公开(公告)号：US07528160B2

公开(公告)日：2009-05-05

申请号：US10541502

申请日：2003-12-31

申请人： Scott Eugene Conner ,  James Allen Knobelsdorf ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Xiaodong Wang ,  Guoxin Zhu ,  Jeffrey Michael Schkeryantz

发明人： Scott Eugene Conner ,  James Allen Knobelsdorf ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Xiaodong Wang ,  Guoxin Zhu ,  Jeffrey Michael Schkeryantz

IPC分类号： A61K31/427 ,  C07D277/24

CPC分类号： C07D263/57 ,  C07D209/10 ,  C07D235/18 ,  C07D277/60 ,  C07D277/66 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： The present invention is directed to a method of treatment by modulating a peroxisome proliferator activated receptor by employing a compound of Structural Formula (I). The variables in I are defined herein. Also included are compounds, methods of making compounds, and pharmaceutical compositions. The compounds of the present invention are believed to be effective in treating and preventing Syndrome X, Type H diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, atherosclerosis, and other disorders related to Syndrome X and cardiovascular diseases.

摘要翻译： 本发明涉及通过使用结构式（I）的化合物调节过氧化物酶体增殖物激活受体的治疗方法。 I中的变量在此定义。 还包括化合物，制备化合物的方法和药物组合物。 认为本发明的化合物可有效治疗和预防X综合征，H型糖尿病，高血糖症，高脂血症，肥胖症，凝血病，高血压，动脉粥样硬化以及与X综合征和心血管疾病相关的其他疾病。

公开(公告)号：US07153878B2

公开(公告)日：2006-12-26

申请号：US10505089

申请日：2003-02-13

申请人： Scott Eugene Conner ,  James Allen Knobelsdorf ,  Nathan Bryan Mantlo ,  Jeffrey Michael Schkeryantz ,  Quanrong Shen ,  Alan M Warshawsky ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  James Allen Knobelsdorf ,  Nathan Bryan Mantlo ,  Jeffrey Michael Schkeryantz ,  Quanrong Shen ,  Alan M Warshawsky ,  Guoxin Zhu

IPC分类号： A61K31/426 ,  A61K31/429 ,  A61K31/421 ,  A61K31/5377 ,  A61K31/506 ,  A61K31/497 ,  A61K31/443 ,  A61K31/4439 ,  A61K31/4525

CPC分类号： C07D263/32 ,  C07D277/24 ,  C07D277/26 ,  C07D277/28 ,  C07D277/30 ,  C07D403/10 ,  C07D413/04 ,  C07D413/10 ,  C07D417/04 ,  C07D417/10 ,  C07D417/14

摘要： The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts thereof, Formula I. (Formula I); wherein: (a) R5 is selected from the group consisting of (C1–C6)alkyl, (C1–C6)alkenyl, aryl (C0–C4)alkyl, aryloxy(C0–C4)alkyl, arylthio(C0–C4)alkyl, and further wherein when R5 is alkyl, R5 can optionally combine with W to form a 6 membered cycloheteroalkyl ring that is fused with the oxazole or thiazole ring to which the R5 group is attached; (b) R9 is selected from the group consisting of C1–C5alkyl, C1–C5alkenyl, and arylC0–C3alkyl. (c) T1 is selected from the group consisting of C and N, (d) W is selected from the group consisting of CH2, C(O)N(R21), N(R21), N(R21)CH2, O, OCH2, S, and SO2; and (e) X is selected from the group consisting of C, CH2C, and CCH2

摘要翻译： 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，式I（式I）; 其中：（a）R 5选自（C 1 -C 6 -C 6）烷基，（C 1 -C 6 - C 烷基，芳基（C 0 -C 4 -C 4）烷基，芳氧基（C 1 -C 4）烷基， 烷基，芳硫基（C 0 -C 4 -C 4）烷基，并且其中当R 5为烷基时，R 5可任意地与W结合形成6元 与R5基团连接的恶唑或噻唑环稠合的环杂烷基环; （b）R 9选自C 1 -C 5烷基，C 1 -C 5烷基，C 1 -C 5 - 烯基和芳基C 0 -C 3烷基。 （c）T 1选自C和N，（d）W选自CH 2，C（O）N（ R 21），N（R 21），N（R 21）CH 2，O，OCH 2，S和SO 2; 和（e）X选自C，CH 2 C和CCH 2，

