公开(公告)号：US06713514B1

公开(公告)日：2004-03-30

申请号：US09552477

申请日：2000-04-18

Applicant: Hartmuth C. Kolb ,  Gerard McGeehan ,  Zhi-Cai Shi ,  Laxma Reddy Kolla ,  Cullen Cavallaro

Inventor： Hartmuth C. Kolb ,  Gerard McGeehan ,  Zhi-Cai Shi ,  Laxma Reddy Kolla ,  Cullen Cavallaro

IPC: A61K31195

CPC classification number: C07C323/42 ,  C07C237/30 ,  C07C237/38 ,  C07C2601/08 ,  C07C2601/14

Abstract: N-(substituted)carbamoylaryl- and heteroaryl substituted aminopropanoic and butanoic acid compounds which are highly selective agonists for the PPAR-&ggr; receptor or prodrugs of agonists for the PPAR-&ggr; receptor, and are useful in the treatment of Type II diabetes (NIDDM). Specifically disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein: Z is aryl or heteroaryl; n and m are 0, 1 or 2; A is a carboxylic acid or ester; or A is where D, F and G are hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene or an (un)substituted sulfide; R4 is oxo, hydrogen, hydroxy, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; Y is hydrogen, (un)substituted amino, (un)substituted alkoxy, methylene, an (un)substituted sulfide, (un)substituted sulfonyl or an (un)substituted sulfoxide; and R5, R6 and R8 are hydrogen, lower alkyl, lower alkoxy, cycloalkyl, keto, acyl, or sulfonyl; or R5 and R6 together form a ring.

Abstract translation: 作为PPAR-γ受体的高选择性激动剂或PPAR-γ受体激动剂前药的N-（取代的）氨基甲酰基芳基和杂芳基取代的氨基丙酸和丁酸化合物，可用于治疗II型糖尿病（NIDDM） 。 具体公开的是下式的化合物或其药学上可接受的无毒盐，其中：Z是芳基或杂芳基; n和m是0,1或2; A是羧酸或酯; 或A是其中D，F和G是氢，（未）取代的氨基，（未）取代的烷氧基，亚甲基或（取代的）取代的硫醚; R 4是氧代，氢，羟基，低级烷基，低级烷氧基，环烷基，酮基，酰基， 或磺酰基; Y是氢，（未）取代的氨基，（未）取代的烷氧基，亚甲基，（未）取代的硫醚，（未）取代的磺酰基或（取代的）取代的亚砜; R 5，R 6和R 8是氢，低级烷基，低级烷氧基，环烷基，酮基，酰基或磺酰基; 或R 5和R 6一起形成环。

公开(公告)号：US08491869B2

公开(公告)日：2013-07-23

申请号：US12661777

申请日：2010-03-23

Applicant: Umesh B. Gangadharmath ,  Hartmuth C. Kolb ,  Peter J. H. Scott ,  Joseph C. Walsh ,  Wei Zhang ,  Anna Katrin Szardenings ,  Anjana Sinha ,  Gang Chen ,  Eric Wang ,  Vani P. Mocharia ,  Chul Yu ,  Changhui Liu ,  Daniel Kurt Cashion ,  Dhanalakshmi Kasi

Inventor： Umesh B. Gangadharmath ,  Hartmuth C. Kolb ,  Peter J. H. Scott ,  Joseph C. Walsh ,  Wei Zhang ,  Anna Katrin Szardenings ,  Anjana Sinha ,  Gang Chen ,  Eric Wang ,  Vani P. Mocharia ,  Chul Yu ,  Changhui Liu ,  Daniel Kurt Cashion ,  Dhanalakshmi Kasi

IPC: A61K51/00 ,  A61M36/14

CPC classification number: A61K51/0455 ,  A61K51/04 ,  A61K51/0453 ,  A61K51/0459 ,  A61K51/0463 ,  C07B59/002 ,  C07D215/06 ,  C07D235/14 ,  C07D277/62 ,  C07D401/04 ,  C07D403/06 ,  C07D413/10 ,  C07D413/14 ,  C07D487/04

Abstract: Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering ti a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.

