公开(公告)号：US5830911A

公开(公告)日：1998-11-03

申请号：US906361

申请日：1997-08-05

申请人： Amedeo A. Failli ,  Robert J. Steffan ,  Anthony F. Kreft ,  Thomas J. Caggiano ,  Craig E. Caufield

发明人： Amedeo A. Failli ,  Robert J. Steffan ,  Anthony F. Kreft ,  Thomas J. Caggiano ,  Craig E. Caufield

IPC分类号： C07D209/88 ,  C07D491/04 ,  A61K31/40 ,  C07D209/86

CPC分类号： C07D491/04 ,  C07D209/88

摘要： This invention provides compounds of formula I having the structure ##STR1## wherein R is (CH.sub.2).sub.n COOR.sup.4 ; R.sup.1 is hydrogen, alkyl, alkenyl, alkynyl, alkylcycloalkyl, and alkoxyalkyl; R.sup.4 is hydrogen or alkyl; R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, arylalkoxy, fluoroalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, nitro, --SCF.sub.3, --COR.sup.3, alkanoyloxy, hydroxy, trifluoromethyl, amino, alkylamino, dialkylamino, alkylamido, or alkylsulfonamido; wherein at least one of R.sup.5, R.sup.6, R.sup.7, or R.sup.8 is cyano; R.sup.3 is alkyl, hydroxy, alkoxy, amino, alkylamino; X is --O-- or --C--; and n=1-4 or a pharmaceutically acceptable salt thereof, which are useful in the treatment of arthritic disorders, colorectal cancer, and Alzheimer's disease.

摘要翻译： 本发明提供具有结构图1的式I化合物，其中R是（CH 2）n COOR 4; R1是氢，烷基，烯基，炔基，烷基环烷基和烷氧基烷基; R4是氢或烷基; R5，R6，R7和R8各自独立地为氢，卤素，烷基，烯基，炔基，烷氧基，芳基烷氧基，氟烷氧基，烷硫基，烷基亚磺酰基，烷基磺酰基，氰基，硝基，-SCF3，-COR3，烷酰氧基，羟基， ，氨基，烷基氨基，二烷基氨基，烷基酰氨基或烷基磺酰氨基; 其中R 5，R 6，R 7或R 8中的至少一个为氰基; R3是烷基，羟基，烷氧基，氨基，烷基氨基; X是-O-或-C-; 和n = 1-4或其药学上可接受的盐，其可用于治疗关节炎疾病，结肠直肠癌和阿尔茨海默氏病。

公开(公告)号：US5439590A

公开(公告)日：1995-08-08

申请号：US68116

申请日：1993-05-25

申请人： Robert J. Steffan

发明人： Robert J. Steffan

IPC分类号： C02F1/00 ,  C02F1/28 ,  C02F3/10 ,  C02F3/06

CPC分类号： C02F3/10 ,  C02F1/283 ,  C02F1/285 ,  C02F2101/322 ,  C02F2101/36 ,  Y02W10/15 ,  Y10S210/908

摘要： The present invention features methods and apparatus for processing waste material held in an aqueous medium. A sorbent is added to the aqueous medium. The sorbent reduces the effective concentration of waste material allowing biodegration of the waste material in solution. A preferred sorbent is rubber derived from ground or shredded tires.

摘要翻译： 本发明的特征在于用于处理保持在水性介质中的废料的方法和装置。 将吸附剂加入到水性介质中。 吸附剂降低废料的有效浓度，使废料在溶液中生物降解。 优选的吸附剂是来自磨碎或切碎轮胎的橡胶。

