公开(公告)号：US06525202B2

公开(公告)日：2003-02-25

申请号：US09903754

申请日：2001-07-12

Applicant: Baihua Hu ,  Fuk-Wah Sum ,  Michael S. Malamas

Inventor： Baihua Hu ,  Fuk-Wah Sum ,  Michael S. Malamas

IPC: C07D21158

CPC classification number: C07D401/10 ,  C07D211/58 ,  C07D223/12 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D417/10 ,  C07D417/14

Abstract: This invention provides compounds of Formula I having the structure wherein, R1, R2, R3, R4, R5, T, T1, T2, and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

Abstract translation: 本发明提供具有其中R1，R2，R3，R4，R5，T，T1，T2和X如上所定义的结构的式I化合物或其药学上可接受的盐，其可用于治疗或抑制代谢紊乱 与胰岛素抵抗或高血糖相关（通常与肥胖或葡萄糖不耐受相关），动脉粥样硬化，胃肠道疾病，神经源性炎症，青光眼，高眼压症和尿频; 并且特别可用于治疗或抑制II型糖尿病。

公开(公告)号：US06172057B2

公开(公告)日：2001-01-09

申请号：US09026371

申请日：1998-02-19

Applicant: Aranapakam Mudumbai Venkatesan ,  George Theodore Grosu ,  Jamie Marie Davis ,  Baihua Hu ,  Derek Cecil Cole ,  Jannie Lea Baker ,  Marcy Pamela Jacobson ,  Matthew Robin O'Dell

Inventor： Aranapakam Mudumbai Venkatesan ,  George Theodore Grosu ,  Jamie Marie Davis ,  Baihua Hu ,  Derek Cecil Cole ,  Jannie Lea Baker ,  Marcy Pamela Jacobson ,  Matthew Robin O'Dell

IPC: A01N4346

CPC classification number: C07D209/48 ,  A61K31/165 ,  A61K31/192 ,  A61K31/341 ,  A61K31/351 ,  A61K31/381 ,  A61K31/40 ,  A61K31/4418 ,  A61K31/445 ,  A61K31/451 ,  A61K31/495 ,  A61K31/5375 ,  C07C317/44 ,  C07C317/46 ,  C07C323/60 ,  C07C2601/08 ,  C07C2601/18 ,  C07D207/12 ,  C07D211/66 ,  C07D213/32 ,  C07D213/56 ,  C07D213/70 ,  C07D213/71 ,  C07D213/74 ,  C07D213/89 ,  C07D215/14 ,  C07D215/36 ,  C07D231/18 ,  C07D233/64 ,  C07D233/78 ,  C07D233/84 ,  C07D235/28 ,  C07D239/26 ,  C07D257/04 ,  C07D263/58 ,  C07D277/36 ,  C07D277/74 ,  C07D285/14 ,  C07D295/088 ,  C07D307/10 ,  C07D307/38 ,  C07D307/64 ,  C07D309/12 ,  C07D333/18 ,  C07D333/28 ,  C07D333/34 ,  C07D409/04

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection. The compounds of this invention are represented by the formula where R1, R2, R3 and R4 are described herein.

Abstract translation: 基质金属蛋白酶（MMPs）是一组涉及结缔组织和基底膜的病理破坏的酶。 这些含锌的内肽酶由几种酶组成，包括胶原酶，基质溶胶蛋白和明胶酶。 TNF-α转化酶（TACE）是促炎细胞因子，从膜结合的TNF-α前体蛋白催化TNF-α的形成。 预期MMP和TACE的小分子抑制剂具有治疗各种疾病状态的潜力。 本发明提供用于治疗关节炎，肿瘤转移，组织溃疡，异常伤口愈合，牙周病，骨病，糖尿病的基质金属蛋白酶（MMP）和TNF-α转换酶（TACE）的低分子量非肽抑制剂 （胰岛素抵抗）和HIV感染。 本发明的化合物由本文所述的R1，R2，R3和R4表示。

公开(公告)号：US07906548B2

公开(公告)日：2011-03-15

申请号：US12539074

申请日：2009-08-11

Applicant: John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

Inventor： John C. McKew ,  Steve Y. Tam ,  Katherine L. Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark L. Behnke ,  Baihua Hu ,  James D. Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC: A01N43/38

CPC classification number: A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