公开(公告)号：US07655641B2

公开(公告)日：2010-02-02

申请号：US10542579

申请日：2004-02-10

申请人： Scott Eugene Conner ,  Lynn Stacy Gossett ,  Jonathan Edward Green ,  Winton Dennis Jones, Jr. ,  Nathan Bryan Mantlo ,  Donald Paul Matthews ,  Daniel Ray Mayhugh ,  Daryl Lynn Smith ,  Jennifer Ann Vance ,  Xiaodong Wang ,  Alan M Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Yanping Xu ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Lynn Stacy Gossett ,  Jonathan Edward Green ,  Winton Dennis Jones, Jr. ,  Nathan Bryan Mantlo ,  Donald Paul Matthews ,  Daniel Ray Mayhugh ,  Daryl Lynn Smith ,  Jennifer Ann Vance ,  Xiaodong Wang ,  Alan M Warshawsky ,  Leonard Larry Winneroski, Jr. ,  Yanping Xu ,  Guoxin Zhu

IPC分类号： A61K31/66 ,  A61K31/38 ,  C07D409/12 ,  C07D209/04

CPC分类号： C07D207/08 ,  A61K31/00 ,  A61K45/06 ,  C07C311/13 ,  C07C311/17 ,  C07C311/19 ,  C07C311/29 ,  C07C317/14 ,  C07C323/49 ,  C07C323/52 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D209/08 ,  C07D209/48 ,  C07D213/64 ,  C07D213/71 ,  C07D213/74 ,  C07D215/36 ,  C07D231/12 ,  C07D231/18 ,  C07D263/32 ,  C07D271/12 ,  C07D277/36 ,  C07D307/79 ,  C07D307/82 ,  C07D319/18 ,  C07D333/34 ,  C07D333/62 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  A61K2300/00

摘要： The present invention is directed to a compound of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates or stereoisomers thereof, which are useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.

摘要翻译： 本发明涉及式（I）化合物及其药学上可接受的盐，溶剂合物，水合物或立体异构体，其可用于治疗或预防由过氧化物酶体增殖物激活受体（PPAR）介导的病症，例如综合征X型 II型糖尿病，高血糖症，高脂血症，肥胖症，凝血病，高血压，动脉硬化以及与X综合症和心血管疾病有关的其他疾病。

公开(公告)号：US07396850B2

公开(公告)日：2008-07-08

申请号：US10537282

申请日：2003-12-31

申请人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Guoxin Zhu

IPC分类号： A61K31/415 ,  C07D231/10

CPC分类号： C07D231/12 ,  C07D233/20 ,  C07D233/22 ,  C07D233/64 ,  C07D249/06 ,  C07D253/04 ,  C07D261/08

摘要： The present invention is directed to a compound, {2-Methyl-4-[3-methyl-1-(4-trifluoromethyl-phenyl)-1H-pyrazol-4-ylmethylsulfanyl]-phenoxy}-acetic acid and pharmaceutical uses thereof.

摘要翻译： 本发明涉及化合物{2-甲基-4- [3-甲基-1-（4-三氟甲基 - 苯基）-1H-吡唑-4-基甲基硫烷基] - 苯氧基} - 乙酸及其药物用途。

公开(公告)号：US07259175B2

公开(公告)日：2007-08-21

申请号：US10505103

申请日：2003-02-13

申请人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

IPC分类号： A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/4439 ,  C07D417/10 ,  C07D413/10

CPC分类号： C07D413/04 ,  C07D263/32 ,  C07D277/24 ,  C07D277/26 ,  C07D413/10 ,  C07D417/04 ,  C07D417/10

摘要： The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts thereof, Formula I: wherein: (a) R5 is selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkenyl, substituted aryl(C0-C4)alkyl, substituted aryloxy(C0-C4)alkyl, substituted arylthio(C0-C4)alkyl, unsubstituted aryl(C0-C4)alkyl, unsubstituted aryloxy(C0-C4)alkyl, and unsubstituted arylthio(C0-C4)alkyl; (b) T1 is C or N; (c) Q is selected from the group consisting of O, a single bond, O(CH2)q and C; (d) q is 1 or 2; (e) W is selected from the group consisting of O, S, (CH2)rN(R20)(CH2)k, NHSO2, C(O)N(R20)(CH2)r, (CH2)rN(R20)C(O), and SO2; (f) X is CmH2m; (g) m is 0, 1 or 2; (h) A is an functional group selected from the group consisting of carboxyl, C1-C3 alkylnitrile, carboxamide, and (CH2)n COOR19; and (i) R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4alkyl and optionally substituted arylmethyl

