公开(公告)号：WO2011143426A1

公开(公告)日：2011-11-17

申请号：PCT/US2011/036246

申请日：2011-05-12

申请人： VERTEX PHARMACEUTICALS INCORPORATED ,  CHARRIER, Jean-Damien ,  BINCH, Haley, Marie ,  HURLEY, Dennis, James ,  CLEVELAND, Thomas ,  JOSHI, Pramod ,  FANNING, Lev Tyler, Dewey ,  PINDER, Joanne ,  O'DONNELL, Michael ,  VIRANI, Anisa, Nizarali ,  KNEGTEL, Ronald, Marcellus Alphonsus ,  DURRANT, Steven, John ,  YOUNG, Stephen, Clinton ,  PIERRE-HENRI ,  KAY, David ,  REAPER, Philip, Michael

发明人： CHARRIER, Jean-Damien ,  BINCH, Haley, Marie ,  HURLEY, Dennis, James ,  CLEVELAND, Thomas ,  JOSHI, Pramod ,  FANNING, Lev Tyler, Dewey ,  PINDER, Joanne ,  O'DONNELL, Michael ,  VIRANI, Anisa, Nizarali ,  KNEGTEL, Ronald, Marcellus Alphonsus ,  DURRANT, Steven, John ,  YOUNG, Stephen, Clinton ,  PIERRE-HENRI ,  KAY, David ,  REAPER, Philip, Michael

IPC分类号： C07D413/14 ,  A61K31/497 ,  A61K31/444 ,  A61P35/00

CPC分类号： C07D413/14

摘要： The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I wherein the variables are as defined herein.

摘要翻译： 本发明涉及可用作ATR蛋白激酶抑制剂的吡嗪和吡啶化合物。 本发明还涉及包含本发明化合物的药学上可接受的组合物; 使用本发明化合物治疗各种疾病，病症和病症的方法; 制备本发明化合物的方法; 用于制备本发明化合物的中间体; 以及在体外应用中使用化合物的方法，如生物和病理现象中激酶的研究; 由这种激酶介导的细胞内信号转导途径的研究; 和新型激酶抑制剂的比较评估。 本发明的化合物具有式I，其中变量如本文所定义。

公开(公告)号：WO2009111428A4

公开(公告)日：2010-01-28

申请号：PCT/US2009035803

申请日：2009-03-03

申请人： UNIV TULANE ,  UNIV TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  US AGRICULTURE ,  ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

发明人： ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

IPC分类号： C07D493/02 ,  A61K31/353 ,  A61P5/24 ,  A61P35/00 ,  C07D311/04 ,  C07D311/74 ,  C07D493/14

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开和要求的两种不同的方法用于合成甘氨酸蛋白I加血糖素II作为混合物，并以其纯形式。 立体化学异构体和各种合成中间体也由它们的新物质组合物合成和要求保护。 要求所有化合物及其混合物用于可用于治疗或预防癌症或具有选择性雌激素受体调节剂的制剂的制剂，所述制剂包括增强型或医用食品，膳食补充剂和伦理药剂。

公开(公告)号：WO2009111428A3

公开(公告)日：2009-12-10

申请号：PCT/US2009035803

申请日：2009-03-03

申请人： UNIV TULANE ,  UNIV TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  US AGRICULTURE ,  ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

发明人： ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

IPC分类号： C07D493/02 ,  A61K31/353 ,  A61P5/24 ,  A61P35/00 ,  C07D311/04 ,  C07D311/74 ,  C07D493/14

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开和要求的两种不同的方法用于合成甘氨酸蛋白I加血糖素II作为混合物，并以其纯形式。 立体化学异构体和各种合成中间体也由它们的新物质组合物合成和要求保护。 要求所有化合物及其混合物用于可用于治疗或预防癌症或具有选择性雌激素受体调节剂的制剂的制剂，所述制剂包括增强型或医用食品，膳食补充剂和伦理药剂。

公开(公告)号：WO2005026137A3

公开(公告)日：2005-07-21

申请号：PCT/US2004029206

申请日：2004-09-07

申请人： VERTEX PHARMA ,  MILLER MARK T ,  HADIDA RUAH SARA S ,  SINGH ASHAVINI K ,  CLEVELAND THOMAS ,  MAKINGS LEWIS R ,  HAMILTON MATTHEW ,  GROOTENHUIS PETER D J

发明人： MILLER MARK T ,  HADIDA RUAH SARA S ,  SINGH ASHAVINI K ,  CLEVELAND THOMAS ,  MAKINGS LEWIS R ,  HAMILTON MATTHEW ,  GROOTENHUIS PETER D J

IPC分类号： A61K31/426 ,  A61K31/427 ,  A61P43/00 ,  C07D263/48 ,  C07D277/46 ,  C07D277/82 ,  C07D417/02 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12

CPC分类号： A61K31/426 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/5377 ,  C07D263/48 ,  C07D277/46 ,  C07D277/82 ,  C07D295/15 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  G01N33/5076

摘要： The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including CF Transmembrane Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

