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1. 发明授权

US5739169A Aromatic compounds for inhibiting immune response 失效
标题翻译：用于抑制免疫反应的芳香族化合物
公开(公告)号：US5739169A
公开(公告)日：1998-04-14
申请号：US656468
申请日：1996-05-31
申请人： Timothy D. Ocain , Huai Gao , Jeffrey I. Krieger , Theresa M. Sampo
发明人： Timothy D. Ocain , Huai Gao , Jeffrey I. Krieger , Theresa M. Sampo
IPC分类号： C07C229/58 , C07C233/43 , C07D257/04 , A61K31/135 , A01N33/02 , C07C229/00
CPC分类号： C07D257/04 , C07C229/58 , C07C233/43
摘要： Novel compounds ##STR1## wherein R.sup.1 to R.sup.13 are independently selected from C.sub.2 -C.sub.4 linear and branched alkyls, H, NH.sub.2, CH.sub.3, OR.sup.14, fluorine, chlorine, iodine, NO.sub.2, CF.sub.3, NHCOCH.sub.3, NHCOOtBu, NHR.sup.15, NR.sup.16 R.sup.17 and phenyl, for use as immunosuppressive agents to prevent or significantly reduce graft rejection in organ and bone marrow transplantation are described. The novel compounds can also be used as an immunosuppressant drug for T-lymphocyte mediated autoimmune diseases, such as diabetes, and may be useful in alleviating psoriasis and contact dermatitis. Additionally, the novel compounds can be used for antiproliferation and gene therapy.
摘要翻译：其中R 1至R 13独立地选自C 2 -C 4直链和支链烷基，H，NH 2，CH 3，OR 14，氟，氯，碘，NO 2，CF 3，NHCOCH 3，NHCOOtBu，NHR 15，NR 16 R 17和苯基，用作免疫抑制剂以预防或显着降低器官和骨髓移植中的移植物排斥。新型化合物也可用作T淋巴细胞介导的自身免疫性疾病如糖尿病的免疫抑制药物，可用于缓解牛皮癣和接触性皮炎。另外，新型化合物可用于抗增殖和基因治疗。

2. 发明授权

US07279562B2 Rapamycin conjugates 有权
标题翻译：雷帕霉素缀合物
公开(公告)号：US07279562B2
公开(公告)日：2007-10-09
申请号：US10124386
申请日：2002-04-18
申请人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain
发明人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain
IPC分类号： G01N1/13 , G01N1/04
CPC分类号： C07K16/14 , A61K31/435 , A61K47/643 , A61K47/6835 , C07K16/1292 , C12N9/0065 , G01N33/533 , G01N33/9446 , Y10S530/809
摘要： Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monoclonal antibody.
摘要翻译：提供的雷帕霉素缀合物可用作产生雷帕霉素特异性抗体的免疫原性分子，用于测量雷帕霉素或其衍生物的水平; 用于分离雷帕霉素结合蛋白; 并检测对雷帕霉素或其衍生物特异的抗体。本发明还提供了雷帕霉素特异性单克隆抗体。

3. 发明授权

US06328970B1 Rapamycin position 27 conjugates 失效
标题翻译：雷帕霉素27位缀合物
公开(公告)号：US06328970B1
公开(公告)日：2001-12-11
申请号：US09576952
申请日：2000-05-24
申请人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain , Amadeo A. Failli
发明人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain , Amadeo A. Failli
IPC分类号： A61K3900
CPC分类号： G01N33/533 , A61K31/435 , A61K47/643 , A61K47/6835
摘要： Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin or a derivative thereof, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides monoclonal antibodies specific for rapamycin or a ring opened derivative of rapamycin.
摘要翻译：提供雷帕霉素缀合物，其可用作产生雷帕霉素或其衍生物特异性抗体的免疫原性分子，用于测量雷帕霉素或其衍生物的水平; 用于分离雷帕霉素结合蛋白; 并检测对雷帕霉素或其衍生物特异的抗体。本发明还提供对雷帕霉素特异性的单克隆抗体或雷帕霉素的开环衍生物。

