公开(公告)号：US20080181883A1

公开(公告)日：2008-07-31

申请号：US12060350

申请日：2008-04-01

Applicant: Raymond P. Zinkowski ,  Daniel J. Kerkman ,  Russel E. Kohnken ,  John F. DeBernardis ,  Peter Davies

Inventor： Raymond P. Zinkowski ,  Daniel J. Kerkman ,  Russel E. Kohnken ,  John F. DeBernardis ,  Peter Davies

IPC: A61K39/395 ,  C07K14/00 ,  C07K1/14 ,  A61P25/28

CPC classification number: G01N33/6896 ,  C07K14/4711 ,  C07K16/4241 ,  G01N33/564 ,  G01N2333/4709 ,  G01N2800/2821

Abstract: The invention relates, among other things, a preparation comprising Alzheimer's disease antigen (A68), as well as methods of obtaining this purified antigen, and methods of using this purified antigen, for instance, for diagnosing Alzheimer's disease and for detecting human autoantibodies to the Alzheimer disease antigen. The antigen preparation according to the invention is purified in that it is substantially free of immunoglobulin G. The invention further relates to methods of making Alzheimer disease antigens that can be used instead of or along with the A68 antigen preparation (e.g., for diagnosing AD), such as recombinant human tau, tau isolated from various species including human, and phosphorylated recombinant human tau or isolated tau, as well as A68 anti-idiotypic antibodies.

Abstract translation: 本发明尤其涉及包含阿尔茨海默氏病抗原（A68）的制剂，以及获得该纯化抗原的方法，以及使用该纯化抗原的方法，例如用于诊断阿尔茨海默病和检测人类自身抗体 阿尔茨海默病抗原 根据本发明的抗原制剂被纯化，因为其基本上不含免疫球蛋白G.本发明还涉及可以代替或与A68抗原制剂（例如，用于诊断AD）一起使用的阿尔茨海默病抗原的制备方法， ，例如从包括人在内的各种物种分离的重组人tau，以及磷酸化重组人tau或分离的tau，以及A68抗独特型抗体。

公开(公告)号：US5476873A

公开(公告)日：1995-12-19

申请号：US229860

申请日：1994-04-19

Applicant: Dee W. Brooks ,  Andrew O. Stewart ,  Daniel J. Kerkman ,  Pramila A. Bhatia ,  Anwer Basha ,  Jonathan G. Martin

Inventor： Dee W. Brooks ,  Andrew O. Stewart ,  Daniel J. Kerkman ,  Pramila A. Bhatia ,  Anwer Basha ,  Jonathan G. Martin

IPC: C07C275/64 ,  C07D213/40 ,  C07D213/64 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D213/69 ,  C07D215/22 ,  C07D215/227 ,  C07D217/24 ,  C07D239/34 ,  C07D241/18 ,  C07D263/56 ,  C07D277/34 ,  C07D307/52 ,  C07D307/56 ,  C07D307/58 ,  C07D307/64 ,  C07D307/81 ,  C07D333/20 ,  C07D333/28 ,  C07D333/32 ,  C07D333/34 ,  C07D333/58 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07C259/06 ,  A61K31/17 ,  C07C273/18

CPC classification number: C07D213/40 ,  C07C275/64 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D213/69 ,  C07D215/227 ,  C07D217/24 ,  C07D239/34 ,  C07D241/18 ,  C07D263/56 ,  C07D277/34 ,  C07D307/52 ,  C07D307/56 ,  C07D307/58 ,  C07D307/64 ,  C07D307/81 ,  C07D333/20 ,  C07D333/28 ,  C07D333/32 ,  C07D333/34 ,  C07D333/58 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12

Abstract: Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Abstract translation: 结构的化合物，其中p和q为0或1，但不能都相同，M为药学上可接受的阳离子或代谢可裂解基团，B为价键或直链或支链亚烷基，R为 烷基，环烷基或-NR1R2，其中R1和R2是氢，烷基，环烷基或烷酰基，A是任选取代的碳环芳基，呋喃基，苯并[b]呋喃基，噻吩基或苯并[b]噻吩基是脂氧合酶 从而抑制白细胞三烯的生物合成。 这些化合物可用于治疗或改善过敏性和炎性疾病状态。

