公开(公告)号：US20060135614A1

公开(公告)日：2006-06-22

申请号：US10520902

申请日：2003-07-08

申请人： Neeraj Garg ,  Mahmoud Ghadim ,  Thomas Ericsson ,  Lars Malm ,  Denis Ryono

发明人： Neeraj Garg ,  Mahmoud Ghadim ,  Thomas Ericsson ,  Lars Malm ,  Denis Ryono

IPC分类号： A61K31/198 ,  C07C237/28

CPC分类号： C07C235/52 ,  C07C235/34

摘要： This invention relates to novel compounds, which are thyroid receptor ligands, and to methods of preparing such compounds. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described herein is administered in a therapeutically effective amount.

摘要翻译： 本发明涉及作为甲状腺受体配体的新化合物及其制备方法。 此外，提供了一种用于预防，抑制或治疗与代谢功能障碍相关或与T3调节基因的表达相关的疾病或病症的方法，其中本文所述的化合物以治疗有效量施用。

公开(公告)号：US07016809B1

公开(公告)日：2006-03-21

申请号：US09669604

申请日：2000-09-26

申请人： Jacob K. Gotwals ,  Neeraj Garg

发明人： Jacob K. Gotwals ,  Neeraj Garg

IPC分类号： G06F11/00 ,  G06F11/30

CPC分类号： G06F11/2257 ,  G06F11/3409 ,  G06F11/3447 ,  G06F11/3612 ,  G06F2201/88

摘要： An improvement in applying and interpreting encoded knowledge about computer system performance engineering and in enabling a user to more readily understand and apply that knowledge to improve computer system performance. Textual and graphical depictions of insights, advice, behaviors, and explanations can be presented, all related to improving computer system performance. Fuzzy logic can be employed to accommodate incomplete measurement data and to present results in a qualitative format, presenting relevant data as being high, low, substantial, etc., rather than simply presenting the values of the associated counters leading to those determinations. Intermediate values used to generate the results can also be processed with qualitative rather than quantitative values.

摘要翻译： 改进应用和解释关于计算机系统性能工程的编码知识，并使用户能够更容易地理解和应用该知识来提高计算机系统的性能。 可以呈现关于见解，建议，行为和解释的文字和图形描述，这些都与提高计算机系统性能有关。 可以使用模糊逻辑来适应不完整的测量数据并以定性格式呈现结果，将相关数据呈现为高，低，实质等，而不是简单地呈现导致这些确定的相关联的计数器的值。 用于生成结果的中间值也可以使用定性而不是定量值进行处理。

公开(公告)号：US06989402B1

公开(公告)日：2006-01-24

申请号：US09868889

申请日：1999-12-23

申请人： Jon Hangeland ,  Minsheng Zhang ,  Yolanda Caringal ,  Denis Ryono ,  Yi-Lin Li ,  Johan Malm ,  Ye Liu ,  Neeraj Garg ,  Chris Litten ,  Ana Maria Garcia Collazo ,  Konrad Koehler

发明人： Jon Hangeland ,  Minsheng Zhang ,  Yolanda Caringal ,  Denis Ryono ,  Yi-Lin Li ,  Johan Malm ,  Ye Liu ,  Neeraj Garg ,  Chris Litten ,  Ana Maria Garcia Collazo ,  Konrad Koehler

IPC分类号： A61K31/44 ,  A61K31/192 ,  A61K31/40 ,  A61K31/4174 ,  C07D211/56 ,  C07D213/72 ,  C07D229/38 ,  C07D265/30 ,  C07D241/04 ,  C07D207/14

CPC分类号： C07D207/27 ,  C07C235/32 ,  C07C235/52 ,  C07C307/06 ,  C07C311/51 ,  C07C323/41 ,  C07C323/60 ,  C07D207/09 ,  C07D211/24 ,  C07D211/34 ,  C07D211/58 ,  C07D211/96 ,  C07D213/40 ,  C07D223/12 ,  C07D231/38 ,  C07D233/64 ,  C07D257/04 ,  C07D285/06 ,  C07D285/135 ,  C07D295/13 ,  C07D295/185 ,  C07D333/20

