公开(公告)号：WO2008021936A3

公开(公告)日：2008-04-17

申请号：PCT/US2007075553

申请日：2007-08-09

Applicant: SQUIBB BRISTOL MYERS CO ,  BACHAND CAROL ,  BELEMA MAKONEN ,  DEON DANIEL H ,  GOOD ANDREW C ,  GOODRICH JASON ,  JAMES CLINT A ,  LAVOIE RICO ,  LOPEZ OMAR D ,  MARTEL ALAIN ,  MEANWELL NICHOLAS A ,  NGUYEN VAN N ,  ROMINE JEFFREY LEE ,  RUEDIGER EDWARD H ,  SNYDER LAWRENCE B ,  ST LAURENT DENIS R ,  YANG FUKANG ,  LANGLEY DAVID R ,  HAMANN LAWRENCE G

Inventor： BACHAND CAROL ,  BELEMA MAKONEN ,  DEON DANIEL H ,  GOOD ANDREW C ,  GOODRICH JASON ,  JAMES CLINT A ,  LAVOIE RICO ,  LOPEZ OMAR D ,  MARTEL ALAIN ,  MEANWELL NICHOLAS A ,  NGUYEN VAN N ,  ROMINE JEFFREY LEE ,  RUEDIGER EDWARD H ,  SNYDER LAWRENCE B ,  ST LAURENT DENIS R ,  YANG FUKANG ,  LANGLEY DAVID R ,  HAMANN LAWRENCE G

IPC: A61K31/501 ,  A61K31/497 ,  A61K31/506 ,  A61P31/12

CPC classification number: C07D403/14 ,  A61K31/4178 ,  A61K31/4545 ,  A61K31/5377 ,  A61K31/695 ,  A61K45/06 ,  C07D401/14 ,  C07F7/10

Abstract: The present disclosure relates to compounds of formula (I), 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.

Abstract translation: 本公开涉及式（I）的化合物，用于治疗丙型肝炎病毒（HCV）感染的组合物和方法。 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：WO2008021928A3

公开(公告)日：2008-03-27

申请号：PCT/US2007075545

申请日：2007-08-09

Applicant: SQUIBB BRISTOL MYERS CO ,  BACHAND CAROL ,  BELEMA MAKONEN ,  DEON DANIEL H ,  GOOD ANDREW C ,  GOODRICH JASON ,  JAMES CLINT A ,  LAVOIE RICO ,  LOPEZ OMAR D ,  MARTEL ALAIN ,  MEANWELL NICHOLAS A ,  NGUYEN VAN N ,  ROMINE JEFFREY LEE ,  RUEDIGER EDWARD H ,  SNYDER LAWRENCE B ,  ST LAURENT DENIS R ,  YANG FUKANG ,  LANGLEY DAVID R ,  HAMANN LAWRENCE G

Inventor： BACHAND CAROL ,  BELEMA MAKONEN ,  DEON DANIEL H ,  GOOD ANDREW C ,  GOODRICH JASON ,  JAMES CLINT A ,  LAVOIE RICO ,  LOPEZ OMAR D ,  MARTEL ALAIN ,  MEANWELL NICHOLAS A ,  NGUYEN VAN N ,  ROMINE JEFFREY LEE ,  RUEDIGER EDWARD H ,  SNYDER LAWRENCE B ,  ST LAURENT DENIS R ,  YANG FUKANG ,  LANGLEY DAVID R ,  HAMANN LAWRENCE G

IPC: A61K31/506 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/497 ,  A61K31/501 ,  A61P31/12 ,  C07D401/14 ,  C07D403/14

CPC classification number: C07D401/14 ,  C07D403/14

Abstract: The present disclosure relates to compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein A and B are selected from phenyl and a six-membered heteroaromatic ring containing one, two or three nitrogen atoms; provided that at least one of A and B is other than phenyl, 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.