公开(公告)号：US4618683A

公开(公告)日：1986-10-21

申请号：US673458

申请日：1984-11-20

Applicant: John F. DeBernardis ,  Daniel J. Kerkman ,  William J. McClellan

Inventor： John F. DeBernardis ,  Daniel J. Kerkman ,  William J. McClellan

IPC: C07D209/56 ,  C07D209/62 ,  C07D209/66 ,  C07D405/06 ,  C07D405/12 ,  C07D491/056 ,  C07D491/02 ,  A61K31/40

CPC classification number: C07D405/06 ,  C07C255/00 ,  C07D209/62 ,  C07D209/66

Abstract: Disclosed herein are tetrahydro-benzo[e]isoindolines represented by the formula ##STR1## wherein R, R.sub.1 and R.sub.2 are independently selected from hydrogen, loweralkyl of 1 to 4 carbon atoms, hydroxy, loweralkoxy of 1 to 3 carbon atoms, allyloxy, benzyloxy, benzoyloxy, thiomethyl, halo, ##STR2## wherein t is 0 or 1, n is 0 to 5 and R.sub.11 and R.sub.14 are independently selected from hydrogen, halo, hydroxy, loweralkyl of 1 to 4 carbon atoms, loweralkoxy of 1 to 3 carbon atoms or amino; orR and R.sub.1, or R.sub.1 and R.sub.2 can be taken together to form a methylenedioxy or ethylenedioxy bridge; with the proviso that at least one of R, R.sub.1 or R.sub.2 must be other than hydrogen and the proviso that two of R, R.sub.1, or R.sub.2 must be other than methoxy in the 7 and 8 positions when the remaining one of R, R.sub.1 or R.sub.2 is hydrogen; andR.sub.3 is hydrogen, loweralkyl of 1 to 4 carbon atoms, halo-substituted loweralkyl of 1 to 4 carbon atoms, amino-substituted loweralkyl of 1 to 4 carbon atoms, amino-substituted arylalkyl, allyl, thioloweralkyl, loweralkanol, or ##STR3## wherein R.sub.12 and R.sub.13 are independently selected from hydrogen, hydroxy, amino, loweralkoxy of 1 to 3 carbon atoms and s is 1 to 3; or ##STR4## wherein m is 0, 1 or 2, p is 0 or 1, R.sub.7 is hydrogen or loweralkyl of 1 to 4 carbon atoms and R.sub.8 and R.sub.9 are independently selected from hydrogen, hydroxy, methoxy, loweralkyl of 1 to 4 carbon atoms, or halo, or R.sub.8 and R.sub.9 can be taken together to form a methylenedioxy or ethylenedioxy bridge; or 1,4-benzodioxan of the formula ##STR5## wherein q is 1, 2 or 3, and R.sub.10 is hydrogen, methoxy, amino, or halo; and the pharmaceutically acceptable salts thereof.

Abstract translation: 本文公开的是由下式表示的四氢 - 苯并[e]异吲哚啉其中R 1，R 2和R 2独立地选自氢，1至4个碳原子的低级烷基，羟基，1至3个碳原子的低级烷氧基，烯丙氧基，苄氧基 ，苯甲酰氧基，硫代甲基，卤素，其中t为0或1，n为0至5，R 11和R 14独立地选自氢，卤素，羟基，1至4个碳原子的低级烷基，1至3碳的低级烷氧基 原子或氨基; 或R和R 1，或R 1和R 2可以一起形成亚甲二氧基或亚乙二氧基桥; 条件是R，R 1或R 2中的至少一个必须不是氢，并且条件是R，R 1或R 2中的两个在7和8位中必须不同于甲氧基，当R，R 1或 R2是氢; R 3为氢，1至4个碳原子的低级烷基，1至4个碳原子的卤素取代的低级烷基，1至4个碳原子的氨基取代的低级烷基，氨基取代的芳基烷基，烯丙基，硫代低级烷基，低级链烷醇， 其中R 12和R 13独立地选自氢，羟基，氨基，1至3个碳原子的低级烷氧基，s为1至3; 或其中m为0,1或2，p为0或1，R 7为氢或1至4个碳原子的低级烷基，R 8和R 9独立地选自氢，羟基，甲氧基，1至4碳的低级烷基 原子或卤素，或R8和R9可以一起形成亚甲二氧基或亚乙二氧基桥; 或式“IMAGE”的1,4-苯并二恶烷，其中q为1,2或3，R 10为氢，甲氧基，氨基或卤素; 及其药学上可接受的盐。

