公开(公告)号：WO2004063166A1

公开(公告)日：2004-07-29

申请号：PCT/US2003/039119

申请日：2003-12-31

Applicant: ELI LILLY AND COMPANY ,  CONNER, Scott, Eugene ,  MA, Tianwei ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  SCHKERYANTZ, Jeffrey, Michael ,  WARSHAWSKY, Alan, M. ,  ZHU, Guoxin

Inventor： CONNER, Scott, Eugene ,  MA, Tianwei ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  SCHKERYANTZ, Jeffrey, Michael ,  WARSHAWSKY, Alan, M. ,  ZHU, Guoxin

IPC: C07D231/12

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

Abstract: 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 O, C, 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) Z1 and Z2 are each independently selected from the group consisting of N, O, and C with the proviso that at least one of Z1 and Z2 is N; (f) Z3 is selected from the group consisting of N, O, and C. (g) R8 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C4 alkylenyl and halo; (h) R9 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, aryl- C0-C4 alkyl, heteroaryl, C1-C6 allyl, and OR29.

Abstract translation: 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O，C，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）Z1和Z2各自独立地选自N，O和C，条件是Z1和Z2中的至少一个是N; （f）Z 3选自N，O和C.（g）R 8选自氢，C 1 -C 6烷基，C 1 -C 4亚烷基和卤素; （h）R 9选自氢，C 1 -C 4烷基，C 1 -C 4亚烷基，卤素，芳基-C 0 -C 4烷基，杂芳基，C 1 -C 6烯丙基和OR 29。

公开(公告)号：WO0011023A3

公开(公告)日：2000-06-15

申请号：PCT/US9918908

申请日：1999-08-18

Applicant: LILLY CO ELI ,  BORROMEO PETER STANLEY ,  COHEN JEFFREY DANIEL ,  GREGORY GEORGE STUART ,  HENLE STACY KAY ,  HITCHCOCK STEPHEN ANDREW ,  JUNGHEIM LOUIS NICKOLAUS ,  MAYHUGH DANIEL RAY ,  SHEPHERD TIMOTHY ALAN ,  TURNER WILLIAM WILSON JR

Inventor： BORROMEO PETER STANLEY ,  COHEN JEFFREY DANIEL ,  GREGORY GEORGE STUART ,  HENLE STACY KAY ,  HITCHCOCK STEPHEN ANDREW ,  JUNGHEIM LOUIS NICKOLAUS ,  MAYHUGH DANIEL RAY ,  SHEPHERD TIMOTHY ALAN ,  TURNER WILLIAM WILSON JR

IPC: A61K9/08 ,  A61K9/72 ,  A61K38/00 ,  A61P31/10 ,  A61P33/00 ,  C07K1/06 ,  C07K7/50 ,  C07K7/54 ,  C07K7/56 ,  C07K7/64 ,  A61K38/12

CPC classification number: C07K7/50 ,  A61K38/00 ,  C07K7/56

Abstract: 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.

Abstract translation: 提供了用于修饰棘白菌素型化合物的环肽环体系以产生具有抗真菌活性的新型类似物的方法。 本发明的方法包括打开环肽环，切割末端鸟氨酸单元，插入至少一个新氨基酸或其他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，进一步修饰的位点，增加或减少环核内氨基酸或肽单元的数目，以及增加或减少环内肽的总数 戒指。 本发明还提供了新型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：WO2005097806A1

公开(公告)日：2005-10-20

申请号：PCT/US2005/009301

申请日：2005-03-17

Applicant: ELI LILLY AND COMPANY ,  BELL, Michael, Gregory ,  CAO, Guoqing ,  ESCRIBANO, Ana, Maria ,  FERNANDEZ, Maria, Carmen ,  LANDER, Peter, Ambrose ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

Inventor： BELL, Michael, Gregory ,  CAO, Guoqing ,  ESCRIBANO, Ana, Maria ,  FERNANDEZ, Maria, Carmen ,  LANDER, Peter, Ambrose ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

IPC: C07D495/04

CPC classification number: C07D495/04 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention discloses compounds of formula (I) wherein A, n, q, K, W, X, Y, Z, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.