Abstract translation: 本公开涉及式（I）化合物或其药学上可接受的盐，其中A和B选自苯基和含有一个，两个或三个氮原子的六元杂芳环; 条件是A和B中的至少一个不是苯基，用于治疗丙型肝炎病毒（HCV）感染的组合物和方法。 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：WO2012051405A1

公开(公告)日：2012-04-19

申请号：PCT/US2011/056124

申请日：2011-10-13

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  SAULNIER, Mark G. ,  VYAS, Dolatrai M. ,  LANGLEY, David R. ,  FRENNESSON, David B.

Inventor： SAULNIER, Mark G. ,  VYAS, Dolatrai M. ,  LANGLEY, David R. ,  FRENNESSON, David B.

IPC: C07K1/113 ,  C07K1/107 ,  C07D277/42

CPC classification number: C07K7/64 ,  C07D277/42 ,  C07D417/04 ,  C07K1/1136 ,  C07K5/123 ,  C07K5/126

Abstract: The invention provides methods of preparing macrocycles including macrocycle stabilized peptides (MSPs). Macrocycles and MSPs are prepared according to nucleophilic capture of an iminoquinomethide type intermediate generated from a suitably substituted 2-amino-thiazol-5-yl carbinol. The preferred nucleophile may be selected from an electron rich aromatic moiety in the case of macrocycles and, in the case of MSPs, at least one amino acid comprises an electron rich aromatic moiety. In addition, the concept can be extended to other related 5-membered heterocyclic systems in place of the thiazole, such as imidazole or oxazole. The conditions for the generation of the corresponding iminoquinomethide type intermediates may be similar or different than the conditions used for the 2-amino-thiazol-5-yl carbinol.

Abstract translation: 本发明提供了制备大环化合物包括大环稳定肽（MSP）的方法。 根据由适当取代的2-氨基 - 噻唑-5-基甲醇产生的亚氨基喹喔啉型中间体的亲核捕获制备大环和MSP。 在大环化合物的情况下，优选的亲核试剂可以选自富含电子的芳族部分，在MSP的情况下，至少一个氨基酸包含富电子的芳族部分。 此外，该概念可以扩展到其它相关的5元杂环体系代替噻唑，例如咪唑或恶唑。 产生相应的亚氨基喹喔啉型中间体的条件可以与用于2-氨基 - 噻唑-5-基甲醇的条件相似或不同。

公开(公告)号：WO2012044531A1

公开(公告)日：2012-04-05

申请号：PCT/US2011/052965

申请日：2011-09-23

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  CIANCI, Christopher W. ,  GERRITZ, Samuel ,  KIM, Sean ,  LANGLEY, David R. ,  LI, Guo ,  PEARCE, Bradley C. ,  PENDRI, Annapurna ,  SHI, Shuhao ,  ZHAI, Weixu ,  ZHU, Shirong

Inventor： CIANCI, Christopher W. ,  GERRITZ, Samuel ,  KIM, Sean ,  LANGLEY, David R. ,  LI, Guo ,  PEARCE, Bradley C. ,  PENDRI, Annapurna ,  SHI, Shuhao ,  ZHAI, Weixu ,  ZHU, Shirong

IPC: C07D403/06 ,  C07D413/06 ,  C07D413/14 ,  A61K31/496 ,  A61P31/12 ,  A61P31/16

CPC classification number: C07D413/06 ,  C07D403/06 ,  C07D413/14

Abstract: A compound of the following Formula (I) is set forth, including pharmaceutically acceptable salts thereof: wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar is aryl or heteroaryl; R is -CH 3 , -CH 2 F, -CHF 2 or -CH=CH 2 ; V is -H, -CH 3 or =0; W is -NO 2 , -CI, -Br, -CH 2 OH, or -CN; X is -CI, -Br, -F, -CH 3 , -OCH 3 , or -CN; Y is -CH or -N; and Z is -CH or -N. This compound is useful in compositions for the prevention and treatment of influenza virus.

