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11. 发明授权

US5840893A Compounds for treating infectious diseases 失效
标题翻译：用于治疗传染病的化合物
公开(公告)号：US5840893A
公开(公告)日：1998-11-24
申请号：US584857
申请日：1996-01-05
申请人： Michael I. Bukrinsky , Anthony Cerami , Peter Ulrich , Bradley J. Berger
发明人： Michael I. Bukrinsky , Anthony Cerami , Peter Ulrich , Bradley J. Berger
IPC分类号： C07C279/16 , C07C279/26 , C07D239/48 , C07D251/48 , C07D251/42
CPC分类号： C07D239/48 , C07C279/16 , C07C279/26 , C07D251/48
摘要： There is disclosed compound according to the formula: ##STR1## wherein A, independently,=CH.sub.3 or CH.sub.2 CH.sub.3, P=1 or 2; and ##STR2## wherein X=NH.sub.2, CH.sub.3 or CH.sub.2 CH.sub.3 ; X'=CH.sub.3 or CH.sub.2 CH.sub.3 ; Y=NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 ; and Z=H, CH.sub.3 or CH.sub.2 CH.sub.3 ; or ##STR3## wherein Y' and Z', independently,=H, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 or N.sup.+ (CH.sub.3).sub.3 ; Q is N or CH; and salts thereof.
摘要翻译：公开了根据下式的化合物：其中A独立地为= CH 3或CH 2 CH 3，P = 1或2; （1）其中X = NH2，CH3或CH2CH3;（2）其中X = NH2，CH3或CH2CH3; X'= CH 3或CH 2 CH 3; Y = NH 2，NHCH 3，N（CH 3）2; 和Z = H，CH 3或CH 2 CH 3; （6）其中Y'和Z'独立地为= H，NH 2，NHCH 3，N（CH 3）2或N +（CH 3）2 ）3; Q是N或CH; 及其盐。

12. 发明授权

US5811075A Method and agents for removing advanced glycosylation endproducts 失效
公开(公告)号：US5811075A
公开(公告)日：1998-09-22
申请号：US487398
申请日：1995-06-07
申请人： Helen Vlassara , Michael Brownlee , Anthony Cerami
发明人： Helen Vlassara , Michael Brownlee , Anthony Cerami
IPC分类号： A61K8/43 , A61K8/44 , A61K31/155 , A61K39/00 , A61K51/12 , A61Q11/00 , A61Q19/08 , C07K16/28 , G01N33/573 , A61K49/00 , C12Q1/00
CPC分类号： A61K8/44 , A61K31/155 , A61K39/0005 , A61K51/1203 , A61K8/43 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/6842 , A61K2039/6081 , C07K2317/77 , G01N2333/922 , G01N2800/042
摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.

13. 发明授权

US5733933A Methods and materials for the diagnosis and treatment of conditions such as stroke 失效
公开(公告)号：US5733933A
公开(公告)日：1998-03-31
申请号：US473009
申请日：1995-06-07
申请人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
发明人： Richard J. Bucala , Helen Vlassara , Anthony Cerami , Kevin J. Tracey
IPC分类号： A61K31/155 , A61K38/17 , A61K39/00 , A61Q11/00 , C07K16/28 , G01N33/573 , G01N33/92
CPC分类号： G01N33/92 , A61K31/155 , A61K38/1709 , A61K39/0005 , C07K16/28 , G01N33/573 , A61K2039/6081 , G01N2333/922 , G01N2800/2871 , G01N2800/324
摘要： The in vivo oxidation of lipids and lipid-containing molecules has been discovered to be initiated by the concurrent reaction of such lipid materials with reducing sugars such as glucose, advanced glycosylation endproducts such as AGE-peptides, or a compound which forms advanced glycosylation endproducts, to form materials or particles known as AGE-lipids. AGE-lipids have been implicated in the aging process, the abnormal formation of lipofuscin and in various disease states such as diabetes, atherosclerosis, and stroke. Methods of treating stroke, and especially inhibiting the infarct size of stroke, using agents which inhibit the formation of AGE-lipids are disclosed. Additionally, a method of screening for neuroprotective agents which can be used to reduce the size and severity of the infarct size is disclosed.