Abstract translation: 本发明公开了式（I）的化合物，其中A，n，q，K，W，X，Y，Z，R 1，R 2，R 3，R 4，R 5 >和R 6如本文所定义，并且其药物组合物和使用方法被公开用于治疗血脂异常及其后遗症。

公开(公告)号：WO2004073606A2

公开(公告)日：2004-09-02

申请号：PCT/US2004/002015

申请日：2004-02-10

Applicant: ELI LILLY AND COMPANY ,  CONNER, Scott, Eugene ,  GOSSETT, Lynn, Stacy ,  GREEN, Jonathan, Edward ,  JONES, Winton, Dennis Jr. ,  MANTLO, Nathan, Bryan ,  MATTHEWS, Donald, Paul ,  MAYHUGH, Daniel, Ray ,  SMITH, Daryl, Lynn ,  VANCE, Jennifer, Ann ,  WANG, Xiaodong ,  WARSHAWSKY, Alan, M ,  WINNEROSKI, Leonard, Larry Jr. ,  XU, Yanping ,  ZHU, Guoxin

Inventor： CONNER, Scott, Eugene ,  GOSSETT, Lynn, Stacy ,  GREEN, Jonathan, Edward ,  JONES, Winton, Dennis Jr. ,  MANTLO, Nathan, Bryan ,  MATTHEWS, Donald, Paul ,  MAYHUGH, Daniel, Ray ,  SMITH, Daryl, Lynn ,  VANCE, Jennifer, Ann ,  WANG, Xiaodong ,  WARSHAWSKY, Alan, M ,  WINNEROSKI, Leonard, Larry Jr. ,  XU, Yanping ,  ZHU, Guoxin

IPC: A61K

CPC classification number: 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

Abstract: 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.

Abstract translation: 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， II型糖尿病，高血糖症，高脂血症，肥胖症，凝血病，高血压，动脉硬化以及与综合症X和心血管疾病相关的其它疾病。

公开(公告)号：WO2010009062A1

公开(公告)日：2010-01-21

申请号：PCT/US2009/050440

申请日：2009-07-14

Applicant: ELI LILLY AND COMPANY ,  KHILEVICH, Albert ,  LIU, Bin ,  MAYHUGH, Daniel, Ray ,  SCHKERYANTZ, Jeffrey, Michael ,  ZHANG, Deyi

Inventor： KHILEVICH, Albert ,  LIU, Bin ,  MAYHUGH, Daniel, Ray ,  SCHKERYANTZ, Jeffrey, Michael ,  ZHANG, Deyi

IPC: C07D233/92 ,  A61K31/4164 ,  A61P25/00

CPC classification number: C07D233/92

Abstract: The present invention provides certain imidazole carboxamide derivatives, pharmaceutical compositions thereof, methods of using the same for preparing a medicament useful in the treatment of conditions associated with the mGluR 2 receptor, such as depression and anxiety, and processes of the following Formula (I) for preparing the same.

Abstract translation: 本发明提供某些咪唑羧酰胺衍生物，其药物组合物，其用于制备可用于治疗与mGluR2受体相关的病症（例如抑郁症和焦虑症）的药物的方法，以及下式（I）的方法 准备一样

公开(公告)号：WO2005037796A1

公开(公告)日：2005-04-28

申请号：PCT/US2004/030907

申请日：2004-10-07

Applicant: ELI LILLY AND COMPANY ,  CAO, Guoqing ,  ESCRIBANO, Ana Maria ,  FERNANDEZ, Maria Carmen ,  FIELDS, Todd ,  GERNERT, Douglas, Linn ,  CIOFFI, Christopher, Lawrence ,  HERR, Robert, Jason ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

Inventor： CAO, Guoqing ,  ESCRIBANO, Ana Maria ,  FERNANDEZ, Maria Carmen ,  FIELDS, Todd ,  GERNERT, Douglas, Linn ,  CIOFFI, Christopher, Lawrence ,  HERR, Robert, Jason ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

IPC: C07D223/16

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

Abstract: Compounds of formula I wherein n, m, p, q, Y, R 1 R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating artherosclerosis and its sequelae.

Abstract translation: 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化合物及其 公开了用于治疗动脉粥样硬化及其后遗症的药物组合物和使用方法。

公开(公告)号：WO0238553A3

公开(公告)日：2003-05-01

申请号：PCT/US0142928

申请日：2001-11-09

Applicant: LILLY CO ELI ,  MANTLO NATHAN BRYAN ,  COLLADO CANO IVAN ,  DOMINIANNI SAMUEL JAMES ,  ETGEN GARRET JAY JUNIOR ,  GARCIA-PAREDES CRISTINA ,  JOHNSTON RICHARD DUANE ,  LETOURNEAU MICHAEL EDWARD ,  MARTINELLI MICHAEL JOHN ,  MAYHUGH DANIEL RAY ,  SAEED ASHRAF ,  THOMPSON RICHARD CRAIG ,  WANG XIADONG ,  COFFEY DAVID SCOTT ,  SCHMID CHRISTOPHER RANDALL ,  VICENZI JEFFREY THOMAS ,  XU YANPING