摘要翻译： 本发明涉及ATP结合盒（“ABC”）转运体或其片段的调节剂，包括CF跨膜调节剂（“CFTR”），其组合物及其方法。 本发明还涉及使用这种调节剂治疗ABC转运蛋白介导的疾病的方法。

公开(公告)号：WO2006118871A3

公开(公告)日：2006-11-09

申请号：PCT/US2006/015637

申请日：2006-04-24

申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF AGRICULTURE ,  TULANE CENTER FOR BIOENVIRONMENTAL RESEARCH ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

发明人： CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

IPC分类号： A01N65/00

摘要： The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their hormonal activity and their effects on human health and disease. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The health benefits of soy may therefore be dependent upon the amounts of the various hormonally active phytochemicals present. We have identified increased biosynthesis of the isoflavonoid phytoalexin compounds, Glyceollins I, Il and III, in soy plants grown under stressed conditions (elicited soy), which exhibit marked anti-estrogenic effects on ER function. Here we demonstrate that specific glyceollins, isolated from elicited soy, displayed anti-estrogenic activity, suppressing basal and estrogen stimulated colony formation of ER-positive estrogen dependent breast cancer cells and inhibiting ER-dependent gene expression of progesterone receptor (PgR) and stromal derived factor-1 (SDFI/CXCL^). Examining the effects of glyceollin on in vivo tumor formation/growth we demonstrate the ability of glyceollins to significantly suppress basal and estrogen-stimulated tumor growth of ER-positive MCF-7 breast and BG-1 ovarian carcinoma cells in ovariectomized female nude mice. We further demonstrate that the effects of glyceollins on suppression of tumor growth correlate with inhibition of estrogen stimulated PgR expression. In contrast to the uterotropic activity of tamoxifen the glyceollins displayed no uterine agonist activity. The Glyceollin (l-lll) compounds may represent an important component of the health effects of soy as well as represent novel anti-estrogens useful in the prevention or treatment of breast and ovarian carcinoma.

公开(公告)号：WO2016057572A1

公开(公告)日：2016-04-14

申请号：PCT/US2015/054316

申请日：2015-10-06

申请人： MILLER, Mark Thomas ,  ANDERSON, Corey ,  ARUMUGAM, Vijayalaksmi ,  BEAR, Brian Richard ,  BINCH, Hayley Marie ,  CLEMENS, Jeremy J. ,  CLEVELAND, Thomas ,  CONROY, Erica ,  COON, Timothy Richard ,  FRIEMAN, Bryan A. ,  GROOTENHUIS, Peter Diederik Jan ,  GROSS, Raymond Stanley ,  HADIDA-RUAH, Sara Sabina ,  HARIPADA, Khatuya ,  JOSHI, Pramod Virupax ,  KRENITSKY, Paul John ,  LIN, Chun-Chieh ,  MARELIUS, Gulin Erdgogan ,  MELILLO, Vito ,  MCCARTNEY, Jason ,  NICHOLLS, Georgia McGaughey ,  PIERRE, Fabrice Jean Denis ,  SILINA, Alina ,  TERMIN, Andreas P. ,  UY, Johnny ,  ZHOU, Jinglan

发明人： MILLER, Mark Thomas ,  ANDERSON, Corey ,  ARUMUGAM, Vijayalaksmi ,  BEAR, Brian Richard ,  BINCH, Hayley Marie ,  CLEMENS, Jeremy J. ,  CLEVELAND, Thomas ,  CONROY, Erica ,  COON, Timothy Richard ,  FRIEMAN, Bryan A. ,  GROOTENHUIS, Peter Diederik Jan ,  GROSS, Raymond Stanley ,  HADIDA-RUAH, Sara Sabina ,  HARIPADA, Khatuya ,  JOSHI, Pramod Virupax ,  KRENITSKY, Paul John ,  LIN, Chun-Chieh ,  MARELIUS, Gulin Erdgogan ,  MELILLO, Vito ,  MCCARTNEY, Jason ,  NICHOLLS, Georgia McGaughey ,  PIERRE, Fabrice Jean Denis ,  SILINA, Alina ,  TERMIN, Andreas P. ,  UY, Johnny ,  ZHOU, Jinglan

IPC分类号： A01N41/06 ,  A61K31/18

CPC分类号： A61K31/506 ,  A61J1/035 ,  A61K31/404 ,  A61K31/415 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4525 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/497 ,  C07D209/18 ,  C07D209/42 ,  C07D209/49 ,  C07D213/64 ,  C07D213/73 ,  C07D213/82 ,  C07D213/84 ,  C07D231/12 ,  C07D231/14 ,  C07D231/20 ,  C07D235/24 ,  C07D239/34 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14 ,  C07D407/12 ,  C07D413/14 ,  C07D417/12

摘要： The present invention features a compound of formula (I): (I) or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

摘要翻译： 本发明的特征在于式（I）化合物：（I）或其药学上可接受的盐，其中R1，R2，R3，W，X，Y，Z，n，o，p和q如本文所定义， 治疗CFTR介导的疾病，如囊性纤维化。 本发明还特征在于药物组合物，治疗方法及其试剂盒。

