公开(公告)号：US06987105B2

公开(公告)日：2006-01-17

申请号：US10258343

申请日：2001-04-26

申请人： Nicholas G. Bazan ,  Julio Alvarez Builla Gomez

发明人： Nicholas G. Bazan ,  Julio Alvarez Builla Gomez

IPC分类号： A61P27/02

CPC分类号： C07D495/22 ,  A61K31/551

摘要： A new method to synthesize the platelet-activating factor antagonist which is a derivative of thienotriazolodiazepene, tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methosy-4 phenyl carbamoyl)-9 pyrido[4,3-:4,5] thieno[3,2-f] triazolo-1,2,4 [4,3-α] diazepine-1,4] (1) is disclosed. The compound synethesized by this new method has been designated “LAU-8080” which has the same structure as the compound currently named in the literature as “BN-50730.” LAU-8080 was shown to prevent photoreceptor cell death, inhibit pathological neovascularization in the retina, and minimize the loss of neurons due to ischemic-reperfusion damage due to stroke. Thus LAU-8080 can be used to treat the retinal diseases of age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. It can also be used to minimize the neuronal damage due to stroke.

公开(公告)号：US06979682B2

公开(公告)日：2005-12-27

申请号：US10082821

申请日：2002-02-25

申请人： Jay D. Hunt ,  Haydee E. Bazan ,  Victor L. Marcheselli ,  Julio Alvarez Builla Gomez ,  Nicholas G. Bazan

发明人： Jay D. Hunt ,  Haydee E. Bazan ,  Victor L. Marcheselli ,  Julio Alvarez Builla Gomez ,  Nicholas G. Bazan

IPC分类号： A61K31/00 ,  A61K31/336 ,  A61K31/39 ,  A61K31/551 ,  A61K38/21 ,  A61K31/55

CPC分类号： A61K31/39 ,  A61K31/00 ,  A61K31/336 ,  A61K31/551 ,  A61K38/21 ,  A61K2300/00

摘要： A novel use of platelet-activating factor antagonists that bind to intracellular PAF binding sites such as BN-50730 (tetrahedra-4,7,8,10 methyl-1 (chloro-1 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4′,3′-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4) has been discovered. These intracellular-binding platelet-activating factor antagonists were found to inhibit both in vivo and in vitro tumor growth and angiogenesis where the angiogenesis is stimulated by basic fibroblast growth factor.

摘要翻译： 结合细胞内PAF结合位点如BN-50730（四面体-4,7,8,10甲基-1（氯-1苯基）-6（甲氧基-4-苯基 - 氨基甲酰基） -9吡啶并[4'，3'-4,5]噻吩并[3,2-f]三唑-1,2,4 [4,3-a]二氮杂-1,4）。 发现这些细胞内结合的血小板活化因子拮抗剂抑制体内和体外肿瘤生长和血管生成，其中血管发生受碱性成纤维细胞生长因子的刺激。

公开(公告)号：US06566359B1

公开(公告)日：2003-05-20

申请号：US10151984

申请日：2002-05-20

申请人： Nicholas G. Bazan ,  Carlos Sunkel ,  Victor L. Marcheselli ,  Julio Builla-G.

发明人： Nicholas G. Bazan ,  Carlos Sunkel ,  Victor L. Marcheselli ,  Julio Builla-G.

IPC分类号： A61K315377

CPC分类号： C07D231/12 ,  A61K31/5377 ,  C07D211/90 ,  C07D233/56 ,  C07D249/08 ,  C07D401/12

摘要： A new series of derivatives of 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid and their synthesis have been discovered. Surprisingly, by modifying the substituent of the 3-carboxylic acid group, new compounds were produced with high activity as PAF receptor antagonists. These compounds were shown to protect neurons from brain damage that normally occurs in response to stroke and other cerebrovascular diseases. These compounds are also protective against edema generation resulting from traumatic breakdown of the blood-brain barrier. Moreover, these compounds were found to be non-toxic and cytoprotective of cells undergoing oxidative stress that would normally trigger apoptotic cell death; and to have activity as (a) antagonists of an intracellular platelet activating factor (“PAF”)-binding site, (b) inhibitors of PAF- and cytokine-mediated c-aminoterminal jun kinase (JNK) and extracellular regulated kinase (ERK), and (c) transcriptional inhibitors of COX-2 expression.

摘要翻译： 已经发现了一系列2,4,6-三甲基-1,4-二氢吡啶-3,5-二羧酸的衍生物及其合成。 令人惊奇的是，通过改变3-羧酸基团的取代基，产生具有高活性的新化合物作为PAF受体拮抗剂。 显示这些化合物可以保护神经元免受通常发生在脑卒中和其他脑血管疾病中的脑损伤。 这些化合物还可以防止血脑屏障创伤性破坏引起的水肿发生。 此外，发现这些化合物是经历氧化应激的细胞的无毒和细胞保护，其通常将引发凋亡性细胞死亡; 并且具有作为（a）细胞内血小板活化因子（“PAF”）结合位点的拮抗剂的活性，（b）PAF-和细胞因子介导的C-氨基末端jun激酶（JNK）和细胞外调节激酶（ERK）的抑制剂， ，和（c）COX-2表达的转录抑制剂。

公开(公告)号：US06653311B1

公开(公告)日：2003-11-25

申请号：US10179534

申请日：2002-06-25

申请人： Nicholas G. Bazan ,  Carlos Sunkel ,  Julio Alvarez Builla-G.

发明人： Nicholas G. Bazan ,  Carlos Sunkel ,  Julio Alvarez Builla-G.

IPC分类号： C07D40102

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D241/20

摘要： We have synthesized a series of new derivatives of (2-azinylamino) quinone, that have the general formula shown below. Several compounds of this new series of derivatives have been shown to be inhibitors of 5-lipoxygenase, with minimal or no effect on cycloxygenase-1 and 2-(COX-1 and COX-2) activity. where: A is N, CH, or, CCl; B is N, CH, CCH3, or Cph; X is H, Cl, Br, or I; Y is H, or CH3; R1 is H, CH3, OCH3, or Ph; and R2 is H, CH3, OCH3, or Ph; or R1—R2 is (CH═CH)2; and R3 is H or CH3.

摘要翻译： 我们合成了一系列新的（2-氮杂乙氨基）醌衍生物，具有下列通式。 已经显示这种新系列衍生物的几种化合物是5-脂氧合酶的抑制剂，对环氧化酶-1和2-（COX-1和COX-2）活性具有最小或没有影响。其中：A是N，CH， 或CCl; B为N，CH，CCH 3或Cph; X为H，Cl，Br或I; Y为H或CH 3; R 1为H，CH 3，OCH 3或Ph; R 2是H，CH 3，OCH 3或Ph; 或R 1 -R 2为（CH = CH）2; R 3为H或CH 3。