摘要翻译： 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，式I：其中：（a）R 5选自（C 1 -C 3） （C 1 -C 6）烷基，（C 1 -C 6 -C 6）链烯基，取代的芳基（C 0 -C 6 - 取代的芳氧基（C 0 -C 4 -C 4烷基）烷基，取代的芳硫基（C 0 -C 4 - 烷基，未取代的芳基（C 0 -C 4 -C 4）烷基，未取代的芳氧基（C 0 -C 4 - 烷基和未取代的芳硫基（C 0 -C 4 -C 4）烷基; （b）T1为C或N; （c）Q选自O，单键，O（CH 2 CH 2）q C和C; （d）q为1或2; （e）W选自O，S，（CH 2）n N（R 20）（CH 2 CH 2） C（O）N（R 20）（CH 2）n），（CH

公开(公告)号：US07384965B2

公开(公告)日：2008-06-10

申请号：US10539477

申请日：2003-12-31

申请人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

IPC分类号： A61K31/428 ,  A61K31/426 ,  A61K31/421 ,  A61K31/423 ,  C07D277/66 ,  C07D263/57

CPC分类号： C07D209/10 ,  C07D235/18 ,  C07D263/57 ,  C07D277/60 ,  C07D277/66 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： The present invention is directed to compounds represented by the following structural formula, Formula I: wherein (a) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (b) U ia an aliphatic linker; (c) Y is selected from the group consisting of C, O, S, NH and a single bond; (d) E is C(R3) (R4) A or A and wherein (i) A is selected from the group consisting of carboxyl, tetrazole, C1-C6 alkylnitrile, carboxamidek, sulfonamide and acylsulfonamide; (e) B is selected from the group consisting of S, O, C, and N; (f) Z is selected from the group consisting of N and C; with the proviso that when B is C then Z is N.

摘要翻译： 本发明涉及由以下结构式（I）表示的化合物：其中（a）X选自单键，O，S，S（O）2和 N; （b）Uia一个脂族连接体; （c）Y选自C，O，S，NH和单键; （d）E是C（R3）（R4）A或A，其中（i）A选自羧基，四唑，C 1 -C 6 烷基腈，羧酰胺，磺酰胺和酰基磺酰胺; （e）B选自S，O，C和N; （f）Z选自N和C; 条件是当B为C时，则Z为N.

公开(公告)号：US07598266B2

公开(公告)日：2009-10-06

申请号：US12099929

申请日：2008-04-09

申请人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

IPC分类号： A61K31/437 ,  A61K31/4353 ,  C07D471/04

CPC分类号： C07D209/10 ,  C07D235/18 ,  C07D263/57 ,  C07D277/60 ,  C07D277/66 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： The present invention is directed to compounds represented by the following structural formula, Formula I: wherein: (a) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (b) U is an aliphatic linker; (c) Y is selected from the group consisting of C, O, S, NH and a single bond; (d) E is C(R3)(R4)A or A and wherein (i) A is selected from the group consisting of carboxyl, tetrazole, C1-C6 alkylnitrile, carboxamide, sulfonamide and acylsulfonamide; (e) B is selected from the group consisting of S, O, C, and N; (f) Z is selected from the group consisting of N and C; with the proviso that when B is C then Z is N.

摘要翻译： 本发明涉及由以下结构式（I）表示的化合物：其中：（a）X选自单键，O，S，S（O）2和N; （b）U是脂族连接体; （c）Y选自C，O，S，NH和单键; （d）E是C（R3）（R4）A或A，其中（i）A选自羧基，四唑，C 1 -C 6烷基腈，甲酰胺，磺酰胺和酰基磺酰胺; （e）B选自S，O，C和N; （f）Z选自N和C; 条件是当B为C时，则Z为N.

公开(公告)号：US20090054479A1

公开(公告)日：2009-02-26

申请号：US12099929

申请日：2008-04-09

申请人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

发明人： Scott Eugene Conner ,  Nathan Bryan Mantlo ,  Guoxin Zhu

IPC分类号： A61K31/437 ,  C07D277/66 ,  A61K31/428 ,  C07D263/57 ,  A61P3/10 ,  A61K31/423 ,  C07D471/04

CPC分类号： C07D209/10 ,  C07D235/18 ,  C07D263/57 ,  C07D277/60 ,  C07D277/66 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： The present invention is directed to compounds represented by the following structural formula, Formula I: wherein: (a) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (b) U is an aliphatic linker; (c) Y is selected from the group consisting of C, O, S, NH and a single bond; (d) E is C(R3)(R4)A or A and wherein (i) A is selected from the group consisting of carboxyl, tetrazole, C1-C6 alkylnitrile, carboxamide, sulfonamide and acylsulfonamide; (e) B is selected from the group consisting of S, O, C, and N; (f) Z is selected from the group consisting of N and C; with the proviso that when B is C then Z is N.

