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1.发明授权
公开(公告)号：EP0873355B1
公开(公告)日：2006-04-19
申请号：EP96944416.5
申请日：1996-12-20
申请人： TELIK, INC.
CPC分类号： C07K5/0215 , A61K38/00
摘要： Compounds of formula (1) and the amides, esters, mixed ester/amides and salts thereof are useful as tethered prodrugs that slow the rate of clearance of an active biomolecule through the MRP pump. In the compounds of formula (1), S is S=O, O=S=O, S=NH, HN=S=O, Se=O, O=Se=O, Se=NH, HN=Se=O, S R' wherein R' is alkyl (1-6C), or S is -O-C=O or -HN-C=O; YCO is selected from the group consisting of gamma -Gly, beta -Asp, Glu, Asp, gamma -GluGly, beta -AspGly, GluGly and AspGly; AAC is an amino acid linked through a peptide bond to the remainder of said compound of formula (1); each R is independently H or a noninterfering substituent; (conj) is a conjugated system; m is 0 or 1; each of the dotted lines represents a covalent bond between the biomolecule and C*, C , or a carbon in the conjugated system if present with the proviso that one and only one said bond is present; and "biomolecule" represents a moiety which becomes biologically active when covalent bond (a) is cleaved to donate an electron pair to biomolecule.
摘要翻译： 式（1）化合物及其酰胺，酯，混合酯/酰胺及其盐可用作减慢活性生物分子通过MRP泵的清除速率的束缚前药。 在式（1）化合物中，S为S = O，O = S = O，S = NH，HN = S = O，Se = O，O = Se = O，Se = NH，HN = Se = O ，S + R'，其中R'是烷基（1-6C），或S是-OC = O或-HN-C = O; YCO选自γ-Gly，β-Asp，Glu，Asp，γ-Glugly，β-AspGly，GluGly和AspGly; AAC是通过肽键与所述式（1）化合物的其余部分连接的氨基酸; 每个R独立地为H或不干扰取代基; （conj）是一个共轭体系; m是0或1; 每条虚线表示生物分子与C *，C +或共轭体系中的碳之间的共价键，条件是存在一个且仅一个所述键; “生物分子”表示当共价键（a）被切割以将电子对提供给生物分子时变成生物活性的部分。
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公开(公告)号：EP0832101B1
公开(公告)日：2004-08-11
申请号：EP96918420.9
申请日：1996-06-07
申请人： TELIK, INC.
CPC分类号： C07K5/0215 , A61K38/00
摘要： Compounds of formula (1) or of formula (2) or the amides, esters or salts thereof, wherein: Sx is S=O, O=S=O, S=NH, HN=S=O, Se=O, O=Se=O, Se=NH, HN=Se=O, S+R3 wherein R3 is alkyl (1-6C) or O-C=O or HN-C=O; each R of R?1, and R2¿ is independently H or a noninterfering substituent; wherein (conj) represents a conjugated system capable of transmitting electrons; n is 0 or 1; YCO is selected from the group consisting of K-Glu, K-Glu-Gly, Glu, Glu-Gly, JAsp, J-Asp-Gly, Asp and Asp-Gly; AA¿C? is an amino acid linked through a peptide bond to the remainder of said compound of formula (1); and N(Z) represents a reduced nitrogen-containing leaving group and L represents an electron-withdrawing leaving group, are useful as prodrugs and to generate active components released by the activity of glutathione S-transferase.
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公开(公告)号：EP0831877B1
公开(公告)日：2004-10-27
申请号：EP96918156.9
申请日：1996-06-05
申请人： TELIK, INC.