公开(公告)号：US5389638A

公开(公告)日：1995-02-14

申请号：US119789

申请日：1993-09-10

Applicant: John F. DeBernardis ,  Daniel J. Kerkman ,  Robert E. Zelle ,  William McClellan

Inventor： John F. DeBernardis ,  Daniel J. Kerkman ,  Robert E. Zelle ,  William McClellan

IPC: C07D217/04 ,  C07D401/04 ,  C07D491/04 ,  C07D491/056 ,  A61K31/47 ,  C07D217/18 ,  C07D401/06

CPC classification number: C07D401/04 ,  C07D217/04 ,  C07D491/04

Abstract: The present invention provides a tetrahydroisoquinoline compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof which is an antagonist for alpha-2 adrenoreceptors and/or which inhibits biogenic amine uptake.

Abstract translation: 本发明提供了下式的四氢异喹啉化合物或其药学上可接受的盐，其为α-2肾上腺素受体的拮抗剂和/或抑制生物胺吸收。

公开(公告)号：US5326776A

公开(公告)日：1994-07-05

申请号：US21839

申请日：1993-02-24

Applicant: Martin Winn ,  Biswanath De ,  Thomas M. Zydowsky ,  Daniel J. Kerkman ,  John F. DeBernardis ,  Saul H. Rosenberg ,  Kazumi Shiosaki ,  Fatima Z. Basha ,  Kenneth P. Spina ,  Thomas W. von Geldern ,  Steven Boyd ,  Diane M. Yamamoto ,  Anthony K. L. Fung

Inventor： Martin Winn ,  Biswanath De ,  Thomas M. Zydowsky ,  Daniel J. Kerkman ,  John F. DeBernardis ,  Saul H. Rosenberg ,  Kazumi Shiosaki ,  Fatima Z. Basha ,  Kenneth P. Spina ,  Thomas W. von Geldern ,  Steven Boyd ,  Diane M. Yamamoto ,  Anthony K. L. Fung

IPC: C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  A61K31/41 ,  A61K31/415 ,  C07D403/10

CPC classification number: C07D403/12 ,  C07D413/10 ,  C07D417/12

Abstract: Compounds are disclosed having the formula: ##STR1## wherein the substituents are defined herein. The compounds of the invention are angiotensin II receptor antagonists.

Abstract translation: 公开了具有下式的化合物：其中取代基在本文中定义。 本发明的化合物是血管紧张素II受体拮抗剂。

公开(公告)号：US5250548A

公开(公告)日：1993-10-05

申请号：US844351

申请日：1992-03-02

Applicant: Martin Winn ,  Biswanath De ,  Thomas M. Zydowsky ,  Daniel J. Kerkman ,  John F. DeBernardis ,  Saul H. Rosenberg ,  Kazumi Shiosaki ,  Fatima Z. Basha ,  Andrew S. Tasker ,  Thomas W. von Geldern ,  Jeffrey A. Kester ,  Steven Boyd ,  Diane M. Yamamoto ,  Anthony K. L. Fung

Inventor： Martin Winn ,  Biswanath De ,  Thomas M. Zydowsky ,  Daniel J. Kerkman ,  John F. DeBernardis ,  Saul H. Rosenberg ,  Kazumi Shiosaki ,  Fatima Z. Basha ,  Andrew S. Tasker ,  Thomas W. von Geldern ,  Jeffrey A. Kester ,  Steven Boyd ,  Diane M. Yamamoto ,  Anthony K. L. Fung

IPC: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14 ,  A61K31/44

CPC classification number: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14

Abstract: Compounds are disclosed having the formula: ##STR1## The compounds of the invention are angiotensin II receptor antagonists.

