公开(公告)号：US20110286961A1

公开(公告)日：2011-11-24

申请号：US12957512

申请日：2010-12-01

申请人： Makonen Belema ,  Jeffrey Lee Romine ,  Van N. Nguyen ,  Gan Wang ,  Omar D. Lopez ,  Denis R. St. Laurent ,  Qi Chen ,  John A. Bender ,  Zhong Yang ,  Piyasena Hewawasam ,  Ningning Xu ,  Nicholas A. Meanwell ,  John A. Easter ,  Bao-Ning Su ,  Michael J. Smith

发明人： Makonen Belema ,  Jeffrey Lee Romine ,  Van N. Nguyen ,  Gan Wang ,  Omar D. Lopez ,  Denis R. St. Laurent ,  Qi Chen ,  John A. Bender ,  Zhong Yang ,  Piyasena Hewawasam ,  Ningning Xu ,  Nicholas A. Meanwell ,  John A. Easter ,  Bao-Ning Su ,  Michael J. Smith

IPC分类号： A61K31/4178 ,  C07D405/14 ,  A61K38/21 ,  A61P31/14 ,  A61K38/20 ,  A61K31/7088 ,  A61K31/4745 ,  C07D403/14 ,  A61K31/7056

CPC分类号： C07D403/14 ,  C07D405/14

摘要： The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

公开(公告)号：US07399758B2

公开(公告)日：2008-07-15

申请号：US11507731

申请日：2006-08-22

申请人： Nicholas A. Meanwell ,  Robert G. Gentles ,  Min Ding ,  John A. Bender ,  John F. Kadow ,  Piyasena Hewawasam ,  Thomas W. Hudyma ,  Xiaofan Zheng

发明人： Nicholas A. Meanwell ,  Robert G. Gentles ,  Min Ding ,  John A. Bender ,  John F. Kadow ,  Piyasena Hewawasam ,  Thomas W. Hudyma ,  Xiaofan Zheng

IPC分类号： A61P31/00 ,  A61K31/55 ,  C07D223/14

CPC分类号： C07D487/04

摘要： The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.

摘要翻译： 本发明包括式I的化合物，其药学上可接受的盐，组合物和使用该化合物的方法。 该化合物具有抗丙型肝炎病毒（HCV）的活性，可用于治疗HCV感染者。

公开(公告)号：US06271249B1

公开(公告)日：2001-08-07

申请号：US09538520

申请日：2000-03-29

申请人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

发明人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

IPC分类号： A61K31402

CPC分类号： C07D263/58 ,  C07D233/64 ,  C07D233/70 ,  C07D233/76 ,  C07D235/12 ,  C07D249/12 ,  C07D249/14 ,  C07D271/113 ,  C07D413/10

摘要： Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: wherein “Het” is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; Ra, Rb and Rc each are independently selected from hydrogen, halogen, OH, CF3, NO2, or provided Rc is not hydrogen; and when Ra and Rb are hydrogen, Rc may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol-2-yl, and pyridin-2-yl; Rd and Re each are independently selected from hydrogen, halogen, CF3, NO2 or imidazol-1-yl; m, n and p each are independently selected from an integer of 0 or 1; and Rf and Rg each are independently hydrogen; C1-4 alkyl; or Rf and Rg, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

摘要翻译： 式1的新型化合物可用于治疗对大电导钙激活钾通道的开放剂起反应的病症：其中“Het”是选择性杂环部分组之一; Z独立地选自O或S; R a，R b和R c各自独立地选自氢，卤素，OH，CF 3，NO 2，或提供的R c不是氢; 当R a和R b为氢时，R c可以是选自咪唑-1-基，吗啉代甲基，N-甲基咪唑-2-基和吡啶-2-基的杂环部分; Rd和Re各自独立地选自氢，卤素，CF 3，NO 2或咪唑-1-基; m，n和p各自独立地选自0或1的整数; Rf和Rg各自独立地为氢; C 1-4烷基 或R f和R g与它们所连接的氮原子一起是选自N-甲基哌嗪，吗啉，硫代吗啉，N-苄基哌嗪和咪唑啉酮的杂环部分。

