公开(公告)号：EP0747056A2

公开(公告)日：1996-12-11

申请号：EP96303874.0

申请日：1996-05-30

申请人： ELI LILLY AND COMPANY

发明人： Cullinan, George Joseph ,  Fontana, Steven Anthony ,  Fuchs-Young, Robin Sharon Lee ,  Glasebrook, Andrew Lawrence

IPC分类号： A61K31/565

CPC分类号： A61K31/4535 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/55

摘要： The present invention provides a method for minimizing the bone loss effect of a compound of formula I
wherein R is -CH 2 CON(CH 3 )-n-CH 2 CH 2 CH 2 CH 3 or -SO(CH 2 ) 3 CF 2 CF 3 , or a pharmaceutically acceptable salt thereof, and wherein said formula I compound is administered to a mammal in need of treatment, comprising concurrently or sequentially administering to said mammal an effective amount of a compound of formula II
wherein
   each R 1 is independently -H, -OH, -O(C 1 -C 4 alkyl), -OCOC 6 H 5 , -OCO(C 1 -C 6 alkyl), or -OSO 2 (C 4 -C 6 alkyl); and
   R 2 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof.
Also provided is a method for minimizing bone loss induced by the administration of a formula I compound comprising concurrently or sequentially administering a bone anabolic agent. Pharmaceutical compositions are also provided.

公开(公告)号：EP0895989B1

公开(公告)日：2005-05-18

申请号：EP98306198.7

申请日：1998-08-04

申请人： ELI LILLY AND COMPANY

发明人： Dodge, Jeffrey Alan ,  Glasebrook, Andrew Lawrence ,  Lugar, Charles Willis

IPC分类号： C07D207/08 ,  C07D211/22 ,  C07D295/112 ,  C07D265/30 ,  C07D221/20 ,  C07D207/27 ,  C07C211/05 ,  C07C211/06 ,  C07C211/58 ,  C07C275/30 ,  A61K31/445 ,  A61K31/545 ,  A61K31/13 ,  A61K31/135

CPC分类号： C07D207/08 ,  C07C217/20 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07D207/27 ,  C07D211/22 ,  C07D221/20 ,  C07D295/088 ,  C07D295/112 ,  C07D473/08

公开(公告)号：EP0724879A3

公开(公告)日：1996-09-11

申请号：EP96300767.9

申请日：1996-02-05

申请人： ELI LILLY AND COMPANY

发明人： Glasebrook, Andrew Lawrence ,  Zuckerman, Steven Harold

IPC分类号： A61K31/40 ,  A61K31/445 ,  A61K31/55

CPC分类号： A61K31/4535 ,  A61K31/4025 ,  A61K31/55

摘要： A method of inhibiting the effects of IL-6 comprising administering to a human in need thereof an effective amount of a compound having the formula

   wherein R 1 and R 3 are independently hydrogen, -CH 3 ,

or

wherein Ar is optionally substituted phenyl;
   R 2 is selected from the group consisting of pyrrolidine, hexamethyleneimino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

摘要翻译： 一种抑制IL-6作用的方法，包括给予有需要的人有效量的具有下式的化合物：其中R1和R3独立地为氢，-CH3或其中Ar为任选取代的苯基; R2选自吡咯烷，六亚甲基亚氨基和哌啶子基; 或其溶剂化物的药学上可接受的盐。

公开(公告)号：EP0659413A3

公开(公告)日：1995-10-11

申请号：EP94309470.6

申请日：1994-12-19

申请人： ELI LILLY AND COMPANY

发明人： Bryant, Henry Uhlman ,  Glasebrook, Andrew Lawrence ,  Grese, Timothy Alan ,  Phillips, David Lynn

IPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/38

CPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/4535

摘要： A method of inhibiting one or more CNS disorders in a post-menopausal woman comprising administering to a female human in need of treatment an effective amount of a compound having the formula

   wherein R¹ and R³ are independently hydrogen, -CH₃,

wherein Ar is optionally substituted phenyl;
   R² is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

公开(公告)号：EP0659413A2

公开(公告)日：1995-06-28

申请号：EP94309470.6

申请日：1994-12-19

申请人： ELI LILLY AND COMPANY

发明人： Bryant, Henry Uhlman ,  Glasebrook, Andrew Lawrence ,  Grese, Timothy Alan ,  Phillips, David Lynn

IPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/38

CPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/4535

摘要： A method of inhibiting one or more CNS disorders in a post-menopausal woman comprising administering to a female human in need of treatment an effective amount of a compound having the formula

   wherein R¹ and R³ are independently hydrogen, -CH₃,

wherein Ar is optionally substituted phenyl;
   R² is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

摘要翻译： 一种抑制绝经后妇女的一种或多种CNS紊乱的方法，包括给予需要治疗的女性有效量的具有下式的化合物：其中R 1和R 3独立地是氢，-CH 3，其中Ar是任选取代的 苯基; R 2选自吡咯烷，六亚甲基氨基和哌啶子基; 或其溶剂化物的药学上可接受的盐。

公开(公告)号：EP0895989A1

公开(公告)日：1999-02-10

申请号：EP98306198.7

申请日：1998-08-04

申请人： ELI LILLY AND COMPANY

发明人： Dodge, Jeffrey Alan ,  Glasebrook, Andrew Lawrence ,  Lugar, Charles Willis

IPC分类号： C07D207/08 ,  C07D211/22 ,  C07D295/112 ,  C07D265/30 ,  C07D221/20 ,  C07D207/27 ,  C07C211/05 ,  C07C211/06 ,  C07C211/58 ,  C07C275/30 ,  A61K31/445 ,  A61K31/545 ,  A61K31/13 ,  A61K31/135

CPC分类号： C07D207/08 ,  C07C217/20 ,  C07C275/28 ,  C07C275/30 ,  C07C275/34 ,  C07D207/27 ,  C07D211/22 ,  C07D221/20 ,  C07D295/088 ,  C07D295/112 ,  C07D473/08

摘要： A class of substituted benzylnaphthylene compounds of the structure
where R 1 and R 2 are independently hydrogen, alkyl of one to six carbon atoms, acyl of two to six carbon atoms, or phenacyl; X is -(CH 2 ) 1-6 ; Y is absent or is selected from 1,4-piperazinylene; ureido; N-(lower alkyl)ureido; N'-(lower alkyl)ureido; or N, N'-(di-lower alkyl ureido; and Z is 1-, 2- or 3-pyrrolidinyl; 1-, 2-, or 3-[1-(lower alkyl) pyrrolidinyl]; 1- 2-,3- or 4-piperidinyl; 1-, 2-, 3- or 4-[1-lower alkyl)piperidinyl]; N,N-dialkyl; 1-azepinyl; 1- or 2-naphthylamino, 4-morpholinyl, dimethyl-4-morpholinyl, 3-azaspiro[5.5]undecan-3-yl; pyrrolidinon-1-yl; unsubstituted phenyl; or phenyl substituted with acyl of two to four carbon atoms, alkyl of one to four carbon atoms, halo, or alkoxy of one to four carbon atoms; with the proviso that n is not 2 or 3 when Z is 1-pyrrolidinyl, 1-piperidinyl, 1-azepinyl, 4-morpholinyl, N,N-dimethylamino or N,N-diethylamino; are selective estrogen receptor modulators useful in the prophylaxis or treatment of breast cancer.

摘要翻译： 一类结构的取代苄基萘酚化合物，其中R 1和R 2独立地是氢，1-6个碳原子的烷基，2至6个碳原子的酰基或苯甲酰甲基; X是 - （CH 2）1-6; Y不存在或选自1,4-哌嗪基; 脲; N-（低级烷基）脲基; N' - （低级烷基）脲基; 或N，N' - （二 - 低级烷基脲基）和Z是1-，2-或3-吡咯烷基; 1-，2-或3-（低级烷基）吡咯烷基; 1- 或4-哌啶基; 1-，2-，3-或4-低级烷基）哌啶基; N，N-二烷基; 1-吖庚因基; 1-或2-萘基氨基，4-吗啉基，二甲基-4-吗啉基，3-氮杂螺[5. 5 - 十一烷-3-基] 吡咯烷酮-1-基; 未取代的苯基; 或被2至4个碳原子的酰基取代的苯基，1至4个碳原子的烷基，卤素或1-4个碳原子的烷氧基; 条件是当Z是1-吡咯烷基，1-哌啶基，1-氮杂基，4-吗啉基，N，N-二甲基氨基或N，N-二乙基氨基时，n不是2或3。 是可用于预防或治疗乳腺癌的选择性雌激素受体调节剂。

