公开(公告)号：US20130190369A1

公开(公告)日：2013-07-25

申请号：US13751530

申请日：2013-01-28

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: C07D261/04

CPC classification number: C07D261/04 ,  A61K31/42 ,  A61K31/421 ,  A61K45/06 ,  Y02A50/385 ,  Y02A50/411 ,  A61K2300/00

Abstract: Provided are various compounds of Formula I (I). Also provided are various compounds of Formula II (II). Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract translation: 提供式I（I）的各种化合物。 还提供式II（II）的各种化合物。 还提供了包含上述化合物的药物组合物。 此外，提供了哺乳动物抑制巨噬细胞迁移抑制因子（MIF）活性的方法，以及治疗或预防哺乳动物炎症的方法。 还提供了治疗具有败血症，败血病和/或内毒素性休克的哺乳动物的方法。 还提供了治疗具有自身免疫疾病的哺乳动物的方法以及治疗具有肿瘤的哺乳动物的方法。

公开(公告)号：US08193247B2

公开(公告)日：2012-06-05

申请号：US12225572

申请日：2007-03-23

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: A61K31/13 ,  C07C249/00 ,  A61P29/00

CPC classification number: C07C251/86 ,  C07C281/02 ,  C07C311/49

Abstract: Provided are various compounds of Formula (I): Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract translation: 提供式（I）的各种化合物：还提供包含上述化合物的药物组合物。 此外，提供了哺乳动物抑制巨噬细胞迁移抑制因子（MIF）活性的方法，以及治疗或预防哺乳动物炎症的方法。 还提供了治疗具有败血症，败血病和/或内毒素性休克的哺乳动物的方法。 还提供了治疗具有自身免疫疾病的哺乳动物的方法以及治疗具有肿瘤的哺乳动物的方法。

公开(公告)号：US20110136911A1

公开(公告)日：2011-06-09

申请号：US12735161

申请日：2008-12-18

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: A61K31/198 ,  C07C229/36 ,  A61P29/00 ,  A61P7/00 ,  A61P37/06 ,  A61P31/04 ,  A61P3/10 ,  A61P17/06 ,  A61P9/00 ,  A61P31/14 ,  A61P25/28 ,  A61P9/10 ,  A61P37/08 ,  A61P31/22 ,  A61P31/18 ,  A61P33/06 ,  A61P17/00 ,  A61P17/02 ,  A61P11/00

CPC classification number: A61K31/198 ,  Y02A50/385 ,  Y02A50/411

Abstract: Methods and compositions are disclosed for the use of dextrothyroxine (D-T4) to treat sepsis, inflammation, and conditions and diseases in which it is desirable to inhibit macrophage migration inhibitory factor (MIF).

Abstract translation: 公开了用于使用甲状腺素（D-T4）治疗败血症，炎症以及期望抑制巨噬细胞迁移抑制因子（MIF）的病症和疾病的方法和组合物。

公开(公告)号：US07807696B2

公开(公告)日：2010-10-05

申请号：US10574612

申请日：2004-10-07

Applicant: Yousef Al-Abed ,  Kevin J. Tracey

Inventor： Yousef Al-Abed ,  Kevin J. Tracey

IPC: A61K31/44 ,  C07D413/02

CPC classification number: C07D413/14 ,  C07D413/04

Abstract: Compounds of Formula (I), pharmaceutical compositions comprising compounds of Formulae (I a) or (VII) and a method of treating a subject with an inflammatory cytokine-mediated disorder comprising administering to the subject a compound of Formulae (I a) or (VII a). The variables of Formulae (I), (I a), (VII) and (VII a) are described herein.

Abstract translation: 式（I）的化合物，包含式（Ia）或（VII）的化合物的药物组合物和用炎性细胞因子介导的病症治疗受试者的方法，其包括向受试者施用式（Ia）或（ VII a）。 本文描述了式（I），（Ia），（VII）和（VIIa）的变量。

公开(公告)号：US20090318509A1

公开(公告)日：2009-12-24

申请号：US12227777

申请日：2007-06-04

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: A61K31/4406 ,  C07D213/80 ,  C07C69/76 ,  C07C69/74 ,  A61K31/4409 ,  A61K31/24 ,  A61K31/215 ,  A61P37/02

CPC classification number: C07C291/04 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14

Abstract: Provided are compounds of formula (I) and other compounds. Also provided are pharmaceutical compositions comprising these compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal, and methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock.