4. 发明授权

US5504091A Biotin esters of rapamycin 失效
标题翻译：雷帕霉素的生物素酯
公开(公告)号：US5504091A
公开(公告)日：1996-04-02
申请号：US224206
申请日：1994-04-14
申请人： Katherine L. Molnar-Kimber , Timothy D. Ocain , Steven K. Vernon , John J. Huang
发明人： Katherine L. Molnar-Kimber , Timothy D. Ocain , Steven K. Vernon , John J. Huang
IPC分类号： C07D519/00 , G01N33/94 , A61K31/395
CPC分类号： C07D519/00 , G01N33/9446 , Y10S435/975 , Y10T436/141111
摘要： A compound of the structure ##STR1## R.sup.1 and R.sup.2 are each, independently, hydrogen or ##STR2## X is ##STR3## Y is ##STR4## Z is --CH.sub.2 --, --S--S--, or ##STR5## R.sup.3 is hydrogen, alkyl, arylalkyl, alkenyl, alkynyl, --(CH.sub.2).sub.q CO.sub.2 R.sup.5, --(CH.sub.2).sub.r NR.sup.6 R.sup.7, carbamylalkyl, aminoalkyl, hydroxyalkyl, guanylalkyl, mercaptoalkyl, alkylthioalkyl, indolylmethyl, hydroxyphenylmethyl, imidazoylmethyl, halo, trifluoromethyl, or phenyl which is optionally mono-, di-, or tri-substituted;R.sup.4, R.sup.6, and R.sup.7 are each, independently, hydrogen, alkyl, or arylalkyl;R.sup.5 is hydrogen, alkyl, arylalkyl, alkenyl, alkynyl, or phenyl which is optionally mono-, di-, or tri-substituted;h=0-1;j=0-1;m=0-6;n=0-6;p=0-10;q=0-10;r=0-6;with the proviso that R.sup.1 and R.sup.2 are not both hydrogen, or a pharmaceutically acceptable salt thereof which is useful for inducing immunosuppression; in the treatment of transplantation rejection, host vs. graft disease, autoimmune diseases, diseases of inflammation, solid tumors, fungal infections, adult T-cell leukemia/lymphoma, and hyperproliferative vascular disorders; for measuring levels of rapamycin; for isolating rapamycin-binding proteins; and detecting monoclonal antibodies specific for rapamycin or derivatives thereof.
摘要翻译：结构式I R1和R2的化合物各自独立地为氢或Y是Z，其中Z是-CH 2 - ，-SS-或者R 3是氢，烷基，芳基烷基，烯基，炔基， - （CH 2）q CO 2 R 5， - （CH 2）r NR 6 R 7，氨基甲酰基烷基，氨基烷基，羟基烷基，脒基烷基，巯基烷基，烷基硫代烷基，吲哚基甲基，羟基苯基甲基，咪唑基甲基，卤素，三氟甲基或苯基，二取代或三取代的; R4，R6和R7各自独立地为氢，烷基或芳基烷基; R5是氢，烷基，芳基烷基，烯基，炔基或任选被一或二或三取代的苯基; h = 0-1; j = 0-1; m = 0-6; n = 0-6; p = 0-10; q = 0-10; r = 0-6; 条件是R1和R2不同时为氢，或其药学上可接受的盐，可用于诱导免疫抑制; 在移植排斥反应的治疗中，宿主与移植物疾病，自身免疫疾病，炎症疾病，实体瘤，真菌感染，成人T细胞白血病/淋巴瘤和过度增殖性血管疾病; 用于测量雷帕霉素的含量; 用于分离雷帕霉素结合蛋白; 并检测对雷帕霉素或其衍生物特异性的单克隆抗体。