Abstract translation: 式（I）的成像剂和用于检测神经障碍的方法包括给予需要能够结合tau蛋白和β-淀粉样肽的式（I）化合物的化合物。 本发明还涉及成像Abeta和tau聚集体的方法，包括引入可检测量的包含放射性标记的式（I）化合物的药物制剂，并检测患者中与淀粉样蛋白沉积物和/或tau蛋白相关的标记化合物。 这些方法和组合使得临床前诊断和监测AD和其他神经障碍的进展。

公开(公告)号：US08354092B2

公开(公告)日：2013-01-15

申请号：US12862955

申请日：2010-08-25

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J. H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J. H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

IPC: A61K51/00 ,  C07D249/00 ,  C07D343/00

CPC classification number: C07D417/04 ,  C07D249/04 ,  C07D249/06 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C12Q1/485 ,  G01N2500/04 ,  G01N2500/10

Abstract: The present application discloses methods for identifying inhibitors with high binding-affinity for the carbonic anhydrase-IX (CA-IX) enzyme using click chemistry and uses the candidates thereof as positron emission tomography (PET) imaging agents.

Abstract translation: 本申请公开了使用点击化学法鉴定对碳酸酐酶IX（CA-IX）酶具有高结合亲和力的抑制剂的方法，并将其候选用作正电子发射断层摄影（PET）成像剂。

公开(公告)号：US08173073B2

公开(公告)日：2012-05-08

申请号：US12915149

申请日：2010-10-29

Applicant: Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  Lawrence Diener ,  Sean Ford ,  Reza Miraghaie

Inventor： Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  Lawrence Diener ,  Sean Ford ,  Reza Miraghaie

IPC: G21C1/00 ,  B01J19/00 ,  B01J8/00 ,  G01N23/00 ,  G01N30/02

CPC classification number: C07H5/02 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/0086 ,  B01J2219/00873 ,  B01J2219/00891 ,  B01J2219/00907 ,  B01J2219/00909

Abstract: Methods and devices for a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in a fast, efficient and compact manner are disclosed. In particular, the various embodiments of the present invention provide an automated, stand-alone, hands-free operation of the entire radiosynthesis cycle on a microfluidic device with unrestricted gas flow through the reactor, starting with target water and yielding purified PET radiotracer within a period of time shorter than conventional chemistry systems. Accordingly, one aspect of the present invention is related to a microfluidic chip for radiosynthesis of a radiolabeled compound, comprising a reaction chamber, one or more flow channels connected to the reaction chamber, one or more vents connected to said reaction chamber, and one or more integrated valves to effect flow control in and out of said reaction chamber.

Abstract translation: 公开了以快速，有效和紧凑的方式全面自动合成用于成像的放射性化合物的方法和装置，例如通过正电子发射断层摄影（PET）。 特别地，本发明的各种实施例提供了在具有不受限制的气体流过反应器的微流体装置上的整个放射合成循环的自动，独立，免手动操作，从目标水开始并产生纯化的PET放射性示踪器 时间比传统化学系统短。 因此，本发明的一个方面涉及用于放射性标记的化合物的放射合成的微流体芯片，包括反应室，连接到反应室的一个或多个流动通道，连接到所述反应室的一个或多个通气口，以及一个或多个 更一体化的阀来实现进出所述反应室的流量控制。

公开(公告)号：US08075851B2

公开(公告)日：2011-12-13

申请号：US11540344

申请日：2006-09-29

Applicant: Arkadij M Elizarov ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  James R. Heath

Inventor： Arkadij M Elizarov ,  Hartmuth C. Kolb ,  R. Michael Van Dam ,  James R. Heath

IPC: B01L3/00

CPC classification number: B01F11/0042 ,  B01F11/0071 ,  B01F13/0059 ,  B01J19/0093 ,  B01J2219/00286 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00414 ,  B01J2219/00418 ,  B01J2219/00495 ,  B01J2219/00585 ,  B01J2219/00599 ,  B01J2219/00731 ,  B01J2219/00759 ,  B01J2219/00783 ,  B01J2219/00788 ,  B01J2219/00822 ,  B01J2219/00824 ,  B01J2219/00826 ,  B01J2219/00828 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/00858 ,  B01J2219/0086 ,  B01J2219/00862 ,  B01J2219/00873 ,  B01J2219/00889 ,  B01J2219/00891 ,  B01J2219/00907 ,  B01J2219/00916 ,  B01J2219/00927 ,  B01J2219/00986

Abstract: Described herein are automated, integrated microfluidic device comprising a chemical reaction chip comprising for performing chemical reaction, a microscale column integrated with the chip and configured for liquid flow from the column to at least one flow channel, and wherein the fluid flow into the column is controlled by on-chip valves; and comprising at least two on-chip valves for controlling fluid flow in the microfluidic device.