Abstract translation: 公开了具有下式的化合物：本发明的化合物是血管紧张素II受体拮抗剂。

公开(公告)号：US5210206A

公开(公告)日：1993-05-11

申请号：US819537

申请日：1992-01-10

Applicant: Howard E. Morton ,  Biswanath De ,  Daniel J. Kerkman

Inventor： Howard E. Morton ,  Biswanath De ,  Daniel J. Kerkman

IPC: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14

CPC classification number: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14 ,  Y02P20/55

Abstract: The present invention relates to a process for the preparation of a compound of the formula: ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen, loweralkyl, loweralkoxy-substituted loweralkyl, lower alkenyl, lower alkynyl, cycloalkyl and cycloalkylalkyl; R.sub.2 is selected from the group consisting of hydrogen, loweralkyl, loweralkoxy-substituted loweralkyl, halogen and loweralkoxy; R.sub.3 is selected from hydrogen, loweralkyl, and halogen; R* and R** are independently selected from loweralkyl and P.sub.1 is hydrogen or an nitrogen-protecting group; or an acid addition salt thereof.

Abstract translation: 本发明涉及一种制备下式化合物的方法：其中R 1选自氢，低级烷基，低级烷氧基取代的低级烷基，低级烯基，低级炔基，环烷基和环烷基烷基; R2选自氢，低级烷基，低级烷氧基取代的低级烷基，卤素和低级烷氧基; R3选自氢，低级烷基和卤素; R *和R **独立地选自低级烷基，P1是氢或氮保护基; 或其酸加成盐。

公开(公告)号：US06864062B2

公开(公告)日：2005-03-08

申请号：US10017822

申请日：2001-12-12

Applicant: Raymond P. Zinkowski ,  Daniel J. Kerkman ,  Russell E. Kohnken ,  John F. DeBernardis ,  Peter Davies

Inventor： Raymond P. Zinkowski ,  Daniel J. Kerkman ,  Russell E. Kohnken ,  John F. DeBernardis ,  Peter Davies

IPC: G01N33/53 ,  C07K1/113 ,  C07K1/22 ,  C07K14/47 ,  C07K16/42 ,  C12P21/02 ,  C12P21/08 ,  G01N27/447 ,  G01N33/564 ,  G01N33/68 ,  G01N33/559

CPC classification number: G01N33/6896 ,  C07K14/4711 ,  C07K16/4241 ,  G01N33/564 ,  G01N2333/4709 ,  G01N2800/2821

Abstract: The invention relates, among other things, a preparation comprising Alzheimer's disease antigen (A68), as well as methods of obtaining this purified antigen, and methods of using this purified antigen, for instance, for diagnosing Alzheimer's disease and for detecting human autoantibodies to the Alzheimer disease antigen. The antigen preparation according to the invention is purified in that it is substantially free of immunoglobulin G. The invention further relates to methods of making Alzheimer disease antigens that can be used instead of or along with the A68 antigen preparation (e.g., for diagnosing AD), such as recombinant human tau, tau isolated from various species including human, and phosphorylated recombinant human tau or isolated tau, as well as A68 anti-idiotypic antibodies.