摘要： New thyroid receptor ligands are provided which have general formula (I) in which: n is an integer from 0 to 4; R1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, at least one of R2 and R3 being other than hydrogen; R4 is a carboxylic acid amide (CONR′R″) or an acylsulphonamide (CONHSO2R′) derivative, or a pharmaceutically acceptable salt thereof, and all stereoisomers thereof; or when n is equal to or greater than one, R4 may be a heteroaromatic moiety which may be substituted or unsubstituted, or an amine (NR′R″). R5 is hydrogen or an acyl (such as acetyl or benzoyl) or other group capable of bioconversion to generate the free phenol structure (wherein R5=H). In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a T3 regulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.

摘要翻译： 提供了具有通式（I）的新甲状腺受体配体，其中：n为0至4的整数; R 1是卤素，三氟甲基或1至6个碳的烷基或3至7个碳的环烷基; R 2和R 3相同或不同，为氢，卤素，1至4个碳的烷基或3至5个碳的环烷基，R 1， SUB 2和R 3不是氢; R 4是羧酸酰胺（CONR'R“）或酰基磺酰胺（CONHSO 2 R'）衍生物或其药学上可接受的盐及其所有立体异构体; 或当n等于或大于1时，R 4可以是可被取代或未取代的杂芳族部分，或胺（NR'R“）。 R 5是氢或酰基（例如乙酰基或苯甲酰基）或能够生物转化以产生游离酚结构（其中R 5 = H）的其它基团。 此外，提供了一种用于预防，抑制或治疗与代谢功能障碍相关的疾病或依赖于T 3 N调节基因的表达的方法，其中如上所述的化合物以 治疗有效量。 与代谢功能障碍相关或依赖于T 3受体基因表达的这种疾病的实例包括肥胖症，高胆固醇血症，动脉粥样硬化，心律失常，抑郁症，骨质疏松症，甲状腺机能减退，甲状腺肿，甲状腺癌以及 青光眼，充血性心力衰竭和皮肤疾病。

公开(公告)号：US20050171104A1

公开(公告)日：2005-08-04

申请号：US10510645

申请日：2003-02-10

申请人： Mahmoud Rahimi-Ghadim ,  Neeraj Garg ,  Johan Malm

发明人： Mahmoud Rahimi-Ghadim ,  Neeraj Garg ,  Johan Malm

IPC分类号： A61K31/192 ,  A61K31/42 ,  A61K31/421 ,  A61K31/4245 ,  A61K31/4402 ,  A61K31/53 ,  A61K31/59 ,  A61P1/16 ,  A61P3/00 ,  A61P5/14 ,  A61P5/16 ,  A61P9/00 ,  A61P9/04 ,  A61P9/06 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P17/14 ,  A61P25/32 ,  A61P31/14 ,  A61P43/00 ,  C07C59/72 ,  C07C65/26 ,  C07D209/12 ,  C07D213/30 ,  C07D251/18 ,  C07D261/08 ,  C07D263/32 ,  C07D271/06 ,  C07D413/04 ,  A61K31/194 ,  A61K31/44

CPC分类号： C07D213/30 ,  C07D209/12 ,  C07D251/18 ,  C07D261/08 ,  C07D263/32 ,  C07D271/06 ,  C07D413/04

摘要： This invention relates to novel compounds according to the general formula: which are thyroid receptor ligands, preferably antagonists, partial antagonists or partial agonists and to methods for using such compounds in the treatment of cardiac and metabolic disorders, such as cardiac arrhythmias, thyro-toxicosis, subclinical hyperthyrodism and liver diseases.

摘要翻译： 本发明涉及根据通式的新化合物：其为甲状腺受体配体，优选拮抗剂，部分拮抗剂或部分激动剂，以及使用这些化合物治疗心脏和代谢紊乱如心律失常，甲状腺中毒的方法 ，亚临床甲状腺功能亢进和肝脏疾病。