-micromolar growth inhibitors. A number of the analogs inhibit the thioredoxin—thioredoxin reductase system.

摘要翻译： 双萘基醚的氧化环化允许8-9步骤中棕榈霉素CP1和脱氧阿司咪霉素A的简明综合，5-羟基-8-甲氧基-1-四氢萘酮的总产率为15-35％。 创建了一个古老的棕榈霉素类似物库。 这些萘醌螺旋酮对MCF-7和MDA-MB-231人乳腺癌细胞的生物学评价显示出几种低微摩尔生长抑制剂。 许多类似物抑制硫氧还蛋白硫氧还蛋白还原酶系统。

公开(公告)号：US06392055B1

公开(公告)日：2002-05-21

申请号：US09909076

申请日：2001-07-19

申请人： Peter Wipf ,  Jonathan T. Reeves ,  Billy W. Day ,  Raghavan Balachandran

发明人： Peter Wipf ,  Jonathan T. Reeves ,  Billy W. Day ,  Raghavan Balachandran

IPC分类号： C07D27722

CPC分类号： C07D277/20 ,  C07C43/23 ,  C07D263/32 ,  C07D277/10 ,  C07D307/42 ,  C07D307/80 ,  C07D333/16

摘要： The present invention provides an efficient synthetic strategy for the preparation of analogs that incorporate important structural elements of the marine natural product curacin A, the compositions and various uses of the compositions. The most active of these compounds at nanomolar concentrations inhibit tubulin polymerization, show growth inhibition activity, inhibited colchicines binding to tubulin and block mitotic progression. The compounds of the present invention represent some of the most potent synthetic curacin A analogs synthesized, with an activity profile rivaling that of the natural product despite the simplified structure, greater water solubility, and increased chemical stability.