7695-82-1Relevant academic research and scientific papers
Synthesis and in vitro evaluation of 18F labeled tyrosine derivatives as potential positron emission tomography (PET) imaging agents
Wang, Limin,Qu, Wenchao,Lieberman, Brian,Ploessl, Karl,Kung, Hank F.
scheme or table, p. 3482 - 3485 (2010/08/22)
Three new 18F labeled fluoroalkyl tyrosine derivatives, O-(2-[18F]fluoroethyl)-α-methyltyrosine (FEMT, [ 18F]2), O-(2-[18F]fluoroethyl)-2-l-azatyrosine (FEAT, [18F]3), O-(2-[18F]fluoroethyl
Structure-Activity Relationships of Small Phosphopeptides, Inhibitors of Grb2 SH2 Domain, and Their Prodrugs
Liu, Wang-Qing,Vidal, Michel,Olszowy, Catherine,Million, Emmanuelle,Lenoir, Christine,Dh?tel, Hélène,Garbay, Christiane
, p. 1223 - 1233 (2007/10/03)
To develop potential antitumor agents directed toward HER2/ErbB2 overexpression in cancer, we have designed inhibitors of the recognition between the phosphotyrosine of the receptor and the SH2 domain of the adaptor protein Grb2. In the first part of the paper, we report the synthesis of mimetics of the constrained (α-Me)phosphotyrosine residue such as (α-Me)-4-phosphonomethylphenylalanine (-CH2PO3H 2), (α-Me) 4-phosphonodifluoromethylphenylalanine (-CF 2PO3H2), and (α -Me)-4-phosphonophenylalanine (-PO3H2). The incorporation of these residues in the mAZ-pTyr-Xaa-Asn-NH2 series provided compounds with very high affinity for the Grb2 SH2 domain, in the 10 -8-10-9 range of Kd values. These compounds behave as potent antagonists of the Grb2-Shc interaction. Our results highlight the importance of the doubly negative charge borne by the pY + 1 amino acid in accordance with the interactions observed in the complex crystallized between mAZ-pTyr-(αMe)pTyr-Asn-NH2 and the Grb2 SH2 domain. mAZ-pTyr-(αMe)pTyr-Asn-NH2 was derivatized as the S-acetyl thioester (SATE) of the phosphotyrosine residues, and its surrogates provided prodrugs with very potent antiproliferative activity on cells overexpressing HER2/ErbB2, with ED50 values amounting to 0.1 μM. Finally a new prodrug is put forth under the form of a monobenzyl ester of phosphate group that is as active as and much easier to synthesize than SATE prodrugs. These compounds show promising activity for further testing on in vivo models.
BENZAMIDINE DERIVATIVES SUBSTITUTED BY AMINO ACID AND HYDROXY ACID DERIVATIVES AND THEIR USE AS ANTI-COAGULANTS
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, (2008/06/13)
This invention is directed to benzamidine derivatives substituted by amino acid and hydroxy acid derivatives which are useful as anti-coagulants. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.
