公开(公告)号：US08598354B2

公开(公告)日：2013-12-03

申请号：US13153350

申请日：2011-06-03

Applicant: Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen ,  Jeremy Burrows ,  Dennis Kyle ,  Roman Manetsch ,  Richard M. Cross ,  Andrii Monastyrskyi ,  David L. Flanigan

Inventor： Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen ,  Jeremy Burrows ,  Dennis Kyle ,  Roman Manetsch ,  Richard M. Cross ,  Andrii Monastyrskyi ,  David L. Flanigan

IPC: C07D215/233 ,  A61K31/47 ,  A61P31/00 ,  A61P33/00 ,  A61P33/02 ,  A61P33/06

CPC classification number: C07D215/233 ,  C07D215/42 ,  C07D215/60 ,  C07D239/90 ,  C07D279/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D413/04 ,  C07D491/052

Abstract: Compounds of formula I: or formula II: or a pharmaceutically acceptable salt of formula I or formula II, wherein: R1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl; R2 is methyl or haloalkyl; R4 is hydroxyl, carbonyloxy, or carbonyldioxy; and R3 is aliphatic, aryl, aralkyl, or alkylaryl; and R5, R6, R7 and R8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO2R10, wherein R10 is H, alkyl, amino or haloalkyl; provided that in formula I, R5 and R7 are not both H or R6 is not H or methoxy; and in formula II that if R4 is carbonyldioxy then R7 is not methoxy.

Abstract translation: 式I化合物或式II化合物或式I或式II的药学上可接受的盐，其中：R 1是H，羟基，烷氧基，酰基，烷基，环烷基，芳基或杂芳基; R2是甲基或卤代烷基; R4是羟基，羰基氧基或羰基二氧基; 并且R 3是脂族，芳基，芳烷基或烷基芳基; 和R 5，R 6，R 7和R 8各自独立地为H，卤素，烷氧基，烷基，卤代烷基，芳基，硝基，氰基，氨基，酰胺基，酰基，羧基，取代的羧基或-SO 2 R 10，其中R 10为H，烷基，氨基 或卤代烷基; 条件是在式Ⅰ中，R5和R7不同时为H或R6不为H或甲氧基; 在式II中，如果R 4是羰基二氧基，那么R 7不是甲氧基。

公开(公告)号：US07829578B1

公开(公告)日：2010-11-09

申请号：US11633509

申请日：2006-12-05

Applicant: Michael K. Riscoe ,  Rolf W. Winter ,  Jane X. Kelly ,  Martin J. Smilkstein ,  David J. Hinrichs

Inventor： Michael K. Riscoe ,  Rolf W. Winter ,  Jane X. Kelly ,  Martin J. Smilkstein ,  David J. Hinrichs

IPC: C07D215/38 ,  A61K31/04

CPC classification number: A61K31/4706 ,  A61K31/04 ,  A61K31/44 ,  A61K45/06 ,  C07D213/68 ,  C07D215/233 ,  C07D221/08 ,  C07D311/86 ,  Y02A50/411 ,  A61K2300/00

Abstract: Aromatic ketones having an extended fluoro-alkyl or fluoro-alkoxy moiety are disclosed. In particular aspects, the compounds comprise substituted 9-acridone, 9-xanthone, 4(1H)-quinolone, 4(1H) pyridone, 1,4-naphthoquinone, 9,10-anthraquinone derivatives. These preparations possess potent pharmacological activity for inhibiting malaria and mosquito-borne (Plasmodium) diseases. The haloalkyl/alkoxy aromatic compounds possess significant pharmacological activity, with IC50 values in the nanomolar and sub-nanomolar range, and reduced toxicity against host derived cells and tissues. Methods of using the fluoro-alkyl/alkoxy aromatic compounds in the treatment of malaria and other human and animal diseases are also disclosed. Agricultural uses of the fluoro-alkyl/alkoxy aromatic compounds, such as in control of fungal diseases and in the production of important commercial crops (apples, etc.), are also presented.