14. 发明授权

US5733932A Compounds and methods of use to derivatize neighboring lysine residues in proteins under physiological conditions 失效
标题翻译：用于在生理条件下衍生蛋白质中相邻赖氨酸残基的化合物和方法
公开(公告)号：US5733932A
公开(公告)日：1998-03-31
申请号：US463405
申请日：1995-06-05
申请人： Michael I. Bukrinsky , Anthony Cerami , Peter Ulrich
发明人： Michael I. Bukrinsky , Anthony Cerami , Peter Ulrich
IPC分类号： C07C279/16 , C07C279/26 , C07D239/48 , C07D251/48 , A61K31/155 , C07C279/18
CPC分类号： C07D239/48 , C07C279/16 , C07C279/26 , C07D251/48
摘要： The present invention encompasses the use of the compounds of formula as given below to detect certain specific protein structures which are present in nuclear localization sequences ##STR1## wherein A is, independently CH.sub.3 or CH.sub.2 CH.sub.3 and R is ##STR2## and salts thereof.
摘要翻译：本发明包括如下给出的式的化合物用于检测存在于核定位序列中的某些特异性蛋白质结构，其中A独立地是CH3或CH2CH3且R是其盐。及其盐。

15. 发明授权

US5616688A Macrophage-derived inflammatory mediator (MIP-1.alpha. and MIP-1.beta.) 失效
标题翻译：巨噬细胞来源的炎症介质（MIP-1α和MIP-1β）
公开(公告)号：US5616688A
公开(公告)日：1997-04-01
申请号：US207888
申请日：1994-03-07
申请人： Anthony Cerami , Bruce Beutler , Stephen D. Wolpe
发明人： Anthony Cerami , Bruce Beutler , Stephen D. Wolpe
IPC分类号： A61K38/00 , A61K38/19 , A61P29/00 , C07K14/52 , C07K16/24 , G01N33/68 , C07K1/00 , C07K14/00 , G01N33/53 , G01N33/555
CPC分类号： G01N33/68 , C07K14/523 , C07K16/24 , C07K16/241 , G01N33/6863 , G01N33/6872 , A61K38/00 , C12N2501/21 , C12N2501/22 , G01N2333/52 , G01N2400/40 , Y10S930/14
摘要： An inflammatory cytokine is disclosed which has been isolated from cells that have been incubated with a stimulator material. The inflammatory cytokine comprises a protein that is capable of binding to heparin, inducing localized inflammation characterized by polymorphonuclear cell infiltration when administered subcutaneously and inducing in vitro polymorphonuclear cell chemokinesis, while lacking the ability to suppress the activity of the anabolic enzyme lipoprotein lipase, cause the cytotoxicity of cachectin/TNF-sensitive cells, stimulate the blastogenesis of endotoxin-resistant C3H/HeJ thymocytes, or induce the production of cachectin/TNF by primary thioglycollate-elicited mouse macrophage cells. A particular inflammatory cytokine MIP-1 has been isolated and has been found to comprise a peptide doublet of similar molecular weights of about 8,000 daltons, and to show a pI of about 4.6. The doublet has been resolved into its component peptides, MIP-1.alpha. and MIP-1.beta. for which distinct cDNA's have been cloned and sequenced. Diagnostic and therapeutic utilities are proposed, and testing procedures, materials in kit form and pharmaceutical compositions are likewise set forth.
摘要翻译：公开了已经与已经与刺激剂材料一起温育的细胞分离的炎性细胞因子。炎性细胞因子包含能够结合肝素的蛋白质，诱导局部炎症，其特征在于皮下投与多形核细胞浸润，诱导体外多形核细胞趋化因子，同时缺乏抑制合成代谢酶脂蛋白脂肪酶活性的能力，导致缓激肽/ TNF敏感细胞的细胞毒性，刺激内毒素抗性C3H / HeJ胸腺细胞的胚胎发生，或诱导由初级巯基乙酸酯诱导的小鼠巨噬细胞产生恶性胶质瘤/ TNF。已经分离了特定的炎性细胞因子MIP-1，并且已经发现其包含约8,000道尔顿的类似分子量的肽双链，并显示约4.6的pI。双螺旋已被解析成其组分肽，MIP-1α和MIP-1β，其中克隆和测序不同的cDNA。提出了诊断和治疗用途，同样阐述了测试程序，试剂盒形式的材料和药物组合物。