公开(公告)号：US5602169A

公开(公告)日：1997-02-11

申请号：US635316

申请日：1996-04-19

申请人： Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff

发明人： Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P11/08 ,  A61P13/00 ,  A61P13/02 ,  A61P15/00 ,  A61P25/08 ,  A61P25/28 ,  C07D209/34 ,  C07D209/38 ,  C07D209/60 ,  C07D209/12

CPC分类号： C07D209/34 ,  C07D209/38 ,  C07D209/60

摘要： There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## whereinR is hydrogen, hydroxy or fluoro;R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl; or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.

摘要翻译： 提供了式（I）所示的新的取代的3-苯基羟吲哚衍生物，其中R是氢，羟基或氟; R 1，R 2，R 3和R 4各自独立地为氢，C 1-4烷基，卤素，三氟甲基，苯基，对甲基苯基或对三氟甲基苯基; 或R 1和R 2，R 2和R 3或R 3和R 4连接在一起形成苯并稠环; R5是氢或C1-4烷基; R6为氯或三氟甲基; 或其无毒的药学上可接受的盐，溶剂合物或水合物，其是大电导钙激活的钾通道的开放剂，并且可用于治疗对钾通道开放有反应的病症。

公开(公告)号：US08796466B2

公开(公告)日：2014-08-05

申请号：US12729940

申请日：2010-03-23

申请人： John A. Bender ,  Piyasena Hewawasam ,  John F. Kadow ,  Omar D. Lopez ,  Nicholas A. Meanwell ,  Van N. Nguyen ,  Jeffrey Lee Romine ,  Lawrence B. Snyder ,  Denis R. St. Laurent ,  Gan Wang ,  Ningning Xu ,  Makonen Belema

发明人： John A. Bender ,  Piyasena Hewawasam ,  John F. Kadow ,  Omar D. Lopez ,  Nicholas A. Meanwell ,  Van N. Nguyen ,  Jeffrey Lee Romine ,  Lawrence B. Snyder ,  Denis R. St. Laurent ,  Gan Wang ,  Ningning Xu ,  Makonen Belema

IPC分类号： A61K31/4178 ,  A61K31/4184 ,  A61P31/14 ,  C07D403/14 ,  C07D405/14

CPC分类号： C07D403/04 ,  C07D403/14 ,  C07D405/14

摘要： This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.

公开(公告)号：US06077861A

公开(公告)日：2000-06-20

申请号：US197887

申请日：1998-11-23

申请人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

发明人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

IPC分类号： C07D271/02 ,  A61K31/4164 ,  A61K31/4166 ,  A61K31/4196 ,  A61K31/4245 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/54 ,  C07D233/64 ,  C07D233/70 ,  C07D233/74 ,  C07D233/76 ,  C07D235/12 ,  C07D249/08 ,  C07D249/12 ,  C07D249/14 ,  C07D263/58 ,  C07D271/10 ,  C07D271/113 ,  C07D413/10

CPC分类号： C07D263/58 ,  C07D233/64 ,  C07D233/70 ,  C07D233/76 ,  C07D235/12 ,  C07D249/12 ,  C07D249/14 ,  C07D271/113 ,  C07D413/10

摘要： Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein "Het" is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, NO.sub.2, or ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol-2-yl, and pyridin-2-yl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

摘要翻译： 式1的新型化合物可用于治疗对大电导钙激活钾通道的开放剂起反应的病症：其中“Het”是选择性杂环部分组之一; Z独立地选自O或S; R a，R b和R c各自独立地选自氢，卤素，OH，CF 3，NO 2，或者R c不是氢; 当R a和R b为氢时，R c可以是选自咪唑-1-基，吗啉代甲基，N-甲基咪唑-2-基和吡啶-2-基的杂环部分; Rd和Re各自独立地选自氢，卤素，CF 3，NO 2或咪唑-1-基; m，n和p各自独立地选自O或1的整数; Rf和Rg各自独立地为氢; C 1-4烷基; 或R f和R g与它们所连接的氮原子一起是选自N-甲基哌嗪，吗啉，硫代吗啉，N-苄基哌嗪和咪唑啉酮的杂环部分。