Abstract translation: 公开了具有延伸的氟烷基或氟 - 烷氧基部分的芳族酮。 在特定方面，化合物包括取代的9-吖啶酮，9-呫吨酮，4（1H） - 喹诺酮，4（1H）吡啶酮，1,4-萘醌，9,10-蒽醌衍生物。 这些制剂具有有效的药理活性，可用于抑制疟疾和蚊子（疟原虫）疾病。 卤代烷基/烷氧基芳族化合物具有显着的药理活性，IC50值在纳摩尔和亚纳摩尔范围内，对宿主衍生的细胞和组织的毒性降低。 还公开了使用氟 - 烷基/烷氧基芳族化合物治疗疟疾和其他人和动物疾病的方法。 还介绍了氟 - 烷基/烷氧基芳族化合物的农业用途，如控制真菌病和重要的商业作物（苹果等）的生产。

公开(公告)号：US20100069428A1

公开(公告)日：2010-03-18

申请号：US12312503

申请日：2007-11-13

Applicant: Michael K. Riscoe ,  Rolf Winter ,  Jane X. Kelly ,  David J. Hinrichs ,  Martin J. Smilkstein

Inventor： Michael K. Riscoe ,  Rolf Winter ,  Jane X. Kelly ,  David J. Hinrichs ,  Martin J. Smilkstein

IPC: A61K31/473 ,  C07D219/06 ,  A61P33/06

CPC classification number: C07D219/14 ,  A61K31/4706 ,  A61K31/473 ,  C07D219/06 ,  C07D401/06 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/414 ,  Y02A50/423 ,  Y02A50/491

Abstract: A class of acridone compounds has been discovered that exhibits chemosensitizing and antiparasitic activity. Described herein are pharmaceutical compositions and methods for their use to treat parasitic infections, such as malaria and toxoplasmosis, and to sensitize resistant cells, such as multidrug resistant cells to other therapeutic agents. The pharmaceutical compositions and methods may also be used to treat and/or prevent psychotic diseases such as schizophrenia.

Abstract translation: 已经发现一类具有化学敏感性和抗寄生虫活性的吖啶酮化合物。 本文描述了用于治疗寄生虫感染如疟疾和弓形虫病的药物组合物和方法，并使抗药性细胞（例如多药耐药性细胞）对其它治疗剂敏感。 药物组合物和方法也可用于治疗和/或预防精神病如精神分裂症。

公开(公告)号：US08592447B2

公开(公告)日：2013-11-26

申请号：US12312503

申请日：2007-11-13

Applicant: Michael K. Riscoe ,  Rolf Winter ,  Jane X. Kelly ,  David J. Hinrichs ,  Martin J. Smilkstein

Inventor： Michael K. Riscoe ,  Rolf Winter ,  Jane X. Kelly ,  David J. Hinrichs ,  Martin J. Smilkstein

IPC: A61K31/44 ,  C07D219/04

CPC classification number: C07D219/14 ,  A61K31/4706 ,  A61K31/473 ,  C07D219/06 ,  C07D401/06 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/414 ,  Y02A50/423 ,  Y02A50/491

Abstract: A class of acridone compounds has been discovered that exhibits chemosensitizing and antiparasitic activity. Described herein are pharmaceutical compositions and methods for their use to treat parasitic infections, such as malaria and toxoplasmosis, and to sensitize resistant cells, such as multidrug resistant cells to other therapeutic agents. The pharmaceutical compositions and methods may also be used to treat and/or prevent psychotic diseases such as schizophrenia.

公开(公告)号：US20120115904A1

公开(公告)日：2012-05-10

申请号：US13153350

申请日：2011-06-03

Applicant: Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen ,  Jeremy Burrows ,  Dennis Kyle ,  Roman Manetsch ,  Richard M. Cross ,  Andrii Monastyrskyi ,  David L. Flanigan

Inventor： Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen ,  Jeremy Burrows ,  Dennis Kyle ,  Roman Manetsch ,  Richard M. Cross ,  Andrii Monastyrskyi ,  David L. Flanigan

IPC: A61K31/47 ,  A61P33/00 ,  A61P33/02 ,  A61P31/00 ,  C07D215/233 ,  A61P33/06

CPC classification number: C07D215/233 ,  C07D215/42 ,  C07D215/60 ,  C07D239/90 ,  C07D279/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D413/04 ,  C07D491/052