公开(公告)号：US5389639A

公开(公告)日：1995-02-14

申请号：US174120

申请日：1993-12-29

申请人： Amedeo A. Failli ,  Robert J. Steffan

发明人： Amedeo A. Failli ,  Robert J. Steffan

IPC分类号： A61K31/435 ,  A61P37/06 ,  C07D498/18 ,  A61K31/445 ,  C07D487/04

CPC分类号： C07D498/18

摘要： This invention provides a compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or ##STR2## R.sup.3 is --(CH.sub.2).sub.q CO.sub.2 R.sup.6 ;R.sup.4 is hydrogen, alkyl, or arylalkyl;R.sup.5 is hydrogen or COOR.sup.7 ;R.sup.6 is hydrogen, alkyl, alkenyl, arylalkyl, fluorenylmethyl, or phenyl which is optionally substituted;R.sup.7 is alkyl, alkenyl, arylalkyl, fluorenylmethyl, or phenyl which is optionally substituted;m is 0-4;n is 0-4;p is 1-2;q is 0-4;wherein R.sup.3, R.sup.4, m, and n are independent in each of the ##STR3## subunits when p=2; with the proviso that R.sup.1 and R.sup.2 are not both hydrogen; and further provided that if R.sup.5 is CO.sub.2 R.sup.7, then R.sup.6 is hydrogen; and still further provided that if R.sup.6 is not hydrogen, then R.sup.5 is hydrogen;or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.

摘要翻译： 本发明提供了一种结构化合物，其中R 1和R 2各自独立地为氢或R 3为 - （CH 2）q CO 2 R 6; R4是氢，烷基或芳烷基; R5是氢或COOR7; R6是氢，烷基，烯基，芳烷基，芴基甲基或任选取代的苯基; R 7是烷基，烯基，芳烷基，芴基甲基或任选被取代的苯基; m为0-4; n为0-4; p是1-2; q为0-4; 当p = 2时，R 3，R 4，m和n在每个亚基中是独立的; 条件是R1和R2不同时为氢; 并且进一步规定如果R 5是CO 2 R 7，那么R 6是氢; 并且还进一步规定，如果R6不是氢，则R5是氢; 或其药学上可接受的盐，其可用作免疫抑制，抗炎，抗真菌，抗增殖和抗肿瘤剂。

公开(公告)号：US5120842B1

公开(公告)日：1993-07-06

申请号：US67838091

申请日：1991-04-01

申请人： AMEDEO A FAILLI ,  ROBERT J STEFFAN

发明人： AMEDEO A FAILLI ,  ROBERT J STEFFAN

IPC分类号： A61K31/695 ,  A61P29/00 ,  A61P31/04 ,  A61P31/10 ,  A61P35/00 ,  A61P37/06 ,  C07F7/18 ,  A61K31/395 ,  C07D491/16

CPC分类号： C07F7/1856

摘要： The invention provides compounds of structure wherein R is -SiR R R ; R is hydrogen , -SiR R R or acyl; and R , R and R are each, independently, alkyl, alkenyl, aralkyl, triphenylmethyl, or phenyl which by virtue of its of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases and diseases of inflammation; by virtue of its antitumor activity is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections. This invention also provides a method of using rapamycin 42- silyl ethers for the preparation of 31-substiuted rapamycin derivatives.

公开(公告)号：US07592363B2

公开(公告)日：2009-09-22

申请号：US11194263

申请日：2005-08-01

申请人： Robert J. Steffan ,  Edward M. Matelan ,  Stephen M. Bowen ,  John W. Ullrich ,  Jay E. Wrobel ,  Edouard Zamaratski ,  Lars Kruger ,  Annabel L. Olsen Hedemyr ,  Aiping Cheng ,  Tomas Hansson ,  Rayomand J. Unwalla ,  Christopher P. Miller ,  Patrik P. Rhönnstad

发明人： Robert J. Steffan ,  Edward M. Matelan ,  Stephen M. Bowen ,  John W. Ullrich ,  Jay E. Wrobel ,  Edouard Zamaratski ,  Lars Kruger ,  Annabel L. Olsen Hedemyr ,  Aiping Cheng ,  Tomas Hansson ,  Rayomand J. Unwalla ,  Christopher P. Miller ,  Patrik P. Rhönnstad

IPC分类号： A61K31/4162 ,  C07D231/56

CPC分类号： C07D403/04 ,  C07D231/56 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D403/10 ,  C07D405/04 ,  C07D409/04 ,  C07D491/10

摘要： This invention provides compounds of Formula (I) or (Ia): that are useful in the treatment or inhibition of LXR mediated diseases.

