1025796-40-0Relevant academic research and scientific papers
Novel β- And γ-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen
Kim, Kyul,Kwon, Hongmok,Barinka, Cyril,Motlova, Lucia,Nam, Sangjin,Choi, Doyoung,Ha, Hyunsoo,Nam, Hwanhee,Son, Sang-Hyun,Minn, Il,Pomper, Martin G.,Yang, Xing,Kutil, Zsofia,Byun, Youngjoo
, p. 3261 - 3273 (2020)
Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine the effect of β- and γ-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the β- and γ-amino acid analogues with (S)- or (R)-configuration with keeping α-(l)-Glu as the S1′-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a β-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors.
HETERODIMERS OF GLUTAMIC ACID
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Page/Page column 11, (2008/12/07)
Compounds of Formula (Ia) wherein R is a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl, a C1-C6 substituted or unsubstituted alkyl or —NR′R′, Q is C(O), O, NR′, S, S(O)2, C(O)2 (CH2)pY is C(O), O, NR′, S, S(O)2, C(O)2 (CH2)p Z is H or C1-C4 alkyl,R′ is H, C(O), S(O)2, C(O)2, a C6-C12 substituted or unsubstituted aryl, a C6-C12 substituted or unsubstituted heteroaryl or a C1-C6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C6-C12 heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.
