公开(公告)号：EP1278759B1

公开(公告)日：2005-12-21

申请号：EP01935025.5

申请日：2001-05-02

申请人： TELIK, INC.

发明人： HERR, Jason, R. ,  LUM, Robert, T. ,  SCHOW, Steven, R. ,  MENG, Fanying ,  KOZLOWSKI, Michael, R. ,  ZHICHKIN, Pavel

IPC分类号： C07F9/24 ,  A61K31/664 ,  A61P35/04

CPC分类号： C07F9/2458 ,  C07F9/2408

摘要： The present invention relates to chemical compounds, methods of treatment, pharmaceutical compositions, and processes for their preparation. The compounds possess anti-tumor activities or are capable of being modified to have anti-tumor activities, and therefore, this invention particularly relates to the use of the compounds in methods for the treatment of tumors and especially for the treatment of cancer, as well as to the processes for their preparation.

公开(公告)号：EP1278759A1

公开(公告)日：2003-01-29

申请号：EP01935025.5

申请日：2001-05-02

申请人： TELIK, INC.

发明人： HERR, Jason, R. ,  LUM, Robert, T. ,  SCHOW, Steven, R. ,  MENG, Fanying ,  KOZLOWSKI, Michael, R. ,  ZHICHKIN, Pavel

IPC分类号： C07F9/24 ,  A61K31/664 ,  A61P35/04

CPC分类号： C07F9/2458 ,  C07F9/2408

摘要： The present invention relates to chemical compounds, methods of treatment, pharmaceutical compositions, and processes for their preparation. The compounds possess anti-tumor activities or are capable of being modified to have anti-tumor activities, and therefore, this invention particularly relates to the use of the compounds in methods for the treatment of tumors and especially for the treatment of cancer, as well as to the processes for their preparation.

公开(公告)号：EP1200396A1

公开(公告)日：2002-05-02

申请号：EP00952351.5

申请日：2000-07-28

申请人： TELIK, INC.

发明人： SPEVAK, Wayne, R. ,  SONGYUAN, Shi ,  PRASAD, V., V., S., V., Manchem ,  KOZLOWSKI, Michael, R. ,  SCHOW, Steven, R. ,  LUM, Robert, T. ,  ROBINSON, Louise ,  PARK, Jeong, Weong

IPC分类号： C07C309/51 ,  C07C309/59 ,  C07D213/81 ,  C07D213/82 ,  C07D307/85 ,  C07C311/21 ,  C07C311/29 ,  C07C311/13 ,  C07C237/42 ,  A61K31/16 ,  A61K31/18 ,  A61K31/33

CPC分类号： C07D241/44 ,  C07C237/42 ,  C07C309/51 ,  C07C309/59 ,  C07C311/13 ,  C07C311/21 ,  C07C311/29 ,  C07D213/81 ,  C07D213/82 ,  C07D215/48 ,  C07D307/68 ,  C07D307/85

摘要： Methods for treating conditions associated with hyperglycemia, especially Type II diabetes, with novel naphthylsulfonic acids and related compounds are provided. Compounds of formula (1) where: R?1 and R2¿ are, independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, R3 is a substituent on the B ring; and is -SO¿2OR?6, -C(O)OR6, -SO2NR62-C(O)NR62 or tetrazolyl; the linker -WY- between the naphthyl and phenyl intersects the A ring of the naphthyl and is, independently, -C(O)NR?7-, -NR7¿C(O)-, -C(O)O-, -OC(O)-, -CH=CH-, -NR7CH2-, -CH2NR?7-, -NR7C(O)NR7- -NR7¿C(O)O-, -OC(O)NR?7-, -NR7SO¿2O-, -OSO2NR7-, -OC(O)O-, -SO¿2?NR?7-, -NR7SO¿2-, -OSO2-, or -SO2O-; each R?6 and R7¿ is, independently, hydrogen or lower alkyl; optionally in the form of single stereoisomers or mixtures of stereoisomers, or the pharmaceutically acceptable salts thereof; are useful in methods of stimulating the kinase activity of the insulin receptor, enhancing the activation of the insulin receptor by insulin, and stimulating the uptake of glucose into cells. A variety of antidiabetic compounds and pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.

公开(公告)号：EP1143992A2

公开(公告)日：2001-10-17

申请号：EP00908420.3

申请日：2000-01-27

申请人： TELIK, INC.

发明人： REDELMEIER, Thomas ,  KAUVAR, Lawrence, M. ,  LUM, Robert, T. ,  LYTTLE, Matthew, H. ,  MACSATA, Robert, W. ,  SCHOW, Steven, R. ,  VILLAR, Hugo, O. ,  KOZLOWSKI, Michael, R.

IPC分类号： A61K38/06 ,  A61K9/127

CPC分类号： A61K9/127 ,  A61K9/1075 ,  A61K38/063

摘要： Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.

公开(公告)号：EP1181271B1

公开(公告)日：2005-01-19

申请号：EP00936360.7

申请日：2000-05-25

申请人： TELIK, INC.

发明人： SPEVAK, Wayne ,  LUM, Robert, T. ,  SHI, Songyuan ,  MANCHEM, Prasad ,  KOZLOWSKI, Michael, R. ,  SCHOW, Steven, R.