摘要翻译： 本发明提供式（I）或（Ia）化合物：其可用于治疗或抑制LXR介导的疾病。

公开(公告)号：US06455566B1

公开(公告)日：2002-09-24

申请号：US09145909

申请日：1998-09-02

申请人： Robert J. Steffan ,  Amedeo A. Failli

发明人： Robert J. Steffan ,  Amedeo A. Failli

IPC分类号： A61K31415

CPC分类号： C07D275/03 ,  A61K31/415 ,  C07D231/40 ,  C07D263/48 ,  C07D277/48 ,  C07D277/82 ,  C07D277/84 ,  C07D285/135

摘要： Antiatherosclerotic agents are provided which are represented by Formulas I or II: wherein R is  wherein R9, R10, R11, R12, R13, and R14 are each, independently, hydrogen or a lower alkyl of 1-6 carbon atoms; R6, and R7 are each, independently, hydrogen, lower alkyl of 1-6 carbon atoms, or CH2COOR8, where R8 is a lower alkyl of 1-6 carbon atoms; and X is O or S; R1 is hydrogen or a lower alkyl of 1-6 carbon atoms; R2, R3, and R4 are each, independently, hydrogen or halogen; and R5 is a lower alkyl of 1-6 carbon atoms; or a pharmaceutically acceptable salt thereof.

摘要翻译： 提供由式I或II表示的抗动脉粥样硬化剂：其中R是其中R 9，R 10，R 11，R 12，R 13和R 14各自独立地是氢或1-6个碳原子的低级烷基; R 6和R 7是 各自独立地为氢，1-6个碳原子的低级烷基或CH2COOR8，其中R8是1-6个碳原子的低级烷基; 且X为O或S; R 1为氢或1-6个碳原子的低级烷基; R 2，R 3和R 4各自独立地为氢或卤素; 和R 5是1-6个碳原子的低级烷基;或其药学上可接受的盐。

公开(公告)号：US06344451B1

公开(公告)日：2002-02-05

申请号：US09495506

申请日：2000-02-01

申请人： Robert J. Steffan ,  Amedeo A. Failli

发明人： Robert J. Steffan ,  Amedeo A. Failli

IPC分类号： A61K3155

CPC分类号： C07D487/14 ,  A61K31/551

摘要： The present invention provides compounds of the formula: wherein: X, Y and Z are independently selected from O, S, CH, CH2, N, or NR4; W is moiety selected from (CH2)n; n=1-2; R1, R2 are independently, hydrogen, straight chain alkyl (C1-C6), branched chain alkyl (C3-C7), cycloalkyl (C3-C7), alkoxyalkyl (C2-C7), halogen, straight or branched chain alkoxy (C1-C6), hydroxy, CF3, or perfluoroalkyl (C2-C6); R3 is hydrogen or a straight chain alkyl group (C1-C6), branched chain alkyl (C3-C7), cycloalkyl (C3-C7), alkoxyalkyl (C2-C7), or hydroxyalkyl (C1-C6); R4 is selected from hydrogen, or (lower alkyl (C1-C6); and R5 is selected from halogen or hydrogen; or a pharmaceutically acceptable salt thereof: as well as methods and pharmaceutical compositions utilizing these compounds for the treatment of disorder which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination.

摘要翻译： 本发明提供下式的化合物：其中：X，Y和Z独立地选自O，S，CH，CH 2，N或NR 4; W是选自（CH 2）n; n = 1-2; R 1 ，R2独立地为氢，直链烷基（C1-C6），支链烷基（C3-C7），环烷基（C3-C7），烷氧基烷基（C2-C7），卤素，直链或支链烷氧基（C1-C6 ），羟基，CF 3或全氟烷基（C 2 -C 6）; R 3是氢或直链烷基（C 1 -C 6），支链烷基（C 3 -C 7），环烷基（C 3 -C 7） ）或羟基烷基（C 1 -C 6）; R 4选自氢或（低级烷基（C 1 -C 6））;和R 5选自卤素或氢;或其药学上可接受的盐：以及利用它们的方法和药物组合物 用于治疗可通过加压素激动剂活性治疗或减轻的疾病的化合物，包括尿崩症，夜间遗尿，夜尿症，尿失禁，出血和凝血障碍或暂时性 排尿迟缓。