公开(公告)号：US5565483A

公开(公告)日：1996-10-15

申请号：US477047

申请日：1995-06-07

申请人： Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff

发明人： Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff

IPC分类号： A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P11/08 ,  A61P13/00 ,  A61P13/02 ,  A61P15/00 ,  A61P25/08 ,  A61P25/28 ,  C07D209/34 ,  C07D209/38 ,  C07D209/60 ,  A61K31/405 ,  C07D209/12 ,  C07D209/90

CPC分类号： C07D209/34 ,  C07D209/38 ,  C07D209/60

摘要： There is provided novel substituted 3-phenyl oxindole derivatives of the formula ##STR1## wherein R is hydrogen, hydroxy or fluoro; R.sup.1, R.sup.2, R.sup.3and R.sup.4 each are independently hydrogen, C.sub.1-4 alkyl, halogen, trifluoromethyl, phenyl, p-methylphenyl or p-trifluoromethylphenyl; or R.sup.1 and R.sup.2, R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are joined together to form a benzo fused ring;R.sup.5 is hydrogen or C.sub.1-4 alkyl; andR.sup.6 is chlorine or trifluoromethyl;or a nontoxic pharmaceutically acceptable salt, solvate or hydrate thereof, which are openers of the large-conductance calcium-activated potassium channels and are useful in the treatment of disorders which are responsive to the opening of the potassium channels.

摘要翻译： 提供了式（I）所示的新的取代的3-苯基羟吲哚衍生物，其中R是氢，羟基或氟; R 1，R 2，R 3和R 4各自独立地为氢，C 1-4烷基，卤素，三氟甲基，苯基，对甲基苯基或对三氟甲基苯基; 或R 1和R 2，R 2和R 3或R 3和R 4连接在一起形成苯并稠环; R5是氢或C1-4烷基; R6为氯或三氟甲基; 或其无毒的药学上可接受的盐，溶剂化物或水合物，其是大电导钙激活的钾通道的开放剂，并且可用于治疗对钾通道开放有反应的病症。

公开(公告)号：US08377980B2

公开(公告)日：2013-02-19

申请号：US12957512

申请日：2010-12-01

申请人： Makonen Belema ,  Jeffrey Lee Romine ,  Van N. Nguyen ,  Gan Wang ,  Omar D. Lopez ,  Denis R. St. Laurent ,  Qi Chen ,  John A. Bender ,  Zhong Yang ,  Piyasena Hewawasam ,  Ningning Xu ,  Nicholas A. Meanwell ,  John A. Easter ,  Bao-Ning Su ,  Michael J. Smith

发明人： Makonen Belema ,  Jeffrey Lee Romine ,  Van N. Nguyen ,  Gan Wang ,  Omar D. Lopez ,  Denis R. St. Laurent ,  Qi Chen ,  John A. Bender ,  Zhong Yang ,  Piyasena Hewawasam ,  Ningning Xu ,  Nicholas A. Meanwell ,  John A. Easter ,  Bao-Ning Su ,  Michael J. Smith

IPC分类号： A61K31/4178 ,  C07D233/64

CPC分类号： C07D403/14 ,  C07D405/14

摘要： The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

摘要翻译： 本公开内容涉及用于治疗丙型肝炎病毒（HCV）感染的化合物，组合物和方法。 还公开了含有这些化合物的药物组合物和使用这些化合物治疗HCV感染的方法。

公开(公告)号：US07132504B2

公开(公告)日：2006-11-07

申请号：US10985106

申请日：2004-11-10

申请人： Paul Michael Scola ,  Fiona McPhee ,  Nicholas A Meanwell ,  Piyasena Hewawasam ,  Jeffrey Allen Campbell