16. 再颁专利

USRE35465E Method and agents for removing advanced glycosylation endproducts 失效
标题翻译：去除高级糖基化终产物的方法和试剂
公开(公告)号：USRE35465E
公开(公告)日：1997-02-25
申请号：US437064
申请日：1995-05-09
申请人： Helen Vlassara , Michael Brownlee , Anthony Cerami
发明人： Helen Vlassara , Michael Brownlee , Anthony Cerami
IPC分类号： A61K8/43 , A61K31/155 , A61K31/4178 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/68 , A61K31/415
CPC分类号： A61K8/43 , A61K31/155 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K39/0005 , A61Q19/08 , C07K16/28 , G01N33/573 , G01N33/68 , G01N33/6842 , G01N33/6893 , A61K2039/6081 , G01N2333/922
摘要： The present invention relates to a method and associated agents for the inhibition and treatment of protein aging in animals by stimulating the bodies of the animals to increase their recognition and affinity for advanced glycosylation end products. Specifically, the method contemplates the administration of certain agents such as advanced glycosylation endproducts, such endproducts as are bound to the carrier, monokines that stimulate phagocytic cells to increase their activity toward advanced glycosylation endproducts, and mixtures of these materials either alone, or in conjunction with other co-stimulatory agents. Numerous diagnostic and therapeutic applications are defined, and pharmaceutical compositions are also contemplated.
摘要翻译：本发明涉及通过刺激动物的体内增加其对晚期糖基化终产物的识别和亲和力来抑制和治疗动物中蛋白质老化的方法和相关药剂。具体地说，该方法考虑到某些药物的施用，例如晚期糖基化终产物，结合载体的终产物，刺激吞噬细胞增加其对晚期糖基化终产物的活性的单核因子，以及这些材料的混合物，单独或联合与其他共刺激剂。定义了许多诊断和治疗应用，并且也考虑了药物组合物。

17. 发明授权

US5599984A Guanylhydrazones and their use to treat inflammatory conditions 失效
标题翻译：桂脒及其用于治疗炎症的用途
公开(公告)号：US5599984A
公开(公告)日：1997-02-04
申请号：US315170
申请日：1994-09-29
申请人： Marina Bianchi , Anthony Cerami , Kevin J. Tracey , Peter Ulrich
发明人： Marina Bianchi , Anthony Cerami , Kevin J. Tracey , Peter Ulrich
IPC分类号： C07D233/61 , A61K31/00 , A61K31/155 , A61K31/167 , A61K31/17 , A61K31/175 , A61K31/195 , A61K31/198 , A61K31/415 , A61K31/4164 , A61K31/44 , A61K31/4402 , A61K31/4418 , A61K31/60 , A61P3/00 , A61P9/00 , A61P29/00 , A61P31/00 , A61P33/00 , A61P35/00 , A61P43/00 , C07C275/38 , C07C275/40 , C07C281/18 , C07D213/42 , C07C233/05
CPC分类号： A61K31/621 , A61K31/00 , A61K31/155 , A61K31/167 , A61K31/17 , A61K31/175 , A61K31/195 , A61K31/4164 , A61K31/44 , A61K31/60 , C07C275/38 , C07C275/40 , C07C281/18 , Y10S514/825 , Y10S514/886 , Y10S514/903
摘要： This invention concerns new methods and compositions that are useful in preventing and ameliorating cachexia, the clinical syndrome of poor nutritional status and bodily wasting associated with cancer and other chronic diseases. More particularly, the invention relates to aromatic guanylhydrazone (more properly termed amidinohydrazone) compositions and their use to inhibit the uptake of arginine by macrophages and/or its conversion to urea. These compositions and methods are also useful in preventing the generation of nitric oxide (NO) by cells, and so to prevent NO-mediated inflammation and other responses in persons in need of same. In another embodiment, the compounds can be used to inhibit arginine uptake in arginine-dependent tumors and infections.
摘要翻译：本发明涉及可用于预防和改善恶病质的新方法和组合物，与癌症和其它慢性疾病相关的营养状况不佳的临床综合征以及身体的消耗。更具体地说，本发明涉及芳香脒腙（更合适地称为脒基腙）组合物及其用于抑制巨噬细胞摄取精氨酸和/或转化成尿素的用途。这些组合物和方法也可用于预防细胞产生一氧化氮（NO），并且因此可以防止需要相同的人的NO介导的炎症和其他反应。在另一个实施方案中，所述化合物可用于抑制精氨酸依赖性肿瘤和感染中的精氨酸摄取。

18. 发明授权

US5468777A Method and agents for preventing and reversing the staining of teeth 失效
标题翻译：防止和反转牙齿染色的方法和试剂
公开(公告)号：US5468777A
公开(公告)日：1995-11-21
申请号：US236228
申请日：1994-04-29
申请人： Dennis S. France , Anthony Cerami , Peter C. Ulrich , Laura A. Norton , David L. Neer
发明人： Dennis S. France , Anthony Cerami , Peter C. Ulrich , Laura A. Norton , David L. Neer
IPC分类号： A61K8/44 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , A61K7/16
CPC分类号： C07D405/14 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/447 , A61Q11/00 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , G01N33/6893 , A61K2039/6081 , G01N2333/922
摘要： The present invention relates to methods and agents for preventing and reversing the staining of teeth caused by the nonenzymatic browning of proteins in the oral cavity. Suitable agents for the inhibition of nonenzymatic browning may be formulated as rinses and toothpastes, and include cysteine and cysteine derivatives. These preparations may further include known anti-plaque agents, such as chlorhexidine.
摘要翻译：本发明涉及用于预防和逆转由口腔内的蛋白质的非酶褐变引起的牙齿染色的方法和试剂。用于抑制非酶褐变的合适的试剂可以配制成漂洗剂和牙膏，并且包括半胱氨酸和半胱氨酸衍生物。这些制剂还可以包括已知的抗斑块剂，如氯己定。