摘要翻译： 本发明涉及由以下结构式（I）表示的化合物：其中：（a）X选自单键，O，S，S（O）2和N; （b）U是脂族连接体; （c）Y选自C，O，S，NH和单键; （d）E是C（R3）（R4）A或A，其中（i）A选自羧基，四唑，C 1 -C 6烷基腈，甲酰胺，磺酰胺和酰基磺酰胺; （e）B选自S，O，C和N; （f）Z选自N和C; 条件是当B为C时，则Z为N.

公开(公告)号：US07304062B2

公开(公告)日：2007-12-04

申请号：US10415673

申请日：2001-11-09

申请人： Samuel James Dominianni ,  Garret Jay Etgen ,  Richard Duane Johnston ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  Christopher Randall Schmid ,  Yanping Xu

发明人： Samuel James Dominianni ,  Garret Jay Etgen ,  Richard Duane Johnston ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  Christopher Randall Schmid ,  Yanping Xu

IPC分类号： A61K31/5377 ,  A61K31/4709 ,  A61K31/4196 ,  C07D413/06 ,  C07D249/12 ,  C07D215/12

CPC分类号： C07C281/06 ,  C07C257/22 ,  C07C281/04 ,  C07D249/12 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06 ,  C07D417/12

摘要： The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-2-alkyl, heteroaryl-C0-2-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl. X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH2)nCOOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, arylC0-C4alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl.

摘要翻译： 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，溶剂合物和水合物，R 1是选自C 1 -C 8烷基的取代或未取代的基团， 烷基，芳基-C 0-2 - - 烷基，杂芳基-C 0-2-2 - 烷基，C 3 -C 6环烷基芳基-C 0-2-2 - 烷基或苯基。 W是O或S.R 2是H或选自C 1 -C 6烷基，C 3 -C 3烷基的取代或未取代的基团， C 6环烷基和杂芳基。 X是连接子的一个碳原子可以被O，NH或S取代的C 2 -C 5亚烷基连接基，Y是C，O，S，NH 或单一债券。 此外，E是（CH 2 SO 2）n COOH，其中n是0,1,2或3，或C（R 3）（R 4）A，其中A是 酸性官能团如羧基，羧酰胺取代或未取代的磺酰胺，或取代或未取代的四唑。 R 3是H，饱和或不饱和的C 1 -C 5烷基，C 1 -C 5烷氧基。 另外，R 4是H，卤素，取代或未取代的选自C 1 -C 5烷基，C 1 -C 3烷基， 5个烷氧基，C 3 -C 6环烷基，芳基C 0 -C 4烷基和苯基 ，或R 3和R 4结合形成C 3 -C 4环烷基。

公开(公告)号：US07749992B2

公开(公告)日：2010-07-06

申请号：US10574649

申请日：2004-10-07

申请人： Guoqing Cao ,  Ana Maria Escribano ,  Maria Carmen Fernandez ,  Todd Fields ,  Douglas Linn Gernert ,  Christopher Lawrence Cioffi ,  Robert Jason Herr ,  Nathan Bryan Mantlo ,  Eva Maria Martin De La Nava ,  Ana Isabel Mateo Herranz ,  Daniel Ray Mayhugh ,  Xiaodong Wang

发明人： Guoqing Cao ,  Ana Maria Escribano ,  Maria Carmen Fernandez ,  Todd Fields ,  Douglas Linn Gernert ,  Christopher Lawrence Cioffi ,  Robert Jason Herr ,  Nathan Bryan Mantlo ,  Eva Maria Martin De La Nava ,  Ana Isabel Mateo Herranz ,  Daniel Ray Mayhugh ,  Xiaodong Wang

IPC分类号： A61P3/06 ,  A61P9/10 ,  A61K31/55 ,  C07D223/14 ,  C07D223/16 ,  C07D223/32 ,  C07D225/06 ,  C07D403/04 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D413/04 ,  C07D491/04

CPC分类号： C07D223/16 ,  C07D223/14 ,  C07D223/32 ,  C07D225/06 ,  C07D403/04 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D413/04 ,  C07D491/04

摘要： Compounds of formula I wherein n, m, p, q, y, R1 R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating artherosclerosis and its sequelae.

摘要翻译： 其中n，m，p，q，y，R 1，R 2，R 3，R 4，R 5和R 6如本文所定义的式I化合物，其药物组合物和使用方法被公开用于治疗动脉粥样硬化及其后遗症。