Abstract translation: 阐述了下式（I）的化合物，包括其药学上可接受的盐：其中Het是具有-N，-O或-S的5或6元杂环，其与 -Ar取代基或与-Ar取代基的连接点相邻; Ar是芳基或杂芳基; R为-CH 3，-CH 2 F，-CHF 2或-CH = CH 2 2; V是-H，-CH 3或= O; W为-NO 2，-Cl，-Br，-CH 2 OH或-CN; X是-Cl，-Br，-F，-CH 3，-OCH 3或-CN; Y是-CH或-N; Z是-CH或-N。 该化合物可用于预防和治疗流感病毒的组合物中。

公开(公告)号：WO2008144380A1

公开(公告)日：2008-11-27

申请号：PCT/US2008/063689

申请日：2008-05-15

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  BACHAND, Carol ,  BELEMA, Makonen ,  DEON, Daniel, H. ,  GOOD, Andrew, C. ,  GOODRICH, Jason ,  HAMANN, Lawrence, G. ,  JAMES, Clint, A. ,  LANGLEY, David, R. ,  LAVOIE, Rico ,  LOPEZ, Omar, D. ,  MARTEL, Alain ,  MEANWELL, Nicholas, A. ,  NGUYEN, Van, N. ,  ROMINE, Jeffrey, Lee ,  RUEDIGER, Edward, H. ,  SNYDER, Lawrence, B. ,  ST. LAURENT, Denis, R. ,  YANG, Fukang ,  WANG, Gan

Inventor： BACHAND, Carol ,  BELEMA, Makonen ,  DEON, Daniel, H. ,  GOOD, Andrew, C. ,  GOODRICH, Jason ,  HAMANN, Lawrence, G. ,  JAMES, Clint, A. ,  LANGLEY, David, R. ,  LAVOIE, Rico ,  LOPEZ, Omar, D. ,  MARTEL, Alain ,  MEANWELL, Nicholas, A. ,  NGUYEN, Van, N. ,  ROMINE, Jeffrey, Lee ,  RUEDIGER, Edward, H. ,  SNYDER, Lawrence, B. ,  ST. LAURENT, Denis, R. ,  YANG, Fukang ,  WANG, Gan

IPC: C07D413/14 ,  C07D403/04 ,  C07D403/14 ,  A61K31/40 ,  A61P31/12

CPC classification number: C07D413/14 ,  C07D403/04 ,  C07D403/14

Abstract: The present disclosure relates to compounds of the following formula (I) or a pharmaceutically acceptable salt thereof, wherein A and B are each phenyl; D and E are each five-membered aromatic rings containing one, two, or three i hcteroatoms independently selected from nitrogen, oxygen, and sulfur; provided that ', at least one of D and E is other than imidazole; compositions and methods for the treatment of Hepatitis C virus (HCV) inf ection. Also disclosed are pharmaceutical compositions containing such compounds and methods f or using these compounds in the treatment of HCV inf ection.

Abstract translation: 本公开涉及下式（I）的化合物或其药学上可接受的盐，其中A和B各自为苯基; D和E分别是含有独立地选自氮，氧和硫的一个，两个或三个独立原子的五元芳环; 条件是'，D和E中的至少一个不是咪唑; 用于治疗丙型肝炎病毒（HCV）感染的组合物和方法。 还公开了含有这些化合物的药物组合物和f或使用这些化合物治疗HCV感染的方法。

公开(公告)号：WO2008005956A3

公开(公告)日：2008-03-06

申请号：PCT/US2007072697

申请日：2007-07-03

Applicant: SQUIBB BRISTOL MYERS CO ,  MASTALERZ HAROLD ,  WITTMAN MARK D ,  ZIMMERMANN KURT ,  SAULNIER MARK G ,  VELAPARTHI UPENDER ,  VYAS DOLATRAI M ,  ZHANG GUIFEN ,  JOHNSON WALTER LEWIS ,  FRENNESSON DAVID B ,  SANG XIAOPENG ,  LIU PEIYING ,  LANGLEY DAVID R

Inventor： MASTALERZ HAROLD ,  WITTMAN MARK D ,  ZIMMERMANN KURT ,  SAULNIER MARK G ,  VELAPARTHI UPENDER ,  VYAS DOLATRAI M ,  ZHANG GUIFEN ,  JOHNSON WALTER LEWIS ,  FRENNESSON DAVID B ,  SANG XIAOPENG ,  LIU PEIYING ,  LANGLEY DAVID R

IPC: C07D487/04 ,  A61K31/53 ,  A61P25/00 ,  A61P35/00

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: The invention provides compounds of formula I [INSERT CHEMICAL STRUCTURE HERE] (I) and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.