公开(公告)号：EP0724879A2

公开(公告)日：1996-08-07

申请号：EP96300767.9

申请日：1996-02-05

申请人： ELI LILLY AND COMPANY

发明人： Glasebrook, Andrew Lawrence ,  Zuckerman, Steven Harold

IPC分类号： A61K31/40 ,  A61K31/445 ,  A61K31/55

CPC分类号： A61K31/4535 ,  A61K31/4025 ,  A61K31/55

摘要： A method of inhibiting the effects of IL-6 comprising administering to a human in need thereof an effective amount of a compound having the formula

   wherein R 1 and R 3 are independently hydrogen, -CH 3 ,

or

wherein Ar is optionally substituted phenyl;
   R 2 is selected from the group consisting of pyrrolidine, hexamethyleneimino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

摘要翻译： 一种抑制IL-6的作用的方法，包括向有需要的人施用有效量的具有式CHEM的化合物，其中R 1和R 3独立地是氢，-CH 3，CHEM， 或，其中Ar是任选取代的苯基; R 2选自吡咯烷，六亚甲基亚氨基和哌啶子基; 或其药学上可接受的盐的溶剂合物。

公开(公告)号：EP0659413B1

公开(公告)日：2001-10-17

申请号：EP94309470.6

申请日：1994-12-19

申请人： ELI LILLY AND COMPANY

发明人： Bryant, Henry Uhlman ,  Glasebrook, Andrew Lawrence ,  Grese, Timothy Alan ,  Phillips, David Lynn

IPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/38

CPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/4535

公开(公告)号：EP0747056B1

公开(公告)日：1999-12-15

申请号：EP96303874.0

申请日：1996-05-30

申请人： ELI LILLY AND COMPANY

发明人： Cullinan, George Joseph ,  Fontana, Steven Anthony ,  Fuchs-Young, Robin Sharon Lee ,  Glasebrook, Andrew Lawrence

IPC分类号： A61K31/445 ,  A61K31/40 ,  A61K31/55 ,  A61K31/535 ,  A61K31/565 ,  A61K38/29

CPC分类号： A61K31/4535 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/55

公开(公告)号：EP0747056A3

公开(公告)日：1997-03-05

申请号：EP96303874.0

申请日：1996-05-30

申请人： ELI LILLY AND COMPANY

发明人： Cullinan, George Joseph ,  Fontana, Steven Anthony ,  Fuchs-Young, Robin Sharon Lee ,  Glasebrook, Andrew Lawrence

IPC分类号： A61K31/565

CPC分类号： A61K31/4535 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/55

摘要： The present invention provides a method for minimizing the bone loss effect of a compound of formula I
wherein R is -CH 2 CON(CH 3 )-n-CH 2 CH 2 CH 2 CH 3 or -SO(CH 2 ) 3 CF 2 CF 3 , or a pharmaceutically acceptable salt thereof, and wherein said formula I compound is administered to a mammal in need of treatment, comprising concurrently or sequentially administering to said mammal an effective amount of a compound of formula II
wherein
   each R 1 is independently -H, -OH, -O(C 1 -C 4 alkyl), -OCOC 6 H 5 , -OCO(C 1 -C 6 alkyl), or -OSO 2 (C 4 -C 6 alkyl); and    R 2 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof. Also provided is a method for minimizing bone loss induced by the administration of a formula I compound comprising concurrently or sequentially administering a bone anabolic agent. Pharmaceutical compositions are also provided.

摘要翻译： 本发明提供了用于使其中R为-CH 2 CON（CH 3）-n-CH 2 CH 2 CH 2 CH 3或-SO（CH 2）3 CF 2 CF 3的式I化合物或其可药用盐的骨损失作用最小化的方法，并且其中所述式I 化合物给予需要治疗的哺乳动物，所述方法包括对所述哺乳动物同时或相继施用有效量的式II化合物，其中每个R 1独立地为-H，-OH，-O（C 1 -C 4烷基）， - OCOC 6 H 5 ，-OCO（C 1 -C 6烷基）或-OSO 2（C 4 -C 6烷基）; R2为1-哌啶基，1-吡咯烷基，甲基-1-吡咯烷基，二甲基-1-吡咯烷基，4-吗啉代，二甲基氨基，二乙基氨基或1-六亚甲基亚氨基; 或其药学上可接受的盐。 还提供了用于最小化由施用式I化合物引起的骨损失的方法，所述方法包括同时或顺序施用骨合成代谢剂。 还提供了药物组合物。