Abstract: This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

Abstract translation: 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶A2酶的活性的抑制剂的方法，以及用于医学治疗，预防和抑制疾病和病症，包括哮喘，中风，动脉粥样硬化，多发性硬化，帕金森病， 关节炎疾病，风湿病，中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由白细胞三烯引起或增强的炎症，血小板引起或增强的炎症 活化因子，由前列腺素引起或增强的疼痛，由白三烯引起或加剧的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US20100184786A1

公开(公告)日：2010-07-22

申请号：US12622058

申请日：2009-11-19

Applicant: Jeremy Mark Travins ,  Ronald Charles Bernotas ,  Jay Edward Wrobel ,  David Harry Kaufman ,  Baihua Hu ,  James Winfield Jetter ,  David John O'Neill ,  Charles William Mann

Inventor： Jeremy Mark Travins ,  Ronald Charles Bernotas ,  Jay Edward Wrobel ,  David Harry Kaufman ,  Baihua Hu ,  James Winfield Jetter ,  David John O'Neill ,  Charles William Mann

IPC: A61K31/517 ,  C07D239/74 ,  A61P9/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P29/00 ,  A61Q19/08 ,  A61K8/49

CPC classification number: C07D239/72

Abstract: Disclosed are polar quinazoline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): in which, R1, R2, R3, R4, R5, R6, R22, R23, R24, R25, R26, R27, R28, R29, W, W1, W2, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, Rj, Rm, Rn, Ro, Rp, Rq, Rr, Rs, Rt, Ru, and n can be as defined anywhere herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.

Abstract translation: 公开了基于极性喹唑啉的肝脏X受体调节剂（LXR）及相关方法。 调节剂包括式（I）化合物：其中R1，R2，R3，R4，R5，R6，R22，R23，R24，R25，R26，R27，R28，R29，W，W1，W2，Ra，Rb ，Rc，Rd，Re，Rf，Rg，Rh，Ri，Rj，Rm，Rn，Ro，Rp，Rq，Rr，Rs，Rt，Ru和n可以如本文任何地方所定义。 通常，这些化合物可用于治疗或预防由LXR介导的一种或多种疾病，病症，病症或症状。

公开(公告)号：US20100120778A1

公开(公告)日：2010-05-13

申请号：US12614167

申请日：2009-11-06

Applicant: Baihua Hu ,  Jay Edward Wrobel ,  James Winfield Jetter ,  David John O'Neill ,  Charles William Mann ,  Rayomand Jal Unwalla

Inventor： Baihua Hu ,  Jay Edward Wrobel ,  James Winfield Jetter ,  David John O'Neill ,  Charles William Mann ,  Rayomand Jal Unwalla

IPC: A61K31/498 ,  C07D241/36 ,  A61P1/16 ,  A61P9/10 ,  A61P9/00 ,  A61P3/04 ,  A61P3/06 ,  A61P25/28 ,  A61P3/10 ,  A61P29/00 ,  A61P19/04

CPC classification number: C07D241/44 ,  C07D241/42

Abstract: Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): wherein: each of L1 and L2 is, independently, a bond, —O— or —NH—; R2 is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is (i) substituted with 1 R9, and (ii) optionally further substituted with from 1-4 Re; and each of R4 and R5 is, independently (i) hydrogen; or (ii) halo; or (iii) C1-C6 alkyl or C1-C6 haloalkyl, each of which is optionally substituted with from 1-3 Ra; and R1, R3, R6, R9, Ra and Re are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.

Abstract translation: 公开了基于喹喔啉的肝脏X受体调节剂（LXR）和相关方法。 调节剂包括式（I）的化合物：其中：L1和L2各自独立地是键，-O-或-NH-; R 2是包括5-10个原子的C 6 -C 10芳基或杂芳基，其各自为（i）被1个R9取代，和（ii）任选地被1-4个Re取代; 并且R 4和R 5各自独立地是（i）氢; 或（ii）卤素; 或（iii）C 1 -C 6烷基或C 1 -C 6卤代烷基，其各自任选被1-3个R a取代; 并且R1，R3，R6，R9，Ra和Re在本文中定义。 通常，这些化合物可用于治疗或预防由LXR介导的一种或多种疾病，病症，病症或症状。

公开(公告)号：US20070043101A1

公开(公告)日：2007-02-22

申请号：US11505527

申请日：2006-08-16

Applicant: Baihua Hu ,  James Jetter

Inventor： Baihua Hu ,  James Jetter

IPC: A61K31/403 ,  C07D403/02 ,  C07D209/26

CPC classification number: C07D209/08 ,  C07D209/26

Abstract: The present invention relates generally to substituted indoles and methods of using them.