Abstract translation: 提供式（I）化合物和其它化合物。 还提供了包含这些化合物的药物组合物。 此外，还提供了哺乳动物抑制巨噬细胞迁移抑制因子（MIF）活性的方法，哺乳动物治疗或预防炎症的方法以及治疗具有败血症，败血病和/或内毒素性休克的哺乳动物的方法。

公开(公告)号：US20090137647A1

公开(公告)日：2009-05-28

申请号：US12225571

申请日：2007-03-23

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: A61K31/42 ,  C07D261/04 ,  A61P29/00 ,  A61P37/02 ,  A61P35/00

CPC classification number: C07D261/04 ,  A61K31/42 ,  A61K31/421 ,  A61K45/06 ,  Y02A50/385 ,  Y02A50/411 ,  A61K2300/00

Abstract: Provided are various compounds of Formula I (I). Also provided are various compounds of Formula II (II). Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also providcd are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

Abstract translation: 提供式I（I）的各种化合物。 还提供式II（II）的各种化合物。 还提供了包含上述化合物的药物组合物。 此外，提供了哺乳动物抑制巨噬细胞迁移抑制因子（MIF）活性的方法，以及治疗或预防哺乳动物炎症的方法。 还提供了治疗具有败血症，败血病和/或内毒素性休克的哺乳动物的方法。 还提供了治疗具有自身免疫性疾病的哺乳动物的方法，以及治疗具有肿瘤的哺乳动物的方法。

公开(公告)号：US07491740B2

公开(公告)日：2009-02-17

申请号：US10164630

申请日：2002-06-10

Applicant: Yousef Al-Abed

Inventor： Yousef Al-Abed

IPC: A01N43/80 ,  A01N43/08 ,  A61K31/42 ,  A61K31/34 ,  C07D261/02 ,  C07D413/00

CPC classification number: A61K31/421 ,  C07D261/04

Abstract: Methods of use and pharmaceutical compositions for a genus of low molecular weight compounds comprising optionally substituted isoxazoline ring systems that act as inhibitors of MIF (macrophage migration inhibitory factor) are disclosed. Specifically, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

Abstract translation: 公开了用作低分子量化合物的药物组合物的方法，其包含用作MIF抑制剂（巨噬细胞迁移抑制因子）的任选取代的异恶唑啉环体系。 具体地说，该化合物可用于治疗涉及炎症活性或促炎细胞因子应答的各种疾病，例如自身免疫性疾病（包括风湿性关节炎，胰岛素依赖性糖尿病，多发性硬化，移植物抗宿主病，狼疮综合征），哮喘， 关节炎，ARDS，牛皮癣，白细胞介素-2毒性，增殖性血管疾病和各种形式的败血症和败血性休克，以及其他基本MIF反应特征的病症，包括例如肿瘤生长和新生血管形成（血管生成）。

公开(公告)号：US20160296574A1

公开(公告)日：2016-10-13

申请号：US15036470

申请日：2014-11-17

Applicant: Osama Mansour Murad ,  Yousef Al-Abed

Inventor： Osama Mansour Murad ,  Yousef Al-Abed

IPC: A61K36/17 ,  A61K31/34 ,  A61K9/00 ,  A61K31/7032 ,  A61K9/19

CPC classification number: A61K36/17 ,  A61K9/4858 ,  A61K31/34 ,  A61K31/35 ,  A61K31/58 ,  A61K31/7032 ,  A61K45/06 ,  A61K2236/331 ,  A61K2236/37 ,  A61K2236/51 ,  A61K2236/53

Abstract: Ephedra alata aqueous extracts, powders and constituents thereof are encompassed herein, as are compositions thereof. Methods of using same for treating inflammatory diseases, autoimmune diseases, cancers, viral diseases, and neurodegenerative diseases are also envisioned.

