公开(公告)号：WO2011003065A3

公开(公告)日：2011-05-19

申请号：PCT/US2010040906

申请日：2010-07-02

Applicant: GENENTECH INC ,  GIBBONS PAUL ,  HANAN EMILY ,  LIU WENDY ,  LYSSIKATOS JOSEPH P ,  MAGNUSON STEVEN R ,  MENDONCA ROHAN ,  PASTOR RICHARD ,  RAWSON THOMAS E ,  SIU MICHAEL ,  ZAK MARK E ,  ZHOU AIHE ,  ZHU BING-YAN

Inventor： GIBBONS PAUL ,  HANAN EMILY ,  LIU WENDY ,  LYSSIKATOS JOSEPH P ,  MAGNUSON STEVEN R ,  MENDONCA ROHAN ,  PASTOR RICHARD ,  RAWSON THOMAS E ,  SIU MICHAEL ,  ZAK MARK E ,  ZHOU AIHE ,  ZHU BING-YAN

IPC: C07D487/04 ,  A61K31/437 ,  A61P35/00 ,  C07D403/12

CPC classification number: C07D487/04

Abstract: A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are defined herein, are useful as inhibitors of one or more Janus kinases. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient are disclosed.

Abstract translation: 其中R 1，R 2和R 3在本文中定义的式I化合物，对映异构体，非对映异构体，互变异构体或其药学上可接受的盐可用作一种或多种Janus激酶的抑制剂。 公开了包含式I化合物和药学上可接受的载体，佐剂或载体的药物组合物，以及对患者中Janus激酶活性的抑制作出反应的疾病或病症的严重程度的治疗或减轻的方法。

公开(公告)号：WO2005060963A8

公开(公告)日：2005-12-01

申请号：PCT/IB2004004056

申请日：2004-12-06

Applicant: PFIZER ,  EDWARDS MARTIN PAUL ,  JOHNSON THEODORE OTTO JR ,  NAIR SAJIV KRISHNAN ,  SIU MICHAEL ,  TAYLOR WENDY DIANNE ,  CRIPPS STEPHAN JAMES ,  WANG YONG ,  CHENG HENGMIAO ,  SMITH CHRISTOPHER RONALD

Inventor： EDWARDS MARTIN PAUL ,  JOHNSON THEODORE OTTO JR ,  NAIR SAJIV KRISHNAN ,  SIU MICHAEL ,  TAYLOR WENDY DIANNE ,  CRIPPS STEPHAN JAMES ,  WANG YONG ,  CHENG HENGMIAO ,  SMITH CHRISTOPHER RONALD

IPC: A61K31/44 ,  A61K31/4436 ,  A61K31/4545 ,  C07C311/36 ,  C07C311/37 ,  C07D209/08 ,  C07D213/02 ,  C07D213/76 ,  C07D215/38 ,  C07D235/06 ,  C07D239/42 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04 ,  A61P3/04 ,  A61P3/10

CPC classification number: C07D209/08 ,  C07D213/76 ,  C07D215/38 ,  C07D235/06 ,  C07D239/42 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D513/04

Abstract: The present invention relates to compounds with the formula (I), or a pharmaceutically acceptable salt thereof, wherein: R is selected from the group consisting of (C1-C6)alkyl, -(CR R )t(C3-C12)cycloalkyl, -(CR R )t(C6-C12)aryl, and -(CR R )t(4-10)-membered heterocyclyl; b and k are each independently selected from 1 and 2; j is selected from the group consisting of 0, 1, and 2; t, u, p, q, and v are each independently selected from the group consisting of 0, 1, 2, 3, 4, and 5; T is a (6-10)-membered heterocyclyl containing at least one nitrogen atom; R is selected from the group consisting of H, (C1-C6)alkyl, -(CR R )t(C3-C12)cycloalkyl, -(CR R )t(C6-C12)aryl, and -(CR R )t(4-10)-membered heterocyclyl; each R and R is independently selected from H and (C1-C6)alkyl, the carbon atoms of T, R , R , R and R may each be optionally, substituted by I to 5 R groups; R is defined in the claims; The compounds of the present invention are 11 ß-hsd-1 inhibitors, and are therefore believed to be useful in the treatment of diabetes, obesity, glaucoma, osteoporosis, cognitive disorders, immune disorders, depression, hypertension, and metabolic diseases.