5. 发明授权

US07045532B2 ACE-2 modulating compounds and methods of use thereof 失效
标题翻译： ACE-2调节化合物及其使用方法
公开(公告)号：US07045532B2
公开(公告)日：2006-05-16
申请号：US09999781
申请日：2001-10-31
申请人： Susan L. Acton , Timothy D. Ocain , Alexandra E. Gould , Natalie A. Dales , Bing Guan , James A. Brown , Michael Patane , Vivek J. Kadambi , Michael Solomon , Alain Stricker-Krongrad
发明人： Susan L. Acton , Timothy D. Ocain , Alexandra E. Gould , Natalie A. Dales , Bing Guan , James A. Brown , Michael Patane , Vivek J. Kadambi , Michael Solomon , Alain Stricker-Krongrad
IPC分类号： A61K31/194 , A61K31/198 , A61K31/39 , A61K31/415 , A61K31/4172
CPC分类号： C07D231/12 , A61K31/00 , A61K31/195 , A61K31/196 , A61K31/341 , A61K31/36 , A61K31/381 , A61K31/40 , A61K31/4035 , A61K31/4164 , A61K31/42 , A61K31/421 , A61K31/422 , A61K31/426 , A61K31/433 , A61K31/44 , A61K31/4439 , C07B2200/07 , C07C229/16 , C07C229/24 , C07C229/26 , C07C229/36 , C07C271/20 , C07C275/24 , C07C323/52 , C07C323/58 , C07C2601/02 , C07C2601/14 , C07D209/20 , C07D213/55 , C07D233/64 , C07D235/16 , C07D249/08 , C07D261/08 , C07D277/06 , C07D277/30 , C07D277/40 , C07D277/42 , C07D333/24 , C07D405/06 , C07K16/40
摘要： ACE-2 inhibitors for the treatment of body weight and related disorders are disclosed. ACE-2 inhibitors include peptides and small molecules. Examples of small molecule ACE-2 inhibitors include compounds of formula (I): Z-Λ (I) Wherein Z is a zinc coordinating moiety and Λ is an amino-acid mimicking moiety, and pharmaceutically acceptabale salts thereof. Methods of using the inhibitors and pharmaceutical compositions containing the inhibitors to treat a body weight disorder, to decrease appetite, to increase muscle mass, to decrease body fat, to treat diabetes and to treat a state associated with altered lipid metabolism, are also described.
摘要翻译：公开了用于治疗体重和相关疾病的ACE-2抑制剂。 ACE-2抑制剂包括肽和小分子。小分子ACE-2抑制剂的实例包括式（I）的化合物：<？in-line-formula description =“In-line formula”end =“lead”？> Z-Lambda（I） formula description =“In-line Formulas”end =“tail”？>其中Z是锌配位部分，Lambda是氨基酸模拟部分及其药学上可接受的盐。还描述了使用抑制剂和含有抑制剂的药物组合物治疗体重紊乱，降低食欲，增加肌肉量，降低体脂肪，治疗糖尿病和治疗与脂质代谢改变相关的状态的方法。

6. 发明授权

US5095119A Renin inhibitors 失效
标题翻译：肾素抑制剂
公开(公告)号：US5095119A
公开(公告)日：1992-03-10
申请号：US614881
申请日：1990-11-16
申请人： Timothy D. Ocain , David D. Deininger
发明人： Timothy D. Ocain , David D. Deininger
IPC分类号： C07D207/26 , C07D207/27 , C07D209/46 , C07D209/48 , C07D221/14 , C07D263/22 , C07D403/12 , C07D471/04 , C07D487/04
CPC分类号： C07D207/27 , C07D209/46 , C07D209/48 , C07D221/14 , C07D263/22 , C07D403/12 , C07D471/04 , C07D487/04
摘要： A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alkyl, phenyl, benzyl or phenethyl; Y is --CH.sub.2--, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.
摘要翻译：下式的化合物：其中A是其中X是= CH-或= N-的 R2是氢，烷基，苯基，苄基或苯乙基; Y是-CH 2 - ， - NH-或-O-; Z为-H2或= O; B是His，Leu，Ile，Nva，Nle，Ala或Val; 且R 1为氢，烷基，苯基或苯基烷基; 或其药学上可接受的盐是肾素抑制剂。

7. 发明授权

US06541612B2 Monoclonal antibodies obtained using rapamycin position 27 conjugates as an immunogen 失效
标题翻译：使用雷帕霉素27位缀合物作为免疫原获得的单克隆抗体
公开(公告)号：US06541612B2
公开(公告)日：2003-04-01
申请号：US09773562
申请日：2001-02-02
申请人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain , Amadeo A. Failli
发明人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain , Amadeo A. Failli
IPC分类号： C07K1644
CPC分类号： G01N33/533 , A61K31/435 , A61K47/643 , A61K47/6835
摘要： Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin or a derivative thereof, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides monoclonal antibodies specific for rapamycin or a ring opened derivative of rapamycin.
摘要翻译：提供雷帕霉素缀合物，其可用作产生雷帕霉素或其衍生物特异性抗体的免疫原性分子，用于测量雷帕霉素或其衍生物的水平; 用于分离雷帕霉素结合蛋白; 并检测对雷帕霉素或其衍生物特异的抗体。本发明还提供对雷帕霉素特异性的单克隆抗体或雷帕霉素的开环衍生物。