Abstract translation: 本发明提供了式I化合物[插入其中的化学结构]（I）及其药学上可接受的盐。 式I化合物抑制酪氨酸激酶活性，从而使它们可用作抗癌剂并用于治疗阿尔茨海默氏病。

公开(公告)号：WO2012134967A3

公开(公告)日：2013-03-21

申请号：PCT/US2012030221

申请日：2012-03-23

Applicant: SQUIBB BRISTOL MYERS CO ,  BALDWIN ERIC T ,  MCDONNELL PATRICIA ANN ,  EDAVETTAL SUZANNE ,  LEWIS HAL ,  PEARCE BRADLEY C ,  LANGLEY DAVID R ,  CIANCI CHRISTOPHER W ,  DISCOTTO LINDA ,  GERRITZ SAMUEL ,  SHI SHUHAO ,  ZHU SHIRONG

Inventor： BALDWIN ERIC T ,  MCDONNELL PATRICIA ANN ,  EDAVETTAL SUZANNE ,  LEWIS HAL ,  PEARCE BRADLEY C ,  LANGLEY DAVID R ,  CIANCI CHRISTOPHER W ,  DISCOTTO LINDA ,  GERRITZ SAMUEL ,  SHI SHUHAO ,  ZHU SHIRONG

IPC: A61K38/00

CPC classification number: C07K14/005 ,  A61K38/00 ,  C12N2760/16122 ,  G01N33/6875

Abstract: The binding mode of the antiviral compounds have been characterized through a variety of biophysical and structural studies, elaborating on the proposed aggregation mechanism of action. We demonstrate the direct binding of these antiviral compounds to NP using thermal shift enhancement assay (TSE) and NMR. In addition, we have completed a detailed analysis of the oligomerization mechanism of action using dynamic light scattering, analytical ultracentrifugation, and surface plasmon resonance (SPR). Structure determination using x-ray crystallography confirmed the proposed compound-induced oligomerization mechanism of action. The co-crystal structure revealed that two compounds bound in an anti-parallel fashion bridging two NP monomers, inducing a novel non-native NP oligomer. Taken together, our data suggest a complex binding mode in which the compounds bind NP specifically in stoichiometric fashion inducing the formation of an NP oligomer without obstructing the RNA binding pocket or interfering with the native NP homo-oligomerization.

Abstract translation: 抗病毒化合物的结合模式已经通过各种生物物理和结构研究来表征，详细阐述了提出的聚集作用机制。 我们使用热移位增强测定（TSE）和NMR证明了这些抗病毒化合物与NP的直接结合。 另外，我们已经完成了使用动态光散射，分析超速离心和表面等离子体共振（SPR）的作用的低聚机理的详细分析。 使用x射线晶体学的结构测定证实了所提出的化合物诱导的低聚作用机制。 共晶结构显示两种化合物以反平行方式结合，桥接两个NP单体，诱导新型非天然NP寡聚体。 综合起来，我们的数据表明了复合结合模式，其中化合物以化学计量的方式特异性结合NP，诱导NP寡聚体的形成，而不会阻碍RNA结合口袋或干扰天然的NP均聚低聚。

公开(公告)号：WO2013033059A1

公开(公告)日：2013-03-07

申请号：PCT/US2012/052603

申请日：2012-08-28

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  WANG, Tao ,  ZHANG, Zhongxing ,  LANGLEY, David R. ,  KADOW, John F. ,  MEANWELL, Nicholas A.

Inventor： WANG, Tao ,  ZHANG, Zhongxing ,  LANGLEY, David R. ,  KADOW, John F. ,  MEANWELL, Nicholas A.