Abstract translation: 本发明涉及具有式（I）化合物或其药学上可接受的盐，其中：R 1选自（C 1 -C 6）烷基， - （CR 3 R 4） ）（C 3 -C 12）环烷基， - （CR 3 R 4）t（C 6 -C 12）芳基和 - （CR 3 R 4）t（4-10） - 杂环基; b和k各自独立地选自1和2; j选自0，1和2; t，u，p，q和v各自独立地选自0,1,2,3,4和5; T是含有至少一个氮原子的（6-10） - 杂环基; R 2选自H，（C 1 -C 6）烷基， - （CR 3 R 4）t（C 3 -C 12）环烷基， - （CR 3 R 4） t（C 6 -C 12）芳基和 - （CR 3 R 4）t（4-10） - 杂环基; 每个R 3和R 4独立地选自H和（C 1 -C 6）烷基，T，R 1，R 2，R 3和R 4的碳原子， 可各自任选被I至5个R 5基团取代; R 5定义在权利要求中; 本发明的化合物是11β-hsd-1抑制剂，因此被认为可用于治疗糖尿病，肥胖，青光眼，骨质疏松症，认知障碍，免疫疾病，抑郁症，高血压和代谢疾病。

公开(公告)号：WO2011123674A1

公开(公告)日：2011-10-06

申请号：PCT/US2011/030769

申请日：2011-03-31

Applicant: ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  CLARK, Christopher, T. ,  COOK, Adam ,  GUNAWARDANA, Indrani, W. ,  HUNT, Kevin W. ,  KALLAN, Nicholas, C. ,  SIU, Michael ,  THOMAS, Allen, A. ,  VOLGRAF, Matthew

Inventor： CLARK, Christopher, T. ,  COOK, Adam ,  GUNAWARDANA, Indrani, W. ,  HUNT, Kevin W. ,  KALLAN, Nicholas, C. ,  SIU, Michael ,  THOMAS, Allen, A. ,  VOLGRAF, Matthew

IPC: C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D263/64 ,  A61K31/41 ,  A61P25/28

CPC classification number: C07D401/14 ,  C07D263/64 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10

Abstract: The invention provides novel spirotetrahydronaphthalene compounds of Formula α that inhibit β-secretase cleavage of APP and are useful as therapeutic agents for treating neurodegenerative diseases.

Abstract translation: 本发明提供新颖的抑制APP分泌​​酶切割的式（a）的四氢四氢化合物，可用作治疗神经变性疾病的治疗剂。

公开(公告)号：WO2011003065A2

公开(公告)日：2011-01-06

申请号：PCT/US2010/040906

申请日：2010-07-02

Applicant: GENENTECH, INC. ,  GIBBONS, Paul ,  HANAN, Emily ,  LIU, Wendy ,  LYSSIKATOS, Joseph P. ,  MAGNUSON, Steven R. ,  MENDONCA, Rohan ,  PASTOR, Richard ,  RAWSON, Thomas E. ,  SIU, Michael ,  ZAK, Mark E. ,  ZHOU, Aihe ,  ZHU, Bing-Yan

Inventor： GIBBONS, Paul ,  HANAN, Emily ,  LIU, Wendy ,  LYSSIKATOS, Joseph P. ,  MAGNUSON, Steven R. ,  MENDONCA, Rohan ,  PASTOR, Richard ,  RAWSON, Thomas E. ,  SIU, Michael ,  ZAK, Mark E. ,  ZHOU, Aihe ,  ZHU, Bing-Yan

IPC: C07D487/04 ,  C07D403/12 ,  A61K31/437 ,  A61P35/00

CPC classification number: C07D487/04

Abstract: A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 and R 3 are defined herein, are useful as inhibitors of one or more Janus kinases. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient are disclosed.

Abstract translation: 式I化合物，其对映异构体，非对映异构体，互变异构体或可药用盐，其中R 1， 3如本文所定义，可用作一种或多种Janus激酶的抑制剂。 公开了包含式I化合物和药学上可接受的载体，佐剂或媒介物的药物组合物，以及治疗或减轻患者中抑制Janus激酶活性的疾病或病症的严重程度或减轻其严重程度的方法。 p>

公开(公告)号：WO2009123971A1

公开(公告)日：2009-10-08

申请号：PCT/US2009/038795

申请日：2009-03-30

Applicant: GENENTECH, INC. ,  F. HOFFMANN- LA ROCHE AG ,  DO, Steven ,  GOLDSMITH, Richard ,  HEFFRON, Tim ,  KOLESNIKOV, Aleksandr ,  STABEN, Steven ,  OLIVERO, Alan, G. ,  SIU, Michael ,  SUTHERLIN, Daniel, P. ,  ZHU, Bing-yan ,  GOLDSMITH, Paul ,  BAYLISS, Tracy ,  FOLKES, Adrian ,  PEGG, Neil

