公开(公告)号：US06743794B2

公开(公告)日：2004-06-01

申请号：US10130800

申请日：2002-05-21

申请人： Rosanne Bonjouklian ,  Jeffrey Daniel Cohen ,  Joseph Michael Gruber ,  Douglas Webb Johnson ,  Louis Nickolaus Jungheim ,  Julian Stanley Kroin ,  Peter Ambrose Lander ,  Ho-Shen Lin ,  Mark Christopher Lohman ,  Brian Stephen Muehl ,  Bryan Hurst Norman ,  Vinod Francis Patel ,  Michael Enrico Richett ,  Kenneth Jeff Thrasher ,  Sreenivasarao Vepachedu ,  Wesley Todd White ,  Yongping Xie ,  Jeremy Schulenburg York ,  Brandon Lee Parkhurst ,  Qiupang Wang

发明人： Rosanne Bonjouklian ,  Jeffrey Daniel Cohen ,  Joseph Michael Gruber ,  Douglas Webb Johnson ,  Louis Nickolaus Jungheim ,  Julian Stanley Kroin ,  Peter Ambrose Lander ,  Ho-Shen Lin ,  Mark Christopher Lohman ,  Brian Stephen Muehl ,  Bryan Hurst Norman ,  Vinod Francis Patel ,  Michael Enrico Richett ,  Kenneth Jeff Thrasher ,  Sreenivasarao Vepachedu ,  Wesley Todd White ,  Yongping Xie ,  Jeremy Schulenburg York ,  Brandon Lee Parkhurst ,  Qiupang Wang

IPC分类号： A61K31496

CPC分类号： C07D471/04

摘要： The present invention further relates to a method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I).

公开(公告)号：US07101891B2

公开(公告)日：2006-09-05

申请号：US10473236

申请日：2002-03-27

申请人： Jeffrey Daniel Cohen ,  Louis Nickolaus Jungheim ,  Brian Stephen Muehl ,  Kenneth Jeff Thrasher

发明人： Jeffrey Daniel Cohen ,  Louis Nickolaus Jungheim ,  Brian Stephen Muehl ,  Kenneth Jeff Thrasher

IPC分类号： C07D498/14 ,  A61K31/435

CPC分类号： C07D498/04

摘要： The present invention relates to a compound of formula (I), which are useful for inhibiting resistant neoplasms where the resistance is conferred in part or in total by MRP1

摘要翻译： 本发明涉及式（I）化合物，其可用于抑制耐药性，其中抗药性部分或全部由MRP1赋予

公开(公告)号：US06992097B2

公开(公告)日：2006-01-31

申请号：US10453833

申请日：2003-06-03

申请人： Kenneth Lee Hauser ,  Jeffrey Alan Dodge ,  Mark Louis Heiman ,  Scott Alan Jones ,  Charles Arthur Alt ,  Henry Uhlman Bryant ,  Jeffrey Daniel Cohen ,  James Densmore Copp ,  Kennan Joseph Fahey ,  William Harlan Gritton ,  Louis Nickolaus Jungheim ,  Joseph Henry Kennedy ,  Charles Willis Lugar, III ,  Brian Stephen Muehl ,  Alan David Palkowitz ,  Andrew Michael Ratz ,  Gary Anthony Rhodes ,  Roger Lewis Robey ,  David Edward Seyler ,  Timothy Alan Shepherd ,  Kenneth Jeff Thrasher ,  William George Trankle

发明人： Kenneth Lee Hauser ,  Jeffrey Alan Dodge ,  Mark Louis Heiman ,  Scott Alan Jones ,  Charles Arthur Alt ,  Henry Uhlman Bryant ,  Jeffrey Daniel Cohen ,  James Densmore Copp ,  Kennan Joseph Fahey ,  William Harlan Gritton ,  Louis Nickolaus Jungheim ,  Joseph Henry Kennedy ,  Charles Willis Lugar, III ,  Brian Stephen Muehl ,  Alan David Palkowitz ,  Andrew Michael Ratz ,  Gary Anthony Rhodes ,  Roger Lewis Robey ,  David Edward Seyler ,  Timothy Alan Shepherd ,  Kenneth Jeff Thrasher ,  William George Trankle

IPC分类号： A61K31/415 ,  C07D233/44

CPC分类号： C07D207/416 ,  A61K45/06 ,  C07D207/16 ,  C07D207/42 ,  C07D231/40 ,  C07D233/88 ,  C07D401/06 ,  C07D403/06 ,  C07D403/12 ,  C07D409/12 ,  C07D417/06 ,  C07D487/08

摘要： This invention relates to novel compounds which are useful in the modulation of endogenous growth hormone levels in a mammal. The invention further relates to novel intermediates for use in the synthesis of said compounds, as well as novel processes employed in these syntheses. Also included are methods of treating a mammal which include the administration of said compounds.