Abstract translation: 本文描述的是包括用于进行化学反应的化学反应芯片的自动化集成微流体装置，与芯片集成的微量柱，并且构造成用于从柱流到至少一个流动通道的液体流，并且其中流入塔的流体流是 由片上阀控制; 并且包括用于控制微流体装置中的流体流动的至少两个片上阀。

公开(公告)号：US20110256057A1

公开(公告)日：2011-10-20

申请号：US13113580

申请日：2011-05-23

Applicant: Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Gang Chen ,  Qianwa Liang ,  Tieming Zhao

Inventor： Hartmuth C. Kolb ,  Kai Chen ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Gang Chen ,  Qianwa Liang ,  Tieming Zhao

IPC: A61K51/08 ,  A61P35/00 ,  A61K38/12

CPC classification number: A61K51/08 ,  A61K38/00 ,  A61K47/60 ,  A61K51/082 ,  C07K5/021 ,  C07K7/54 ,  C07K7/64

Abstract: The present application is directed to radiolabeled cyclic polyazapeptides, pharmaceutical compositions comprising radiolabeled cyclic polyazapeptides, and methods of using the radiolabeled cyclic polyazapeptides. Such polyazapeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Abstract translation: 本申请涉及放射性标记的环状多氮杂肽，包含放射性标记的环状多氮杂肽的药物组合物，以及使用放射性标记的环状多氮杂肽的方法。 这种多分子肽可用于成像研究，如正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）。

公开(公告)号：US20110150714A1

公开(公告)日：2011-06-23

申请号：US12986323

申请日：2011-01-07

Applicant: Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  Reza Miraghaie ,  Todd L. Graves ,  Artem Lebedev ,  Keith E. Schleiffer

Inventor： Arkadij M. Elizarov ,  Carroll Edward Ball ,  Jianzhong Zhang ,  Hartmuth C. Kolb ,  Reza Miraghaie ,  Todd L. Graves ,  Artem Lebedev ,  Keith E. Schleiffer

IPC: G21C1/00 ,  B81B7/00 ,  B01D15/00

CPC classification number: B01J19/0093 ,  B01J2219/0081 ,  B01J2219/00826 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/0086 ,  B01J2219/00871 ,  B01J2219/00873 ,  B01J2219/00889 ,  B01J2219/00905 ,  B01J2219/00936

Abstract: Macro- and microfluidic devices and related technologies, and chemical processes using such devices. More specifically, the devices may be used for a fully automated synthesis of radioactive compounds for imaging, such as by positron emission tomography (PET), in an efficient, compact and safe to the operator manner. In particular, embodiments of the present invention relate to an automated, multi-run, microfluidic instrument for the multi-step synthesis of radiopharmaceuticals, such as PET probes, comprising a remote shielded mini-cell containing radiation-handing components.

Abstract translation: 宏观和微流体装置及相关技术以及使用这种装置的化学过程。 更具体地，这些装置可以用于以有效，紧凑和安全的操作者方式全面自动化合成用于成像的放射性化合物，例如通过正电子发射断层摄影（PET）。 特别地，本发明的实施例涉及一种用于多步合成放射性药物的自动化，多运行微流控仪器，例如PET探针，其包括含有辐射递送部件的远程屏蔽微型电池。

公开(公告)号：US20110136252A1

公开(公告)日：2011-06-09

申请号：US12224557

申请日：2007-03-02

Applicant: Hsian-Rong Tseng ,  Hartmuth C. Kolb ,  Jinyi Wang ,  Guodong Sui

Inventor： Hsian-Rong Tseng ,  Hartmuth C. Kolb ,  Jinyi Wang ,  Guodong Sui

IPC: G01N1/10 ,  B01L3/00

CPC classification number: B01F13/0059 ,  B01F5/061 ,  B01F5/0646 ,  B01F5/0647 ,  B01F5/10 ,  B01F5/108 ,  B01F2005/0621 ,  B01F2005/0636 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00479 ,  B01J2219/0059 ,  B01J2219/00599 ,  B01L3/5027 ,  Y10T436/2575

Abstract: A microfluidic device allows for different reactions to be conducted in parallel with the use of nanoliter quantities of reagents.