Inventor： DO, Steven ,  GOLDSMITH, Richard ,  HEFFRON, Tim ,  KOLESNIKOV, Aleksandr ,  STABEN, Steven ,  OLIVERO, Alan, G. ,  SIU, Michael ,  SUTHERLIN, Daniel, P. ,  ZHU, Bing-yan ,  GOLDSMITH, Paul ,  BAYLISS, Tracy ,  FOLKES, Adrian ,  PEGG, Neil

IPC: C07D495/04 ,  C07D513/04 ,  A61K31/38 ,  A61K31/429 ,  A61P35/00

CPC classification number: C07F5/02 ,  A61K31/381 ,  A61K31/4155 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/429 ,  A61K31/4365 ,  A61K31/4436 ,  A61K31/496 ,  A61K31/53 ,  C07D495/04 ,  C07D495/14 ,  C07D513/14

Abstract: Benzopyran and benzoxepin compounds of Formulas I and II, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formulas I and II for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract translation: 式I和II的苯并吡喃和苯并辛菌素化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物和药学上可接受的盐，可用于抑制脂质激酶，包括p110α和PI3K的其他同种型，并用于治疗疾病如癌症 由脂质激酶介导。 公开了使用式I和II的化合物在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：WO2012071458A1

公开(公告)日：2012-05-31

申请号：PCT/US2011/061930

申请日：2011-11-22

Applicant: ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  COOK, Adam ,  GUNAWARDANA, Indrani, W. ,  HUESTIS, Malcolm ,  HUNT, Kevin, W. ,  KALLAN, Nicholas, C. ,  METCALF, Andrew, T. ,  NEWHOUSE, Brad ,  SIU, Michael ,  TANG, Tony, P. ,  THOMAS, Allen, A. ,  VOLGRAF, Matthew

Inventor： COOK, Adam ,  GUNAWARDANA, Indrani, W. ,  HUESTIS, Malcolm ,  HUNT, Kevin, W. ,  KALLAN, Nicholas, C. ,  METCALF, Andrew, T. ,  NEWHOUSE, Brad ,  SIU, Michael ,  TANG, Tony, P. ,  THOMAS, Allen, A. ,  VOLGRAF, Matthew

IPC: C07D491/20 ,  C07D498/20 ,  C07D491/107 ,  C07D498/10 ,  C07D513/10 ,  C07D513/20 ,  A61K31/4439 ,  A61K31/527 ,  A61K31/444 ,  A61K31/506 ,  A61K31/424 ,  A61K31/429 ,  A61K31/437 ,  A61P25/28

CPC classification number: C07D498/20 ,  C07D491/107 ,  C07D491/20 ,  C07D498/10 ,  C07D513/10 ,  C07D513/20

Abstract: The invention provides novel tricyclic compounds of Formula I' that inhibit β-secretase cleavage of APP and are useful as therapeutic agents for treating neurodegenerative diseases.

Abstract translation: 本发明提供抑制APP的β-分泌酶切割的新颖的式I'三环化合物，并且可用作治疗神经变性疾病的治疗剂。

公开(公告)号：WO2006134467A1

公开(公告)日：2006-12-21

申请号：PCT/IB2006/001581

申请日：2006-06-06

Applicant: PFIZER INC. ,  DRESS, Klaus, Ruprecht ,  NAIR, Sajiv, Krishman ,  SIU, Michael ,  TAYLOR, Wendy, Dianne

Inventor： DRESS, Klaus, Ruprecht ,  NAIR, Sajiv, Krishman ,  SIU, Michael ,  TAYLOR, Wendy, Dianne

IPC: C07D417/12 ,  C07D213/75 ,  A61K31/4439 ,  A61P9/00

CPC classification number: C07D213/75 ,  C07D417/12

Abstract: The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds described herein, their pharmaceutically acceptable salts, hydrates and solvates, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11βHSD1).