Abstract: Compounds of formula I: or formula II: or a pharmaceutically acceptable salt of formula I or formula II, wherein: R1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl; R2 is methyl or haloalkyl; R4 is hydroxyl, carbonyloxy, or carbonyldioxy; and R3 is aliphatic, aryl, aralkyl, or alkylaryl; and R5, R6, R7 and R8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO2R10, wherein R10 is H, alkyl, amino or haloalkyl; provided that in formula I, R5 and R are not both H or R6 is not H or methoxy; and in formula II that if R4 is carbonyldioxy then R7 is not methoxy.

Abstract translation: 式I化合物或式II化合物或式I或式II的药学上可接受的盐，其中：R 1是H，羟基，烷氧基，酰基，烷基，环烷基，芳基或杂芳基; R2是甲基或卤代烷基; R4是羟基，羰基氧基或羰基二氧基; 并且R 3是脂族，芳基，芳烷基或烷基芳基; 和R 5，R 6，R 7和R 8各自独立地为H，卤素，烷氧基，烷基，卤代烷基，芳基，硝基，氰基，氨基，酰胺基，酰基，羧基，取代的羧基或-SO 2 R 10，其中R 10为H，烷基，氨基 或卤代烷基; 条件是在式I中，R 5和R不同时为H或R 6不为H或甲氧基; 在式II中，如果R 4是羰基二氧基，那么R 7不是甲氧基。

公开(公告)号：US20120010237A1

公开(公告)日：2012-01-12

申请号：US13153347

申请日：2011-06-03

Applicant: Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen

Inventor： Michael K. Riscoe ,  Jane X. Kelly ,  Rolf W. Winter ,  David J. Hinrichs ,  Martin J. Smilkstein ,  Aaron Nilsen

IPC: A61K31/47 ,  A61P33/00

CPC classification number: C07D215/60 ,  C07D215/233 ,  C07D215/42 ,  C07D239/90 ,  C07D279/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D413/04 ,  C07D491/052

Abstract: A method for inhibiting a parasitic or infectious disease in a subject, wherein the parasitic or infectious disease is selected from one caused by Eimeria sp., Babesia sp., Theileria sp. or Neospora caninum, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I: or formula II: or a pharmaceutically acceptable salt of formula I or formula II, wherein: R1 is H, hydroxyl, alkoxy, acyl, alkyl, cycloalkyl, aryl, or heteroaryl; R2 is methyl, haloalkyl, or heteroaryl; R4 is hydroxyl, carbonyloxy, or carbonyldioxy; R3 is aliphatic, aryl, aralkyl, or alkylaryl; and R5, R6, R7 and R8 are each individually H, halogen, alkoxy, alkyl, haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, or —SO2R10, wherein R10 is H, alkyl, amino or haloalkyl; provided that in formula I, R5 and R7 are not H or R6 is not H or methoxy; and in formula II that if R4 is carbonyldioxy then R7 is not methoxy.

Abstract translation: 一种抑制受试者中寄生虫或感染性疾病的方法，其中寄生虫或感染性疾病选自艾美球虫（Eimeria sp。），巴贝虫属（Babesia sp。），The虫属 或新孢子虫（Neospora caninum），所述方法包括向受试者施用治疗有效量的式I或式II化合物或其药学上可接受的式I或式II的盐，其中：R 1是H，羟基，烷氧基，酰基， 烷基，环烷基，芳基或杂芳基; R2是甲基，卤代烷基或杂芳基; R4是羟基，羰基氧基或羰基二氧基; R3是脂族，芳基，芳烷基或烷基芳基; 和R 5，R 6，R 7和R 8各自独立地为H，卤素，烷氧基，烷基，卤代烷基，芳基，硝基，氰基，氨基，酰胺基，酰基，羧基，取代的羧基或-SO 2 R 10，其中R 10为H，烷基，氨基 或卤代烷基; 条件是在式I中，R 5和R 7不是H或R 6不是H或甲氧基; 在式II中，如果R 4是羰基二氧基，那么R 7不是甲氧基。