公开(公告)号：US6011053A

公开(公告)日：2000-01-04

申请号：US145942

申请日：1998-09-02

申请人： Robert J. Steffan ,  Amedeo A. Failli

发明人： Robert J. Steffan ,  Amedeo A. Failli

IPC分类号： A61K31/404 ,  A61K31/4155 ,  C07D209/08 ,  C07D403/12 ,  A61K31/40 ,  A61K31/415

CPC分类号： C07D403/12 ,  A61K31/404 ,  A61K31/4155 ,  C07D209/08

摘要： Antiatherosclerotic agents are provided having the structure: ##STR1## wherein R is a lower alkyl of 1-6 carbon atoms, ##STR2## wherein R.sub.5, R.sub.6, and R.sub.7 are lower alkyl of 1-6 carbon atoms; and R.sub.8, R.sub.9 and R.sub.10 are each, independently, hydrogen or halogen;R.sub.1 and R.sub.2 are each, independently, hydrogen or a lower alkyl of 1-6 carbon atoms; andR.sub.3 and R.sub.4 are each, independently, hydrogen, a lower alkyl of 1-6 carbon atoms or halogen;or a pharmaceutically acceptable salt thereof.

摘要翻译： 提供具有以下结构的抗动脉粥样硬化剂：其中R是1-6个碳原子的低级烷基，其中R5，R6和R7是1-6个碳原子的低级烷基; 并且R 8，R 9和R 10各自独立地为氢或卤素; R1和R2各自独立地为氢或1-6个碳原子的低级烷基; 并且R 3和R 4各自独立地为氢，1-6个碳原子的低级烷基或卤素; 或其药学上可接受的盐。

公开(公告)号：US5446048A

公开(公告)日：1995-08-29

申请号：US309816

申请日：1994-09-21

申请人： Amedeo A. Failli ,  Robert J. Steffan ,  Craig E. Caufield ,  David C. Hu ,  Alexander A. Grinfeld

发明人： Amedeo A. Failli ,  Robert J. Steffan ,  Craig E. Caufield ,  David C. Hu ,  Alexander A. Grinfeld

IPC分类号： C07D498/18 ,  A61K31/44

CPC分类号： C07D498/18

摘要： A compound of the structure ##STR1## wherein R.sup.1 is ##STR2## R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or --CO.sub.2 R.sup.8 ;R.sup.4 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, aminoalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, or --CO.sub.2 R.sup.8 ;R.sup.5 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, or --CO.sub.2 R.sup.8 ;R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.7 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, fluorenylmethyl, or Ar;Y is O or S;X is .dbd.N--O--(CH.sub.2).sub.f --Z or .dbd.N--O--Ar;Z is hydrogen, alkenyl, alkynyl, alkoxy, cyano, fluoro, trifluoromethyl, --NR.sup.5 R.sup.6, aryloxy, or Ar;Ar is aryl which may be optionally mono-, di-, or tri-substituted;a=0-4;b=0-1;c=0-4;d=0-6;e=0-6; andf=0-6;or a pharmaceutically acceptable salt thereof, with the proviso that when f is 0, Z is hydrogen and further provided that when R.sup.3 or R.sup.5 is --CO.sub.2 R.sup.8, R.sup.8 is not hydrogen which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.

