公开(公告)号：US08314090B2

公开(公告)日：2012-11-20

申请号：US12614048

申请日：2009-11-06

Applicant: J. Jeffry Howbert ,  Venkat Reddy Kusukuntla ,  Alexander Tretyakov ,  Nathan Nielsen ,  Pavel Krasik ,  Ji-Long Jiang ,  Hong Woon Yang

Inventor： J. Jeffry Howbert ,  Venkat Reddy Kusukuntla ,  Alexander Tretyakov ,  Nathan Nielsen ,  Pavel Krasik ,  Ji-Long Jiang ,  Hong Woon Yang

IPC: A61P31/00 ,  A61K31/55 ,  C07D223/16

CPC classification number: C07D403/10 ,  C07D223/16

Abstract: The disclosure describes method of synthesis of substituted benzazepine derivatives. Preferred methods according to the disclosure allow for large-scale preparation of benzazepine compounds having low levels of metal impurities. In some embodiments, preferred methods according to the disclosure also allow for the preparation of benzazepine derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. The methods disclosed herein find utility in synthetic organic chemistry as well as medicinal chemistry.

Abstract translation: 本公开描述了取代的苯并氮杂衍生物的合成方法。 根据本公开的优选方法允许大规模制备具有低水平金属杂质的苯并氮杂化合物。 在一些实施方案中，根据本公开的优选方法还允许制备苯并氮杂衍生物，而不使用色谱纯化方法，并且比以前使用的制备此类化合物的方法更好的产率。 本文公开的方法可用于合成有机化学以及药物化学。

公开(公告)号：US20100029585A1

公开(公告)日：2010-02-04

申请号：US12533596

申请日：2009-07-31

Applicant: J. Jeffry Howbert ,  Muralikrishna Duvvuri ,  Robert Hershberg ,  Gregory Dietsch

Inventor： J. Jeffry Howbert ,  Muralikrishna Duvvuri ,  Robert Hershberg ,  Gregory Dietsch

IPC: A61K31/724 ,  A61P35/00

CPC classification number: A61K31/55 ,  A61K9/0019 ,  A61K9/08 ,  A61K9/19 ,  A61K31/724 ,  A61K47/40 ,  A61K47/48969 ,  A61K47/6951 ,  B82Y5/00 ,  C07D223/16 ,  C08B37/0012 ,  Y02A50/393

Abstract: The present invention is directed generally to stable formulations of a TLR agonist preferably a TLR7 or a TLR8 agonist, for use in the treatment of cancer, preferably solid tumors and lymphomas. Specifically, the present invention is directed to stable formulations of up to 50 mg/ml of a TLR agonist which comprise a cyclodextrin.

Abstract translation: 本发明一般涉及用于治疗癌症，优选实体瘤和淋巴瘤的TLR激动剂，优选TLR7或TLR8激动剂的稳定制剂。 具体地，本发明涉及高达50mg / ml的包含环糊精的TLR激动剂的稳定制剂。

公开(公告)号：US06906046B2

公开(公告)日：2005-06-14

申请号：US10015828

申请日：2001-12-11

Applicant: Randy W. Jackson ,  Ihab Darwish ,  Ted A. Baughman ,  J. Jeffry Howbert

Inventor： Randy W. Jackson ,  Ihab Darwish ,  Ted A. Baughman ,  J. Jeffry Howbert

IPC: C07F7/08 ,  C07F7/02

CPC classification number: C07F7/081

Abstract: Benzobicyclooctane compounds, their use in inhibiting cellular events involving TNF-α and IL-8, and in the treatment of inflammation events in general; a combinatorial library of diverse bicyclooctanes and process for their synthesis as a library and as individual compounds.

Abstract translation: 苯并双环辛烷化合物，其用于抑制涉及TNF-α和IL-8的细胞事件，以及一般治疗炎症事件; 多元双环辛烷的组合文库及其作为文库和单独化合物合成的方法。

公开(公告)号：US5399565A

公开(公告)日：1995-03-21

申请号：US151608

申请日：1993-11-12

Applicant: Beverley Greenwood ,  David R. Helton ,  J. Jeffry Howbert ,  Steven J. Mitan ,  Kurt Rasmussen

Inventor： Beverley Greenwood ,  David R. Helton ,  J. Jeffry Howbert ,  Steven J. Mitan ,  Kurt Rasmussen

IPC: C07D231/08 ,  C07D233/54 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D417/04 ,  A61K31/415

CPC classification number: C07D231/08 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D417/04

Abstract: Novel substituted pyrazolidinones have been found to exhibit significant binding to cholecystokinin (CCK) receptors and gastrin receptors in the brain and/or peripheral sites such as the pancreas, stomach, and ileum. The pyrazolidinones are CCK and gastrin receptor antagonists and find therapeutic application in the treatment of gastrointestinal disorders, central nervous system disorders and for appetite regulation in warm-blood vertebrates. Pharmaceutical formulations for such indications are described.