8. 发明授权

US5708022A Method for inhibiting immune response 失效
标题翻译：抑制免疫反应的方法
公开(公告)号：US5708022A
公开(公告)日：1998-01-13
申请号：US482308
申请日：1995-06-07
申请人： Cecilia M. Bastos , Timothy D. Ocain
发明人： Cecilia M. Bastos , Timothy D. Ocain
IPC分类号： C07F15/00 , A61K31/28
CPC分类号： C07F15/0053
摘要： Use of ruthenium complexes as immunosuppressive agents to prevent or significantly reduce graft rejection in organ and bone marrow transplantation is described. The ruthenium complexes can also be used as immunosuppressant drugs for T-lymphocyte mediated autoimmune diseases, such as diabetes, and may be useful in alleviating psoriasis and contact dermatitis. The ruthenium complexes can also be used therapeutically in the treatment of hyperproliferative vascular disease.
摘要翻译：描述了使用钌络合物作为免疫抑制剂以预防或显着降低器官和骨髓移植中的移植排斥反应。钌络合物也可用作T淋巴细胞介导的自身免疫疾病如糖尿病的免疫抑制药物，可用于缓解牛皮癣和接触性皮炎。钌络合物也可用于治疗过度增生性血管疾病。

9. 发明授权

US5075451A Pyrrolimidazolones useful as renin inhibitors 失效
标题翻译：可用作肾素抑制剂的吡咯咪唑酮
公开(公告)号：US5075451A
公开(公告)日：1991-12-24
申请号：US614363
申请日：1990-11-16
申请人： Timothy D. Ocain , David D. Deininger
发明人： Timothy D. Ocain , David D. Deininger
IPC分类号： C07D207/26 , C07D207/27 , C07D209/46 , C07D209/48 , C07D221/14 , C07D263/22 , C07D403/12 , C07D471/04 , C07D487/04
CPC分类号： C07D207/27 , C07D209/46 , C07D209/48 , C07D221/14 , C07D263/22 , C07D403/12 , C07D471/04 , C07D487/04
摘要： A compound of the formula: ##STR1## wherein A is ##STR2## in which X is .dbd.CH-- or .dbd.N--; R.sup.2 is hydrogen, alkyl, phenyl, benzyl or phenethyl; Y is --CH.sub.2 --, --NH-- or --O--; and Z is --H.sub.2 or .dbd.O; B is His, Leu, Ile, Nva, Nle, Ala or Val; and R.sup.1 is hydrogen, alkyl, phenyl or phenylalkyl; or a pharmaceutically acceptable salt thereof are renin inhibitors.
摘要翻译：下式的化合物：其中A是其中X是= CH-或= N-的 R2是氢，烷基，苯基，苄基或苯乙基; Y是-CH 2 - ， - NH-或-O-; Z为-H2或= O; B是His，Leu，Ile，Nva，Nle，Ala或Val; 且R 1为氢，烷基，苯基或苯基烷基; 或其药学上可接受的盐是肾素抑制剂。

10. 发明授权

US07279561B1 Anti-rapamycin monoclonal antibodies 失效
标题翻译：抗雷帕霉素单克隆抗体
公开(公告)号：US07279561B1
公开(公告)日：2007-10-09
申请号：US09576951
申请日：2000-05-24
申请人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain
发明人： Katherine L. Molnar-Kimber , Craig E. Caufield , Timothy D. Ocain
IPC分类号： C07K16/00 , C07K1/10 , C07K1/13 , C12N5/12 , C12P21/08
CPC分类号： C07K16/14 , A61K31/435 , A61K47/643 , A61K47/6835 , C07K16/1292 , C12N9/0065 , G01N33/533 , G01N33/9446 , Y10S530/809
摘要： Provided are rapamycin conjugates which are useful as immunogenic molecules for the generation of antibodies specific for rapamycin, for measuring levels of rapamycin or derivatives thereof; for isolating rapamycin binding proteins; and detecting antibodies specific for rapamycin or derivatives thereof. This invention also provides a rapamycin specific monclonal antibody.
摘要翻译：提供的雷帕霉素缀合物可用作产生雷帕霉素特异性抗体的免疫原性分子，用于测量雷帕霉素或其衍生物的水平; 用于分离雷帕霉素结合蛋白; 并检测对雷帕霉素或其衍生物特异的抗体。本发明还提供雷帕霉素特异性单克隆抗体。

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