发明人： KAUVAR, Lawrence, M. , LYTTLE, Matthew, H. , MORGAN, Amy, S. , BORCH, Richard F, University Rochester Med. Ctr
IPC分类号： A61K38/06
CPC分类号： A61K38/06 , A61K38/063
摘要： Compounds of formula (1) and the esters, amides, amide/esters and salts thereof, wherein YCO is gamma -glu or beta -asp; G* is phenylglycine or glycine; Z is CH2, O or S; and X is a hydrocarbon radical of 1-20C; are useful in modulating hematopoiesis in bone marrow, mitigating the bone-marrow-destructive effects of a chemotherapeutic agent, and in potentiating the toxicity of chemotherapeutic agents.
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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.
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.
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公开(公告)号：EP0882228A1
公开(公告)日：1998-12-09
申请号：EP96936307.0
申请日：1996-10-10
申请人： Telik, Inc.
发明人： MOCHLY-ROSEN, Daria , RON, Dorit , KAUVAR, Lawrence, M. , NAPOLITANO, Eugene, W. , VORONOVA, Anna , VASQUEZ, Nicki, J.
CPC分类号： C07K5/1024 , A61K38/00 , C07K14/00 , C07K14/4722 , C07K14/705 , C12N9/1205 , G01N33/505 , G01N33/566
摘要： Methods for assessing libraries of candidate modulators of intracellular signaling transmission pathways are described. The methods assess the ability of candidates from the library to inhibit the binding of peptides which represent participants in the signaling pathways as either a signal-generating protein or its cognate partner binding at a noncatalytic site. Specific peptides useful in this regard have been identified. In one application, modulators of the immune system can be identified by determining the ability of candidate substances to affect the interaction of PKC-theta or a fragment thereof with its cognate. The interaction can be measured using binding of the cognate as an index, or can be measured using a physiological response.
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公开(公告)号：EP0960335B1
公开(公告)日：2005-05-25
申请号：EP98903515.9
申请日：1998-01-15
申请人： Telik, Inc.
发明人： KAUVAR, Lawrence, M. , SPORTSMAN, Richard , VILLAR, Hugo, O. , SPEVAK, Wayne, R. , KOHANSKI, Ron, A. , SATYAM, Apparao , KOEHLER, Ryan
CPC分类号： C12Q1/48 , C07C309/34 , C12Q1/34 , G01N33/582 , G01N2333/62 , G01N2333/72 , G01N2333/9121
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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.
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.
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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.
CPC分类号： G01N33/6845 , G01N33/53 , G01N33/5308 , G01N33/68 , G01N33/94
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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.
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.
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公开(公告)号：EP0960335A2
公开(公告)日：1999-12-01
申请号：EP98903515.0
申请日：1998-01-15
申请人： Telik, Inc.
发明人： KAUVAR, Lawrence, M. , SPORTSMAN, Richard , VILLAR, Hugo, O. , SPEVAK, Wayne, R. , KOHANSKI, Ron, A. , SATYAM, Apparao , KOEHLER, Ryan
IPC分类号： G01N33 , A61K31 , A61K38 , A61K45 , A61P3 , A61P43 , C07C309 , C07K14 , C12N15 , C12Q1 , C40B20 , C40B40 , C40B50
CPC分类号： C12Q1/48 , C07C309/34 , C12Q1/34 , G01N33/582 , G01N2333/62 , G01N2333/72 , G01N2333/9121
摘要： Methods to identify compounds from the group consisting of a composition are described. Successful substances alter the conformation of the two-lobed cytoplasmic kinase domain or preferentially bind sites which have been identified as modulator binding sites in the insulin receptor β chain. Also, modulation of the activity of the insulin receptor, enhancement of glucose uptake by cells, and other effects significant in the control and management of diabetes are accomplished using compounds of formula (1), wherein each Ar is independently an aromatic moiety; each A is independently a proton-accepting substituent; each R is independently a noninterfering substituent; m is 0, 1 or 2; n is 1-6; and each linker is independently -CH2-, -N=N-, -CH=CH-, -NHCO-, or -NHCONH- or an isostere thereof, wherein when n is 1, at least one Ar must comprise at least 2 fused aromatic rings. Compounds in the genus of formula (1) can also be used for structure activity studies to identify features responsible for the relevant activities.
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