摘要翻译： 其中R1是氢，烷基，烯基，炔基，三氟甲基，芳基烷基或Ar的结构化合物 R3是氢，烷基，烯基，炔基，三氟甲基，芳烷基或-CO2R8; R4是烷基，烯基，炔基，三氟甲基，芳基烷基，Ar，氨基烷基，硫代烷基，烷硫基烷基，羟基烷基或-CO 2 R 8; R5是氢，烷基，烯基，炔基，三氟甲基，芳基烷基，Ar或-CO 2 R 8; R6是氢，烷基，烯基，炔基，三氟甲基，芳烷基或Ar; R7是烷基，烯基，炔基，三氟甲基，芳烷基或Ar; R8是氢，烷基，烯基，炔基，三氟甲基，芳基烷基，芴基甲基或Ar; Y为O或S; X = N-O-（CH 2）f-Z或= N-O-Ar; Z是氢，烯基，炔基，烷氧基，氰基，氟，三氟甲基，-NR5R6，芳氧基或Ar; Ar是可任选被单，二或三取代的芳基; a = 0-4; b = 0-1; c = 0-4; d = 0-6; e = 0-6; 和f = 0-6; 或其药学上可接受的盐，条件是当f为0时，Z为氢，并且还提供当R3或R5为-CO2R8时，R8不为氢，可用作免疫抑制，抗炎，抗真菌，抗增殖和抗肿瘤 代理商

公开(公告)号：US5346893A

公开(公告)日：1994-09-13

申请号：US65107

申请日：1993-05-19

申请人： Amedeo Failli ,  Wenling Kao ,  Robert J. Steffan ,  Robert L. Vogel

发明人： Amedeo Failli ,  Wenling Kao ,  Robert J. Steffan ,  Robert L. Vogel

IPC分类号： C07D498/18 ,  A61K31/395 ,  C07D491/06

CPC分类号： C07D498/18

摘要： The invention concerns compounds of formula (I) ##STR1## where R.sup.1 is alkyl, haloalkyl, alkenyl, or alkynyl containing 1 to 6 carbon atoms; or an aromatic moiety selected from phenyl, naphthyl and 4-(phenylaza) phenyl wherein said aromatic group is optionally substituted by one or more substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, hydroxy, amino, mono- or di-(C.sub.1 -C.sub.6)alkylamino, carboxy, (C.sub.1 -C.sub.6 alkoxy)carbonyl, C.sub.2 -C.sub.7 alkanoyl, (C.sub.1 -C.sub.6) thioalkyl, halo, cyano, nitro, trifuluoromethyl, trifluoromethoxy or R.sup.1 is a heteroaromatic group of 5 to 10 ring atoms containing oxygen, nitrogen and/or sulfur as heteroatom(s) wherein said heteroaromatic group is optionally substituted by one or more substituents selected form C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, hydroxy, amino, mono- or di-(C.sub.1 -C.sub.6)alkylamino, carboxy, (C.sub.1 -C.sub.6 alkoxy)carbonyl, C.sub.2 -C.sub.7 alkanoyl, (C.sub.1 -C.sub.6) thioalkyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy or R.sup.1 is NHCO.sub.2 R.sup.2 wherein R.sup.2 is lower alkyl containing 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof, which compounds are useful in the treatment of transplantation rejection, host versus graft disease, autoimmune diseases and diseases of inflammation.

摘要翻译： 本发明涉及式（I）的化合物：其中R 1是含有1至6个碳原子的烷基，卤代烷基，烯基或炔基; 或选自苯基，萘基和4-（苯基苯基）苯基的芳族部分，其中所述芳族基团任选被一个或多个选自C 1 -C 6烷基，C 1 -C 6烷氧基，羟基，氨基，单 - 或二 - C1-C6）烷基氨基，羧基，（C1-C6烷氧基）羰基，C2-C7烷酰基，（C1-C6）硫代烷基，卤素，氰基，硝基，三氟甲基，三氟甲氧基或R1是含有5-10个环原子的杂芳族基团 氧，氮和/或硫作为杂原子，其中所述杂芳基任选被一个或多个选自C 1 -C 6烷基，C 1 -C 6烷氧基，羟基，氨基，单 - 或二 - （C 1 -C 6） 烷基氨基，羧基，（C1-C6烷氧基）羰基，C2-C7烷酰基，（C1-C6）硫代烷基，卤素，氰基，硝基，三氟甲基，三氟甲氧基或R1是NHCO2R2，其中R2是含有1至6个碳原子的低级烷基; 或其药学上可接受的盐，该化合物可用于治疗移植排斥反应，宿主与移植物疾病，自身免疫疾病和炎症疾病。