Abstract translation: 本发明尤其涉及包含阿尔茨海默氏病抗原（A68）的制剂，以及获得该纯化抗原的方法，以及使用该纯化抗原的方法，例如用于诊断阿尔茨海默病和检测人类自身抗体 阿尔茨海默病抗原 根据本发明的抗原制剂被纯化，因为其基本上不含免疫球蛋白G.本发明还涉及可以代替或与A68抗原制剂（例如，用于诊断AD）一起使用的阿尔茨海默病抗原的制备方法， ，例如从包括人在内的各种物种分离的重组人tau，以及磷酸化重组人tau或分离的tau，以及A68抗独特型抗体。

公开(公告)号：US5185363A

公开(公告)日：1993-02-09

申请号：US768621

申请日：1991-09-30

Applicant: Dee W. Brooks ,  Daniel J. Kerkman ,  Jonathan G. Martin ,  Andrew O. Stewart ,  James B. Summers

Inventor： Dee W. Brooks ,  Daniel J. Kerkman ,  Jonathan G. Martin ,  Andrew O. Stewart ,  James B. Summers

IPC: C07C275/64 ,  C07C323/47 ,  C07D333/36 ,  C07D335/08 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12

CPC classification number: C07D409/04 ,  C07C275/64 ,  C07C323/47 ,  C07D333/36 ,  C07D335/08 ,  C07D409/06 ,  C07D409/12

Abstract: Substituted phenyl, naphthyl, and thienyl N-hydroxy urea compounds form a class of potent inhibitors of 5- and 12-lipoxygenase and are thus useful compounds in the treatment of inflammatory disease states where leukotrienes and other products of lipoxygenase enzyme activity are implicated.

Abstract translation: PCT No.PCT / US90 / 01488 Sec。 371日期1991年9月30日 102（e）1991年9月30日PCT 1991年3月20日PCT公布。 WO90 / 12008 PCT出版物 1990年10月18日。取代的苯基，萘基和噻吩基N-羟基脲化合物形成一类5-和12-脂肪氧合酶的有效抑制剂，因此是治疗炎性疾病状态的有用化合物，其中白细胞三烯和其它产物 涉及脂氧合酶活性。

公开(公告)号：US5559144A

公开(公告)日：1996-09-24

申请号：US435399

申请日：1995-05-05

Applicant: Dee W. Brooks ,  Andrew O. Stewart ,  Daniel J. Kerkman ,  Pramila A. Bhatia ,  Anwer Basha ,  Jonathan G. Martin

Inventor： Dee W. Brooks ,  Andrew O. Stewart ,  Daniel J. Kerkman ,  Pramila A. Bhatia ,  Anwer Basha ,  Jonathan G. Martin

IPC: C07C275/64 ,  C07D213/40 ,  C07D213/64 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D213/69 ,  C07D215/22 ,  C07D215/227 ,  C07D217/24 ,  C07D239/34 ,  C07D241/18 ,  C07D263/56 ,  C07D277/34 ,  C07D307/52 ,  C07D307/56 ,  C07D307/58 ,  C07D307/64 ,  C07D307/81 ,  C07D333/20 ,  C07D333/28 ,  C07D333/32 ,  C07D333/34 ,  C07D333/58 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  A61K31/34 ,  A61K31/38 ,  C07D307/46 ,  C07D333/22

CPC classification number: C07D213/40 ,  C07C275/64 ,  C07D213/643 ,  C07D213/65 ,  C07D213/68 ,  C07D213/69 ,  C07D215/227 ,  C07D217/24 ,  C07D239/34 ,  C07D241/18 ,  C07D263/56 ,  C07D277/34 ,  C07D307/52 ,  C07D307/56 ,  C07D307/58 ,  C07D307/64 ,  C07D307/81 ,  C07D333/20 ,  C07D333/28 ,  C07D333/32 ,  C07D333/34 ,  C07D333/58 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12

Abstract: Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Abstract translation: 结构的化合物，其中p和q为0或1，但不能都相同，M为药学上可接受的阳离子或代谢可裂解基团，B为价键或直链或支链亚烷基，R为 烷基，环烷基或-NR1R2，其中R1和R2是氢，烷基，环烷基或烷酰基，A是任选取代的碳环芳基，呋喃基，苯并[b]呋喃基，噻吩基或苯并[b]噻吩基是脂氧合酶的有效抑制剂 从而抑制白细胞三烯的生物合成。 这些化合物可用于治疗或改善过敏性和炎性疾病状态。