- Discovery of clinical candidate BMS-906024: A potent pan-notch inhibitor for the treatment of leukemia and solid tumors
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Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in
- Gavai, Ashvinikumar V.,Quesnelle, Claude,Norris, Derek,Han, Wen-Ching,Gill, Patrice,Shan, Weifang,Balog, Aaron,Chen, Ke,Tebben, Andrew,Rampulla, Richard,Wu, Dauh-Rurng,Zhang, Yingru,Mathur, Arvind,White, Ronald,Rose, Anne,Wang, Haiqing,Yang, Zheng,Ranasinghe, Asoka,D'Arienzo, Celia,Guarino, Victor,Xiao, Lan,Su, Ching,Everlof, Gerry,Arora, Vinod,Shen, Ding Ren,Cvijic, Mary Ellen,Menard, Krista,Wen, Mei-Li,Meredith, Jere,Trainor, George,Lombardo, Louis J.,Olson, Richard,Baran, Phil S.,Hunt, John T.,Vite, Gregory D.,Fischer, Bruce S.,Westhouse, Richard A.,Lee, Francis Y.
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p. 523 - 527
(2015/05/27)
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- PRODRUGS OF 1,4-BENZODIAZEPINONE COMPOUNDS
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Disclosed are compounds of Formula (I) and salts thereof, wherein: a) R1 is H or CH3, and R2 is Ry; or b) R1 is Rx and R2 is H; wherein Rx and Ry are disclosed herein.
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Paragraph 00147
(2014/04/04)
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- BISFLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS
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Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R1 is —CH2CF3 or —CH2CH2CF3; R2 is —CH2CF3, —CH2CH2CF3, or —CH2CH2CH2CF3; R3 is H or —CH3; each Ra is independently F, Cl, —CN, —OCH3, and/or —NHCH2CH2OCH3; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.
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Page/Page column 26
(2012/10/08)
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- 5-PHENYL-LH-BENZ0 [E] [1, 4] DIAZEPINE COMPOUNDS SUBSTITUTED WITH AN HYDROXAMIC ACID GROUP AS HISTONE DEACETYLASE INHIBITORS
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Novel hydroxamate histone deacetylase inhibitors of formula (I) wherein X is C=O or CH2 used as antineoplastic agent.
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Page/Page column 24
(2009/07/25)
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- Induced association of μ opioid (MOP) and type 2 cholecystokinin (CCK2) receptors by novel bivalent ligands
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Both μ-opioid (MOP) and type 2 cholecystokinin (CCK2) receptors are present in areas of the central nervous system that are involved in modulation of pain processing. We conducted bioluminescence resonance energy transfer (BRET) studies on COS
- Zheng, Yaguo,Akgiin, Eyup,Harikumar, Kaleeckal G.,Hopson, Jessika,Powers, Michael D.,Lunzer, Mary M.,Miller, Laurence J.,Portoghese, Philip S.
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experimental part
p. 247 - 258
(2009/10/09)
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- Synthesis and in vitro characterization of radioiodinatable benzodiazepines selective for type 1 and Type 2 cholecystokinin receptors
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Radiolabeled antagonists of specific peptide receptors identify a higher number of receptor binding sites than agonists and may thus be preferable for in vivo tumor targeting. In this study, two novel radioiodinated1,4- benzodiazepines, (S)-1-(3-iodopheny
- Akgün, Eyup,K?rner, Meike,Gao, Fan,Harikumar, Kaleeckal G.,Waser, Beatrice,Reubi, Jean Claude,Portoghese, Philip S.,Miller, Laurence J.
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scheme or table
p. 2138 - 2147
(2009/12/31)
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- Synthesis and Resolution of 3-Amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones
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Two efficient synthetic routes to the 3-amino-1,4-benzodiazepin-2-ones 2 and 3 were developed.The first sequence was carried out in 55-60percent overall yield and involves a novel mercuric ion assisted ammonia displacement of the (alkylthio)glycinamide 14 to produce the key intermediate α-aminoglycinamide 15.The second approach features a practical two-step amination of the parent 1,4-benzodiazepine ring system 24 to afford the title compound 3 in 49percent overall yield from 2-aminobenzophenone.The 3-amino-1,4-benzodiazepine 3 was resolved via the separation of the corresponding diastereomeric phenylalanyl amides.The desired (-)-3 enantiomer was then liberated by use of the Edman degradation.
- Bock, Mark G.,DiPardo, Robert M.,Evans, Ben E.,Rittle, Kenneth E.,Veber, Daniel F.,et al.
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p. 3232 - 3239
(2007/10/02)
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- A NEW AMINE RESOLUTION METHOD AND ITS APPLICATION TO 3-AMINOBENZODIAZEPINES
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A new method for the resolution of amines and its application to 3-aminobenzodiazepines 1 is described.The method involves the synthesis and separation of a pair of phenylalanyl amide diastereomers followed by removal of phenylalanine via the Edman degrad
- Rittle, Kenneth E.,Evans, Ben E.,Bock, Mark G.,DiPardo, Robert M.,Whitter, Willie L.,et al.
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p. 521 - 522
(2007/10/02)
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