Inventor： MANTLO NATHAN BRYAN ,  COLLADO CANO IVAN ,  DOMINIANNI SAMUEL JAMES ,  ETGEN GARRET JAY JUNIOR ,  GARCIA-PAREDES CRISTINA ,  JOHNSTON RICHARD DUANE ,  LETOURNEAU MICHAEL EDWARD ,  MARTINELLI MICHAEL JOHN ,  MAYHUGH DANIEL RAY ,  SAEED ASHRAF ,  THOMPSON RICHARD CRAIG ,  WANG XIADONG ,  COFFEY DAVID SCOTT ,  SCHMID CHRISTOPHER RANDALL ,  VICENZI JEFFREY THOMAS ,  XU YANPING

IPC: A61K31/4196 ,  A61K31/42 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/5377 ,  A61P3/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/00 ,  A61P43/00 ,  C07C257/22 ,  C07C281/04 ,  C07C281/06 ,  C07D249/12 ,  C07D401/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D407/06 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06 ,  C07D417/12 ,  A61K31/427

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

Abstract: he present invention is directed to compounds represented by the following structural formula (I'), 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.

Abstract translation: 本发明涉及由以下结构式（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，R 1是选自C 1 -C 8烷基，芳基-C 0-2 - 烷基， 杂芳基-C 0-2 - 烷基，C 3 -C 6环烷基芳基-C 0-2 - 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 6环烷基和杂芳基的取代或未取代的基团。 X是C2-C5亚烷基连接体，连接体的一个碳原子可被O，NH或S取代.Y是C，O，S，NH或单键。 此外，E是（CH 2）n COOH，其中n是0,1,2或3或C（R3）（R4）A，其中A是酸性官能团，例如羧基，羧酰胺取代或未取代的磺酰胺，或取代或 未取代的四唑。 R3是H，饱和或不饱和的C1-C5烷基，C1-C5烷氧基。 另外，R 4为H，卤素，取代或未取代的选自C 1 -C 5烷基，C 1 -C 5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的基团，形成C 3 -C 4环烷基。

公开(公告)号：WO2005097805A1

公开(公告)日：2005-10-20

申请号：PCT/US2005/009294

申请日：2005-03-17

Applicant: ELI LILLY AND COMPANY ,  BELL, Michael, Gregory ,  CAO, Guoqing ,  ESCRIBANO, Ana, Maria ,  FERNANDEZ, Maria, Carmen ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

Inventor： BELL, Michael, Gregory ,  CAO, Guoqing ,  ESCRIBANO, Ana, Maria ,  FERNANDEZ, Maria, Carmen ,  MANTLO, Nathan, Bryan ,  MARTIN DE LA NAVA, Eva, Maria ,  MATEO HERRANZ, Ana, Isabel ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong

IPC: C07D495/04

CPC classification number: C07D495/04 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention discloses compounds of formula I wherein A, n, m, j, q, K, W, X, K, Z, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.

Abstract translation: 本发明公开了式I化合物，其中A，n，m，j，q，K，W，X，K，Z，R 1，R 2，R 3，R 4，R 5和R 6如本文所定义，其药物组合物和使用方法被公开用于治疗血脂异常及其后遗症。

公开(公告)号：WO2004092131A1

公开(公告)日：2004-10-28

申请号：PCT/US2003/041698

申请日：2003-12-31

Applicant: ELI LILLY AND COMPANY ,  LIGAND PHARMACEUTICALS, INC. ,  CONNER, Scott, Eugene ,  KNOBELSDORG, James, Allen ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong ,  ZHU, Guoxin ,  SCHKERYANTZ, Jeffrey, Michael ,  MICHELLYS, Pierre-Yves

Inventor： CONNER, Scott, Eugene ,  KNOBELSDORG, James, Allen ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  WANG, Xiaodong ,  ZHU, Guoxin ,  SCHKERYANTZ, Jeffrey, Michael ,  MICHELLYS, Pierre-Yves

IPC: C07D209/08

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

Abstract: 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 II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, atherosclerosis, and other disorders related to Syndrome X and cardiovascular diseases.

Abstract translation: 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）中的变量在本文中定义。 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在治疗和预防X综合征，II型糖尿病，高血糖症，高脂血症，肥胖，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有关的其它疾病方面是有效的。

公开(公告)号：WO2004063165A1

公开(公告)日：2004-07-29

申请号：PCT/US2003/039117

申请日：2003-12-31

Applicant: ELI LILLY AND COMPANY ,  CONNER, Scott, Eugene ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  ZHU, Guoxin

Inventor： CONNER, Scott, Eugene ,  MANTLO, Nathan, Bryan ,  MAYHUGH, Daniel, Ray ,  ZHU, Guoxin

IPC: C07D231/12

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

Abstract: 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.

Abstract translation: 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。