Abstract translation: 已经发现新的取代的吡唑烷酮在脑和/或外周位点如胰腺，胃和回肠中表现出与胆囊收缩素（CCK）受体和胃泌素受体的显着结合。 吡唑烷酮是CCK和胃泌素受体拮抗剂，可用于治疗胃肠道疾病，中枢神经系统疾病和用于温血脊椎动物食欲调节的治疗应用。 描述了用于这种适应症的药物制剂。

公开(公告)号：US5354778A

公开(公告)日：1994-10-11

申请号：US37954

申请日：1993-03-26

Applicant: James E. Ray ,  John E. Toth ,  J. Jeffry Howbert

Inventor： James E. Ray ,  John E. Toth ,  J. Jeffry Howbert

IPC: A61K31/17 ,  A61K31/64 ,  A61P35/00 ,  C07C311/60 ,  A61K31/18 ,  C07C311/16

CPC classification number: A61K31/64 ,  C07C311/60

Abstract: This invention provides certain N-phenyl-N'-substituted phenylsulfonylureas compounds, formulations, and a method for treating susceptible neoplasms in mammals using the sulfonylurea compounds.

Abstract translation: 本发明提供某些N-苯基-N'-取代的苯基磺酰脲类化合物，制剂以及使用磺酰脲类化合物治疗哺乳动物易感性肿瘤的方法。

公开(公告)号：US20130018042A1

公开(公告)日：2013-01-17

申请号：US13550192

申请日：2012-07-16

Applicant: J. Jeffry Howbert ,  Muralikrishna Duvvuri ,  Robert Hershberg ,  Gregory Dietsch

Inventor： J. Jeffry Howbert ,  Muralikrishna Duvvuri ,  Robert Hershberg ,  Gregory Dietsch

IPC: A61K31/55 ,  A61P31/00 ,  A61P17/00 ,  A61P35/00

CPC classification number: A61K31/55 ,  A61K9/0019 ,  A61K9/08 ,  A61K9/19 ,  A61K31/724 ,  A61K47/40 ,  A61K47/48969 ,  A61K47/6951 ,  B82Y5/00 ,  C07D223/16 ,  C08B37/0012 ,  Y02A50/393

Abstract: The present invention is directed generally to stable formulations of a TLR agonist preferably a TLR7 or a TLR8 agonist, for use in the treatment of cancer, preferably solid tumors and lymphomas. Specifically, the present invention is directed to stable formulations of up to 50 mg/ml of a TLR agonist which comprise a cyclodextrin.

Abstract translation: 本发明一般涉及用于治疗癌症，优选实体瘤和淋巴瘤的TLR激动剂，优选TLR7或TLR8激动剂的稳定制剂。 具体地，本发明涉及高达50mg / ml的包含环糊精的TLR激动剂的稳定制剂。

公开(公告)号：US06444422B2

公开(公告)日：2002-09-03

申请号：US09120686

申请日：1998-07-21

Applicant: Jeffrey Van Ness ,  John C. Tabone ,  J. Jeffry Howbert ,  John T. Mulligan

Inventor： Jeffrey Van Ness ,  John C. Tabone ,  J. Jeffry Howbert ,  John T. Mulligan

IPC: C12Q168

CPC classification number: G06F19/24 ,  C12Q1/6872 ,  G06F19/22 ,  Y10T436/24

Abstract: A method and system for correlating characteristics (e.g., type of nucleotide) of biomolecules (e.g., DNA) to molecular tags with unique molecular weights that are associated with the biomolecule. In one embodiment. the molecular tags are applied to primers used when synthesizing the biomolecule. The system initially receives a mapping of each characteristic of the biomolecules to the corresponding molecular weight of the molecular tag. The system also receives an indication of the molecular weights detected when analyzing the biomolecules to which the molecular tags have been associated. For each molecular weight detected, the system determines based on the received mapping the characteristic corresponding to the detected molecular weight. The system then indicates that the analyzed biomolecule has the determined characteristic.

