- PARP inhibitor cyanine dye conjugate with enhanced cytotoxic and antiproliferative activity in patient derived glioblastoma cell lines
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We describe the synthesis and in vitro activity of drug-dye conjugate 1, which is a combination of the PARP inhibitor rucaparib and heptamethine cyanine dye IR-786. The drug-dye conjugate 1 was evaluated in three different patient-derived glioblastoma cell lines and showed strong cytotoxic activity with nanomolar potency (EC50: 128 nM), which was a 780 fold improvement over rucaparib itself. We also observe a synergistic effect of 1 with temozolomide (TMZ), the standard drug for treatment for glioblastoma even though these cell lines were resistant to TMZ treatment. We envisage such conjugates to be worth exploring for their utility in the treatment of various brain cancers.
- Choi, Peter J.,Cooper, Elizabeth,Denny, William A.,Dragunow, Mike,Faull, Richard,Jose, Jiney,Mee, Edward,Park, Thomas I.-H.,Schweder, Patrick,Turner, Clinton
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Read Online
- TARGETED PROTEIN DEGRADATION
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This invention provides pharmaceutical protein degraders and E3 ubiquitin ligase binders for therapeutic applications as described further herein.
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Page/Page column 357-358
(2020/07/14)
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- INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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The present invention provides compounds, and pharmaceutically acceptable compositions thereof, encompassed by any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof. The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH by administering a therapeutically effective amount of a compound or composition comprising a compound of any of formulae (I), (II), (III), (IV), (V), or (VI), or subgenera thereof, to a patient in need thereof.
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Paragraph 0622; 0644; 0646; 1288; 1289
(2016/01/15)
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- Novel inhibitors of bacterial biofilms and related methods
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Multi-cyclic compounds of chemical structure represented by formula given below and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.
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Paragraph 0407; 0408
(2014/05/06)
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- Inhibitors of bacterial biofilms and related methods
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Certain multi-cyclic compounds and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms.
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Page/Page column 173
(2012/12/13)
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- Development of (S)-N6-(2-(4-(isoquinolin-1-yl)piperazin-1-yl) ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor preferring agonist: Potent in vivo activity in Parkinson's disease anima
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Here we report structure - activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were
- Ghosh, Balaram,Antonio, Tamara,Zhen, Juan,Kharkar, Prashant,Reith, Maarten E. A.,Dutta, Aloke K.
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experimental part
p. 1023 - 1037
(2010/08/06)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF AS ERK INHIBITORS
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Disclosed are the ERK inhibitors of formula 1.0: [Formula (1.0)] and the pharmaceutically acceptable salts, esters and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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- PYRROLIDINE DERIVATIVES AS ERK INHIBITORS
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Disclosed are the ERK inhibitors of Formula (1.0): and the pharmaceutically acceptable salts and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of Formula (1.0).
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Page/Page column 178-179
(2010/11/28)
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- POLYCYCLIC INDAZOLE DERIVATIVES THAT ARE ERK INHIBITORS
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Disclosed are the ERK inhibitors of formula 1.0 and the pharmaceutically acceptable salts and solvates thereof. Q is a piperidine or piperazine ring that can have a bridge or a fused ring. The piperidine ring can have a double bond in the ring. All other substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of formula 1.0.
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Page/Page column 190
(2008/06/13)
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- METHOD OF PREPARING INHIBITORS OF PHOSPHODIESTERASE-4
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In one aspect, the present invention is directed to a one pot method of preparing intermediates of Formula V, which are useful in making inhibitors of phosphodiesterase-4: The present invention is also directed to a method of preparing phosphodiesterase inhibitors comprising the Formula
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- 4,5-DIHYDRO-IMIDAZO[4,5,1-II]QUINOLIN-6-ONES AS PARP INHIBITORS
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Compounds of the formula 1, in which R1 and R2 have the meanings indicated in the description, are novel active PARP inhibitors.
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- Practical asymmetric synthesis of a potent Cathepsin K inhibitor. Efficient palladium removal following Suzuki coupling
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A large-scale, chromatography-free synthesis of a potent and selective Cathepsin K inhibitor 1 is reported. The key asymmetric center was installed by addition of (R)-pantolactone to the in situ-generated ketene 4a. The final step of the convergent synthe
- Chen, Cheng-yi,Dagneau, Philippe,Grabowski, Edward J.J.,Oballa, Renata,O'Shea, Paul,Prasit, Peppi,Robichaud, Joel,Tillyer, Rich,Wang, Xin
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p. 2633 - 2638
(2007/10/03)
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