公开(公告)号：WO2009111428A2

公开(公告)日：2009-09-11

申请号：PCT/US2009/035803

申请日：2009-03-03

申请人： THE ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND ,  THE UNIVERSITY OF TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  UNITED STATES DEPARTMENT OF AGRICULTURE ,  ERHARDT, Paul, W. ,  KHUPSE, Rahul, S. ,  SARVER, Jeffrey, G. ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  WIESE, Thomas, E. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

发明人： ERHARDT, Paul, W. ,  KHUPSE, Rahul, S. ,  SARVER, Jeffrey, G. ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  WIESE, Thomas, E. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

IPC分类号： A61M1/36

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开并要求保护两种不同的方法用于合成作为混合物和作为其纯形式的甘油糖苷I加甘油二酯II。 立体化学异构体和各种合成中间体也被合成并要求其新颖的物质组成。 要求所有化合物及其混合物用于可用于治疗或预防癌症的制剂或可用作选择性雌激素受体调节剂的制剂，所述制剂包括增强或医疗食品，膳食补充剂和道德药物制剂。

公开(公告)号：WO2006127588A3

公开(公告)日：2007-07-26

申请号：PCT/US2006019712

申请日：2006-05-22

申请人： VERTEX PHARMA ,  HADIDA RUAH SARA S ,  HAZLEWOOD ANNA R ,  GROOTENHUIS PETER D J ,  SINGH ASHVANI K ,  CLEVELAND THOMAS ,  VAN GOOR FREDERICK F

发明人： HADIDA RUAH SARA S ,  HAZLEWOOD ANNA R ,  GROOTENHUIS PETER D J ,  SINGH ASHVANI K ,  CLEVELAND THOMAS ,  VAN GOOR FREDERICK F

IPC分类号： C07D239/42 ,  A61K31/505 ,  A61K31/506 ,  C07D403/04 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D491/10

CPC分类号： C07D405/12 ,  C07D239/42 ,  C07D403/02 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/02 ,  C07D417/02 ,  C07D491/10

摘要： 4-amido-pyrimidine compounds, derivatives and compositions thereof, and synthetic methods described herein are useful for modulating ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"). The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

摘要翻译： 4-氨基 - 嘧啶化合物，其衍生物和组合物以及本文所述的合成方法可用于调节ATP结合盒（“ABC”）转运蛋白或其片段，包括囊性纤维化跨膜电导调节剂（“CFTR”）。 本发明还涉及使用这种调节剂治疗ABC转运蛋白介导的疾病的方法。

公开(公告)号：WO2002046880A3

公开(公告)日：2002-06-13

申请号：PCT/US2001/047510

申请日：2001-12-03

申请人： FIRSTWEB BANCORP, INC. ,  KUYKENDALL, James, B. ,  CLEVELAND, Thomas, G., Jr.

发明人： KUYKENDALL, James, B. ,  CLEVELAND, Thomas, G., Jr.

IPC分类号： G06F17/60

摘要： A system for performing push-model fund transfers between at least one user and at least one gateway account. The gateway is operative to receive information from said payor interface identifying a desired fund transfer; to receive incoming funds from the payor into said at least one gateway account after receiving said information; to informing the user that the payor has provided an appropriate amount of funds if said incoming funds received are of an appropriate amount according to said desired fund transfer; and to send corresponding outgoing funds to the user after receiving said incoming funds (1 A).

公开(公告)号：WO0246880A2

公开(公告)日：2002-06-13

申请号：PCT/US0147510

申请日：2001-12-03

申请人： FIRSTWEB BANCORP INC ,  KUYKENDALL JAMES B ,  CLEVELAND THOMAS G JR

发明人： KUYKENDALL JAMES B ,  CLEVELAND THOMAS G JR

IPC分类号： G06F20060101 ,  G06Q20/04 ,  G06Q20/10 ,  G06Q40/00 ,  G06F

CPC分类号： G06Q40/02 ,  G06Q20/04 ,  G06Q20/10 ,  G06Q40/00

摘要： A system for performing push-model fund transfers between at least one user and at least one gateway account. The gateway is operative to receive information from said payor interface identifying a desired fund transfer; to receive incoming funds from the payor into said at least one gateway account after receiving said information; to informing the user that the payor has provided an appropriate amount of funds if said incoming funds received are of an appropriate amount according to said desired fund transfer; and to send corresponding outgoing funds to the user after receiving said incoming funds (1 A).

摘要翻译： 一种用于在至少一个用户和至少一个网关帐户之间执行推模型资金转移的系统。 网关操作以从所述支付者接口接收识别所需资金转移的信息; 在接收到所述信息之后从所述至少一个网关帐户接收来自所述至少一个网关帐户的进入资金; 如果所收到的所接收到的资金根据所述期望的资金转移是适当的金额，通知用户付款人已经提供了适当的金额; 并且在接收到所述进入的资金之后向用户发送相应的流出资金（1A）。