IPC: C07D519/00 ,  A61K31/437 ,  A61P31/18

CPC classification number: C07D471/04 ,  C07D519/00

Abstract: Compounds of Formula I, including pharmaceutically acceptable salts thereof: [ I ] wherein A is selected from the group consisting of: and are useful as HIV attachment inhibitors.

Abstract translation: 式I的化合物，包括其药学上可接受的盐：[I]其中A选自：并且可用作HIV附着抑制剂。

公开(公告)号：WO2012134967A2

公开(公告)日：2012-10-04

申请号：PCT/US2012/030221

申请日：2012-03-23

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  BALDWIN, Eric T. ,  MCDONNELL, Patricia Ann ,  EDAVETTAL, Suzanne ,  LEWIS, Hal ,  PEARCE, Bradley C. ,  LANGLEY, David R. ,  CIANCI, Christopher W. ,  DISCOTTO, Linda ,  GERRITZ, Samuel ,  SHI, Shuhao ,  ZHU, Shirong

Inventor： BALDWIN, Eric T. ,  MCDONNELL, Patricia Ann ,  EDAVETTAL, Suzanne ,  LEWIS, Hal ,  PEARCE, Bradley C. ,  LANGLEY, David R. ,  CIANCI, Christopher W. ,  DISCOTTO, Linda ,  GERRITZ, Samuel ,  SHI, Shuhao ,  ZHU, Shirong

IPC: A61K38/00

CPC classification number: C07K14/005 ,  A61K38/00 ,  C12N2760/16122 ,  G01N33/6875

Abstract: The binding mode of the antiviral compounds have been characterized through a variety of biophysical and structural studies, elaborating on the proposed aggregation mechanism of action. We demonstrate the direct binding of these antiviral compounds to NP using thermal shift enhancement assay (TSE) and NMR. In addition, we have completed a detailed analysis of the oligomerization mechanism of action using dynamic light scattering, analytical ultracentrifugation, and surface plasmon resonance (SPR). Structure determination using x-ray crystallography confirmed the proposed compound-induced oligomerization mechanism of action. The co-crystal structure revealed that two compounds bound in an anti-parallel fashion bridging two NP monomers, inducing a novel non-native NP oligomer. Taken together, our data suggest a complex binding mode in which the compounds bind NP specifically in stoichiometric fashion inducing the formation of an NP oligomer without obstructing the RNA binding pocket or interfering with the native NP homo-oligomerization.

Abstract translation: 抗病毒化合物的结合模式已经通过各种生物物理和结构研究来表征，详细阐述了提出的聚集作用机制。 我们使用热移位增强测定（TSE）和NMR证明了这些抗病毒化合物与NP的直接结合。 另外，我们已经完成了使用动态光散射，分析超速离心和表面等离子体共振（SPR）的作用的低聚机理的详细分析。 使用x射线晶体学的结构测定证实了所提出的化合物诱导的低聚作用机制。 共晶结构显示两种化合物以反平行方式结合，桥接两个NP单体，诱导新型非天然NP寡聚体。 综合起来，我们的数据表明了复合结合模式，其中化合物以化学计量的方式特异性结合NP，诱导NP寡聚体的形成，而不会阻碍RNA结合口袋或干扰天然的NP均聚低聚。

公开(公告)号：WO2012033735A1

公开(公告)日：2012-03-15

申请号：PCT/US2011/050503

申请日：2011-09-06

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  PENDRI, Annapurna ,  LI, Guo ,  GERRITZ, Samuel ,  LANGLEY, David, R. ,  TRAINOR, George, L. ,  MEANWELL, Nicholas, A.

Inventor： PENDRI, Annapurna ,  LI, Guo ,  GERRITZ, Samuel ,  LANGLEY, David, R. ,  TRAINOR, George, L. ,  MEANWELL, Nicholas, A.

IPC: C07D487/04 ,  A61K31/519 ,  A61P31/18

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  C07D519/00 ,  A61K2300/00

Abstract: The disclosure generally relates to compounds of formula (I), including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

Abstract translation: 本发明一般涉及式（I）化合物，包括用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。 本公开提供了HIV的新型抑制剂，含有这些化合物的药物组合物，以及使用这些化合物治疗HIV感染的方法。