摘要翻译： 本发明涉及可用于调节哺乳动物内源性生长激素水平的新化合物。 本发明还涉及用于合成所述化合物的新中间体，以及在这些合成中使用的新方法。 还包括治疗哺乳动物的方法，其包括施用所述化合物。

公开(公告)号：US06939946B2

公开(公告)日：2005-09-06

申请号：US10676575

申请日：2003-09-30

申请人： Peter Stanley Borromeo ,  Jeffrey Daniel Cohen ,  George Stuart Gregory ,  Stacy Kay Henle ,  Stephen Andrew Hitchcock ,  Louis Nickolaus Jungheim ,  Daniel Ray Mayhugh ,  Timothy Alan Shepherd ,  William Wilson Turner, Jr.

发明人： Peter Stanley Borromeo ,  Jeffrey Daniel Cohen ,  George Stuart Gregory ,  Stacy Kay Henle ,  Stephen Andrew Hitchcock ,  Louis Nickolaus Jungheim ,  Daniel Ray Mayhugh ,  Timothy Alan Shepherd ,  William Wilson Turner, Jr.

IPC分类号： A61K9/08 ,  A61K9/72 ,  A61K38/00 ,  A61P31/10 ,  A61P33/00 ,  C07K1/06 ,  C07K7/50 ,  C07K7/54 ,  C07K7/56 ,  C07K7/64

CPC分类号： C07K7/50 ,  A61K38/00 ,  C07K7/56 ,  Y02A50/409

摘要： A method for modifying the cyclic peptide ring system of Echinocandin-type compounds to produce new analogs having antifungal activity is provided. The inventive process comprises opening the cyclic peptide ring, cleaving the terminal ornithine unit, inserting at least one new amino acid or other synthetic unit and closing the ring to produce a new cyclic peptide ring structure. The process allows one to incorporate features such as water-solubility into the cyclic peptide ring nucleus, sites for further modification, increase or decrease the number of amino acid or peptide units within the ring nucleus, and increase or decrease the total number of members within the ring. The invention further provides novel Echinocandin type compounds and their use as antifungal or anti-parasitic agents.

摘要翻译： 提供了一种用于改变棘球in素型化合物的环肽环体系以产生具有抗真菌活性的新类似物的方法。 本发明的方法包括打开环肽环，切割末端鸟氨酸单元，插入至少一个新的氨基酸或其它合成单元并封闭环以产生新的环肽环结构。 该方法允许将诸如水溶性的特征结合到环肽环核中，用于进一步修饰的位点，增加或减少环核内的氨基酸或肽单元的数目，并且增加或减少环核内的成员总数 戒指。 本发明还提供新颖的棘白菌素类化合物及其作为抗真菌剂或抗寄生虫剂的用途。

公开(公告)号：US06653281B1

公开(公告)日：2003-11-25

申请号：US09763114

申请日：2001-05-24

申请人： Peter Stanley Borromeo ,  Jeffrey Daniel Cohen ,  George Stuart Gregory ,  Stacy Kay Henle ,  Stephen Andrew Hitchcock ,  Louis Nickolaus Jungheim ,  Daniel Ray Mayhugh ,  Timothy Alan Shepherd ,  William Wilson Turner, Jr.

发明人： Peter Stanley Borromeo ,  Jeffrey Daniel Cohen ,  George Stuart Gregory ,  Stacy Kay Henle ,  Stephen Andrew Hitchcock ,  Louis Nickolaus Jungheim ,  Daniel Ray Mayhugh ,  Timothy Alan Shepherd ,  William Wilson Turner, Jr.

IPC分类号： A61K3812

CPC分类号： C07K7/50 ,  A61K38/00 ,  C07K7/56 ,  Y02A50/409

摘要： A method for modifying the cyclic peptide ring system of Echinocandin-type compounds to produce new analogs having antifungal activity is provided. The inventive process comprises opening the cyclic peptide ring, cleaving the terminal omithine unit, inserting at least one new amino acid or other synthetic unit and closing the ring to produce a new cyclic peptide ring structure. The process allows one to incorporate features such as water-solubility into the cyclic peptide ring nucleus, sites for further modification, increase or decrease the number of amino acid or peptide units within the ring nucleus, and increase or decrease the total number of members within the ring. The invention further provides novel Echinocandin type compounds and their use as antifungal or anti-parasitic agents.