Abstract translation: 将生物分子（例如DNA）的特征（例如，核苷酸的类型）与分子标签与生物分子相关联的独特分子量相关联的方法和系统。 在一个实施例中。 分子标签应用于合成生物分子时使用的引物。 该系统首先接收生物分子的每个特征与分子标签的相应分子量的映射。 当分析与分子标签相关联的生物分子时，该系统还接收检测到的分子量的指示。 对于检测到的每个分子量，系统基于所接收的映射确定与检测到的分子量相对应的特征。 然后系统表明分析的生物分子具有确定的特征。

公开(公告)号：US5643926A

公开(公告)日：1997-07-01

申请号：US183465

申请日：1994-01-19

Applicant: Raymond F. Brown ,  J. Jeffry Howbert ,  Karen L. Lobb ,  David A. Neel ,  Jon K. Reel ,  Beverley Greenwood

Inventor： Raymond F. Brown ,  J. Jeffry Howbert ,  Karen L. Lobb ,  David A. Neel ,  Jon K. Reel ,  Beverley Greenwood

IPC: C07D231/08 ,  C07D233/54 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D417/04 ,  A61K31/47 ,  A61K31/415 ,  C07D231/18

CPC classification number: C07D401/04 ,  C07D231/08 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D417/04

Abstract: Novel substituted pyrazolidinones have been found to exhibit significant binding to cholecystokinin (CCK) receptors and gastrin receptors in the brain and/or peripheral sites such as the pancreas, stomach, and ileum. The pyrazolidinones are CCK and gastrin receptor antagonists and find therapeutic application in the treatment of gastrointestinal disorders, central nervous system disorders and for appetite regulation in warm-blood vertebrates. Pharmaceutical formulations for such indications are described.

Abstract translation: 已经发现新的取代的吡唑烷酮在脑和/或外周位点如胰腺，胃和回肠中表现出与胆囊收缩素（CCK）受体和胃泌素受体的显着结合。 吡唑烷酮是CCK和胃泌素受体拮抗剂，可用于治疗胃肠道疾病，中枢神经系统疾病和用于温血脊椎动物食欲调节的治疗应用。 描述了用于这种适应症的药物制剂。

公开(公告)号：US5567715A

公开(公告)日：1996-10-22

申请号：US517315

申请日：1995-08-21

Applicant: Robert F. Bruns, Jr. ,  Donald R. Gehlert ,  J. Jeffry Howbert ,  William H. W. Lunn

Inventor： Robert F. Bruns, Jr. ,  Donald R. Gehlert ,  J. Jeffry Howbert ,  William H. W. Lunn

IPC: C07D333/56 ,  A61K31/38 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/4535 ,  A61K31/55 ,  A61P3/06 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/24 ,  A61P25/26 ,  A61P43/00 ,  A61K31/40

CPC classification number: A61K31/4535 ,  A61K31/4025 ,  A61K31/55 ,  Y10S514/909

Abstract: A method of inhibiting a physiological disorder associated with an excess of neuropeptide Y or its symptoms comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Abstract translation: 一种抑制与神经肽Y过量相关的生理障碍或其症状的方法，其包括向有需要的人施用有效量的具有下式的化合物（Ⅰ），其中R1和R3独立地为氢，-CH3 ，其中Ar为任选取代的苯基; R2选自吡咯烷，六亚甲基氨基和哌啶子基; 或其药学上可接受的盐的溶剂合物。

公开(公告)号：US5545641A

公开(公告)日：1996-08-13

申请号：US326672

申请日：1994-10-20

Applicant: Robert F. Bruns, Jr. ,  Donald R. Gehlert ,  J. Jeffry Howbert ,  William H. W. Lunn

Inventor： Robert F. Bruns, Jr. ,  Donald R. Gehlert ,  J. Jeffry Howbert ,  William H. W. Lunn

IPC: C07D333/56 ,  A61K31/38 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/4535 ,  A61K31/505 ,  A61K31/55 ,  A61P11/00 ,  A61P27/16 ,  A61P29/00 ,  A61P37/00 ,  A61P43/00 ,  A61K31/51

CPC classification number: A61K31/4535 ,  A61K31/4025 ,  A61K31/55

Abstract: A method of inhibiting a physiological condition associated with an excess of bradykinin comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Abstract translation: 一种抑制与过量缓激肽相关的生理条件的方法，其包括向有需要的人施用有效量的具有下式的化合物（Ⅰ），其中R1和R3独立地是氢，-CH3， 其中Ar是任选取代的苯基; R2选自吡咯烷，六亚甲基氨基和哌啶子基; 或其药学上可接受的盐的溶剂合物。