19. 发明授权

US5399560A 1,2,4-triazine products resulting from the inhibition of advanced glycosylation 失效
标题翻译：由抑制晚期糖基化产生的1,2,4-三嗪产物
公开(公告)号：US5399560A
公开(公告)日：1995-03-21
申请号：US956722
申请日：1992-10-01
申请人： Anthony Cerami , Hauh-Jyun C. Chen
发明人： Anthony Cerami , Hauh-Jyun C. Chen
IPC分类号： A61K8/49 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K31/495 , A61K31/535 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/00 , C07C281/18 , C07D233/02 , C07D239/04 , C07D243/04 , C07D295/215 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , A61K31/53 , C07D253/065
CPC分类号： G01N33/6842 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K31/495 , A61K31/535 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/4966 , A61Q19/00 , C07C281/18 , C07D233/02 , C07D239/04 , C07D243/04 , C07D295/215 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , G01N33/6893 , A61K2039/6081 , A61Q17/04 , G01N2333/922
摘要： The mechanism of the inhibition of advanced glycosylation by aminoguanidine and other hydrazine type compounds was investigated using a solution of one or two molecules of aminoguanidine or other hydrazine type compound incubated with an Amadori product (1-propylamine-1-deoxy-D-fructose) under physiological conditions. This inhibition was found to proceed through the reactive intermediate 1-propylamino-1, 4-dideoxyosone to form the corresponding triazine and the dehydrazone of 1,4-dideoxyglucosone, respectively.The triazine and dehydrazone products are useful as macrophage stimulants to activate a macrophage to effect removal of advanced glycosylation endproducts (AGEs). Additionally, they can be used in a variety of investigative methods in an effort to measure the extent of nonenzymatic glycosylation of a protein sample wherein aminoguanidine or other hydrazine-type compound is or was present during the glycosylation process.
摘要翻译：使用一种或两种氨基胍或其他肼类化合物与Amadori产物（1-丙胺-1-脱氧-D-果糖）孵育的溶液的溶液，研究氨基胍和其它肼类化合物抑制晚期糖基化的机制，在生理条件下。发现该抑制通过反应性中间体1-丙基氨基-1,4-二脱氧酮进行，分别形成相应的三嗪和1,4-二脱氧葡萄糖酮的脱氢腙。三嗪和脱氢腙产物可用作巨噬细胞兴奋剂以激活巨噬细胞以去除晚期糖基化终产物（AGE）。另外，它们可以用于各种调查方法，以努力测量蛋白质样品的非酶糖基化程度，其中在糖基化过程中存在或存在氨基胍或其他肼型化合物。

20. 发明授权

US5358960A Method for inhibiting advanced glycosylation of proteins using aminosubstituted imidazoles 失效
标题翻译：使用氨基取代咪唑抑制蛋白质晚期糖基化的方法
公开(公告)号：US5358960A
公开(公告)日：1994-10-25
申请号：US986662
申请日：1992-12-08
申请人： Peter Ulrich , Anthony Cerami , Dilip R. Wagle
发明人： Peter Ulrich , Anthony Cerami , Dilip R. Wagle
IPC分类号： A61K8/43 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/58 , G01N33/68
CPC分类号： A61K8/43 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/582 , G01N33/68 , G01N33/6842 , G01N33/6893 , A61K2039/6081 , G01N2333/922 , Y10S514/866
摘要： The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging), Accordingly, a composition is disclosed which comprises 2-aminoimidazoles capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation, The method comprises contacting the target protein with the composition, Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制非酶交联（蛋白质老化）的组合物和方法。因此，公开了一种组合物，其包含2-氨基咪唑，其能够通过与靶蛋白的羰基部分反应来抑制靶蛋白的高级糖基化终产物的形成通过其初始糖基化形成的这种靶蛋白的早期糖基化产物。该方法包括使靶蛋白与组合物接触。本发明的工业和治疗应用都是可以想象的，因为可以处理食物腐败和动物蛋白质老化。

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