公开(公告)号：US07192982B2

公开(公告)日：2007-03-20

申请号：US10479262

申请日：2002-05-30

申请人： Dawn Alisa Brooks ,  Alan M. Warshawsky ,  Chahrzad Montrose-Rafezadeh ,  Anne-Reifel Miller ,  Lourdes Prieto ,  Isabel Rojo ,  Jose Alfredo Martin ,  Maria Rosario Gonzales Garcia ,  Alicia Torrado ,  Rafael Ferritto Crespo ,  Carlos Lamas-Peteira ,  Robert J. Ardecky ,  Maria Martin-Ortega Finger

发明人： Dawn Alisa Brooks ,  Alan M. Warshawsky ,  Chahrzad Montrose-Rafezadeh ,  Anne-Reifel Miller ,  Lourdes Prieto ,  Isabel Rojo ,  Jose Alfredo Martin ,  Maria Rosario Gonzales Garcia ,  Alicia Torrado ,  Rafael Ferritto Crespo ,  Carlos Lamas-Peteira ,  Robert J. Ardecky ,  Maria Martin-Ortega Finger

IPC分类号： A61K37/00 ,  C07C59/00

CPC分类号： C07D209/48 ,  C07C59/68 ,  C07C59/72 ,  C07C59/90 ,  C07C217/20 ,  C07C217/84 ,  C07C217/92 ,  C07C219/10 ,  C07C233/25 ,  C07C233/29 ,  C07C233/60 ,  C07C233/75 ,  C07C235/56 ,  C07C235/64 ,  C07C239/12 ,  C07C255/54 ,  C07C2601/08 ,  C07D209/08 ,  C07D213/30 ,  C07D215/14 ,  C07D217/02 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D257/04 ,  C07D277/64 ,  C07D295/096 ,  C07D295/112 ,  C07D295/185 ,  C07D307/79 ,  C07D307/83 ,  C07D307/91 ,  C07D307/93 ,  C07D311/30 ,  C07D317/20 ,  C07D317/22 ,  C07D317/54 ,  C07D317/64 ,  C07D333/16 ,  C07D333/76 ,  C07D335/02

摘要： Disclosed is a compound represented by Structural Formula (I): Ar is a substituted or unsubstituted aromatic group. Q is a covalent bond, —CH2— or —CH2CH2—; W is a substituted or unsubstituted alkylene or a substituted or unsubstituted heteroalkylene linking group from two to ten atoms in length, preferably from two to seven atoms in length. Phenyl Ring A is optionally substituted with up to four substituents in addition to R1 and W, R1 is (CH2)n—CH(OR2)—(CH2)mE1, —(CH)═C(OR2)—(CH2)mE, —(CH2)n—CH(Y)—(CH2)mE or (CH)═C(Y)—(CH2)mE; wherein E is COOR3, C1–C3 alkylnitrile, carboxamide, sulfonamide, acylsulfonamide or tetrazole and wherein sulfonamide, acylsulfonamide and tetrazole are optionally substituted with one or more substituents independently selected from: C1–C6 alkyl, haloalkyl and aryl-C0-4-alkyl; R2 is H, an aliphatic group, a substituted aliphatic group, haloalkyl, an aromatic group, a substituted aromatic group, —COR4, —COOR4, —CONR5R6, —C(S)R4, —C(S)OR4 or C(S)NR5R6, R3 is H, an aliphatic group, a substituted aliphatic group, an aromatic group or a substituted aromatic group. Y is O—, CH2—, —CH2CH2— or CH═CH— and is bonded to a carbon atom in Phenyl Ring A that is ortho to R1. R4–R6 are independently H, an aliphatic group, a substituted aliphatic group, an aromatic group or a substituted aromatic group. n and m are independently 0, 1 or 2

公开(公告)号：US07351728B2

公开(公告)日：2008-04-01

申请号：US11181640

申请日：2005-07-14

申请人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rito ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Guoxin Zhu

发明人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rito ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Guoxin Zhu

IPC分类号： A61K31/421 ,  C07D263/32

CPC分类号： C07D413/12 ,  C07D263/32 ,  C07D413/04 ,  C07F5/025

摘要： Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (II), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubstituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is II, alkyl or haloalkyl, R4 is II, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