Abstract translation: 麻黄碱水提取物，粉末及其成分在本文中包括，其组合物也如此。 也可以设想使用它们治疗炎性疾病，自身免疫性疾病，癌症，病毒性疾病和神经变性疾病的方法。

公开(公告)号：US08759376B2

公开(公告)日：2014-06-24

申请号：US12891447

申请日：2010-09-27

Applicant: Yousef Al-Abed ,  Kevin J. Tracey

Inventor： Yousef Al-Abed ,  Kevin J. Tracey

IPC: A61K31/44 ,  C07D413/02

CPC classification number: C07D413/14 ,  C07D413/04

Abstract: Compounds of Formula (I), pharmaceutical compositions comprising compounds of Formulae (I a) or (VII) and a method of treating a subject with an inflammatory cytokine-mediated disorder comprising administering to the subject a compound of Formulae (I a) or (VIIa). The variables of Formulae (I), (I a), (VII) and (VII a) are described herein.

Abstract translation: 式（I）的化合物，包含式（Ia）或（VII）的化合物的药物组合物和用炎性细胞因子介导的病症治疗受试者的方法，其包括向受试者施用式（Ia）或（ VIIa）。 本文描述了式（I），（Ia），（VII）和（VIIa）的变量。

公开(公告)号：US08207206B2

公开(公告)日：2012-06-26

申请号：US12599221

申请日：2008-05-06

Applicant: Ferdinando Nicoletti ,  Yousef Al-Abed ,  Gianni Garotta

Inventor： Ferdinando Nicoletti ,  Yousef Al-Abed ,  Gianni Garotta

IPC: A61K31/4245 ,  C07D271/08

CPC classification number: C07D413/12

Abstract: The present invention relates to an isoxazole derivative, the compound of formula (I) herein after referred to as GIT27-NO, which is the NO-donating structurally modified form of (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid, herein after referred to as VGX-1027. Treatment of three tumor cell lines, rat astrocytoma C6, mouse fibrosarcoma L929, and mouse melanoma B16 cells with GIT27-NO resulted in a significant reduction of cell respiration and of number of viable cells, while VGX-1027 was completely ineffective. Hemoglobin, which act as NO-scavenger, restored cell viability, thus indicating the NO-mediated tumoricidal effect of compound (I). GIT27-NO triggered apoptotic cell death in L929 cell cultures, while autophagic cell death is mainly responsible for the diminished viability of C6 and B16 cells. Moreover, GIT27-NO induced the production of reactive oxygen species which can be neutralized by antioxidant N-acetyl cysteine (NAC), indicating that reactive oxygen species (ROS) are at least partly involved in the reduction of cell viability. The anti-tumor activity of GIT27-NO is mediated through activation of MAP kinases (ERK1/2, p38 and JNK) in cell-specific manner. The role of MAP kinases was further confirmed by specific inhibitors of these molecules, PD98059, SB202190, and SP600125. Finally, in vivo treatment with GIT27-NO significantly reduced tumor growth in syngeneic C57BL/6 mice implanted with B16 melanoma.

Abstract translation: 本发明涉及异恶唑衍生物，本文的式（I）化合物在本文中称为GIT27-NO，其是（S，R）-3-苯基-4,5-二氢的NO供体结构修饰形式 -5-异恶唑乙酸，此后称为VGX-1027。 用GIT27-NO处理三种肿瘤细胞系，大鼠星形细胞瘤C6，小鼠纤维肉瘤L929和小鼠黑素瘤B16细胞导致细胞呼吸和活细胞数量的显着降低，而VGX-1027完全无效。 作为NO清除剂的血红蛋白恢复细胞活力，从而表明化合物（I）的NO介导的杀肿瘤作用。 GIT27-NO在L929细胞培养物中引发凋亡细胞死亡，而自噬细胞死亡主要是C6和B16细胞活力下降的主要原因。 此外，GIT27-NO诱导可被抗氧化剂N-乙酰半胱氨酸（NAC）中和的活性氧的产生，表明活性氧（ROS）至少部分参与细胞活力的降低。 GIT27-NO的抗肿瘤活性通过以细胞特异性方式激活MAP激酶（ERK1 / 2，p38和JNK）介导。 MAP激酶的作用由这些分子PD98059，SB202190和SP600125的特异性抑制剂进一步证实。 最后，使用GIT27-NO的体内治疗显着降低植入B16黑素瘤的同基因C57BL / 6小鼠的肿瘤生长。