公开(公告)号：EP1366021B1

公开(公告)日：2007-07-11

申请号：EP02753691.1

申请日：2002-03-01

申请人： TELIK, INC.

发明人： ROBINSON, Louise ,  VILLAR, Hugo, O.

IPC分类号： C07C275/42 ,  C07C275/30 ,  C07C317/42 ,  A61K31/17 ,  A61P35/00 ,  A61P37/00 ,  A61P19/00

CPC分类号： C07C275/30 ,  C07C275/42 ,  C07C309/65 ,  C07C317/42

摘要： Substituted diarylureas, pharmaceutical compositions containing them, and their use for stimulating Fas-mediated apoptosis. The compounds, as single stereoisomers or mixtures of stereoisomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them, are useful in methods of treating autoimmune diseases, infectious diseases, and malignancies.

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：EP1363897A2

公开(公告)日：2003-11-26

申请号：EP02709746.8

申请日：2002-02-28

申请人： TELIK, INC. ,  Sanwa Kagaku Kenkyusho Co., Ltd.

发明人： LABORDE, Edgardo ,  ROBINSON, Louise ,  MENG, Fanying ,  PETERSON, Brian, T. ,  VILLAR, Hugo, O. ,  ANUSKIEWICZ, Steven, E. ,  ISHIWATA, Yoshiro ,  YOKOCHI, Shoji ,  MATSUMOTO, Yukiharu ,  KAKIGAMI, Takuji ,  INAGAKI, Hideaki ,  JOMORI, Takahito ,  MATSUSHIMA, Kouji

IPC分类号： C07D319/18 ,  C07D405/12 ,  C07D409/12 ,  C07D407/12 ,  C07D241/42 ,  C07D417/12 ,  C07D401/12 ,  C07D265/36 ,  C07D215/48 ,  A61K31/357 ,  A61P29/00

CPC分类号： C07D401/12 ,  C07D215/48 ,  C07D241/42 ,  C07D265/36 ,  C07D319/18 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D417/12

摘要： The present invention relates to chemical compounds, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, methods of treatment employing said compounds and compositions, and processes for preparing said compounds. Specifically, this invention relates to novel compounds which are antagonists of MCP-1 function and are useful in the prevention or treatment of chronic or acute inflammatory or autoimmune diseases, especially those associated with aberrant lymphocyte or monocyte accumulation such as arthritis, asthma, atherosclerosis, diabetic nephropathy, inflammatory bowel disease, Crohn's disease, multiple sclerosis, nephritis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, and transplant rejection. More specifically, the invention is related to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases.

公开(公告)号：EP1357913A1

公开(公告)日：2003-11-05

申请号：EP02714858.4

申请日：2002-02-08

申请人： TELIK, INC.

发明人： LABORDE, Edgardo ,  VILLAR, Hugo, O.

IPC分类号： A61K31/41 ,  C07D417/04 ,  C07D409/12 ,  C07D405/04 ,  C07D249/12 ,  C07D271/10 ,  A61P25/28

CPC分类号： C07D271/113 ,  A61K31/41 ,  A61K31/4196 ,  A61K31/4245 ,  A61K31/433 ,  C07D403/04 ,  C07D409/12 ,  C07D417/04

摘要： The invention provides compounds, compositions and methods for inhibiting the glycine transporter (2) and for affecting glycine transporter mediated neuronal activity. Useful compounds comprise compounds of Formula I : wherein n is (0, 1, 2 or 3) and R is independently halogen, hydroxy, lower alkyl optionally substituted with halogen or lower alkoxy optionally substituted with halogen; X is O, S or N-R' (wherein R's is lower alkyl, aryl, heteroaryl, aryl-lower alkylene or heteroaryl-lower alkylene); Q may be absent or present, and when present, it is represented by the formula : in which n, R and X are as defined above; when Q is present, W is a lower alkylene and when Q is absent, W is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl (optionally substituted aryl)-X-CH2-or (optionally substituted heteroaryl)-X-CH2-in which X is as defined above; or a pharmaceutically acceptable salt thereof. These compounds are particularly useful for treating diseases of the nerve and muscle, including psychoses, pain, epilepsy, neurodegenerative diseases, stroke, head trauma, multiple sclerosis and the like, and of muscle disorders, including diseases or conditions associated with increased muscle contraction, such as spasticity and myoclonus. In addition, the compounds may be used to discover other agents with improved activity in assays in which the compounds of the invention are active.

公开(公告)号：EP1315695A2

公开(公告)日：2003-06-04

申请号：EP01968657.5

申请日：2001-09-06

申请人： Telik, Inc.

发明人： Robinson, Louise ,  Cairns, Nicholas ,  Manchem, Prasad V. V. S. V. ,  Chow, Steven R.