摘要翻译： 由以下结构式（I）表示的化合物及其药学上可接受的盐，溶剂合物和水合物，其中R1是未取代或取代的芳基，杂芳基，环烷基，芳基 - 烷基，杂芳基 - 烷基或环烷基 - 烷基，R2是H， 烷基或卤代烷基，多亚甲基链（II）是饱和的或可以含有碳 - 碳双键，而n为2,3,4，W为O或S，Y为未取代的亚苯基，亚萘基或1,2-亚乙基， 3,4四氢萘，R3为II，烷基或卤代烷基，R4为II，烷基，卤代烷基或取代或未取代的苄基，可用于调节过氧化物酶体增殖物激活受体，特别是治疗糖尿病。

公开(公告)号：US06982278B2

公开(公告)日：2006-01-03

申请号：US10343474

申请日：2001-08-23

申请人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rit ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Guoxin Zhu

发明人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rit ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Guoxin Zhu

IPC分类号： A61K31/421 ,  C07D263/30

CPC分类号： C07D413/12 ,  C07D263/32 ,  C07D413/04 ,  C07F5/025

摘要： Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (II), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubsituted or substituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is H, alkyl or haloalkyl. R4 is H, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

摘要翻译： 由以下结构式（I）表示的化合物及其药学上可接受的盐，溶剂合物和水合物，其中R1是未取代或取代的芳基，杂芳基，环烷基，芳基 - 烷基，杂芳基 - 烷基或环烷基 - 烷基，R2是H， 烷基或卤代烷基，多亚甲基链（II）是饱和的或可以含有碳 - 碳双键，而n为2,3,4，W为O或S，Y为未取代或取代的亚苯基，亚萘基或亚乙基， 2,3,4四氢萘，R3是H，烷基或卤代烷基。 R4是H，烷基，卤代烷基或取代或未取代的苄基，可用于调节过氧化物酶体增殖物激活受体，特别是用于治疗糖尿病。

公开(公告)号：US20080146631A1

公开(公告)日：2008-06-19

申请号：US11972668

申请日：2008-01-11

申请人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rito ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski ,  Guoxin Zhu

发明人： Dawn Alisa Brooks ,  Scott Eugene Conner ,  Samuel James Dominianni ,  Alexander Glenn Godfrey ,  Lynn Stacy Gossett ,  Christopher John Rito ,  Allie Edward Tripp ,  Alan M. Warshawsky ,  Leonard Larry Winneroski ,  Guoxin Zhu

IPC分类号： A61K31/421 ,  A61P3/06 ,  A61P3/10 ,  C07D263/32

CPC分类号： C07D413/12 ,  C07D263/32 ,  C07D413/04 ,  C07F5/025

摘要： Compounds represented by the following structural formula (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (II), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubstituted or substituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is H, alkyl or haloalkyl, R4 is H, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a preoxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.

摘要翻译： 由以下结构式（I）表示的化合物及其药学上可接受的盐，溶剂合物和水合物，其中R1是未取代或取代的芳基，杂芳基，环烷基，芳基 - 烷基，杂芳基 - 烷基或环烷基 - 烷基，R2是H， 烷基或卤代烷基，多亚甲基链（II）饱和或可含有碳 - 碳双键，而n为2,3,4，W为O或S，Y为未取代或取代的亚苯基，亚萘基或亚乙基， 2,3,4四氢萘，R3为H，烷基或卤代烷基，R4为H，烷基，卤代烷基或取代或未取代的苄基，可用于调节预氧化物酶体增殖物激活受体，特别是治疗糖尿病。

公开(公告)号：US06825222B2

公开(公告)日：2004-11-30

申请号：US10434425

申请日：2003-05-07

申请人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

发明人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

IPC分类号： A61K31425

CPC分类号： C07D413/10 ,  C07D263/32 ,  C07D277/24

摘要： The present invention is directed to compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof, and methods of making, methods of using and pharmaceutical compositions having compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof: In Structural Formula I, n is 2, 3, or 4; V is O or S; W is O, S, or SO2; R1 is H, a C1-C4 alkyl, phenyl or trifluoromethyl; R2 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, a cycloalkyl, or together with the phenyl to which they are bound form naphthyl or 1,2,3,4-tetrahydronaphthyl; R3 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, or a cycloalkyl; R4 are each, independently, H, a C1-C4 alkyl, an aryl, or benzyl; R5 are each, independently, H, a substituted or unsubstituted aryl or a heteroaryl, provided that at least one R5 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and R6 is H, a C1-C4 alkyl, or an aminoalkyl.