发明人： Paul Michael Scola ,  Fiona McPhee ,  Nicholas A Meanwell ,  Piyasena Hewawasam ,  Jeffrey Allen Campbell

IPC分类号： A61K38/00

CPC分类号： C07K5/0808 ,  A61K38/00 ,  C07K5/0802

摘要： Compounds are disclosed having the general formula: wherein R1, R2, R3, R4, R′, B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

摘要翻译： 公开了具有以下通式的化合物：其中R 1，R 2，R 3，R 4，R '，B，Y和X在说明书中描述。 还公开了包含化合物的组合物和使用该化合物抑制HCV的方法。

公开(公告)号：US5869509A

公开(公告)日：1999-02-09

申请号：US902684

申请日：1997-07-30

申请人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

发明人： Jeffrey L. Romine ,  Scott W. Martin ,  Piyasena Hewawasam ,  Nicholas A. Meanwell ,  Valentin K. Gribkoff ,  John E. Starrett, Jr.

IPC分类号： C07D271/02 ,  A61K31/4164 ,  A61K31/4166 ,  A61K31/4196 ,  A61K31/4245 ,  A61P9/10 ,  A61P25/00 ,  A61P25/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/54 ,  C07D233/64 ,  C07D233/70 ,  C07D233/74 ,  C07D233/76 ,  C07D235/12 ,  C07D249/08 ,  C07D249/12 ,  C07D249/14 ,  C07D263/58 ,  C07D271/10 ,  C07D271/113 ,  C07D413/10 ,  A61K31/42 ,  A61K31/425 ,  C07D271/06

CPC分类号： C07D263/58 ,  C07D233/64 ,  C07D233/70 ,  C07D233/76 ,  C07D235/12 ,  C07D249/12 ,  C07D249/14 ,  C07D271/113 ,  C07D413/10

摘要： Novel compounds of Formula 1 are useful to treat disorders responsive to openers of the large conductance calcium-activated potassium channels: ##STR1## wherein "Het" is one of a select group of heterocyclic moieties; Z is independently for each occurrence selected from O or S; R.sup.a, R.sup.b and R.sup.c each are independently selected from hydrogen, halogen, OH, CF.sub.3, ##STR2## provided R.sup.c is not hydrogen; and when R.sup.a and R.sup.b are hydrogen, R.sup.c may be a heterocyclic moiety selected from the group consisting of imidazol-1-yl, morpholinomethyl, N-methylimidazol- 2-yl, and pyridinyl; R.sup.d and R.sup.e each are independently selected from hydrogen, halogen, CF.sub.3, NO.sub.2 or imidazol-1-yl; m, n and p each are independently selected from an integer of O or 1; and R.sup.f and R.sup.g each are independently hydrogen; C.sub.1-4 alkyl; or R.sup.f and R.sup.g, taken together with the nitrogen atom to which they are attached, is a heterocyclic moiety selected from the group consisting of N-methylpiperazine, morpholine, thiomorpholine, N-benzylpiperazine and imidazolinone.

摘要翻译： 式1的新型化合物可用于治疗对大电导钙激活钾通道的开放剂起反应的病症：其中“Het”是选择性杂环部分组之一; Z独立地选自O或S; Ra，Rb和Rc各自独立地选自氢，卤素，OH，CF 3，提供的R c不是氢; 当R a和R b为氢时，R c可以是选自咪唑-1-基，吗啉代甲基，N-甲基咪唑-2-基和吡啶基的杂环部分。 Rd和Re各自独立地选自氢，卤素，CF 3，NO 2或咪唑-1-基; m，n和p各自独立地选自O或1的整数; Rf和Rg各自独立地为氢; C 1-4烷基; 或R f和R g与它们所连接的氮原子一起是选自N-甲基哌嗪，吗啉，硫代吗啉，N-苄基哌嗪和咪唑啉酮的杂环部分。