Abstract translation: 微流体装置允许使用纳升量的试剂并行进行不同的反应。

公开(公告)号：US20110046378A1

公开(公告)日：2011-02-24

申请号：US12867502

申请日：2009-02-17

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Qianwa Liang ,  Brian A. Duclos ,  Wei Zhang ,  Peter J.H. Scott ,  Kai Chen ,  Zhiyong Gao ,  Tieming Zhao ,  Vani P. Mocharla ,  Dhanalakshmi Kasi ,  Gang Chen ,  Eric Wang ,  Anjana Sinha ,  Chunfang Xia ,  Henry Clifton Padgett ,  Farhad Karimi

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Qianwa Liang ,  Brian A. Duclos ,  Wei Zhang ,  Peter J.H. Scott ,  Kai Chen ,  Zhiyong Gao ,  Tieming Zhao ,  Vani P. Mocharla ,  Dhanalakshmi Kasi ,  Gang Chen ,  Eric Wang ,  Anjana Sinha ,  Chunfang Xia ,  Henry Clifton Padgett ,  Farhad Karimi

IPC: C07D471/04 ,  C07D235/10 ,  C07D311/30 ,  C07D209/88 ,  C07D311/16 ,  C07D217/24 ,  C07D261/08 ,  C07D217/04 ,  C07D215/38 ,  C07D405/04 ,  C07D215/233 ,  C07D407/04 ,  C07D249/06 ,  C07D401/04 ,  C07D209/80 ,  C07D405/12

CPC classification number: C07B59/002

Abstract: Disclosed here in are compounds and methods of diagnosing Alzheimer's Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, wherein the compound is selected from the group consisting of radiolabeled flavones, coumarins, carbazoles, quinolinones, chromenones, imidazoles and triazoles derivatives, allowing the compound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal is suffering from or is at risk of developing Alzheimer's Disease

Abstract translation: 本文公开了在哺乳动物中诊断阿尔茨海默病或其倾向的化合物和方法，所述方法包括向哺乳动物施用诊断有效量的放射性标记的化合物，其中所述化合物选自放射性标记的黄酮，香豆素，咔唑 ，喹啉酮，色烯酮，咪唑和三唑衍生物，使化合物分布到脑组织中，并使脑组织成像，其中与正常对照结合水平相比，化合物与脑组织的结合增加指示哺乳动物 患有或有发生阿尔茨海默病的风险

公开(公告)号：US20100317842A1

公开(公告)日：2010-12-16

申请号：US12862955

申请日：2010-08-25

Applicant: Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J.H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

Inventor： Hartmuth C. Kolb ,  Joseph C. Walsh ,  Dhanalakshmi Kasi ,  Vani P. Mocharla ,  Bing Wang ,  Umesh B. Gangadharmath ,  Brian A. Duclos ,  Kai Chen ,  Wei Zhang ,  Gang Chen ,  Henry Clifton Padgett ,  Farhad Karimi ,  Peter J.H. Scott ,  Zhiyong Gao ,  Qianwa Liang ,  Thomas Lee Collier ,  Tieming Zhao ,  Chunfang Xia

IPC: C07D417/12 ,  C07D417/14 ,  C07D249/06 ,  C07D413/06 ,  C07D403/06 ,  C07D405/12 ,  C07D401/12 ,  C07D453/02 ,  C07D453/04 ,  C07H7/06 ,  C07H17/02

CPC classification number: C07D417/04 ,  C07D249/04 ,  C07D249/06 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C12Q1/485 ,  G01N2500/04 ,  G01N2500/10

Abstract: The present application discloses methods for identifying inhibitors with high binding-affinity for the carbonic anhydrase-IX (CA-IX) enzyme using click chemistry and uses the candidates thereof as positron emission tomography (PET) imaging agents.

Abstract translation: 本申请公开了使用点击化学法鉴定对碳酸酐酶IX（CA-IX）酶具有高结合亲和力的抑制剂的方法，并将其候选用作正电子发射断层摄影（PET）成像剂。