Abstract translation: 本发明一般涉及取代的吲哚及其使用方法。

公开(公告)号：US20060252757A1

公开(公告)日：2006-11-09

申请号：US11365750

申请日：2006-03-01

Applicant: Baihua Hu ,  Jay Wrobel ,  Michael Collini ,  Rayomand Unwalla

Inventor： Baihua Hu ,  Jay Wrobel ,  Michael Collini ,  Rayomand Unwalla

IPC: A61K31/502 ,  C07D237/28 ,  A61K31/655

CPC classification number: C07D413/12 ,  C07D237/28 ,  C07D403/12 ,  C07D409/12

Abstract: This invention relates generally to cinnoline-based modulators of Liver X receptors (LXRs) and related methods.

Abstract translation: 本发明一般涉及基于噌啉的肝X受体调节剂（LXR）及相关方法。

公开(公告)号：US20060014759A1

公开(公告)日：2006-01-19

申请号：US11140390

申请日：2005-05-27

Applicant: John McKew ,  Steven Tam ,  Katherine Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark Behnke ,  Baihua Hu ,  James Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

Inventor： John McKew ,  Steven Tam ,  Katherine Lee ,  Lihren Chen ,  Paresh Thakker ,  Fuk-Wah Sum ,  Mark Behnke ,  Baihua Hu ,  James Clark ,  Wei Li ,  Valerie Clerin ,  Suzana Marusic ,  Kevin Pong

IPC: A61K31/505 ,  C07D239/02

CPC classification number: A61K31/505 ,  C07D209/14 ,  C07D209/16 ,  C07D209/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D487/08 ,  C07D491/10

Abstract: This invention provides methods for the use of substituted indole compounds of the general formula: and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A2 enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor.

Abstract translation: 本发明提供了使用通式的取代的吲哚化合物及其药学上可接受的盐形式的方法。 本发明提供了使用化合物作为各种磷脂酶，特别是磷脂酶2酶的活性抑制剂的方法，以及用于治疗，预防和抑制疾病和病症的方法，包括哮喘，中风， 动脉粥样硬化，多发性硬化，帕金森病，关节炎疾病，风湿病，由中风引起的中枢神经系统损伤，由缺血引起的中枢神经系统损伤，由创伤引起的中枢神经系统损伤，由前列腺素引起或增强的炎症，由...引起或增强的炎症 白细胞三烯，血小板活化因子引起或增强的炎症，前列腺素引起或加剧的疼痛，白细胞三烯引起或增强的疼痛，以及血小板激活因子引起或增强的疼痛。

公开(公告)号：US20050119327A1

公开(公告)日：2005-06-02

申请号：US10947903

申请日：2004-09-23

Applicant: Baihua Hu

Inventor： Baihua Hu

IPC: A61K31/404 ,  A61K31/405 ,  A61P3/10 ,  A61P7/02 ,  A61P9/10 ,  A61P25/28 ,  C07D209/42 ,  C07D409/12 ,  C07D417/12 ,  C07D49/02

CPC classification number: C07D409/12 ,  C07D209/42

Abstract: The present invention relates generally to substituted indoles such as substituted 1H-indole-2-carboxylic acid derivatives, and methods of using them.

Abstract translation: 本发明一般涉及取代的吲哚如取代的1H-吲哚-2-羧酸衍生物及其使用方法。

公开(公告)号：US06821991B2

公开(公告)日：2004-11-23

申请号：US10440788

申请日：2003-05-19

Applicant: Baihua Hu

Inventor： Baihua Hu

IPC: A61K31445

CPC classification number: C07D417/14 ,  A61K31/4412 ,  A61K31/4709 ,  A61K31/5377 ,  C07D277/54 ,  C07D417/10 ,  C07D417/12

Abstract: This invention provides compounds of Formula I having the structure wherein: A, X, Y, Z, R1, R2, R3, R4, R5, and R6 are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

Abstract translation: 本发明提供具有结构的式I化合物，其中A，X，Y，Z，R 1，R 2，R 3，R 4，R 5和R 6如上所定义，或其药学上可接受的盐，其可用于治疗或抑制代谢 与胰岛素抵抗或高血糖相关的疾病（通常与肥胖或葡萄糖不耐受相关），动脉粥样硬化，胃肠道疾病，神经源性炎症和尿频; 并且特别可用于治疗或抑制II型糖尿病。