IPC分类号： C07C235/84 ,  C07C309/28 ,  C07C231/02 ,  C07C231/12 ,  C07C303/22 ,  A61K31/185 ,  G01N33/50

CPC分类号： G01N33/5005 ,  C07C233/81 ,  C07C309/51 ,  G01N33/566 ,  G01N2333/912 ,  G01N2800/042

摘要： The present invention relates to trimesic acid amides, pharmaceutical compositions comprising said compounds, uses of said compounds and compositions, and processes for their preparation. Specifically, this invention relates to means to enhance insulin-dependent glucose uptake. More specifically, the invention concerns compounds and pharmaceutical compositions that active the insulin receptor kinase, which leads to an increased sensitivity to insulin and an increase in glucose uptake, as well as processes for preparation of the compounds. As such, the invention also concerns methods or uses of the compounds for the treatment of animals with hyperglycemia, especially for the treatment of type 2 diabetes.

公开(公告)号：EP0738390B1

公开(公告)日：2003-04-02

申请号：EP95906754.7

申请日：1995-01-05

申请人： TELIK, INC.

发明人： KAUVAR, Lawrence, M. ,  VILLAR, Hugo, O.

IPC分类号： G01N33/53 ,  G01N33/68

CPC分类号： G01N33/6845 ,  G01N33/53 ,  G01N33/5308 ,  G01N33/68 ,  G01N33/94

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.

公开(公告)号：EP0720620B1

公开(公告)日：2000-05-24

申请号：EP94929323.7

申请日：1994-09-23

申请人： TELIK, INC.

发明人： KAUVAR, Lawrence M. ,  LYTTLE, Matthew H.

IPC分类号： C07K5/037 ,  C07K5/093 ,  C07K5/113 ,  C07C323/60 ,  C12N9/10 ,  C12Q1/48 ,  A61K38/45 ,  A61K31/195

CPC分类号： A61K38/06 ,  C07K5/0215 ,  C12N9/1088 ,  G01N30/02 ,  G01N33/573 ,  G01N33/57496 ,  G01N2333/91177 ,  B01D15/3804 ,  B01D15/422

摘要： A compound of formula (1) and the alkyl-type (1-10C), alkenyl-type (1-10C), and arylalkyl-type (7-12C) esters, amides and mixed ester/amides thereof; wherein Z is selected from the group consisting of S, O, and C; n is 1, 2 or 3; wherein when Z is O or S and n is 1, X is a mono- or disubstituted or unsubstituted hydrocarbyl (1-20C) moiety optionally containing 1 or 2 nonadjacent heteroatoms (O, S or N), and wherein said substitution is selected from the group consisting of halo, -NO, -NO2, -NR2, OR, and SR, wherein each R is independently H or lower alkyl (1-4C); wherein when Z is S and n is 2, one X is as above defined and the other X is lower alkyl (1-4C); and wherein when Z is C and n is 3, one X is as above defined and the other two X are independently H or lower alkyl (1-4C); Y-CO is selected from the group consisting of η-Glu, β-Asp, Glu, Asp, ηGlu-Gly, β-Asp-Gly, Glu-Gly, and Asp-Gly, and AAC is an amino acid coupled through a peptide bond to the remainder of the compound of formula (1), are useful as affinity ligands, elution reagents, solution inhibitors, diagnostic reagents and therapeutics. These compounds and analogous tripeptide glutathione analogs can be used as members of panels to obtain specific characteristic profiles for various glutathione-S-transferases.

公开(公告)号：EP0721465B1

公开(公告)日：2000-05-03

申请号：EP94930535.3

申请日：1994-09-30

申请人： TELIK, INC.

发明人： KAUVAR, Lawrence, M. ,  LYTTLE, Matthew, H. ,  SATYAM, Apparao

IPC分类号： C07K5/037 ,  A61K38/04

CPC分类号： A61K38/06 ,  C07K5/0215 ,  C12N9/1088 ,  G01N30/02 ,  G01N33/573 ,  G01N33/57496 ,  G01N2333/91177 ,  B01D15/422 ,  B01D15/3804

摘要： Compounds of formula (1) or the amides, esters or salts thereof, wherein: L is an electron withdrawing leaving group; Sx is S=O, O=S=O, S=NH, HN=S=O, Se=O, O=Se=O, Se=NH, HN=Se=O, S+R4 wherein R4 is alkyl (1-6C), or O-C=O or HN-C=O; each R of R?1, R2 and R3¿ is independently H or a noninterfering substituent; n is 0, 1 or 2; Y-CO is selected from the group consisting of η-Glu, β-Asp, Glu, Asp, η-GluGly, β-AspGly, GluGly and AspGly; and AA¿c? is an amino acid linked through a peptide bond to the ramainder of said compound of Formula (1), are disclosed. These compounds are useful prodrugs for selective treatment of target tissues which contain compatible glutathione S-transferase (GST) isoenzymes, and simultaneously elevate the levels of GM progenitor cells in bone marrow.