IPC分类号： C07C311/47 ,  C07C309/51 ,  C07D257/04 ,  C07D213/76 ,  C07D233/32 ,  C07D335/18 ,  C07C335/32 ,  C07D211/96 ,  A61K31/18 ,  A61K31/395

CPC分类号： C07D257/04 ,  C07C309/51 ,  C07C311/47 ,  C07C335/16 ,  C07C335/18 ,  C07C335/32 ,  C07D211/96 ,  C07D213/76 ,  C07D233/36 ,  C07D239/42 ,  C07D241/20 ,  C07F9/4021

摘要： Compounds of formula (I), wherein R?1 and R2¿ are substituents on the A rings and are, independently, -SO¿2NR?72, -C(O)NR72, -NR7SO2R?7, -NR7C(O)R7, -SO¿2OR7, -C(O)OR7, -OSO¿2R?7, or -OC(O)R?7, R3 and R4¿ are, independently, hydrogen or lower alkyl, or R?3 and R4¿ together are -(CH¿2?)2-, -(CH2)3-, or -(CH2)4-, or R?3 or R4¿ may be an electron pair, R?5 and R6¿ are, independently, hydrogen, alkyl, substituted alkyl, cyano, halo, nitro, -SR8, -C(O)R8, -SO2OR8, -OSO¿2?R?8, -SO¿2NR82, -NR8SO2R8, -OC(O)R8, -C(O)OR8, -C(O)NR82, -NR?8C(O)R8, -OR8¿, or -NR82, each R?7 and R8¿ is, independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, aryl(lower)alkyl, substituted aryl(lower)alkyl, heteroaryl(lower)alkyl, substituted heteroaryl(lower)alkyl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl, each Y is, independently, a non-interfering substituent which is not linked to the naphthalene ring via an azo or amide linkage, each x is independently, 0, 1 or 2, and the linker connects a carbon designated as c to a carbon designated as d, or a pharmaceutically acceptable salt thereof, as a single stereoisomer or mixture of stereoisomers, are useful for treating conditions associated with hyperglycemia, especially Type II diabetes, with dinaphthylureas. These compounds are useful in stimulating the kinase activity of the insulin receptor, activating the insulin receptor, and stimulating the uptake of glucose. Pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.

公开(公告)号：EP1143992B1

公开(公告)日：2005-01-12

申请号：EP00908420.3

申请日：2000-01-27

申请人： TELIK, INC.

发明人： REDELMEIER, Thomas ,  KAUVAR, Lawrence, M. ,  LUM, Robert, T. ,  LYTTLE, Matthew, H. ,  MACSATA, Robert, W. ,  SCHOW, Steven, R. ,  VILLAR, Hugo, O. ,  KOZLOWSKI, Michael, R.

IPC分类号： A61K38/06 ,  A61K9/127

CPC分类号： A61K9/127 ,  A61K9/1075 ,  A61K38/063

摘要： Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.

公开(公告)号：EP1181271A2

公开(公告)日：2002-02-27

申请号：EP00936360.7

申请日：2000-05-25

申请人： Telik, Inc.

发明人： SPEVAK, Wayne ,  LUM, Robert, T. ,  SHI, Songyuan ,  MANCHEM, Prasad ,  KOZLOWSKI, Michael, R. ,  SCHOW, Steven, R.

IPC分类号： C07C311/47 ,  C07C309/51 ,  C07D257/04 ,  C07D213/76 ,  C07D233/32 ,  C07D335/18 ,  C07C335/32 ,  C07D211/96 ,  A61K31/18 ,  A61K31/395

CPC分类号： C07D257/04 ,  C07C309/51 ,  C07C311/47 ,  C07C335/16 ,  C07C335/18 ,  C07C335/32 ,  C07D211/96 ,  C07D213/76 ,  C07D233/36 ,  C07D239/42 ,  C07D241/20 ,  C07F9/4021

摘要： Compounds of formula (I), wherein R?1 and R2¿ are substituents on the A rings and are, independently, -SO¿2NR?72, -C(O)NR72, -NR7SO2R?7, -NR7C(O)R7, -SO¿2OR7, -C(O)OR7, -OSO¿2R?7, or -OC(O)R?7, R3 and R4¿ are, independently, hydrogen or lower alkyl, or R?3 and R4¿ together are -(CH¿2?)2-, -(CH2)3-, or -(CH2)4-, or R?3 or R4¿ may be an electron pair, R?5 and R6¿ are, independently, hydrogen, alkyl, substituted alkyl, cyano, halo, nitro, -SR8, -C(O)R8, -SO2OR8, -OSO¿2?R?8, -SO¿2NR82, -NR8SO2R8, -OC(O)R8, -C(O)OR8, -C(O)NR82, -NR?8C(O)R8, -OR8¿, or -NR82, each R?7 and R8¿ is, independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, aryl(lower)alkyl, substituted aryl(lower)alkyl, heteroaryl(lower)alkyl, substituted heteroaryl(lower)alkyl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl, each Y is, independently, a non-interfering substituent which is not linked to the naphthalene ring via an azo or amide linkage, each x is independently, 0, 1 or 2, and the linker connects a carbon designated as c to a carbon designated as d, or a pharmaceutically acceptable salt thereof, as a single stereoisomer or mixture of stereoisomers, are useful for treating conditions associated with hyperglycemia, especially Type II diabetes, with dinaphthylureas. These compounds are useful in stimulating the kinase activity of the insulin receptor, activating the insulin receptor, and stimulating the uptake of glucose. Pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.