摘要翻译： 本发明涉及由结构式I表示的化合物及其药学上可接受的盐，溶剂合物和水合物及其制备方法，使用方法和具有由结构式I表示的化合物的药物组合物及其药学上可接受的盐，溶剂化物和水合物： 在结构式Ⅰ中，n为2,3或4; V为O或S; W是O，S或SO 2; R1是H，C1-C4烷基，苯基或三氟甲基; R 2各自独立地为H，C 1 -C 6烷基，芳基-C 1 -C 6烷基，环烷基-C 1 -C 4烷基，芳基，环烷基，或与它们所连接的苯基一起形成萘基或1 ，2,3,4-四氢萘基; R 3各自独立地为H，C 1 -C 6烷基，芳基-C 1 -C 6烷基，环烷基-C 1 -C 4烷基，芳基或环烷基; R 4各自独立地为H，C 1 -C 4烷基，芳基或苄基; R5各自独立地为H，取代或未取代的芳基或杂芳基，条件是至少一个R 5为取代或未取代的芳基或取代或未取代的杂芳基; 并且R 6是H，C 1 -C 4烷基或氨基烷基。

公开(公告)号：US06610696B2

公开(公告)日：2003-08-26

申请号：US10121373

申请日：2002-04-11

申请人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

发明人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

IPC分类号： A61K3142

CPC分类号： C07D413/10 ,  C07D263/32 ,  C07D277/24

摘要： The present invention is directed to compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof, and methods of making, methods of using and pharmaceutical compositions having compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof: In Structural Formula I, n is 2, 3, or 4; V is O or S; W is O, S, or SO2; R1 is H, a C1-C4 alkyl, phenyl or trifluoromethyl; R2 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, a cycloalkyl, or together with the phenyl to which they are bound form naphthyl or 1,2,3,4-tetrahydronaphthyl; R3 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, or a cycloalkyl; R4 are each, independently, H, a C1-C4 alkyl, an aryl, or benzyl; R5 are each, independently, H, a substituted or unsubstituted aryl or a heteroaryl, provided that at least one R5 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and R6 is H, a C1-C4 alkyl, or an aminoalkyl.

公开(公告)号：US06417212B1

公开(公告)日：2002-07-09

申请号：US09644457

申请日：2000-08-23

申请人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

发明人： Dawn A. Brooks ,  Christopher J. Rito ,  Anthony J. Shuker ,  Samuel J. Dominianni ,  Alan M. Warshawsky ,  Lynn S. Gossett ,  Donald P. Matthews ,  David A. Hay ,  Robert J. Ardecky ,  Pierre-Yves Michellys ,  John S. Tyhonas

IPC分类号： C07D26336

CPC分类号： C07D413/10 ,  C07D263/32 ,  C07D277/24

摘要： The present invention is directed to compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof, and methods of making, methods of using and pharmaceutical compositions having compounds represented by Structural Formula I and pharmaceutically acceptable salts, solvates and hydrates thereof: In Structural Formula I, n is 2, 3, or 4; V is O or S; W is O, S, or SO2; R1 is H, a C1-C4 alkyl, phenyl or trifluoromethyl; R2 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, a cycloalkyl, or together with the phenyl to which they are bound form naphthyl or 1,2,3,4-tetrahydronaphthyl; R3 are each, independently, H, a C1-C6 alkyl, an aryl-C1-C6 alkyl, a cycloalkyl-C1-C4 alkyl, an aryl, or a cycloalkyl; R4 are each, independently, H, a C1-C4 alkyl, an aryl, or benzyl; R5 are each, independently, H, a substituted or unsubstituted aryl or a heteroaryl, provided that at least one R5 is a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl; and R6 is H, a C1-C4 alkyl, or an aminoalkyl.