摘要翻译： 提供了一种用于改变棘球in素型化合物的环肽环体系以产生具有抗真菌活性的新类似物的方法。 本发明的方法包括打开环肽环，切割末端氨基甲酸单元，插入至少一个新的氨基酸或其它合成单元并闭合环以产生新的环肽环结构。 该方法允许将诸如水溶性的特征结合到环肽环核中，用于进一步修饰的位点，增加或减少环核内的氨基酸或肽单元的数目，并且增加或减少环核内的成员总数 戒指。 本发明还提供新颖的棘白菌素类化合物及其作为抗真菌剂或抗寄生虫剂的用途。

公开(公告)号：US20110263602A1

公开(公告)日：2011-10-27

申请号：US13122216

申请日：2009-11-05

申请人： Jolie Anne Bastian ,  Julia Marie Clay ,  Jeffrey Daniel Cohen ,  Philip Arthur Hipskind ,  Karen Lynn Lobb ,  Daniel Jon Sall ,  Michelle Lee Thompson ,  Takako Wilson (nee Takakuwa)

发明人： Jolie Anne Bastian ,  Julia Marie Clay ,  Jeffrey Daniel Cohen ,  Philip Arthur Hipskind ,  Karen Lynn Lobb ,  Daniel Jon Sall ,  Michelle Lee Thompson ,  Takako Wilson (nee Takakuwa)

IPC分类号： A61K31/5377 ,  A61P35/00 ,  C07D413/14 ,  C07D401/04 ,  C07D401/14 ,  A61K31/501

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D417/14

摘要： The present invention provides novel tetrasubstituted pyridine hedgehog pathway antagonists of the following formula I (I) or a pharmaceutically acceptable salt thereof, wherein: X is C—R1 or N; R1 is hydrogen, fluoro or cyano; R2 is formula II (II), piperidinyl, or gem di-F-substituted cyclohexyl; R3 is methyl or trifluoromethyl; R4 is pyrrolidinyl, morpholinyl or pyridyl, amino or dimethylamino; R5 is trifluoromethyl or methylsulfonyl; R6 is hydrogen or methyl; and R7, R8, R9, R10 and R11 are independently hydrogen fluoro, cyano, chloro, methyl, trifluoromethyl, trifluoromethoxy or methylsulfonyl, provided that at least two of R7, R8, R9, R10 and R11 are hydrogen useful in the treatment of cancer.

摘要翻译： 本发明提供下式I（I）的新型四取代吡啶hedgehog途径拮抗剂或其药学上可接受的盐，其中：X为C-R 1或N; R1是氢，氟或氰基; R2是式II（II），哌啶基或gem二-F取代的环己基; R3是甲基或三氟甲基; R4是吡咯烷基，吗啉基或吡啶基，氨基或二甲基氨基; R5是三氟甲基或甲基磺酰基; R6是氢或甲基; 并且R 7，R 8，R 9，R 10和R 11中的至少两个是可用于治疗癌症的氢，并且R 7，R 8，R 9，R 10和R 11独立地为氢，氰基，氯，甲基，三氟甲基，三氟甲氧基或甲基磺酰基 。

公开(公告)号：US08507490B2

公开(公告)日：2013-08-13

申请号：US13122216

申请日：2009-11-05

申请人： Jolie Anne Bastian ,  Julia Marie Clay ,  Jeffrey Daniel Cohen ,  Philip Arthur Hipskind ,  Karen Lynn Lobb ,  Daniel Jon Sall ,  Michelle Lee Thompson ,  Takako Wilson (nee Takakuwa)

发明人： Jolie Anne Bastian ,  Julia Marie Clay ,  Jeffrey Daniel Cohen ,  Philip Arthur Hipskind ,  Karen Lynn Lobb ,  Daniel Jon Sall ,  Michelle Lee Thompson ,  Takako Wilson (nee Takakuwa)

IPC分类号： C07D401/14 ,  A61K31/501 ,  A61P35/00

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D417/14

摘要： The present invention provides novel tetrasubstituted pyridine hedgehog pathway antagonists of the following formula I (I) or a pharmaceutically acceptable salt thereof, wherein: X is C—R1 or N; R1 is hydrogen, fluoro or cyano; R2 is formula II (II), piperidinyl, or gem di-F-substituted cyclohexyl; R3 is methyl or trifluoromethyl; R4 is pyrrolidinyl, morpholinyl or pyridyl, amino or dimethylamino; R5 is trifluoromethyl or methylsulfonyl; R6 is hydrogen or methyl; and R7, R8, R9, R10 and R11 are independently hydrogen fluoro, cyano, chloro, methyl, trifluoromethyl, trifluoromethoxy or methylsulfonyl, provided that at least two of R7, R8, R9, R10 and R11 are hydrogen useful in the treatment of cancer.

摘要翻译： 本发明提供下式I（I）的新型四取代吡啶hedgehog途径拮抗剂或其药学上可接受的盐，其中：X为C-R 1或N; R1是氢，氟或氰基; R2是式II（II），哌啶基或gem二-F取代的环己基; R3是甲基或三氟甲基; R4是吡咯烷基，吗啉基或吡啶基，氨基或二甲基氨基; R5是三氟甲基或甲基磺酰基; R6是氢或甲基; 并且R 7，R 8，R 9，R 10和R 11中的至少两个是可用于治疗癌症的氢，并且R 7，R 8，R 9，R 10和R 11独立地为氢，氰基，氯，甲基，三氟甲基，三氟甲氧基或甲基磺酰基 。