Abstract translation: 本发明涉及新化合物，其包含本文所述的化合物，其药学上可接受的盐，水合物和溶剂合物的药物组合物，以及该化合物在医药中的用途以及用于制备作用于人11 -β-羟基类固醇脱氢酶1型酶（11βHSD1）。

公开(公告)号：WO2009155551A1

公开(公告)日：2009-12-23

申请号：PCT/US2009/048017

申请日：2009-06-19

Applicant: GENENTECH, INC. ,  ZHU, Bing-Yan ,  SIU, Michael ,  MAGNUSON, Steven, R. ,  PASTOR, Richard ,  HAIYING, He ,  YISONG, Xiao ,  JIFU, Zheng ,  XING, Xu ,  JUNPING, Zhao

Inventor： ZHU, Bing-Yan ,  SIU, Michael ,  MAGNUSON, Steven, R. ,  PASTOR, Richard ,  HAIYING, He ,  YISONG, Xiao ,  JIFU, Zheng ,  XING, Xu ,  JUNPING, Zhao

IPC: A01N43/64 ,  A61K31/41

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61K31/496 ,  A61K31/5377 ,  C07D487/04

Abstract: A compound of Formula (I), enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula (I) and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed. Formula (I).

Abstract translation: 式（I）的化合物，其对映体，非对映体，互变异构体或其药学上可接受的盐，其中R1，R2，R3，R4和R5如本文所定义，可用作JAK激酶抑制剂。 公开了包含式（I）化合物和药学上可接受的载体，佐剂或媒介物的药物组合物，以及治疗或减轻对患者中JAK激酶活性抑制作出反应的疾病或病症的严重性的方法。 式（I）。

公开(公告)号：WO2009155565A1

公开(公告)日：2009-12-23

申请号：PCT/US2009/048041

申请日：2009-06-19

Applicant: GENENTECH, INC. ,  ZHU, Bing-yan ,  SIU, Michael ,  MAGNUSON, Steven, R. ,  PASTOR, Richard ,  HAIYING, He ,  YISONG, Xiao ,  JIFU, Zheng ,  XING, Xu ,  JUNPING, Zhao ,  LIU, Wendy

Inventor： ZHU, Bing-yan ,  SIU, Michael ,  MAGNUSON, Steven, R. ,  PASTOR, Richard ,  HAIYING, He ,  YISONG, Xiao ,  JIFU, Zheng ,  XING, Xu ,  JUNPING, Zhao ,  LIU, Wendy

IPC: A01N43/64 ,  A61K31/41

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K45/06

Abstract: A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.

Abstract translation: 其中R 1，R 2，R 3，R 4和R 5在本文中定义的式I化合物，对映异构体，非对映异构体，互变异构体或其药学上可接受的盐可用作JAK激酶抑制剂。 公开了包含式I化合物和药学上可接受的载体，佐剂或载体的药物组合物，以及治疗或减轻对患者中JAK激酶活性的抑制作用的疾病或病症的严重程度的方法。

公开(公告)号：WO2008049239A1

公开(公告)日：2008-05-02

申请号：PCT/CA2007/001935

申请日：2007-10-26

Applicant: MOUNT SINAI HOSPITAL ,  UNIVERSITY HEALTH NETWORK ,  SIU, Michael, K., W. ,  COLGAN, Terence, J. ,  ROMASCHIN, Alexander, D. ,  DE SOUZA, Leroi, V.

Inventor： SIU, Michael, K., W. ,  COLGAN, Terence, J. ,  ROMASCHIN, Alexander, D. ,  DE SOUZA, Leroi, V.

IPC: C40B40/10 ,  A61K49/00 ,  C07K14/47 ,  C07K14/52 ,  C07K14/705 ,  C07K14/775 ,  C07K14/81 ,  C12N9/12 ,  C12Q1/00 ,  C12Q1/68 ,  C40B30/00 ,  C40B30/04 ,  G01N33/53 ,  G01N33/574

CPC classification number: C12Q1/6886 ,  C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136 ,  C12Q2600/16 ,  G01N33/57442 ,  G01N33/6893 ,  G01N2500/10

Abstract: Methods for detecting endometrial diseases or an endometrium phase in a subject are described comprising measuring endometrial markers or polynucleotides encoding the markers in a sample from the subject. The invention also provides localization or imaging methods for endometrial diseases, and kits for carrying out the methods of the invention. The invention also contemplates therapeutic applications for endometrial diseases employing endometrial markers, polynucleotides encoding the markers, and/or binding agents for the markers.

Abstract translation: 描述了检测受试者子宫内膜疾病或子宫内膜期的方法，其包括测量子宫内膜标志物或编码来自受试者的样品中的标记物的多核苷酸。 本发明还提供子宫内膜疾病的定位或成像方法以及用于实施本发明方法的试剂盒。 本发明还考虑了使用子宫内膜标志物，编码标记物的多核苷酸和/或用于标记物的结合剂的子宫内膜疾病的治疗应用。