摘要翻译： 本发明涉及由结构式I表示的化合物及其药学上可接受的盐，溶剂合物和水合物及其制备方法，使用方法和具有由结构式I表示的化合物的药物组合物及其药学上可接受的盐，溶剂化物和水合物： 在结构式I中，n为2,3或4; V为O或S; W是O，S或SO 2; R1是H，C1-C4烷基，苯基或三氟甲基; R 2各自独立地为H，C 1 -C 6烷基，芳基-C 1 -C 6烷基，环烷基-C 1 -C 4烷基，芳基，环烷基，或与它们所连接的苯基一起形成萘基或1 ，2,3,4-四氢萘基; R 3各自独立地为H，C 1 -C 6烷基，芳基-C 1 -C 6烷基，环烷基-C 1 -C 4烷基，芳基或环烷基; R 4各自独立地为H，C 1 -C 4烷基，芳基或苄基; R5各自独立地为H，取代或未取代的芳基或杂芳基，条件是至少一个R 5为取代或未取代的芳基或取代或未取代的杂芳基; 并且R 6是H，C 1 -C 4烷基或氨基烷基。

公开(公告)号：US07579488B2

公开(公告)日：2009-08-25

申请号：US10579563

申请日：2004-11-16

申请人： Jianliang Lu ,  Tianwei Ma ,  Sunil Nagpal ,  Quanrong Shen ,  Alan M. Warshawsky ,  Jason Matthew Ochoada ,  Ying Kwong Yee

发明人： Jianliang Lu ,  Tianwei Ma ,  Sunil Nagpal ,  Quanrong Shen ,  Alan M. Warshawsky ,  Jason Matthew Ochoada ,  Ying Kwong Yee

IPC分类号： C07D307/87 ,  C07D307/00

CPC分类号： C07D405/12 ,  C07D307/80 ,  C07D407/12

摘要： The present invention relates to novel, non-secosteroidal, phenyl-benzofuran compounds with vitamin D receptor (VDR) modulating activity that are less hypercalcemic than 1α,25 dihydroxy vitamin D3. These compounds are useful for treating bone disease and psoriasis.

摘要翻译： 本发明涉及具有维生素D受体（VDR）调节活性的新颖非壬基苯基 - 苯并呋喃化合物，其比1α，25二羟基维生素D3低高钙血症。 这些化合物可用于治疗骨病和牛皮癣。

公开(公告)号：US06770640B1

公开(公告)日：2004-08-03

申请号：US09467292

申请日：1999-12-17

申请人： Alan M. Warshawsky ,  Michael J. Janusz

发明人： Alan M. Warshawsky ,  Michael J. Janusz

IPC分类号： C07D22312

CPC分类号： C07D403/12 ,  C07D223/12

摘要： The present invention relates to certain novel 1-carboxymethyl-2-oxo-azepan derivatives of the formula useful as inhibitors of matrix metalloproteinases (MMPs). The compounds of formula (1) are especially useful as selective inhibitors of MMP-12. Pharmaceutical compositions containing said compounds as well as methods of treating various disease states responding to inhibition of matrix metalloproteinase are also claimed herein.

摘要翻译： 本发明涉及作为基质金属蛋白酶（MMPs）抑制剂的某些新型1-羧甲基-2-氧代 - 氮杂衍生物。 式（1）的化合物特别可用作MMP-12的选择性抑制剂。 本文还要求含有所述化合物的药物组合物以及治疗对基质金属蛋白酶抑制作用的各种疾病状态的方法。

公开(公告)号：US06262080B1

公开(公告)日：2001-07-17

申请号：US09467304

申请日：1999-12-17

申请人： Alan M. Warshawsky ,  Michael J. Janusz

发明人： Alan M. Warshawsky ,  Michael J. Janusz

IPC分类号： A01N4340

CPC分类号： C07K5/06139 ,  A61K38/00

摘要： The present invention provides novel thio-substitutedamido lactam derivatives of the formula useful in as inhibitors of matrix metallo-proteinases (MMPs).

摘要翻译： 本发明提供了作为基质金属蛋白酶（MMPs）抑制剂的新型硫代取代的酰胺内酰胺衍生物。