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Chemical Structure| 1496997-41-1 Chemical Structure| 1496997-41-1

Structure of Thalidomide-5,6-F
CAS No.: 1496997-41-1

Chemical Structure| 1496997-41-1

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Osawa, Hinata ; Kurohara, Takashi ; Ito, Takahito ; Shibata, Norihito ; Demizu, Yosuke ;

Abstract: An increasing number of research reports are describing modifications of the E3 ligand, in particular, cereblon (CRBN) ligands, to improve the chem. and metabolic stabilities as well as the phys. properties of PROTACs. In this study, phenyl-glutarimide (PG) and 6-fluoropomalidomide (6-F-POM), recently used as CRBN ligands for PROTAC design, were applied to hematopoietic prostaglandin D2 synthase (H-PGDS)-targeted PROTACs. Both PROTAC-5 containing PG and PROTAC-6 containing 6-F-POM were found to have potent activities to induce H-PGDS degradation Furthermore, we obtained in vitro ADME data on the newly designed PROTACS as well as our previously reported PROTACs(H-PGDS) series. Although all PROTACs(H-PGDS) are relatively stable toward metabolism, they had poor PAMPA values. Nevertheless, PROTAC-5 showed Papp values similar to TAS-205, which is in Phase 3 clin. trials, and is expected to be the key to improving the pharmacokinetics of PROTACs.

Keywords: PROTAC ; H-PGDS ; ADME ; Phenyl-glutarimide ; Docking study

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Product Details of [ 1496997-41-1 ]

CAS No. :1496997-41-1
Formula : C13H8F2N2O4
M.W : 294.21
SMILES Code : O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=C(F)C(F)=C3)=O
MDL No. :MFCD32853274
InChI Key :AGHXYRKTAZEQQW-UHFFFAOYSA-N
Pubchem ID :65968512

Safety of [ 1496997-41-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501
 

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